Design, synthesis and biological evaluation of new RNF126-based p300/CBP degraders.

Histone acetyltransferase CREB-binding protein (CBP) and its homologous protein p300 are key transcriptional activators that can activate oncogene transcription, which present promising targets for cancer therapy. Here, we designed and synthesized a series of p300/CBP targeted low molecular weight PROTACs by assembling the covalent ligand of RNF126 E3 ubiquitin ligase and the bromodomain ligand of the p300/CBP. The optimal molecule A8 could effectively degrade p300 and CBP through the ubiquitin-proteasome system in time- and concentration-dependent manners, with half-maximal degradation (DC50) concentrations of 208.35/454.35 nM and 82.24/79.45 nM for p300/CBP in MV4-11 and Molm13 cell lines after 72 h of treatment. And the degradation of p300/CBP by A8 is dependent on the ubiquitin-proteasome pathway and its simultaneous interactions with the target proteins and RNF126. A8 exhibits good antiproliferative activity in a series of p300/CBP-dependent cancer cells. It could transcriptionally inhibit the expression of c-Myc, induce cell cycle arrest in the G0/G1 phase and apoptosis in MV4-11 cells. This study thus provided us a new chemotype for the development of drug-like PROTACs targeting p300/CBP, which is expected to be applied in cancer therapy.

Genome-Wide Association Study Identifies IFIH1 and HLA-DQB1*05:02 Loci Associated With Anti-NMDAR Encephalitis.

BACKGROUND AND OBJECTIVES: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population. METHODS: We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls. RESULTS: Our genome-wide association analysis identified a strong association at the IFIH1 locus on chromosome 2q24.2 (rs3747517, p = 1.06 × 10-8, OR = 1.55, 95% CI, 1.34-1.80), outside of the human leukocyte antigen (HLA) region. Furthermore, through a fine-mapping study of the MHC region, we discovered associations for 3 specific HLA class I and II alleles. Notably, HLA-DQB1*05:02 (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59) demonstrates the strongest association among classical HLA alleles, closely followed by HLA-A*11:01 (p = 4.36 × 10-7; OR, 1.52; 95% CI 1.29-1.79) and HLA-A*02:07 (p = 1.28 × 10-8; OR, 1.87; 95% CI 1.50-2.31). In addition, we uncovered 2 main HLA amino acid variation associated with anti-NMDAR encephalitis including HLA-DQß1-126H (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59), exhibiting a predisposing effect, and HLA-B-97R (p = 3.40 × 10-8; OR, 0.63; 95% CI 0.53-0.74), conferring a protective effect. Computational docking analysis suggested a close relationship between the NR1 subunit of NMDAR and DQB1*05:02. DISCUSSION: Our findings indicate that genetic variation in IFIH1, involved in the type I interferon signaling pathway and innate immunity, along with variations in the HLA class I and class II genes, has substantial implications for the susceptibility to anti-NMDAR encephalitis in the Chinese Han population.

Off-label use of Baricitinib improves moderate and severe atopic dermatitis in China through inhibiting MAPK and PI3K/Akt/mTOR pathway via targeting JAK-STAT signaling of CD4+ cells.

As an inflammatory disease with a disrupted immune system, cytokine disorders in atopic dermatitis (AD) are closely related to the abnormal activation of JAK-STAT signal pathway. The critical relevance of the JAK-STAT signaling pathway to the pathogenesis of AD provides a strong rationale for JAK inhibitor research. Baricitinib, a small-molecule oral JAK inhibitor, has been proven to inhibit JAK-STAT signaling in a variety of diseases, including AD. It is currently available in China for off-label use. However, its efficacy in China and its mechanism are rarely reported. In our study, we found that the immune status of patients with moderate and severe AD was hyperactive. Among the 49 known immunotherapy targets, JAK1 and JAK2 genes on lymphocytes of AD patients were significantly upregulated, which was closely related to the symptom severity in moderate and severe AD patients. Baricitinib can improve immune hyperresponsiveness and clinical symptoms in moderate and severe AD by inhibiting the activation of Th2 cell subsets and the secretion of Th2-type cytokines through MAPK, mTOR and PI3K-Akt signaling pathways, providing an important theoretical basis for clinical off-label use of Baricitinib to treat moderate and severe AD.

Ursodeoxycholic Acid-Decorated Zwitterionic Nanoparticles for Orally Liver-Targeted Close-Looped Insulin Delivery.

