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Abstract Antimicrobial peptides (AMPs) have been widely recognized as a promising solution to combat antimicrobial resistance of microorganisms due to the increasing abuse of antibiotics in medicine and agriculture around the globe. In this study, we propose UniAMP, a systematic prediction framework for discovering AMPs. We observe that feature vectors used in various existing studies constructed from peptide information, such as sequence, composition, and structure, can be augmented and even replaced by information inferred by deep learning models. Specifically, we use a feature vector with 2924 values inferred by two deep learning models, UniRep and ProtT5, to demonstrate that such inferred information of peptides suffice for the task, with the help of our proposed deep neural network model composed of fully connected layers and transformer encoders for predicting the antibacterial activity of peptides. Evaluation results demonstrate superior performance of our proposed model on both balanced benchmark datasets and imbalanced test datasets compared with existing studies. Subsequently, we analyze the relations among peptide sequences, manually extracted features, and automatically inferred information by deep learning models, leading to observations that the inferred information is more comprehensive and non-redundant for the task of predicting AMPs. Moreover, this approach alleviates the impact of the scarcity of positive data and demonstrates great potential in future research and applications.

Abstract Background Prostate cancer (PCa) is the most common malignancy of the male genitourinary system. Understanding the molecular mechanism of PCa and its prognostic markers will assist in the selection of better treatment. Aim To explore the role of LINC01518 in the development of PCa and its prognostic value, and to understand its specific regulatory mechanism. Methods The levels of LINC01518, hsa-miR-320a, and CNKSR2 mRNA were detected by RT-qPCR. ROC curve was constructed to evaluate the prognostic value of LINC01518 in PCa. The effects of LINC01518 on the functions of PCa cells were demonstrated by CCK-8, Transwell test, and the detection of apoptotic markers, after LINC01518 knockdown. The interaction between hsa-miR-320a and LINC01518 or CNKSR2 mRNA was examined by constructing luciferase vectors. Results LINC01518 was abnormally expressed in PCa cells and tumor tissues, and knockdown of it inhibited the growth of PCa cells. LINC01518 predicted castration-resistant prostate cancer (CRPC) outcomes in PCa patients with AUC of 0.803, sensitivity and specificity of 75.4% and 74.6%, respectively. Hsa-miR-320a mimics reduced luciferase activity in PCa cells transfected with WT-LINC01518/CNKSR2 plasmids. Knocking down LINC01518 reduced CNKSR2 level, and this regulatory effect disappeared with the inhibition of hsa-miR-320a. Conclusion High levels of LINC01518 predicted poor prognosis in PCa patients and promoted CNKSR2 expression by competitively binding hsa-miR-320a, contributing to the progression of PCa.

Abstract N6-methyladenosine (m6A) is a prevalent mRNA modification known for its implications in various cancer types, yet its role in chromophobe renal cell carcinoma (chRCC) remains largely unexplored. In this study, we performed m6A-SEAL-seq and RNA-seq analyses on tissues from three chRCC subjects, aiming to uncover m6A alterations in chRCC. Our findings revealed reduced expression levels of four m6A regulators in chRCC tissues and highlighted differences in m6A levels compared to normal tissues. Furthermore, we identified specific genes and cancer-related pathways affected by these differences, including notable candidates like NOTCH1 and FGFR1, implicated in chRCC development. Additionally, we developed a predictive model based on the expression level of m6A associated genes, demonstrating promising prognostic capabilities for patient survival prediction. Overall, our study provides valuable insights into the role of m6A in chRCC and its potential as a prognostic indicator.

Heart failure (HF) remains one of the leading causes of high morbidity and mortality globally. Impaired cardiac energy metabolism plays a critical role in the pathological progression of HF. Various forms of HF exhibit marked differences in energy metabolism, particularly in mitochondrial function and substrate utilization. Recent studies have increasingly highlighted that improving energy metabolism in HF patients as a crucial treatment strategy. Mitochondrial transfer is emerging as a promising and precisely regulated therapeutic strategy for treating metabolic disorders. This paper specifically reviews the characteristics of mitochondrial energy metabolism across different types of HF and explores the modes and mechanisms of mitochondrial transfer between different cell types in the heart, such as cardiomyocytes, fibroblasts, and immune cells. We focused on the therapeutic potential of intercellular mitochondrial transfer in improving energy metabolism disorders in HF. We also discuss the role of signal transduction in mitochondrial transfer, highlighting that mitochondria not only function as energy factories but also play crucial roles in intercellular communication, metabolic regulation, and tissue repair. This study provides new insights into improving energy metabolism in heart failure patients and proposes promising new therapeutic strategies.

