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Abstract The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs’ preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs’ biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials. Graphical Abstract

Abstract Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field. Graphical abstract

Abstract Embryo implantation into the uterus is the gateway for successful pregnancy. Proper migration and invasion of embryonic trophoblast cells are the key for embryo implantation, and dysfunction causes pregnancy failure. Protein glycosylation plays crucial roles in reproduction. However, it remains unclear whether the glycosylation of trophoblasts is involved in trophoblast migration and invasion processes during embryo implantation failure. By Lectin array, we discovered the decreased α1,3-fucosylation, especially difucosylated Lewis Y (LeY) glycan, in the villus tissues of miscarriage patients when compared with normal pregnancy women. Downregulating LeY biosynthesis by silencing the key enzyme fucosyltransferase IV (FUT4) inhibited migration and invasion ability of trophoblast cells. Using proteomics and translatomics, the specific LeY scaffolding glycoprotein of mesoderm-specific transcript (MEST) with glycosylation site at Asn163 was identified, and its expression enhanced migration and invasion ability of trophoblast cells. The results also provided novel evidence showing that decreased LeY modification on MEST hampered the binding of MEST with translation factor eIF4E2, and inhibited implantation-related gene translation initiation, which caused pregnancy failure. The α1,3-fucosylation of MEST by FUT4 may serve as a new biomarker for evaluating the functional state of pregnancy, and a target for infertility treatment.

The yak (Bos grunniens) is a valuable livestock animal endemic to the Qinghai–Tibet Plateau in China with low reproductive rates. Cryptorchidism is one of the primary causes of infertility in male yaks. Compared with normal testes, the tight junctions (TJs) of Sertoli cells (SCs) and the integrity of the blood–testis barrier (BTB) in cryptorchidism are both disrupted. MicroRNAs are hairpin-derived RNAs of about 19–25 nucleotides in length and are involved in a variety of biological processes. Numerous studies have shown the involvement of microRNAs in the reproductive physiology of yak. In this study, we executed RNA sequencing (RNA-seq) to describe the expression profiles of mRNAs and microRNAs in yaks with normal testes and cryptorchidism to identify differentially expressed genes. GO and KEGG analyses were used to identify the biological processes and signaling pathways which the target genes of the differentially expressed microRNAs primarily engaged. It was found that novel-m0230-3p is an important miRNA that significantly differentiates between cryptorchidism and normal testes, and it is down-regulated in cryptorchidism with p < 0.05. Novel-m0230-3p and its target gene CSF1 both significantly contribute to the regulation of cell adhesion and tight junctions. The binding sites of novel-m0230-3p with CSF1 were validated by a dual luciferase reporter system. Then, mimics and inhibitors of novel-m0230-3p were transfected in vitro into SCs, respectively. A further analysis using qRT-PCR, immunofluorescence (IF), and Western blotting confirmed that the expression of cell adhesion and tight-junction-related proteins Occludin and ZO-1 both showed changes. Specifically, both the mRNA and protein expression levels of Occludin and ZO-1 in SCs decreased after transfection with the novel-m0230-3p mimics, while they increased after transfection with the inhibitors, with p < 0.05. These were achieved via the CSF1/CSF1R/Ras signaling pathway. In summary, our findings indicate a negative miRNA-mRNA regulatory network involving the CSF1/CSF1R/Ras signaling pathway in yak SCs. These results provide new insights into the molecular mechanisms of CSF1 and suggest that novel-m0230-3p and its target protein CSF1 could be used as potential therapeutic targets for yak cryptorchidism.