Oral insulin therapies targeting the liver and further simulating close-looped secretion face significant challenges due to multiple trans-epithelial barriers. Herein, ursodeoxycholic acid (UDCA)-decorated zwitterionic nanoparticles (NPs) (UC-CMs@ins) are designed to overcome these barriers, target the liver, and respond to glycemia, thereby achieving oral one-time-per-day therapy. UC-CMs@ins show excellent mucus permeability through the introduction of zwitterion (carboxy betaine, CB). Furthermore, UC-CMs@ins possess superior cellular internalization via proton-assisted amino acid transporter 1 (PAT1, CB-receptor) and apical sodium-dependent bile acid transporter (ASBT, UDCA-receptor) pathways. Moreover, UC-CMs@ins exhibit excellent endolysosomal escape ability and improve the basolateral release of insulin into the bloodstream via the ileal bile acid-binding protein and the heteromeric organic solute transporter (OSTα- OSTß) routes compared with non-UDCA-decorated C-CMs@ins. Therefore, CB and UDCA jointly overcome mucus and intestinal barriers. Additionally, UC-CMs@ins prevent insulin degradation in the gastrointestinal tract for crosslinked structure, improve insulin accumulation in the liver for UDCA introduction, and effectively regulate glycemia for "closed-loop" glucose control. Surprisingly, oral ingestion of UC-CMs@ins shows a superior effect on glycemia (≈22 h, normoglycemia) and improves postprandial glycemic levels in diabetic mice, illustrating the enormous potential of the prepared NPs as a platform for oral insulin administration in diabetes treatment.

PVA-based bulk microneedles capable of high insulin loading and pH-triggered degradation for multi-responsive and sustained hypoglycemic therapy.

"Closed-loop" insulin-loaded microneedle patche shows great promise for improving therapeutic outcomes and life quality for diabetes patients. However, it is typically hampered by limited insulin loading capacity, random degradation, and intricate preparation procedures for the independence of the "closed-loop" bulk microneedles. In this study, we combined the solubility of microneedles and "closed-loop" systems and designed poly(vinyl alcohol)-based bulk microneedles (MNs@GI) through in situ photopolymerization for multi-responsive and sustained hypoglycemic therapy, which significantly simplified the preparation process and improved insulin loading. GOx/insulin co-encapsulated MNs@GI with a phenylboronic ester structure improved glycemic responsiveness to control the insulin release under high glucose conditions and reduced inflammation risk in the normal skin. MNs@GI could further degrade to increase insulin release due to the crosslinked acetal-linkage hydrolysis in the presence of gluconic acid, which was caused by GOx-mediated glucose-oxidation in a hyperglycemic environment. The in vivo results showed that MNs@GI effectively regulated glycemic levels within the normal range for approximately 10 h compared to that of only insulin-loaded microneedles (MNs@INS). Consequently, the highly insulin-loaded, multi-responsive, and pH-triggered MN system has tremendous potential for diabetes treatment.

Genome-wide identification and comprehensive analysis heat shock transcription factor (Hsf) members in asparagus (Asparagus officinalis) at the seeding stage under abiotic stresses.

Heat shock transcription factors (Hsf) are pivotal as essential transcription factors. They function as direct transcriptional activators of genes regulated by thermal stress and are closely associated with various abiotic stresses. Asparagus (Asparagus officinalis) is a vegetable of considerable economic and nutritional significance, abundant in essential vitamins, minerals, and dietary fiber. Nevertheless, asparagus is sensitive to environmental stresses, and specific abiotic stresses harm its yield and quality. In this context, Hsf members have been discerned through the reference genome, and a comprehensive analysis encompassing physical and chemical attributes, evolutionary aspects, motifs, gene structure, cis-acting elements, collinearity, and expression patterns under abiotic stresses has been conducted. The findings identified 18 members, categorized into five distinct subgroups. Members within each subgroup exhibited analogous motifs, gene structures, and cis-acting elements. Collinearity analysis unveiled a noteworthy pattern, revealing that Hsf members within asparagus shared one, two, and three pairs with counterparts in Arabidopsis, Oryza sativa, and Glycine max, respectively.Furthermore, members displayed tissue-specific expression during the seedling stage, with roots emerging as viable target tissue. Notably, the expression levels of certain members underwent modification under the influence of abiotic stresses. This study establishes a foundational framework for understanding Hsf members and offers valuable insights into the potential application of molecular breeding in the context of asparagus cultivation.

Exogenous melatonin enhances the tolerance of tiger nut (Cyperus esculentus L.) via DNA damage repair pathway under heavy metal stress (Cd2+) at the sprout stage.