PurposeThis study aimed to evaluate the comparative reproductive outcomes of ovarian stimulation combined with intrauterine insemination using partner’s sperm (OS-IUI) in eumenorrheic and normogonadotropic oligomenorrheic women.MethodA retrospective cohort study was conducted, including 3833 couples who underwent 5920 cycles of OS-IUI between June 2013 and March 2019. Participants were stratified into two cohorts based on menstrual regularity: eumenorrheic and normogonadotropic oligomenorrheic. The primary outcome measured was the live birth rate (LBR) per cycle and cumulative LBR per couple. Secondary outcomes encompassed the clinical pregnancy rate (CPR) per cycle, miscarriage rate, and multiple pregnancy rate. Propensity score matching (PSM) was utilized to balance maternal baseline characteristics.ResultsPrior to PSM, significant differences in CPR, LBR and cumulative LBR were observed between eumenorrheic and oligomenorrheic women, favoring the latter (CPR: 11.16% vs. 18.75%; LBR: 9.02% vs. 14.96%; cumulative LBR: 13.60% vs. 24.25%, P < 0.001). These differences persisted post-PSM (CPR: 9.74% vs. 19.29%; LBR: 7.30% vs. 16.29%; cumulative LBR 7.76% vs. 19.90%, P

Abstract Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to most chemotherapy drugs, leading to poor chemotherapy efficacy. Recently, Trametinib and Palbociclib have promising prospects in the treatment of pancreatic cancer. This article aims to explore the effects of Trametinib on pancreatic cancer and address the underlying mechanism of resistance as well as its reversal strategies. The GDSC (Genomics of Drug Sensitivity in Cancer) and CTD2 (Cancer Target Discovery and Development) were utilized to screen the potential drug candidate in PDAC cell lines. The dose-increase method combined with the high-dose shock method was applied to induce the Trametinib-resistant PANC-1 and MIA PaCa-2 cell lines. The CCK8 proliferation assay, colony formation assay, flow cytometry, and western blot were conducted to verify the inhibitory effect of Trametinib and Palbociclib. RNA-seq was performed in resistant PDAC cell lines to find the differential expression genes related to drug resistance and predict pathways leading to the reversal of Trametinib resistance. The GDSC and CTD2 database screening revealed that Trametinib demonstrates a significant inhibitory effect on PDAC. We found that Trametinib has a lower IC50 than Gemcitabine in PDAC cell lines. Both Trametinib and Gemcitabine can decrease the proliferation capacity of pancreatic cells, induce cell cycle arrest, and increase apoptosis. Simultaneously, the phosphorylation of the AKT and ERK pathways were inhibited by the treatment of Trametinib. In addition, the RNA-seq of Trametinib-induced resistance PDAC cell lines reveals that the cyclin-dependent kinase (CDK)-RB-E2F regulatory axis and G2/M DNA damage checkpoint might lead the drug resistance. Besides, the combination of Trametinib with Palbociclib could inhibit the proliferation and cell cycle of both resistant cells lines and also restore the sensitivity of drug-resistant cells to Trametinib. Last but not least, the interferon-α and interferon-γ expression were upregulated in resistance cell lines, which might lead to the reversal of drug resistance. The study shows Trametinib has a critical inhibitory effect on PDAC. Besides, the combination of Trametinib with Palbociclib can inhibit the proliferation of PDAC-resistant cells.

Abstract While strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibody‒drug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared with chemotherapeutic drugs, ADCs have the advantages of good tolerance, accurate target recognition, and small effects on noncancerous cells. ADCs occupy an increasingly important position in the therapeutic field. Currently, there are 13 Food and Drug Administration (FDA)‒approved ADCs and more than 100 ADC drugs at different stages of clinical trials. This review briefly describes the efficacy and safety of FDA-approved ADCs, and discusses the related problems and challenges to provide a reference for clinical work.

The thin-film lithium niobate (TFLN)-based electro-optic (EO) modulator is one of the most important devices for optical communications in terms of the advantages of low voltages and large bandwidth. However, the large size of devices limits their applicability in large-scale integrated optical systems, posing a key challenge in maintaining performance advantages under restricted design space. In this paper, we propose a novel TFLN modulator on a quartz substrate incorporating barium titanate (BaTiO3, BTO) as the cladding material. The device is designed with silicon–lithium niobate (Si-LN) hybrid waveguides for operation at a wavelength of 1.55 µm. After theoretical analysis and parameter optimization, the proposed 10 mm long modulator demonstrates high-efficiency modulation, featuring a low half-wave voltage-length product of 1.39 V·cm, a broad 3 dB EO bandwidth of 152 GHz, and low optical loss. This theoretical model provides a novel design solution for TFLN modulators on quartz substrates. Moreover, it is a promising solution for enhancing the integration of photonic devices on the TFLN platform.

With the ever-growing demand for high-speed optical communications, microwave photonics, and quantum key distribution systems, compact electro-optic (EO) modulators with high extinction ratios, large bandwidth, and high tuning efficiency are urgently pursued. However, most integrated lithium–niobate (LN) modulators cannot achieve these high performances simultaneously. In this paper, we propose an improved theoretical model of a chip-scale electro-optic (EO) microring modulator (EO-MRM) based on X-cut lithium–niobate-on-insulator (LNOI) with a hybrid architecture consisting of a 180-degree Euler bend in the coupling region, double-layer metal electrode structure, and ground–signal–signal–ground (G-S-S-G) electrode configuration, which can realize highly comprehensive performance and a compact footprint. After parameter optimization, the designed EO-MRM exhibited an extinction ratio of 38 dB. Compared to the structure without Euler bends, the increase was 35 dB. It also had a modulation bandwidth of 29 GHz and a tunability of 8.24 pm/V when the straight waveguide length was 100 μm. At the same time, the proposed device footprint was 1.92 × 104 μm2. The proposed MRM model provides an efficient solution to high-speed optical communication systems and microwave photonics, which is helpful for the fabrication of high-performance and multifunctional photonic integrated devices.

