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Abstract With the rapid development of autonomous driving technology, path planning has gained significant attention as it holds great potential for improving safety. The Rapidly-exploring Random Tree star(RRT*) algorithm has attracted much attention because of its good adaptability and expansibility. However, how solving problems in the RRT* algorithm such as slow convergence time, significant search range randomness, and unpredictability is a challenge. Therefore, an RRT* enhancement algorithm combining variable probability goal-bias strategy and artificial potential field(APF) method(Improved A-RRT*) is proposed in this paper. Firstly, the variable probability goal-bias strategy is introduced in the sampling process to make random tree expand towards the target direction and improve the directional searchability of the random tree. Secondly, the potential field function in APF is improved to prevent falling into local optimum problems during path generation. Thirdly, improved APF is combined with RRT*, the target generates a gravitational field on random tree, and the obstacle generates a repulsive force on it, leading random tree to grow toward the target region. Finally, the proposed algorithm is compared with RRT* algorithm and its derivative algorithm. The experimental results demonstrate that the proposed algorithm has obvious optimizations in convergence speed and path quality.

Abstract Defects-rich heterointerfaces integrated with adjustable crystalline phases and atom vacancies, as well as veiled dielectric-responsive character, are instrumental in electromagnetic dissipation. Conventional methods, however, constrain their delicate constructions. Herein, an innovative alternative is proposed: carrageenan-assistant cations-regulated (CACR) strategy, which induces a series of sulfides nanoparticles rooted in situ on the surface of carbon matrix. This unique configuration originates from strategic vacancy formation energy of sulfides and strong sulfides-carbon support interaction, benefiting the delicate construction of defects-rich heterostructures in MxSy/carbon composites (M-CAs). Impressively, these generated sulfur vacancies are firstly found to strengthen electron accumulation/consumption ability at heterointerfaces and, simultaneously, induct local asymmetry of electronic structure to evoke large dipole moment, ultimately leading to polarization coupling, i.e., defect-type interfacial polarization. Such “Janus effect” (Janus effect means versatility, as in the Greek two-headed Janus) of interfacial sulfur vacancies is intuitively confirmed by both theoretical and experimental investigations for the first time. Consequently, the sulfur vacancies-rich heterostructured Co/Ni-CAs displays broad absorption bandwidth of 6.76 GHz at only 1.8 mm, compared to sulfur vacancies-free CAs without any dielectric response. Harnessing defects-rich heterostructures, this one-pot CACR strategy may steer the design and development of advanced nanomaterials, boosting functionality across diverse application domains beyond electromagnetic response.

Abstract Although graphene oxide (GO) has extensive recognized application prospects in slow-release fertilizer, plant pest control, and plant growth regulation, the incorporation of GO into nano herbicides is still in its early stages of development. This study selected a pair of sweet corn sister lines, nicosulfuron (NIF)-resistant HK301 and NIF-sensitive HK320, and sprayed them both with 80 mg kg–1 of GO-NIF, with clean water as a control, to study the effect of GO-NIF on sweet corn seedling growth, photosynthesis, chlorophyll fluorescence, and antioxidant system enzyme activity. Compared to spraying water and GO alone, spraying GO-NIF was able to effectively reduce the toxic effect of NIF on sweet corn seedlings. Compared with NIF treatment, 10 days after of spraying GO-NIF, the net photosynthetic rate (A), stomatal conductance (G s ), transpiration rate (E), photosystem II photochemical maximum quantum yield (Fv/Fm), photochemical quenching coefficient (qP), and photosynthetic electron transfer rate (ETR) of GO-NIF treatment were significantly increased by 328.31%, 132.44%, 574.39%, 73.53%, 152.41%, and 140.72%, respectively, compared to HK320. Compared to the imbalance of redox reactions continuously induced by NIF in HK320, GO-NIF effectively alleviated the observed oxidative pressure. Furthermore, compared to NIF treatment alone, GO-NIF treatment effectively increased the activities of superoxide dismutase (SOD), guaiacol peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) in both lines, indicating GO induced resistance to the damage caused by NIF to sweet corn seedlings. This study will provides an empirical basis for understanding the detoxification promoting effect of GO in NIF and analyzing the mechanism of GO induced allogeneic detoxification in cells.