Preeclampsia (PE) is a pregnancy-specific disorder associated with shallow invasion of the trophoblast cells and insufficient remodeling of the uterine spiral artery. Protein glycosylation plays an important role in trophoblast cell invasion. However, the glycobiological mechanism of PE has not been fully elucidated. In the current study, employing the Lectin array, we found that soybean agglutinin (SBA), which recognizes the terminal N-acetylgalactosamine α1,3-galactose (GalNAc α1,3 Gal) glycotype, was significantly increased in placental trophoblast cells from PE patients compared with third-trimester pregnant controls. Upregulating the expression of the key enzyme α1,3 N-acetylgalactosaminyl transferase (GTA) promoted the biosynthesis of terminal GalNAc α1,3 Gal and inhibited the migration/invasion of HTR8/SVneo trophoblast cells. Moreover, the methylation status of GTA promoter in placental tissues from PE patients was lower than that in the third trimester by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) analysis. Elevated GTA expression in combination with the DNA methylation inhibitor 5-azacytidine (5-AzaC) treatment increased the glycotype biosynthesis and impaired the invasion potential of trophoblast cells, leading to preeclampsia. This study suggests that elevated terminal GalNAc α1,3 Gal biosynthesis and GTA expression may be applied as the new markers for evaluating placental function and the auxiliary diagnosis of preeclampsia.

Summary: Decidualization of endometrial stromal cells is a hallmark of endometrial receptivity for embryo implantation, and dysfunctional decidualization is associated with pregnancy failure. Protein glycosylation is an important posttranslational modification that affects the structure and function of glycoproteins. Our results showed that high-mannose epitopes were elevated in the decidual tissues of miscarriage patients compared with early pregnant women by Lectin microarray. Furthermore, the level of mannosyl-oligosaccharide α-1,2 mannosidase IA (MAN1A1), a key enzyme for high-mannose glycan biosynthesis, was decreased in the decidual tissues of miscarriage patients. Screening of lncRNAs showed that lncNEAT1 level was increased in the serum and decidua of miscarriage patients, and negatively correlated with MAN1A1 expression. The results also revealed that specific binding of lncNEAT1 with nucleophosmin (NPM1)-SP1 transcription complex inhibited MAN1A1 expression and hampered endometrial decidualization and embryo implantation potential. The study suggests the new insights into the function of high-mannose glycans/MAN1A1 modification during endometrial decidualization.

Yaks, a valuable livestock species endemic to China’s Tibetan plateau, have a low reproductive rate. Cryptorchidism is believed to be one of the leading causes of infertility in male yaks. In this study, we compared the morphology of the normal testis of the yak with that of the cryptorchidism, and found dysplasia of the seminiferous tubules, impaired tightness of the Sertoli cells, and a disruption of the integrity of the blood–testis barrier (BTB) in the cryptorchidism. Previous studies have shown that CAV1 significantly contributes to the regulation of cell tight junctions and spermatogenesis. Therefore, we hypothesize that CAV1 may play a regulatory role in tight junctions and BTB in Yaks Sertoli cells, thereby influencing the development of cryptorchidism. Additional analysis using immunofluorescence, qRT-PCR, and Western blotting confirmed that CAV1 expression is up-regulated in yak cryptorchidism. CAV1 over-expression plasmids and small RNA interference sequences were then transfected in vitro into yak Sertoli cells. It was furthermore found that CAV1 has a positive regulatory effect on tight junctions and BTB integrity, and that this regulatory effect is achieved through the FAK/ERK signaling pathway. Taken together, our findings, the first application of CAV1 to yak cryptorchidism, provide new insights into the molecular mechanisms of cell tight junctions and BTB. This paper suggests that CAV1 could be used as a potential therapeutic target for yak cryptorchidism and may provide insight for future investigations into the occurrence of cryptorchidism, the maintenance of a normal physiological environment for spermatogenesis and male reproductive physiology in the yak.