Aquatic products contain a large amount of protein, which can promote the production of a variety of biogenic amines through the function of microorganisms. Biogenic amines are a broad category of organic substances that contain nitrogen and have a low molecular weight. The presence of biogenic amines can cause the deterioration and excessive accumulation of aquatic products, which can cause damage to human health. Therefore, it is essential to discover a fast, convenient, and easy to operate method for the determination of biogenic amines in aquatic products. In this paper, the function and research significance of biogenic amines are analyzed from the aspects of their formation, toxicological properties, harm to the human body, and control methods. Several common direct detection techniques and indirect techniques for biogenic amines are briefly introduced especially sensors. This review provides references for efficient detection in the future.

Abstract Intra-abdominal adhesions have consistently posed a challenge for surgeons during procedures. This study aims to investigate the feasibility of utilizing indocyanine green (ICG) in conjunction with near-infrared imaging for the detection of intra-abdominal adhesions. In vitro, we analyzed factors affecting ICG fluorescence. We divided SD rats into groups to study ICG excretion in different digestive tract regions. Additionally, we reviewed surgical videos from previous cholecystectomy cases, categorizing them by ICG injection timing and assessing fluorescence imaging in various digestive tract regions. Finally, we preoperatively injected ICG into two cholecystectomized patients with abdominal adhesions, guiding intraoperative adhesiolysis with near-infrared fluorescence imaging. In vitro, we observed a significant influence of protein and ICG concentrations on ICG fluorescence intensity. Our rat experiments unveiled a strong and highly significant correlation (Kendall’s tau-b = 1, P

Background: Ensuring the rapidity and accuracy of emergency laboratory test results is especially important to save the lives of patients with acute and critical conditions. To better meet the needs of clinicians and patients, detection efficiency can be improved by reducing extra-laboratory sample turnaround times (TATs) through the use of innovative pneumatic tube system (PTS) transport for sample transport. However, concerns remain regarding the potential compromise of sample quality during PTS transit relative to that occurring with manual transportation. This study was performed to evaluate the efficacy of an innovative PTS (Tempus600 PTS) relative to a traditional PTS in terms of sample transit time, sample quality, and the concordance of analytical results with those obtained from manually transported samples. Methods: In total, 30 healthy volunteers aged >18 years were recruited for this study, conducted for five consecutive days. Venous blood samples were collected from six volunteers per day at fixed timepoints. From each volunteer, nine blood samples were collected into tubes with tripotassium ethylene diamine tetraacetic acid anticoagulant, tubes with 3.2 % sodium citrate, and serum tubes with separation gel (n = 3 each) and subjected to all tests conducted in the emergency laboratory in our hospital. 270 blood samples from 30 healthy volunteers were transported and analyzed, yielding 6300 test results. The blood samples were divided randomly into three groups (each containing one tube of each type) and transported to the emergency laboratory manually and with Tempus600 PTS and conventional Swisslog PTS, respectively. The extra-laboratory TATs, sample quality, and test results of the transported blood samples were compared. Results: The sample quality and test results did not differ according to the delivery method. The TAT was much shorter with the Tempus600 than with the other two transport modes (58.40 ± 1.52 s vs. 1711.20 ± 77.56 s for manual delivery and 146.60 ± 1.82 s for the Swisslog PTS; P = 0.002). Conclusion: Blood sample transport with the Tempus600 PTS significantly reduced the extra-laboratory TAT without compromising sample quality or test result accuracy, thereby improving the efficiency of sample analysis and the services provided to clinicians and patients.

Summary: The multi-domain protein UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1 for DNA methylation maintenance during DNA replication. Here, we show that MOF (males absent on the first) acetylates UHRF1 at K670 in the pre-RING linker region, whereas HDAC1 deacetylates UHRF1 at the same site. We also identify that K667 and K668 can also be acetylated by MOF when K670 is mutated. The MOF/HDAC1-mediated acetylation in UHRF1 is cell-cycle regulated and peaks at G1/S phase, in line with the function of UHRF1 in recruiting DNMT1 to maintain DNA methylation. In addition, UHRF1 acetylation significantly enhances its E3 ligase activity. Abolishing UHRF1 acetylation at these sites attenuates UHRF1-mediated H3 ubiquitination, which in turn impairs DNMT1 recruitment and DNA methylation. Taken together, these findings identify MOF as an acetyltransferase for UHRF1 and define a mechanism underlying the regulation of DNA methylation maintenance through MOF-mediated UHRF1 acetylation.

Objective To explore the levels of expression and clinical role of peroxiredoxin 6 ( PRDX6 ) in lung adenocarcinoma. Methods This retrospective study used a series of bioinformatics methods to detect the levels of expression of and mutations in the PRDX6 gene in a range of cancers and lung adenocarcinoma. Immunohistochemistry was used to verify the levels of expression of PRDX6 protein in samples of lung adenocarcinoma compared with normal adjacent tissue. The effect of PRDX6 gene knockdown on the in vitro proliferation of a lung adenocarcinoma cell line was measured. Bioinformatics methods were used to determine the diagnostic value and impact on survival of the PRDX6 gene in patients with lung adenocarcinoma. Results The results showed that the PRDX6 gene was highly expressed in lung adenocarcinoma and there were five mutations at different sites on the gene. PRDX6 promoted the proliferation of the lung adenocarcinoma cell line. The survival duration of lung adenocarcinoma patients with high levels of PRDX6 gene expression was significantly shorter than that of patients with low PRDX6 gene expression. Conclusion PRDX6 is highly expressed in lung adenocarcinoma and higher levels of expression of the PRDX6 gene were associated with a poorer prognosis.