Abstract Purpose To assess the interactive relationship between blood pressure status and diabetic mellitus (DM) with ganglion cell complex (GCC) thickness in elderly individuals in rural China. Methods Participants aged 50 years and older in a rural area of Daxing District, Beijing, were recruited in this study from October 2018 to November 2018. All subjects underwent a comprehensive systemic and ocular examination. Blood pressure status was graded as normotension, controlled hypertension and uncontrolled hypertension according to blood pressure measurements and the use of any medication for hypertension treatment. GCC parameters were measured by spectral-domain optical coherence tomography (SD-OCT). Generalized linear models (GLM) adjusted for related potential confounders were used to assess the interaction between DM and blood pressure status. Results Among 1415 screened subjects (2830 eyes), a total of 1117 eyes were enrolled in the final analysis. GLM analysis showed a significant interactive relationship between DM with uncontrolled hypertension status (β = 3.868, p = 0.011). GCC thickness would decrease 0.255 μm per year as the age increased (β=-0.255, p

With the increasing impacts of climate change and resource depletion, dielectric capacitors, with their exceptional stability, fast charging and discharging rates, and ability to operate under more extreme conditions, are emerging as promising high-demand candidates for high-performance energy storage devices, distinguishing them from traditional electrochemical capacitors and batteries. However, due to the shortcomings of various dielectric ceramics (e.g., paraelectrics (PEs), ferroelectrics (FEs), and antiferroelectrics (AFEs)), their low polarizability, low breakdown strength (BDS), and large hysteresis loss limit their standalone use in the advancement of energy storage ceramics. Therefore, synthesizing novel perovskite-based materials that exhibit high energy density, high energy efficiency, and low loss is crucial for achieving superior energy storage performance. In this review, we outline the recent development of perovskite-based ferroelectric energy storage ceramics from the perspective of combinatorial optimization for tailoring ferroelectric hysteresis loops and comprehensively discuss the properties arising from the different combinations of components. We also provide future guidelines in this realm. Therefore, the combinatorial optimization strategy in this review will open up a practical route toward the application of new high-performance ferroelectric energy storage devices.

Abstract Hair follicle (HF) regeneration during wound healing continues to present a significant clinical challenge. Dermal papilla cell-derived exosomes (DPC-Exos) hold immense potential for inducing HF neogenesis. However, the accurate role and underlying mechanisms of DPC-Exos in HF regeneration in wound healing remain to be fully explained. This study, represents the first analysis into the effects of DPC-Exos on fibroblasts during wound healing. Our findings demonstrated that DPC-Exos could stimulate the proliferation and migration of fibroblasts, more importantly, enhance the hair-inducing capacity of fibroblasts. Fibroblasts treated with DPC-Exos were capable of inducing HF neogenesis in nude mice when combined with neonatal mice epidermal cells. In addition, DPC-Exos accelerated wound re-epithelialization and promoted HF regeneration during the healing process. Treatment with DPC-Exos led to increased expression levels of the Wnt pathway transcription factors β-catenin and Lef1 in both fibroblasts and the dermis of skin wounds. Specifically, the application of a Wnt pathway inhibitor reduced the effects of DPC-Exos on fibroblasts and wound healing. Accordingly, these results offer evidence that DPC-Exos promote HF regeneration during wound healing by enhancing the hair-inducing capacity of fibroblasts and activating the Wnt/β-catenin signaling pathway. This suggests that DPC-Exos may represent a promising therapeutic strategy for achieving regenerative wound healing.

Abstract Periprosthetic infection and prosthetic loosing stand out as prevalent yet formidable complications following orthopedic implant surgeries. Synchronously addressing the two complications is long‐time challenging. Herein, a bioactive glass scaffold (BGS) functionalized with MgCuFe‐layered double hydroxide (LDH)‐derived sulfide nanosheets (BGS/MCFS) is developed for vascularized osteogenesis and periprosthetic infection prevention/treatment. Apart from the antibacterial cations inhibiting bacterial energy and material metabolism, the exceptional near‐infrared‐II (NIR‐II) photothermal performance empowers BGS/MCFS to eliminate periprosthetic infections, outperforming previously reported functionalized BGS. The rough surface topography and the presence of multi‐bioactive metal ions bestow BGS/MCFS with exceptional osteogenic and angiogenic properties, with 8.5‐fold and 2.3‐fold enhancement in bone mass and neovascularization compared with BGS. Transcriptome sequencing highlights the involvement of the TGF‐β signaling pathway in these processes, while single‐cell sequencing reveals a significant increase in osteoblasts and endothelial cells around BGS/MCFS compared to BGS.