Heavy metal (HM) stress is a non-negligible abiotic stress that seriously restricts crop yield and quality, while the sprout stage is the most sensitive to stress and directly impacts the growth and development of the later stage. Melatonin (N-acetyl-5-methoxytryptamine), as an exogenous additive, enhances stress resistance due to its ability to oxidize and reduce. However, few reports on exogenous melatonin to tiger nuts under HM stress have explored whether exogenous melatonin enhances plants' resistance to heavy metals. Here, "Jisha 2″ was used as material, with a stress concentration of 5 mg/L and 100 µmol/L of CdCl2 to explore whether exogenous melatonin enhances plant resistance and molecular mechanism. The result revealed that stress limits growth, while melatonin alleviated the sprout damage under stress from the phenotypes. Moreover, stress-enhanced reactive oxygen species (ROS) accumulation and membrane lipid peroxidation, while melatonin-increased ROS reduce damage via the analysis of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) and malondialdehyde (MDA) content, hydrogen peroxide (H2O2), superoxide anion (O2-), and Electrolyte leakage (El). Further results indicated that HM leads to DNA damage while exogenous melatonin will repair the damage by analyzing random amplified polymorphic DNA (RAPD), DNA cross-linking, 8-hydroxy-20-deoxyguanine level, and relative density of apurinic sites. Furthermore, gene expression in the DNA-repaired pathway exhibited similar results. These results applied that exogenous melatonin released the hurt caused by HM stress, with DNA repair and ROS balance serving as candidate pathways. This study elucidated the mechanism of melatonin's influence and provided theoretical insights into its application in tiger nuts.

Design and test of a FBG acceleration sensor based on multi-stage flexible hinges.

High-precision and high-sensitivity vibration acceleration sensors have been a research hotspot in engineering technology, which play an important role in engineering structural health monitoring, earthquakes, tsunamis, and geological exploration. A novel, to the best of our knowledge, fiber Bragg grating (FBG) acceleration sensor incorporating a mass block and flexible hinge was proposed against the low sensitivity and poor transverse interference resistance of existing FBG acceleration sensors. The FBG accelerometer with the multi-stage flexible hinge was modeled and theoretically analyzed, the structural parameters of the sensor were optimized and actual sensors were developed, and a sensor performance test experiment was carried out in the end. The result suggested that the sensor's natural frequency was as high as 1400 Hz, and its response was flat in the frequency range of 50-800 Hz; its sensitivity was 18.4 pm/g, linearity R 2 was 0.9983, and transverse interference immunity was below 3.2%. The research findings offered a new way of thinking about high-precision and high-sensitivity vibration measurement in engineering technology.

The enrichment of Arg1+ILC2s and ILCregs facilitates the progression of endometriosis: A preliminary study.

Innate lymphoid cells (ILCs) are a kind of lymphocytes that reside in the tissue and have an essential function in the immune microenvironment. However, the relationship between endometriosis (EMS) and ILCs is complex and not fully understood. This study examines several groups of ILCs in the peripheral blood (PB), peritoneal fluid (PF) and endometrium of patients with EMS via flow cytometry. The study observed an increase in PB ILCs, particularly ILC2s and ILCregs subsets and Arg1+ILC2s in the EMS patients were highly activated. EMS patients had significantly higher levels of serum interleukin (IL)-10/33/25 compared to controls. We also found an elevation of Arg1+ILC2s in the PF and higher levels of ILC2s and ILCregs in ectopic endometrium compared with eutopic. Importantly, a positive correlation was observed between the enrichment of Arg1+ILC2s and ILCregs in the PB of EMS patients. The findings indicate that the involvement of Arg1+ILC2s and ILCregs fosters potentially endometriosis progression.

Staphylococcal protein A-modified hydrogel facilitates in situ immunomodulation by capturing anti-HMGB1 for islet grafts.