Small extracellular vesicles (sEVs), including exosomes and microvesicles (MVs), are nano-sized membranous particles shed by almost all cell types. Both play significant roles in cellular communication by transferring proteins, nucleic acids, lipids, and metabolites to recipient cells and impact a broad range of pathophysiological processes, whereby they hold great promise in clinical application as therapeutic cargo carriers. Previous studies have shown that the membrane antibodies on exosomes derived from primary B cells, B cell lines, and hybridoma can present antigen-induced T cell responses. However, whether secretory antibodies can be released by sEVs and play a biological role has been unclear. Antibody against human epidermal growth factor receptor-2 (HER2 antibody) is a humanized monoclonal IgG antibody. In this study, by using a CHO cell line expressing recombinant anti-HER2 monoclonal antibody (CHO-HER2), we demonstrated the packaging of the intact HER2 antibodies in the sEVs (sEVs-HER2), and the involvement of endocytosis in their anti-proliferation effects on the BT474 cells, a HER2-overexpressing cell line. Further unbiased proteomic analysis showed that the heavy and light chains of IgG were the most abundant sEVs proteins and revealed that besides endosomal and lysosomes proteins, the proteins involved in the Golgi apparatus were significantly enriched in sEVs-HER2. Brefeldin A (BFA), a potent inhibitor of protein trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus, significantly suppressed the titer of anti-HER2 antibody in both supernatant and sEVs-HER2. Moreover, the HER2 antibodies in the sEVs could be significantly suppressed by Tipifarnib and Y27632, inhibitors targeting exosomes and MV biogenesis/release, respectively. This study demonstrated that the secretory HER2 antibody could be packaged into sEVs and maintain its anti-proliferation activity. Moreover, this study suggested that the HER2 antibodies could be packaged in both exosomes and MVs and the involvement of the Golgi pathway.

Abstract Background RNA N 6-methyladenosine (m6A) modification is critical for plant growth and crop yield. m6A reader proteins can recognize m6A modifications to facilitate the functions of m6A in gene regulation. ECT2, ECT3, and ECT4 are m6A readers that are known to redundantly regulate trichome branching and leaf growth, but their molecular functions remain unclear. Results Here, we show that ECT2, ECT3, and ECT4 directly interact with each other in the cytoplasm and perform genetically redundant functions in abscisic acid (ABA) response regulation during seed germination and post-germination growth. We reveal that ECT2/ECT3/ECT4 promote the stabilization of their targeted m6A-modified mRNAs, but have no function in alternative polyadenylation and translation. We find that ECT2 directly interacts with the poly(A) binding proteins, PAB2 and PAB4, and maintains the stabilization of m6A-modified mRNAs. Disruption of ECT2/ECT3/ECT4 destabilizes mRNAs of ABA signaling-related genes, thereby promoting the accumulation of ABI5 and leading to ABA hypersensitivity. Conclusion Our study reveals a unified functional model of m6A mediated by m6A readers in plants. In this model, ECT2/ECT3/ECT4 promote stabilization of their target mRNAs in the cytoplasm.

Background: The establishment of the anterior-posterior (A-P) axis is a crucial step during tissue repair and regeneration. Despite the association reported recently of N6-methyladenosine (m6A) with regeneration, the mechanism underlying the regulation of m6A in A-P axis specification during regeneration remains unknown. Herein, we deciphered the m6A landscape at a single-base resolution at multiple time points during A-P axis regeneration and constructed the de novo transcriptome assembly of the Dugesia japonica planarian. Results: Immunofluorescence staining and comparative analysis revealed that m6A is widespread across the planarian and dynamically regulated during regeneration along the A-P axis, exhibiting a strong spatiotemporal feature. The resulting datasets of m6A-modified genes identified 80 anterior-specific genes and 13 posterior-specific genes, respectively. In addition, we showed that YTHDC1 serves as the primary m6A reader to be involved in the m6A-mediated specification of A-P axis during regeneration in Dugesia japonica planarian. Conclusions: Our study provides an RNA epigenetic explanation for the specification of the A-P axis during tissue regeneration in planarian.

Background HbA1c is the validated biomarker for glycemic management in diabetic individuals. Here, we report a compound heterozygote for β0-thal and Hb J-Lomeand evaluate its effect on HbA1c measurements.Methods A 51-year-old female was suspected of harboring a hemoglobin variant following no value of HbA1c levelby Arkray HA-8180 V (48s HbA1c mode), abnormal hematological data, and abnormalhemoglobin analysison capillary electrophoresis (Capillarys 2 Flex Piercing, Hb program). Sanger sequencing of the α and β genes was subsequently performed on the proband.HbA1c was reanalyzed using D10 (Bio-Rad), Capillarys 2 Flex Piercing (Sebia), and Roche Cobas c501 (Roche Diagnostics).Results Sanger sequencing identified a compound heterozygote for β0-thal [β17(A14) Lys > Stop, HBB: c.52A > T] and Hb J-Lome [β59(E3) Lys > Asn, HBB: c.180G > C].HbA1c values ⁣⁣determinedby D10, Capillarys 2 Flex Piercing (HbA1c program), and Roche Cobas c501were 2.3%, no HbA1c value, and 5.1 (32 mmol/mol), respectively. During pedigree analysis, the son of the proband was found to have normal blood glucose (5.55 mmol/L), decreased HbA1c (3.6%, 16 mmol/mol)by Arkray HA-8180 V (48s HbA1c mode), an abnormal band on the electrophoretogram of Capillarys2 (Hb program), and the Hb J-Lome mutation in the β globin gene.Subsequently, HbA1c values ⁣⁣determinedby D10, Capillarys 2 Flex Piercing (HbA1c program), and Roche Cobas c501 were4.0% (20 mmol/mol), no HbA1c value, and 5.0 (31 mmol/mol), respectively.Conclusion Atypically low HbA1c levels or a discrepancy between blood glucose and HbA1c levels should raise concerns about hemoglobin variations.