Hormone-sensitive lipase (HSL) is a key enzyme in animal fat metabolism and is involved in the rate-limiting step of catalyzing the decomposition of fat and cholesterol. It also plays an important regulatory role in maintaining seminiferous epithelial structure, androgen synthesis and primordial germ cell differentiation. We previously reported that HSL is involved the synthesis of steroids in Bactrian camels, although it is unclear what role it plays in testicular development. The present study was conducted to characterize the biological function and expression pattern of the HSL gene in the hypothalamic pituitary gonadal (HPG) axis and the development of testis in Bactrian camels. We analyzed cloning of the cDNA sequence of the HSL gene of Bactrian camels by RT-PCR, as well as the structural features of HSL proteins, using bioinformatics software, such as ProtParam, TMHMM, Signal P 4.1, SOPMA and MEGA 7.0. We used qRT-PCR, Western blotting and immunofluorescence staining to clarify the expression pattern of HSL in the HPG axis and testis of two-week-old (2W), two-year-old (2Y), four-year-old (4Y) and six-year-old (6Y) Bactrian camels. According to sequence analysis, the coding sequence (CDS) region of the HSL gene is 648 bp in length and encodes 204 amino acids. According to bioinformatics analysis, the nucleotide and amino acid sequence of Bactrian camel HSL are most similar to those of Camelus pacos and Camelusdromedarius, with the lowest sequence similarity with Mus musculus. In adult Bactrian camel HPG axis tissues, both HSL mRNA and protein expression were significantly higher in the testis than in other tissues (hypothalamus, pituitary and pineal tissues) (p < 0.05). The expression of mRNA in the testis increased with age and was the highest in six-year-old testis (p < 0.01). The protein expression levels of HSL in 2Y and 6Y testis were clearly higher than in 2W and 4Y testis tissues (p < 0.01). Immunofluorescence results indicate that the HSL protein was mainly localized in the germ cells, Sertoli cells and Leydig cells from Bactrian camel testis, and strong positive signals were detected in epididymal epithelial cells, basal cells, spermatocytes and smooth muscle cells, with partially expression in hypothalamic glial cells, pituitary suspensory cells and pineal cells. According to the results of gene ontology (GO) analysis enrichment, HSL indirectly regulates the anabolism of steroid hormones through interactions with various targets. Therefore, we conclude that the HSL gene may be associated with the development and reproduction of Bactrian camels in different stages of maturity, and these results will contribute to further understanding of the regulatory mechanisms of HSL in Bactrian camel reproduction.

Abstract Bcakground The dry root and rhizome of Salvia miltiorrhiza are used to treat cardiovascular diseases, chronic pain, and thoracic obstruction over 2000 years in Asian countries. For high quality, Sichuan Zhongjiang is regarded as the genuine producing area of S. miltiorrhiza. Given its abnormal pollen development, S. miltiorrhiza from Sichuan (S.m.-SC) relies on root reproduction and zymad accumulation; part of diseased plants present typical viral disease symptoms and seed quality degeneration. This study aim to detected unknown viruses from mosaic-diseased plants and establish a highly efficient virus-free regeneration system to recover germplasm properties. Results Tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were detected from mosaic-diseased plants. Primary apical meristem with two phyllo podium in 0.15–0.5 mm peeled from diseased plants were achieved 73.33% virus-free rate. The results showed that the medium containing MS, 0.5 mg/L 6-BA, 0.1 mg/L NAA, 0.1 mg/L GA3, 30 g/L sucrose and 7.5 g/L agar can achieve embryonic-tissue (apical meristem, petiole and leaf callus) high efficient organogenesis. For callus induction, the optimal condition was detected on the medium containing MS, 2 mg/L TDZ, 0.1 mg/L NAA by using secondary petiole of virus-free plants under 24 h dark/d condition for 21 d. The optimal system for root induction was the nutrient solution with 1/2 MS supplemented with 1 mg/L NAA. After transplant, the detection of agronomic metric and salvianolic acid B content confirmed the great germplasm properties of S.m.-SC virus-free plants. Conclusions A highly efficient virus-free regeneration system of S.m.-SC was established based on the detected viruses to recover superior seed quality. The proposed system laid support to control disease spread, recover good germplasm properties in S.m.-SC.