Islet transplantation is regarded as the most promising therapy for type 1 diabetes. However, both hypoxia and immune attack impair the grafted islets after transplantation, eventually failing the islet graft. Although many studies showed that biomaterials with nanoscale pores, like hydrogels, could protect islets from immune cells, the pores on biomaterials inhibited vascular endothelial cells (VECs) to creep in, which resulted in poor revascularization. Thus, a hydrogel device that can facilitate in situ immune modulations without the cost of poor revascularization should be put forward. Accordingly, we designed a spA-modified hydrogel capturing anti-HMGB1 mAB (mAB-spA Gel): the Staphylococcus aureus protein A (spA) was conjugated on the network of hydrogel to capture anti-HMGB1mAB which can inactivate immune cells, while the pore sizes of the hydrogel were more than 100µm which allows vascular endothelial cells (VECs) to creep in. In this study, we screened the optimal spA concentration in mAB-spA Gel according to the physical properties and antibody binding capability, then demonstrated that it could facilitate in situ immunomodulation without decreasing the vessel reconstruction in vitro. Further, we transplanted islet graft in vivo and showed that the survival of islets was elongated. In conclusion, mAB-spA Gel provided an alternative islet encapsulation strategy for type 1 diabetes. STATEMENT OF SIGNIFICANCE: Although various studies have shown that the backbone of the hydrogels can isolate islets grafts from immune cells and the survival of the islets can be prolonged by this way, it is also reported that when the pore size of the backbone is too small the revascularization will be adversely affected. According to this point, it is hard to adjust hydrogel's pore size to protect the islets from the immune attack while allowing endothelial vascular cells to creep in. To solve this dilemma, we designed an immunomodulatory hydrogel inhibiting the activation of T cells by immunosuppressive IgGs instead of the backbone network, so the hydrogel can prolong the survival of islets without the sacrifice of revascularization.

Crosslinked zwitterionic microcapsules to overcome gastrointestinal barriers for oral insulin delivery.

Oral insulin delivery has been extensively considered to achieve great patient compliance and convenience as well as favourable glucose homeostasis. However, its application is highly limited by the low insulin bioavailability owing to gastrointestinal barriers. Herein, we developed crosslinked zwitterionic microcapsules (CB-MCs@INS) based on a carboxyl betaine (CB)-modified poly(acryloyl carbonate-co-caprolactone) copolymer via the combination of microfluidics and UV-crosslinking to improve oral insulin delivery. CB-MC@INS microcapsules with high drug loading capacity (>40%) protected insulin from acid degradation in the harsh gastric environment. Through the introduction of CB-moieties, CB-MCs@INS possessed superior affinity for epithelial cells and improved insulin transport as compared to non-CB modified MCs@INS (5.15-fold), which was mainly attributed to the CB-mediated cell surface transporter via the PAT1 pathway. Moreover, the oral administration of CB-MCs@INS exhibited an excellent hypoglycaemic effect and maintained normoglycemia for up to 8 h in diabetic mice, demonstrating the great potential of crosslinked zwitterionic microcapsules as an oral insulin delivery platform for diabetes therapy.

Basic helix-loop-helix transcription factor PxbHLH02 enhances drought tolerance in Populus (Populus simonii × P. nigra).

The basic helix-loop-helix (bHLH) transcription factors (TFs) are involved in plant morphogenesis and various abiotic and biotic stress responses. However, further exploration is required of drought-responsive bHLH family members and their detailed regulatory mechanisms in Populus. Two bHLH TF genes, PxbHLH01/02, were identified in Populus simonii × P. nigra and cloned. The aim of this study was to examine the role of bHLH TFs in drought tolerance in P. simonii × P. nigra. The results showed that the amino acid sequences of the two genes were homologous to Arabidopsis thaliana UPBEAT1 (AtUPB1) and overexpression of PxbHLH01/02 restored normal root length in the AtUPB1 insertional mutant (upb1-1). The PxbHLH01/02 gene promoter activity analysis suggested that they were involved in stress responses and hormone signaling. Furthermore, Arabidopsis transgenic lines overexpressing PxbHLH01/02 exhibited higher stress tolerance compared with the wild-type. Populus simonii × P. nigra overexpressing PxbHLH02 increased drought tolerance and exhibited higher superoxide dismutase and peroxidase activities, lower H2O2 and malondialdehyde content, and lower relative conductivity. The results of transcriptome sequencing (RNA-seq) and quantitative real-time PCR suggested that the response of PxbHLH02 to drought stress was related to abscisic acid (ABA) signal transduction. Overall, the findings of this study suggest that PxbHLH02 from P. simonii × P. nigra functions as a positive regulator of drought stress responses by regulating stomatal aperture and promoting ABA signal transduction.

Genome-wide analysis and molecular dissection of the SPL gene family in Fraxinus mandshurica.