Soft robots, especially soft robotic hands, possess prominent potential for applications in close proximity and direct contact interaction with humans due to their softness and compliant nature. The safety perception of users during interactions with soft robots plays a crucial role in influencing trust, adaptability, and overall interaction outcomes in human–robot interaction (HRI). Although soft robots have been claimed to be safe for over a decade, research addressing the perceived safety of soft robots still needs to be undertaken. The current safety guidelines for rigid robots in HRI are unsuitable for soft robots. In this paper, we highlight the distinctive safety issues associated with soft robots and propose a framework for evaluating the perceived safety in human–soft robot interaction (HSRI). User experiments were conducted, employing a combination of quantitative and qualitative methods, to assess the perceived safety of 15 interactive motions executed by a soft humanoid robotic hand. We analyzed the characteristics of safe interactive motions, the primary factors influencing user safety assessments, and the impact of motion semantic clarity, user technical acceptance, and risk tolerance level on safety perception. Based on the analyzed characteristics, we summarize vital insights to provide valuable guidelines for designing safe, interactive motions in HSRI. The current results may pave the way for developing future soft machines that can safely interact with humans and their surroundings.

Abstract Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to cardiac fibrosis and heart failure (HF). Recent studies have demonstrated that EndMT is regulated by autophagy, and we previously showed suppression of excessive autophagy and alleviation of cardiac fibrosis in HF mice with inactivated receptor for advanced glycation end products (RAGE). Thus, we investigated whether reduced cardiac fibrosis due to RAGE knockout occurred by inhibiting EndMT mediated by excessive autophagy. We found a decrease in endothelial cells (CD31+/VE-Cadherin+) and an increase in cells co-expressing CD31 and α-smooth muscle actin (α-SMA, myofibroblast marker) at 8 weeks in heart tissue of mice subjected to transverse aortic constriction (TAC), which implied EndMT. Knockout RAGE decreased EndMT accompanied by decreased expression of autophagy-related proteins (LC3BII/I and Beclin 1), and alleviated cardiac fibrosis and improved cardiac function in TAC mice. Moreover, 3-methyladenine (3-MA) and chloroquine (CQ), inhibitors of autophagy, attenuated EndMT, and cardiac fibrosis in TAC mice. Importantly, EndMT induced by AGEs could be blocked by autophagy inhibitor in vivo and in vitro. These results suggested that AGEs/RAGE-autophagy-EndMT axis involved in the development of cardiac fibrosis and knockout RAGE ameliorated cardiac fibrosis through decreasing EndMT regulated by autophagy, which could be a promising therapeutic strategy for HF.

Nε-lysine acetylation is a reversible posttranslational modification (PTM) involved in multiple physiological functions. Genetic and animal studies have documented the critical roles of protein acetylation in brain development, functions, and various neurological disorders. However, the underlying cellular and molecular mechanism are still partially understood. Here, we profiled and characterized the mouse brain acetylome and investigated the cellular distribution of acetylated brain proteins. We identified 1,818 acetylated proteins, including 5,196 acetylation modification sites, using a modified workflow comprising filter-aided sample preparation (FSAP), acetylated peptides enrichment, and MS analysis without pre- or post-fraction. Bioinformatics analysis indicated these acetylated mouse brain proteins were mainly located in the myelin sheath, mitochondrial inner membrane, and synapse, as well as their involvement in multiple neurological disorders. Manual annotation revealed that a set of brain-specific proteins were acetylation-modified. The acetylation of three brain-specific proteins was verified, including neurofilament light polypeptide (NEFL), 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNP), and neuromodulin (GAP43). Further immunofluorescence staining illustrated that acetylated proteins were mainly distributed in the nuclei of cortex neurons and axons of hippocampal neurons, sparsely distributed in the nuclei of microglia and astrocytes, and the lack of distribution in both cytoplasm and nuclei of cerebrovascular endothelial cells. Together, this study provided a comprehensive mouse brain acetylome and illustrated the cellular-specific distribution of acetylated proteins in the mouse brain. These data will contribute to understanding and deciphering the molecular and cellular mechanisms of protein acetylation in brain development and neurological disorders. Besides, we proposed some problems that need to be solved in future brain acetylome research.