In order to study the effect of germinated mung bean powder on the quality and nutrition of yogurt,different varieties of mung bean were selected in this paper,germinated mung bean sprout powder and pure milk as raw materials,Lactobacillus bulgaricus and Streptococcus thermophilus as fermentation strains,solidified germinated mung bean yoghurt was developed by single factor and orthogonal test; The contents of vitexin,isovitexin and cellulose in the germination mung bean powder were determined by high performance liquid chromatography and enzyme-weight method to explore the effects of adding germination mung bean powder on the quality and nutrition of yogurt.The results showed that the addition of germinated mung bean powder could strengthen the tissue structure of yogurt,increase the number of viable lactic acid bacteria,and give the yogurt a unique mung bean flavor; Moreover,the addition of germinated mung bean powder could enhance the antioxidant properties of yogurt,increase soluble dietary fiber,beneficial ingredients such as vitexin and isovitexin,and give yogurt physiological health functions.The best process for coagulated germination mung bean yogurt was:adding 2% germination mung bean powder,7% sucrose,0.3% CMC stabilizer,adding starter at the ratio of 1.5 g/L,and incubating at 42 ℃ for 5 hours.Under these conditions the germinated mung bean yogurt had a stable structure and good flavor and taste.

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and progressive external ophthalmoplegia (PEO) are established phenotypes of mitochondrial disorders. They are maternally-inherited, multisystem disorder that is characterized by variable clinical, biochemical, and imaging features. We described the clinical and genetic features of a Chinese patient with late-onset MELAS/PEO overlap syndrome, which has rarely been reported. The patient was a 48-year-old woman who presented with recurrent ischemic strokes associated with characteristic brain imaging and bilateral ptosis. We assessed her clinical characteristics and performed mutation analyses. The main manifestations of the patient were stroke-like episodes and seizures. A laboratory examination revealed an increased level of plasma lactic acid and a brain MRI showed multiple lesions in the cortex. A muscle biopsy demonstrated ragged red fibers. Genetic analysis from a muscle sample identified two mutations: TL1 m.3243A>G and POLG c.3560C>T, with mutation loads of 83 and 43%, respectively. This suggested that mitochondrial disorders are associated with various clinical presentations and an overlap between the syndromes and whole exome sequencing is important, as patients may carry multiple mutations.

To study the effect of mung bean germination on its antioxidant activity.Experimental design mung bean germination for 6 days,the antioxidant content of total phenol,flavonoid,vitamin C,antioxidant ability DPPH clearance rate,–OH clearance rate,total reduction ability were selected as indicators,combined with correlation,significance analysis and other methods to analyze the changes of each indicator.The results showed that content of total phenols and flavones increased first and then decreased,vitamin C increased all the time,and the index of antioxidant capacity increased first and then decreased.The total phenol content reached its maximum on the 4th day of germination,and varied from 0.5612 mg/g to 0.7237 mg/g on the 1st to 4th day,increased by 28.95%.On the 3rd day of germination,the flavonol content reached the highest level.The flavonol content varied from 0.6605 mg/g to 0.6974 mg/g on the 1st to 3rd day,increased by 5.59%.Vitamin C varied from 0.7833 mg/100 g to 7.4500 mg/100 g on the 1st to 6th day.From 1st to 3rd day,DPPH clearance rate,–OH clearance rate and total reduction capacity reached the highest levels of 99.28%,97.00% and 79.26% respectively,increased by 4.68%,1.04% and 46.76% respectively.

Abstract Objective This study aimed to test the hypothesis that levobupivacaine has anti-tumour effects on breast cancer cells. Results Colony formation and transwell assay were used to determine breast cancer cells proliferation. Flow Cytometry (annexin V and PI staining) was used to investigate breast cancer cells apoptosis. The effects of levobupivacaine on cellular signalling and molecular response were studied with Quantitative Polymerase Chain Reaction and western blot. Induction of apoptosis was confirmed by cell viability, morphological changes showed cell shrinkage, rounding, and detachments from plates. The results of the western blot and Quantitative Polymerase Chain Reaction indicated activation of active caspase-3 and inhibition of FOXO1. The results of the flow Cytometry confirmed that levobupivacaine inhibited breast cancer cell proliferation and enhanced apoptosis of breast cancer cells. Quantitative Polymerase Chain Reaction and Western blot analysis showed increased p21 and decreased cyclin D. Quantitative Polymerase Chain Reaction and western blot analysis showed that levobupivacaine significantly increased Bax expression, accompanied by a significant decreased Bcl-2 expression and inhibition of PI3K/Akt/mTOR signalling pathway. These findings suggested that levobupivacaine inhibits proliferation and promotes breast cancer cells apoptosis in vitro.