Summary: Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that presents significant challenges for early detection. This study introduces the GlyExo-Capture method for isolating fucosylated extracellular vesicles (Fu-EVs) from serum. We analyze microRNA (miRNA) profiles from Fu-EVs in 88 HCC patients and 179 non-HCC controls using next-generation sequencing (NGS) and identify five miRNAs (hsa-let-7a, hsa-miR-21, hsa-miR-125a, hsa-miR-200a, and hsa-miR-150) as biomarkers for HCC diagnosis. The five-miRNA panel demonstrates exceptional HCC diagnostic performance, with a sensitivity of 0.90 and specificity of 0.92 in a combined cohort of 194 HCC and 412 non-HCC controls, significantly surpassing the performance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP). Notably, the miRNA model achieves recall rates of 85.7% and 90.8% for stage 0 and stage A early-stage HCC, respectively, identifies 88.1% of AFP-negative HCC cases, and effectively differentiates HCC from other cancers. This study provides a high-throughput, rapid, and non-invasive approach for early HCC detection.

Background The main challenge against patients with cancer to derive benefits from immune checkpoint inhibitors targeting PD-1/PD-L1 appears to be the immunosuppressive tumor microenvironment (TME), in which IL-33/ST2 signal fulfills critical functions. However, whether IL-33 limits the therapeutic efficacy of anti-PD-L1 remains uncertain.Methods Molecular mechanisms of IL-33/ST2 signal on anti-PD-L1 treatment lewis lung carcinoma tumor model were assessed by RNA-seq, ELISA, WB and immunofluorescence (IF). A sST2-Fc fusion protein was constructed for targeting IL-33 and combined with anti-PD-L1 antibody for immunotherapy in colon and lung tumor models. On this basis, bifunctional fusion proteins were generated for PD-L1-targeted blocking of IL-33 in tumors. The underlying mechanisms of dual targeting of IL-33 and PD-L1 revealed by RNA-seq, scRNA-seq, FACS, IF and WB.Results After anti-PD-L1 administration, tumor-infiltrating ST2+ regulatory T cells (Tregs) were elevated. Blocking IL-33/ST2 signal with sST2-Fc fusion protein potentiated antitumor efficacy of PD-L1 antibody by enhancing T cell responses in tumor models. Bifunctional fusion protein anti-PD-L1-sST2 exhibited enhanced antitumor efficacy compared with combination therapy, not only inhibited tumor progression and extended the survival, but also provided long-term protective antitumor immunity. Mechanistically, the superior antitumor activity of targeting IL-33 and PD-L1 originated from reducing immunosuppressive factors, such as Tregs and exhausted CD8+ T cells while increasing tumor-infiltrating cytotoxic T lymphocyte cells.Conclusions In this study, we demonstrated that IL-33/ST2 was involved in the immunosuppression mechanism of PD-L1 antibody therapy, and blockade by sST2-Fc or anti-PD-L1-sST2 could remodel the inflammatory TME and induce potent antitumor effect, highlighting the potential therapeutic strategies for the tumor treatment by simultaneously targeting IL-33 and PD-L1.

Abstract Background Staphylococcus aureus and its single or mixed biofilm infections seriously threaten global public health. Phage therapy, which uses active phage particles or phage-derived endolysins, has emerged as a promising alternative strategy to antibiotic treatment. However, high-efficient phage therapeutic regimens have yet to be established. Results In this study, we used an enrichment procedure to isolate phages against methicillin-resistant S. aureus (MRSA) XN108. We characterized phage SYL, a new member of the Kayvirus genus, Herelleviridae family. The phage endolysin LysSYL was expressed. LysSYL demonstrated stability under various conditions and exhibited a broader range of efficacy against staphylococcal strains than its parent phage (100% vs. 41.7%). Moreover, dynamic live/dead bacterial observation demonstrated that LysSYL could completely lyse MRSA USA300 within 10 min. Scan and transmission electron microscopy revealed evident bacterial cell perforation and deformation. In addition, LysSYL displayed strong eradication activity against single- and mixed-species biofilms associated with S. aureus. It also had the ability to kill bacterial persisters, and proved highly effective in eliminating persistent S. aureus when combined with vancomycin. Furthermore, LysSYL protected BALB/c mice from lethal S. aureus infections. A single-dose treatment with 50 mg/kg of LysSYL resulted in a dramatic reduction in bacterial loads in the blood, liver, spleen, lungs, and kidneys of a peritonitis mouse model, which resulted in rescuing 100% of mice challenged with 108 colony forming units of S. aureus USA300. Conclusions Overall, the data provided in this study highlight the strong therapeutic potential of endolysin LysSYL in combating staphylococcal infections, including mono- and mixed-species biofilms related to S. aureus.