BACKGROUND: SQUAMOSA promoter binding protein-like (SPL) is a unique family of transcription factors in plants, which is engaged in regulating plant growth and development, physiological and biochemical processes. Fraxinus mandshurica is an excellent timber species with a wide range of uses in northeastern China and enjoys a high reputation in the international market. SPL family analysis has been reported in some plants while SPL family analysis of Fraxinus mandshurica has not been reported. RESULTS: We used phylogeny, conserved motifs, gene structure, secondary structure prediction, miR156 binding sites, promoter cis elements and GO annotation to systematically analyze the FmSPLs family. This was followed by expression analysis by subcellular localization, expression patterns at various tissue sites, abiotic stress and hormone induction. Because FmSPL2 is highly expressed in flowers it was selected to describe the SPL gene family of Fraxinus mandshurica by ectopic expression. Among them, 10 FmSPL genes that were highly expressed at different loci were selected for expression analysis under abiotic stress (NaCl and Cold) and hormone induction (IAA and ABA). These 10 FmSPL genes showed corresponding trends in response to both abiotic stress and hormone induction. We showed that overexpression of FmSPL2 in transgenic Nicotiana tabacum L. resulted in taller plants, shorter root length, increased root number, rounded leaves, and earlier flowering time. CONCLUSIONS: We identified 36 SPL genes, which were classified into seven subfamilies based on sequence analysis. FmSPL2 was selected for subsequent heterologous expression by analysis of expression patterns in various tissues and under abiotic stress and hormone induction, and significant phenotypic changes were observed in the transgenic Nicotiana tabacum L. These results provide insight into the evolutionary origin and biological significance of plant SPL. The aim of this study was to lay the foundation for the genetic improvement of Fraxinus mandshurica and the subsequent functional analysis of FmSPL2.

Biocontrol potential of Trichoderma harzianum CGMCC20739 (Tha739) against postharvest bitter rot of apples.

This study investigated the biocontrol ability of Trichoderma harzianum CGMCC20739 (Tha739) against apple bitter rot caused by Colletotrichum gloeosporioides. In vitro tests, Tha739 inhibited the mycelial growth of C. gloeosporioides. Microscopic observation showed that Tha739 grew in parallel with, coiled around, and deformed the hyphae of C. gloeosporioides. Tha739-derived metabolites decreased the conidia production of C. gloeosporioides. In vivo tests, the lesion diameters of wounded apples treated with Tha739 1 h before C. gloeosporioides were lower than those of wounded apples treated with Tha739 after pathogen inoculation. In addition, compared with the apples inoculated with C. gloeosporioides only, the disease index of unwounded apples inoculated with Tha739 and C. gloeosporioides decreased by 2.17-fold. Furthermore, compared with the control, the total soluble solid contents of apples treated with Tha739 were 9.02 % and 1.54 % higher at 1 and 3 d, respectively. The titratable acidity contents of apples treated with Tha739 were 10.02 % and 14.58 % higher than those in the control at 1 and 3 d after treatment, respectively. The soluble sugar content and weight loss in Tha739 treatment group and control were not significantly different. The results showed that Tha739 could control apple bitter rot and maintain the nutritional quality of the fruit. Thus, T. harzianum Tha739 is a potentially biocontrol agent for harvested apples.

Generation of an induced pluripotent stem cell line AMUFAHi002-A from polycystic ovary syndrome patient.

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in women of reproductive age. The PCOS leads to obesity, dyslipidemia, insulin resistance, hyperandrogenism, and infertility. We established an induced pluripotent stem cell line (iPSC) from a PCOS patient. This disease-specific iPSC line will be beneficial to study PCOS in vitro, allowing to understand the pathogenic mechanisms and a cell-based model for drug development for PCOS.

Distinct non-clock-like signatures of the basal cell carcinomas from three sisters with a lethal Gorlin-Goltz syndrome.

BACKGROUND: Gorlin-Goltz syndrome (GS) is an inherited disease characterized by predisposition to basal cell carcinomas (BCCs) and various developmental defects, whose numerous disease-causing PTCH1 mutations have been identified in the hedgehog (Hh) signaling pathway. METHODS: In this study, whole exome sequencing was used to screen for both somatic and germline deleterious mutations in three sisters with a lethal GS. The mutations we found were confirmed by subcloning and Sanger sequencing of the genomic DNA. RNA-seq was performed to profile gene expression in paired BCCs samples and the expression levels for selected genes were validated by quantitative PCR. RESULTS: The clinical and histopathologic features were analyzed for the proband in the three-generation GS family. We identified the insertion mutation PTCH1 c.1341dupA (p. L448Tfs*49), which segregated with BCC phenotype and contributed to the death of two in four patients from a Chinese family with GS. Compared with adjacent non-cancerous tissues (ANCT), four second-hit mutations were found in four of the six pairs of BCC from three patients. Of note, somatic genomic alterations in all six BCC samples were mainly clustered into non-clock-like Signature 7 (ultraviolet mutagenesis) and 11 (related to certain alkylating agents). Both RNA-seq and quantitative RT-PCR confirmed that the mRNA levels of PTCH1 and its effector GLI1 were markedly upregulated in six pairs of BCC samples versus ANCT. CONCLUSIONS: The distinct non-clock-like signatures of BCCs indicated that GS was not a life-threatening illness. The main reasons for untimely death of GS patients were PTCH1 mutation, exposure to intense ultraviolet radiationand the poor economic conditions.