This study compared the fungal flora of newly harvested rice in 2017 and that stored for 1 year by traditional culture method and metagenomics techniques. Results showed that the fungi flora in rice changed from various field fungi flora to the storage fungi dominant florasuch as Aspergillus and Penicillium. The results of the two used methods are highly consistent. Exploring the composition and transformations of fungal flora of newly harvested rice and that stored for 1 year can provide important guidance for the prevention of mildew during long-distance transportation.

Autophagy, an evolutionarily conserved cell reprogramming mechanism, exists in all eukaryotic organisms. It is a fundamental and vital degradation/recycling pathway that removes undesirable components, such as cytoplasmic organelles, misfolded proteins, viruses, and intracellular bacteria, to provide energy and essential materials for organisms. The success of male reproduction depends on healthy testes, which are mainly composed of seminiferous tubules and mesenchyme. Seminiferous tubules are composed of Sertoli cells (SCs) and various germ cells, and the main functional part of mesenchyme are Leydig cells (LCs). In recent years, a large amount of evidence has confirmed that autophagy is active in many cellular events associated with the testes. Autophagy is not only important for testicular spermatogenesis, but is also an essential regulatory mechanism for the ectoplasmic specialization (ES) integrity of SCs, as well as for the normal function of the blood–testes barrier (BTB). At the same time, it is active in LCs and is crucial for steroid production and for maintaining testosterone levels. In this review, we expanded upon the narration regarding the composition of the testes; summarized the regulation and molecular mechanism of autophagy in SCs, germ cells, and LCs; and concluded the roles of autophagy in the process of spermatogenesis and testicular endocrinology. Through integrating the latest summaries and advances, we discuss how the role of autophagy is a double-edged sword in the testes and may provide insight for future studies and explorations on autophagy in male reproduction.

Peritoneal metastasis is the main cause of poor prognoses and high mortality in ovarian cancer patients. Abnormal protein glycosylation modification is associated with cancer malignancy. Elevated α1,3-mannosyltransferase 3 (ALG3), which catalyzes the α1,3-mannosylation of glycoproteins, has been found in some malignant tumors. However, the pathological significance of ALG3 and its regulatory mechanism in ovarian cancer metastasis is unclear. The results showed that the level of ALG3/α1,3-mannosylation was higher in human ovarian cancer tissues compared with normal ovarian tissues, as measured by Lectin chip, Western blot and Lectin blot analyses, as well as ovarian tissue microarray analysis. ALG3 was also correlated with the poor prognosis of ovarian cancer patients, according to survival analysis. The downregulation of ALG3 decreased the proliferation, stemness and peritoneal metastasis of ovarian cancer cells. The increase in urokinase plasminogen activator receptor (uPAR) α1,3-mannosylation catalyzed by ALG3 enhanced urokinase plasminogen activator (uPA)/uPAR activation and the interaction of uPAR with a disintegrin and metalloproteinase 8 (ADAM8), which promoted ovarian cancer peritoneal metastasis via the ADAM8/Ras/ERK pathway. Furthermore, decreased ALG3 suppressed ascites formation and the peritoneal metastasis of ovarian cancer cells in mice. This study highlights ALG3 as a potential diagnostic biomarker and prospective therapeutic target for ovarian cancer.