Ni60 coating is prepared utilizing laser cladding on 45 steel assisted by magnetic-ultrasonic-electric field. The effect of multi-physical fields on the cracking tendency, microstructure, phase composition, mechanical properties and corrosive resistance of coating is investigated. As results indicate, the macro-morphology of coating is affected by the multi-physical field and the microstructure is refined, which uniformizes the element distribution and prominently optimizes the tribological and anti-corrosive performance of coating, the number of cracks in the coating under multi-physical field reduce by 76.92%, compared with that without physical field, the average microhardness increases by 37.89%, the average friction coefficient decreases by 61.96%, the average wear loss decreases by 61.05%, the corrosive rate decreases by 93.01%.

Abstract Hard yet flexible coatings with multi‐functionalities are useful for foldable displays and marine industries but rare. In this study, a highly cross‐linked multifunctional hybrid coating with ceramic‐like hardness and polymer‐like flexibility is reported. The coating is prepared via a step‐by‐step strategy, where two types of epoxy‐oligosiloxane nanoclusters are first synthesized by sol‐gel chemistry, and amine‐terminated curing agents are used to cross‐link them at room temperature. The coating is highly transparent (>92% transmittance), hard (6‐7H), and flexible (10 mm bending diameter) because of the unique combination of siloxane nanoclusters and polymer networks. Meanwhile, since the coating contains fouling‐resistant telomer and low‐surface‐tension liquid lubricant polydimethylsiloxane (PDMS), it exhibits excellent anti‐biofouling and self‐cleaning properties. The results indicate that the mechanical and antifouling properties of the coating can be easily tuned and prove that the step‐by‐step strategy is a promising and universal method. The novel coatings can meet the needs of applications in foldable displays, marine industries, and other fields.

Small extracellular vesicles (sEVs) miRNAs are promising diagnosis and prognosis biomarkers for ischemic stroke (IS). This study aimed to determine the impact of IS on the serum sEVs miRNA profile of IS patients and a transient middle cerebral artery occlusion (tMCAO) mouse model. Small RNAseq was used to define the serum sEVs miRNA profile in IS patients and healthy controls (HC), and tMCAO mice and sham controls. Among the 1,444 and 1,373 miRNAs identified in human and mouse serum sEVs, the expression of 424 and 37 miRNAs was significantly altered in the IS patients and tMCAO mice, respectively (| Log2FC| ≥ 1, p < 0.01). Notably, five of the top 25 upregulated miRNAs in IS patients were brain-specific or enriched, including hsa-miR-9-3p, hsa-miR-124-3p, hsa-miR-143-3p, hsa-miR-98-5p, and hsa-miR-93-5p. Upregulation of these four miRNAs was further validated by qPCR. Nine of the 20 upregulated miRNAs in tMCAO mice were also brain-specific or enriched miRNAs. Temporal analysis indicated that the dynamics of mmu-miR-9-5p, mmu-miR-124-3p, mmu-miR-129-5p, and mmu-miR-433-3p were closely correlated with the evolution of ischemic brain injury, as their expression increased at 0.5 days after the onset of ischemia, peaked at day 1 or 3, and returned to normal levels at day 7 and 14. Notably, with the exceptions of mmu-miR-128-3p, the expression of the other eight miRNAs in the mouse serum sEVs was unaffected in the lipopolysaccharide (LPS)-induced neuroinflammation model. Together, in this study, we provided a comprehensive view of the influences of IS on the serum sEVs miRNA profile of IS patients and tMCAO mice and demonstrated the increment of a set of brain-specific miRNAs in serum sEVs after acute cerebral ischemia, which could be promising candidates directly reflecting the ischemic brain injury.

The discovery of immunodominant antigens is of great significance for the development of new especially sensitive diagnostic reagents and effective vaccines in controlling tuberculosis (TB). In the present study, we targeted the T-Cell epitope-rich fragment (nucleotide position 109-552) of Rv1566c from Mycobacterium tuberculosis (MTB) and got a recombinant protein Rv1566c-444 and the full-length protein Rv1566c with Escherichia coli expression system, then compared their performances for TB diagnosis and immunogenicity in a mouse model. The results showed that Rv1566c-444 had similar sensitivity with Rv1566c (44.44% Vs 30.56%) but lower sensitivity than ESAT-6&CFP-10&Rv3615c (44.4% Vs. 94.4%) contained in a commercial kit for distinguishing TB patients from healthy donors. In immunized BALB/c mice, Rv1566c-444 elicited stronger T-helper 1 (Th1) cellular immune response over Rv1566c with higher levels of Th1 cytokine IFN-γ and IFN-γ/IL-4 expression ratio by ELISA; more importantly, with a higher proliferation of CD4+ T cells and a higher proportion of CD4+ TNF-α+ T cells with flow cytometry. Rv1566c-444 also induced a higher level of IL-6 by ELISA and a higher proportion of Rv1566c-444-specific CD8+ T cells and a lower proportion of CD8+ IL-4+ T cells by flow cytometry compared with the Rv1566c group. Moreover, the Rv1566c-444 group showed a high IgG secretion level and the same type of CD4+ Th cell immune response (both IgG1/IgG2a >1) as its parental protein group. Our results showed the potential of the recombinant protein Rv1566c-444 enriched with T-Cell epitopes from Rv1566c as a host T cell response measuring biomarker for TB diagnosis and support further evaluation of Rv1566c-444 as vaccine antigen against MTB challenge in animal models in the form of protein mixture or fusion protein.