RNA-Seq Analysis Demonstrates Different Strategies Employed by Tiger Nuts (Cyperus esculentus L.) in Response to Drought Stress.

Drought stress, an important abiotic stress, has affected global agricultural production by limiting the yield and the quality of crops. Tiger nuts (Cyperus esculentus L.) are C4 crops in the Cyperaceae family, which have high-quality wholesome ingredients. However, data on mechanisms underlying the response of tiger nuts to drought stress are few. Here, the variety of Jisha 1 and 15% polyethylene glycol (PEG; a drought stress simulator) were used to study the mechanisms of stress response in tiger nuts. Our evaluation of the changes in physiological indicators such as electrolyte leakage (El), malondialdehyde (MDA), hydrogen peroxide (H2O2), superoxide anion (O2-) and activities of reactive oxygen species (ROS) showed that 12 h was the most suitable time point to harvest and analyze the response to drought stress. Thereafter, we performed transcriptome (RNA-Seq) analysis in the control (CK) and stress treatment groups and showed that there was a total of 1760 differentially expressed genes (DEGs). Gene Ontology (GO) analysis showed that the DEGs were enriched in abscisic acid (ABA) terms, and pathways such as starch and sucrose metabolism (ko00500), phenylpropanoid biosynthesis (ko00940) and plant hormone signal transduction (ko04075) were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, quantitative real-time PCR (qRT-PCR) analysis of the DEGs demonstrated an upregulation of ABA and lignin content, as well as enzyme activities in enriched pathways, which validated the RNA-Seq data. These results revealed the pathways and mechanisms adopted by the tiger nuts in response to drought stress.

A new L-shaped rigid beam FBG acceleration sensor.

Acceleration detection is an important technology in the fields of seismic monitoring, structural health monitoring and resource exploration. A FBG acceleration sensor with the combination of L-shaped rigid beam and spring structure based on bearings is proposed against the low sensitivity that predominates in the low-frequency vibration measurement by FBG acceleration sensors, where L-shaped rigid beam is utilized to amplify the vibration signal, and is fixed by the bearings at both ends to effectively suppress the transverse crosstalk. The effects of structural parameters on the sensitivity and natural frequency of the sensors were analyzed using Origin theory, and such parameters were optimized; next, static stress and modal simulation analysis was made using COMSOL; in the end, a test system was built to test the performance of the real sensors. According to the findings, the acceleration sensor, whose natural frequency is 57 Hz, is of a flat sensitivity response in the low frequency range of 1-35 Hz, with the dynamic range being 89.83 dB, the acceleration sensitivity being up to 1241.85 pm/g, the coefficient of determination R2 for the sensitivity fit is 0.9997, and the transverse crosstalk being -26.20 dB within the operating frequency band. The findings offer a reference for improving the low-frequency vibration measurement capability of FBG acceleration sensors.

Proteomic alteration of endometrial tissues during secretion in polycystic ovary syndrome may affect endometrial receptivity.

Embryo implantation is a complex developmental process that requires coordinated interactions among the embryo, endometrium, and the microenvironment of endometrium factors. Even though the impaired endometrial receptivity of patients with polycystic ovary syndrome (PCOS) is known, understanding of endometrial receptivity is limited. A proteomics study in three patients with PCOS and 3 fertile women was performed to understand the impaired endometrial receptivity in patients with PCOS during luteal phases. Through isobaric tags for relative and absolute quantitation (iTRAQ) analyses, we identified 232 unique proteins involved in the metabolism, inflammation, and cell adhesion molecules. Finally, our results suggested that energy metabolism can affect embryo implantation, whereas inflammation and cell adhesion molecules can affect both endometrial conversion and receptivity. Our results showed that endometrial receptive damage in patients with PCOS is not a single factor. It is caused by many proteins, pathways, systems, and abnormalities, which interact with each other and make endometrial receptive research more difficult.