Vasculogenic mimicry (VM), a micro vessel-like structure formed by the cancer cells, plays a pivotal role in cancer malignancy and progression. Interleukin-1 beta (IL-1β) is an active pro-inflammatory cytokine and elevated in many tumor types, including breast cancer. However, the effect of IL-1β on the VM of breast cancer has not been clearly elucidated. In this study, breast cancer cells (MCF-7 and MDA-MB-231) were used to study the effect of IL-1β on the changes that can promote VM. The evidence for VM stimulated by IL-1β was acquired by analyzing the expression of VM-associated biomarkers (VE-cadherin, VEGFR-1, MMP-9, MMP-2, c-Fos, and c-Jun) via western blot, immunofluorescent staining, and Immunohistochemistry (IHC). Additionally, morphological evidence was collected via Matrigel-based cord formation assay under normoxic/hypoxic conditions and microvessel examination through Hematoxylin and Eosin staining (H&E). Furthermore, the STRING and Gene Ontology database was also used to analyze the VM-associated interacting molecules stimulated by IL-β. The results showed that the expression of VM biomarkers was increased in both MCF-7 and MDA-MB-231 cells after IL-1β treatment. The increase in VM response was observed in IL-1β treated cells under both normoxia and hypoxia. IL-1β also increased the activation of transcription factor AP-1 complex (c-Fos/c-Jun). The bioinformatics data indicated that p38/MAPK and PI3K/Akt signaling pathways were involved in the IL-1β stimulation. It was further confirmed by the downregulated expression of VM biomarkers and reduced formation of the intersections upon the addition of the signaling pathway inhibitors. The study suggests that IL-1β stimulates the VM and its associated events in breast cancer cells via p38/MAPK and PI3K/Akt signaling pathways. Aiming the VM-associated molecular targets promoted by IL-1β may offer a novel anti-angiogenic therapeutic strategy to control the aggressiveness of breast cancer cells.

Background: Endometrial stromal cell decidualization is critical for embryo implantation. Dysfunctional decidualization leads to implantation failure, miscarriage and even pregnancy associated disorders in subsequent pregnancy trimesters. Protein glycosylation is involved in many physiological and pathological processes. Protein O-fucosyltransferase 1 (poFUT1) is the key enzyme for the O-fucosylation of proteins. However, the role and mechanism of poFUT1 in human endometrial stromal cell decidualization remain elusive. Methods: We employed immunohistochemistry to detect the level of poFUT1 in the uterine endometrium from those of the proliferative phase, secretory phase, early pregnancy women and miscarriage patients. Using human endometrial stromal cells (hESCs) and a mouse model, the underlying mechanisms of poFUT1 in decidualization was investigated. Findings: The level of poFUT1 was increased in the stromal cells of the secretory phase relative to those in the proliferative phase of the menstrual cycle, and decreased in the stromal cells of miscarriage patients compared to women with healthy early pregnancies. Furthermore, we found that poFUT1 promoted hESCs decidualization. The results also demonstrated that poFUT1 increased O-fucosylation on Notch1 in hESCs, which activated Notch1 signaling pathway. Activated Notch1 (NICD), as a specific trans-factor of PRL and IGFBP1 promoters, enhanced PRL and IGFBP1 transcriptional activity, thus inducing hESCs decidualization. Interpretation: Level of poFUT1 is lower in the uterine endometrium from miscarriage patients than early pregnancy women. poFUT1 is critical in endometrial decidualization by controlling the O-fucosylation on Notch1. Our findings provide a new mechanism perspective on poFUT1 in uterine decidualization that may be a useful diagnostic and therapeutic target for miscarriage. Fund: National Natural Science Foundation of China (31770857, 31670810 and 31870794). Liaoning Provincial Program for Top Discipline of Basic Medical Sciences. Keywords: poFUT1, O-fucosylation, Notch1, Decidualization, Miscarriage

Background/Aims: Polycystic ovary syndrome (PCOS), characterized by female infertility and metabolic abnormalities, is one of the most common endocrine disorders. The etiology of PCOS remains unknown. The comprehensive analysis of protein alterations in PCOS patients is meaningful for identifying diagnostic biomarkers of PCOS. Here, we explored the clinical value of serum proteins as novel biomarkers to detect PCOS with low progesterone level. Methods: A total of 43 patients with PCOS and 30 healthy women were enrolled. Protein array was used to detect the variations of serum proteins between PCOS patients and healthy women. The level of five serum proteins was further confirmed by ELISA and western blot. The human ovarian granulosa cells (KGN) was cultured to examine the underlying mechanism of PCOS. CCK8 assay and western blot were carried out to evaluate the alterations in proliferative ability, TUNEL assay and DAPI staining to detect the apoptosis of KGN cells. Results: Among the 507 proteins, we identified 76 differentially expressed serum proteins (≧1.5 fold), with 40 elevated and 36 decreased proteins. Moreover, 47 proteins were newly reported in PCOS. The alterations in the five significantly decreased proteins (EREG, inhibin βA, IDE, PDGF-D and KNG1) were further confirmed by ELISA and western blot. The level of these proteins were directly associated with the low progesterone, and the expression could be upregulated by progesterone. EREG and inhibin βA also promoted the proliferation and inhibited the apoptosis of ovarian granulosa cells. Conclusion: The study highlights that serum proteins are differentially expressed in PCOS patients and healthy women, and EREG and inhibin βA levels are upregulated by progesterone, which are correlated with ovarian functions. The study suggests that EREG and inhibin βA may be applied as novel potential biomarkers for PCOS with low progesterone level.