Ni60 coating-45 steel substrate was prepared by magnetic field assisted laser cladding with four waveforms:steady magnetic field (SMF), alternating magnetic field (AMF), pulsed magnetic field (PMF). The effects of four kinds of magnetic fields on the morphology, microstructure, phase composition and microhardness of the coating were studied, and the magnetic field mechanism on the coating was briefly analyzed. Results revealed that the addition of magnetic field can significantly reduce the number of cracks, facilitate grain refinement and improve the coating hardness. The improvement degree of four kinds of magnetic fields on the coating performance is: PMF > APMF > AMF > SMF. Among them, the coating performance is prominently improved by PMF, but there is a serious segregation of hard phase; The segregation of hard phase and the slender of the structure occur in the APMF.

With the increasing proportion of wind power integration, the volatility of wind power brings huge challenges to the safe and stable operation of the electric power system. At present, the indexes commonly used to evaluate the volatility of wind power only consider its overall characteristics, such as the standard deviation of wind power, the average of power variables, etc., while ignoring the detailed volatility of wind power, that is, the features of the frequency distribution of power variables. However, how to accurately describe the detailed volatility of wind power is the key foundation to reduce its adverse influences. To address this, a quantitative method for evaluating the detailed volatility of wind power at multiple temporal-spatial scales is proposed. First, the volatility indexes which can evaluate the detailed fluctuation characteristics of wind power are presented, including the upper confidence limit, lower confidence limit and confidence interval of power variables under the certain confidence level. Then, the actual wind power data from a location in northern China is used to illustrate the application of the proposed indexes at multiple temporal (year-season-month-day) and spatial scales (wind turbine-wind turbines-wind farm-wind farms) using the calculation time windows of 10 min, 30 min, 1 h, and 4 h. Finally, the relationships between wind power forecasting accuracy and its corresponding detailed volatility are analyzed to further verify the effectiveness of the proposed indexes. The results show that the proposed volatility indexes can effectively characterize the detailed fluctuations of wind power at multiple temporal-spatial scales. It is anticipated that the results of this study will serve as an important reference for the reserve capacity planning and optimization dispatch in the electric power system which with a high proportion of renewable energy. Keywords: Wind power, Detailed volatility, Frequency distribution, Multiple temporal-spatial scales, Typical days, Forecasting accuracy

Most traditional methods for optimizing the blade design have no consideration on the aerofoils of cross-section, which makes the blade design difficult to achieve the optimal solution. To solve this problem, this paper proposed an optimal design method for wind turbine blades considering different cross-section aerofoils. The proposed method took cross-section aerofoils, chord length and torsion angle as design variables, takeing relative thickness and relative camber constraints into consideration and aimed at maximizing annual energy production. Genetic algorithm model for optimizing the design parameters of blades was established. Taking a 1.5 MW wind turbine as example, the proposed design method was verified. The results show that the power coefficient of the optimized blade has been significantly improved by considering the cross-section aerofoils; the power coefficient of wind turbine can be maintained around the optimal value, which makes it easier to control the wind turbine to tracking the power curve and capture the maximum wind energy; and also the annual energy production is increased. At the same time, taking relative thickness and relative camber constraints into consideration makes the method closer to the actual engineering application.

This study centers on automatic sleep staging with a single channel electroencephalography (EEG), with some significant findings for sleep staging. In this study, we proposed a deep learning-based network by integrating attention mechanism and bidirectional long short-term memory neural network (AT-BiLSTM) to classify wakefulness, rapid eye movement (REM) sleep and non-REM (NREM) sleep stages N1, N2 and N3. The AT-BiLSTM network outperformed five other networks and achieved an accuracy of 83.78%, a Cohen’s kappa coefficient of 0.766 and a macro F1-score of 82.14% on the PhysioNet Sleep-EDF Expanded dataset, and an accuracy of 81.72%, a Cohen’s kappa coefficient of 0.751 and a macro F1-score of 80.74% on the DREAMS Subjects dataset. The proposed AT-BiLSTM network even achieved a higher accuracy than the existing methods based on traditional feature extraction. Moreover, better performance was obtained by the AT-BiLSTM network with the frontal EEG derivations than with EEG channels located at the central, occipital or parietal lobe. As EEG signal can be easily acquired using dry electrodes on the forehead, our findings might provide a promising solution for automatic sleep scoring without feature extraction and may prove very useful for the screening of sleep disorders.

The identification of Chinese herbal medicines (CHMs) is directly related to their safety and efficacy. However, the limited number of professionals fails to meet the demand of the vast CHMs market. To make the CHMs identification more convenient and accurate, this study aimed at assessing the feasibility of the automated machine learning (AutoML) technology in CHMs image recognition. Instead of a handcrafted neural network experimental models built on AutoML platform were presented. A dataset of 31,460 images consisting of 315 categories of commonly-used CHMs was built for the model creation. Furthermore, the Huawei ModelArts model was compared with a model built on the Baidu EasyDL platform using the same dataset. Three professionals were also invited to recognize images of 315 categories of CHMs. During the model evaluation, high accuracies of 99.2% and 98.4% were achieved by ModelArts and EasyDL, respectively. In the held-out tests, the accuracies of ModelArts and EasyDL models were 91.2% and 91.85%, respectively. Both models performed very well individually and no statistically significant difference was found in model performance between them. However, the model-training time was only approximately 41 min on ModelArts platform but 118 min on EasyDL. The mean accuracy of the manual recognition for 315 CHMs was 97.46 ± 1.58%. Results revealed that AutoML technology is a fast and simple approach and has great practical potential in the field of CHMs image recognition. Since the Huawei ModelArts platform requires less training time, we recommend it as a priority.