Objective To investigate the correlations between choroidal parameters and primary angle-closure suspect (PACS) in different age subgroups.Methods and analysis Participants aged 50 years or older in a rural area of Daxing District, Beijing, were recruited. Swept-source optical coherence tomography was used to measure the choroidal parameters. Demographic, ocular biometry parameters and choroidal parameters were compared between the PACS and non-PACS (NPACS) eyes. Logistic analysis was performed to explore the association between the choroidal parameters and PACS.Results 192 (26.89%) subjects with PACS and 509 (71.29%) with PACS were analysed. Subjects were divided into two groups: group 1 (50–60 years, n=286) and group 2 (>60 years, n=415). In group 1, the mean subfoveal choroidal thickness of PACS eyes was 341.82±88.23 µm and thicker than NPACS eyes (315.07±83.53 µm, p=0.035). The choroidal volume was greater in PACS eyes (10.61±2.78 mm3) compared with NPACS eyes (9.66±2.49 mm3, p=0.013). In group 2, no significant difference in any choroidal parameters between PACS and NPACS was found. Multivariate regression demonstrated that increased choroidal volume was associated with PACS (OR 1.298, 95% CI 1.117 to 1.510, p

Abstract Background Circular RNAs are enriched in cardiac tissue and play important roles in the pathogenesis of heart diseases. In this study, we aimed to investigate the regulatory mechanism of a conserved heart-enriched circRNA, circPan3, in cardiac hypertrophy. Methods Cardiac hypertrophy was induced by isoproterenol. The progression of cardiomyocyte hypertrophy was assessed by sarcomere organization staining, cell surface area measurement, and expression levels of cardiac hypertrophy markers. RNA interactions were detected by RNA pull-down assays, and methylated RNA immunoprecipitation was used to detect m6A level. Results The expression of circPan3 was downregulated in an isoproterenol-induced cardiac hypertrophy model. Forced expression of circPan3 attenuated cardiomyocyte hypertrophy, while inhibition of circPan3 aggravated cardiomyocyte hypertrophy. Mechanistically, circPan3 was an endogenous sponge of miR-320-3p without affecting miR-320-3p levels. It elevated the expression of HSP20 by endogenously interacting with miR-320-3p. In addition, circPan3 was N6-methylated. Stimulation by isoproterenol downregulated the m6A eraser ALKBH5, resulting in N6-methylation and destabilization of circPan3. Conclusions Our research is the first to report that circPan3 has an antihypertrophic effect in cardiomyocytes and revealed a novel circPan3-modulated signalling pathway involved in cardiac hypertrophy. CircPan3 inhibits cardiac hypertrophy by targeting the miR-320-3p/HSP20 axis and is regulated by ALKBH5-mediated N6-methylation. This pathway could provide potential therapeutic targets for cardiac hypertrophy. Graphical Abstract

As knowledge graphs (KGs) become more widely used in various applications, error detection for KGs has received more attention, which can reduce quality issues such as errors and inconsistencies. With the development of representation learning, embedding-based methods have significantly improved error detection performance. The recent error detection algorithm uses KG structural embedding loss and constructs a reasonable score function, ranking the confidence scores for each triplet. However, these methods ignore the factual semantics of the triplet itself, which primarily exist in the entities and relations descriptions text. Therefore, we propose Semantic and Structural Integrated Contrastive Learning(SeSICL) to simultaneously capture graph structural patterns and deep semantic features from descriptions text. Our method is based on contrastive learning without data augmentation, which utilizes encoder perturbations to generate contrasting views, making SeSICL highly suitable for complex error detection tasks and robust against real-world noise. We evaluate SeSICL on three baseline datasets with abnormal data and fluctuations. SeSICL outperforms the previous state-of-the-art methods, demonstrating our method’s performance and robustness in more complex scenarios.