Abstract Glycosylation of uterine endometrial cells plays important roles to determine their receptive function to blastocysts. Trophoblast-derived pregnancy-associated plasma protein A (PAPPA) is specifically elevated in pregnant women serum, and is known to promote trophoblast cell proliferation and adhesion. However, the relationship between PAPPA and endometrium receptivity, as well as the regulation of N-fucosylation remains unclear. We found that rhPAPPA and PAPPA in the serum samples from pregnant women or conditioned medium of trophoblast cells promoted endometrium receptivity in vitro. Moreover, rhPAPPA increased α1,2-, α1,3- and α1,6-fucosylation levels by up-regulating N-fucosyltransferases FUT1, FUT4 and FUT8 expression, respectively, through IGF-1R/PI3K/Akt signaling pathway in human endometrial cells. Additionally, α1,2-, α1,3- and α1,6-fucosylation of integrin αVβ3, a critical endometrium receptivity biomarker, was up-regulated by PAPPA, thereby enhanced its adhesive functions. Furthermore, PAPPA blockage with antibody inhibited embryo implantation in vivo, mouse embryo adhesion and spreading in vitro, as well as N-fucosylation level of the endometrium in pregnant mice. In summary, this study suggests that PAPPA is essential to maintain a receptive endometrium by up-regulating N-fucosylation, which is a potential useful biomarker to evaluate the receptive functions of the endometrium.

A scorpion peptide reported to exhibit both analgesic and antitumor activity in animal models may present as an alternative therapeutic agent for breast cancer. We aimed to investigate the effect of Buthus martensii Karsch antitumor-analgesic peptide (BmK AGAP) on breast cancer cell stemness and epithelial-mesenchymal transition (EMT). We treated MCF-7 and MDA-MB-231 cells with different concentrations of rBmK AGAP and observed that rBmK AGAP inhibited cancer cell stemness, epithelial-mesenchymal transition (EMT), migration, and invasion. Analysis by qPCR, ELISA, western blot, immunofluorescence staining, sphere formation, colony assay, transwell migration, and invasion assays demonstrated rBmK AGAP treatment decreased the expressions of Oct4, Sox2, N-cadherin, Snail, and increased the expression of E-cadherin. rBmK AGAP inhibited breast cancer cell stemness, EMT, migration, and invasion by down-regulating PTX3 through NF-κB and Wnt/β-catenin signaling Pathway in vitro and in vivo. Xenograft tumor model confirmed inhibition of tumor growth, stem-like features, and EMT by rBmK AGAP. Thus, rBmK AGAP is a potential therapeutic agent against breast cancer and related pain.

Phase change materials have good peak-shaving and valley-filling effects, which are effective for improving the thermal environment of passive thermal storage buildings. In this paper, phase change materials were applied to a solar greenhouse in the plateau area, and the indoor temperature is measured and analyzed under different meteorological conditions. It was concluded that when phase change materials were applied in the central region of Yunnan, where the temperature difference between day and night was large, it had a significant improvement effect on the thermal environment inside the solar greenhouse. The average outdoor air temperature, the maximum outdoor temperature difference between day and night, and solar radiation were the main factors affecting the temperature in the greenhouse. By analyzing and evaluating the effect of using phase change materials in solar greenhouses under different outdoor climate conditions, the advantages and limitations of using phase change greenhouses in different areas of the plateau were discussed.