In recent years, teleoperation has experienced rapid development. Numerous teleoperation applications in diverse areas have been reported. Among all teleoperation-related components, computer vision (CV) is treated as one of the must-have technologies, because it allows users to observe remote scenarios. In addition, CV can further help the user to identify and track the desired targets from complex scenes. It has been proven that efficient CV methods can significantly improve the operation accuracy and relieve user’s physical and mental fatigue. Therefore, furthering understanding about CV techniques and reviewing the latest research outcomes is necessary for teleoperation designers. In this context, this review article was composed.

Ni60A/WC composite coating is prepared on 45 steel substrate by alternating-magnetic-field-assisted laser cladding. We compare the effects of different magnetic field intensity on WC particle distribution, microstructure, phase composition, microhardness and wear; in addition, the mechanism of alternating magnetic fields on cladding layers is briefly analyzed. The results show that an alternating magnetic field can significantly homogenize the distribution of WC particles. WC particles at the bottom are stirred and dispersed to the middle and upper area of the laser pool. The distribution of WC in the bottom region 6 of the coating decreases from 19.1% to 10%, the distribution of WC in the bottom region 5 decreases from 46.46% to 33.3%, the WC distribution in the top region 1 of the coating increases from 0 to 7.7% and the WC distribution in the top region 2 of the coating increases from 8.08% to 12.2%. The stirring of alternating magnetic fields strengthens the solute convection in the laser pool, refines the snowflake-shaped carbide hard phase and improves the coating microhardness and wear property, and adhesive wear and abrasive wear decrease gradually with increasing magnetic field strength.

Histone deacetylase inhibitors (HDACi) are a promising therapeutic intervention for stroke. The involvement of the anti-inflammatory effects of HDACi in their neuroprotection has been reported, but the underlying mechanisms are still uncertain. Given the post-stroke inflammation is a time-dependent process, starting with acute and intense inflammation, and followed by a prolonged and mild one, we proposed whether target the early inflammatory response could achieve the neuroprotection of HDACi? To test this hypothesis, a single dose of suberoylanilide hydroxamic acid (SAHA) (50 mg/kg), a pan HDACi, was intraperitoneally (i.p.) injected immediately or 12 h after ischemia onset in a transient middle cerebral artery occlusion (tMCAO) mouse model. Compared with delayed injection, immediate SAHA treatment provided more protection, evidenced by smaller infarction volume, and a better outcome. This protection was accompanied by suppression of pro-inflammatory cytokines and reduction of activated microglia in the early stage of post-stroke inflammation. Moreover, SAHA treatment suppressed M1 cytokine expression (IL-6, TNF-α, and iNOS) while promoted the transcription of M2 cytokines (Arg-1 and IL-10) in LPS-challenged mouse microglia, and enhanced CD206 (M2 marker) but decreased CD86 (M1 markers) levels in microglia isolated from the ipsilateral hemisphere of MCAO mice. Collectively, our data suggested that the protection of SAHA on ischemic brain injury was closely associated with its inhibition on the early inflammatory response, and this inhibition was related to its reducing microglia activation and priming the activated microglia toward a more protective phenotype.

The magnetic properties and magnetocaloric effect (MCE) of Gd4Sb3-xRx (R = Si, Ge, Sn, x = 0, 0.25, 0.5, 0.75) compounds have been studied systematically. The Curie temperature (Tc) of these compounds can be tuned from 270 K to 305 K depending on the substitution amount. All the compounds undergo a second-order magnetic transition from ferromagnetic (FM) state to paramagnetic (PM) state and exhibit considerable reversible MCE near room temperature. The maximum of magnetic entropy change (ΔSMmax) for a magnetic field change of 7 T can reach 4.25 Jkg-1K-1 in Gd4Sb3 phase and independent on Si substitution amount. By Ge and Sn substitution, reduced ΔSMmax of 3.5 and 4.25 Jkg-1K-1 can be obtained in Gd4Sb2.75Ge0.25 and Gd4Sb2.75Sn0.25 alloys respectively. The considerable MCE with no hysteresis and working temperature near room temperature suggests that these materials could be promising candidates as ambient magnetocaloric materials.

The effects of Ge occupations at Sb and Mn sites in Mn2Sb system had been re-examined along with the influence of hydrostatic pressure. The metamagnetic phase transition from ferrimagnetic (FRI) to antiferromagnetic (AFM) state was observed in Mn2Sb1-xGex (x = 0.05, 0.1) and (Mn1-yGey)2Sb (y = 0.025, 0.04) alloys. The phase transition temperature, Tt, was gradually increased with increased Ge substitution for both Sb and Mn, but slightly decreased under increased hydrostatic pressure in Mn2Sb0.95Ge0.05 alloy. Meanwhile, the slope of critical field as the function of temperature was reduced with increased hydrostatic pressure and Ge substitution amount in (Mn1-yGey)2Sb (y = 0.025, 0.04) alloys. For a field change of 7 T, the maxima of magnetic entropy changes of 6 Jkg-1K-1 and 7.1 Jkg-1K-1 have been achieved in Mn2Sb0.95Ge0.05 and Mn1.95Ge0.05Sb alloys, which are gradually decreased by more Ge substitution and increased hydrostatic pressure.