Abstract Reducing inter-spin distance can enhance magnetic interactions and allow for the realization of outstanding magnetic properties. However, achieving reduced distances is technically challenging. Here, we construct a 3d-4f metal cluster (Dy2VN) inside a C80 cage, affording a heretofore unseen metallofullerene containing both paramagnetic 3d and 4f metal ions. The significantly suppressed 3d-4f (Dy-V) distances, due to the unique cage confinement effect, were observed by crystallographic and theoretical analysis of Dy2VN@I h (7)-C80. These reduced distances result in an enhanced magnetic coupling (J total, Dy-V = 53.30 cm−1; J total, Dy-Dy = −6.25 cm−1), leading to a high magnetic blocking temperature compared to reported 3d-4f single-molecule magnets and strong coercive field of 2.73 Tesla. Our work presents a new class of single-molecule magnets with both paramagnetic 3d and 4f metals confined in a fullerene cage, offering superior and tunable magnetic properties due to the unique cage confinement effect and the diverse composition of the entrapped magnetic core.

Abstract Focal and systemic infections are serious threats to human health. Preclinical models enable the development of new drugs and therapeutic regimens. In vivo, animal bioluminescence (BL) imaging has been used with bacterial reporter strains to evaluate antimicrobial treatment effects. However, high‐sensitivity bioluminescent systems are required because of the limited tissue penetration and low brightness of the BL signals of existing approaches. Here, we report that NanoLuc (Nluc) showed better performance than LuxCDABE in bacteria. However, the retention rate of plasmid constructs in bacteria was low. To construct stable Staphylococcus aureus reporter strains, a partner protein enolase (Eno) was identified by screening of S. aureus strain USA300 for fusion expression of Nluc‐based luciferases, including Nluc, Teluc, and Antares2. Different substrates, such as hydrofurimazine (HFZ), furimazine (FUR), and diphenylterazine (DTZ), were used to optimize a stable reporter strain/substrate pair for BL imaging. S. aureus USA300/Eno‐Antares2/HFZ produced the highest number of photons of orange‐red light in vitro and enabled sensitive BL tracking of S. aureus in vivo, with sensitivities of approximately 10 CFU from mouse skin and 750 CFU from mouse kidneys. USA300/Eno‐Antares2/HFZ was a powerful combination based on the longitudinal evaluation of the therapeutic efficacy of antibiotics. The optimized S. aureus Eno‐Antares2/HFZ pair provides a technological advancement for the in vivo evaluation of antimicrobial treatment.

Accessible and superior electrocatalysts to overcome the sluggish oxygen evolution reaction (OER) are pivotal for sustainable and low-cost hydrogen production through electrocatalytic water splitting. The iron and nickel oxohydroxide complexes are regarded as the most promising OER electrocatalyst attributed to their inexpensive costs, easy preparation, and robust stability. In particular, the Fe-doped NiOOH is widely deemed to be superior constituents for OER in an alkaline environment. However, the facile construction of robust Fe-doped NiOOH electrocatalysts is still a great challenge. Herein, we report the facile construction of Fe-doped NiOOH on Ni(OH)2 hierarchical nanosheet arrays grown on nickel foam (FeNi@NiA) as efficient OER electrocatalysts through a facile in-situ electrochemical activation of FeNi-based Prussian blue analogues (PBA) derived from Ni(OH)2. The resultant FeNi@NiA heterostructure shows high intrinsic activity for OER due to the modulation of the overall electronic energy state and the electrical conductivity. Importantly, the electrochemical measurement revealed that FeNi@NiA exhibits a low overpotential of 240 mV at 10 mA/cm2 with a small Tafel slope of 62 mV dec−1 in 1.0 M KOH, outperforming the commercial RuO2 electrocatalysts for OER.

The epigenetic modifier N6-methyladenosine (m6A), recognized as the most prevalent internal modification in messenger RNA (mRNA), has recently emerged as a pivotal player in immune regulation. Its dysregulation has been implicated in the pathogenesis of various autoimmune conditions. However, the implications of m6A modification within the immune microenvironment of Sjögren's syndrome (SS), a chronic autoimmune disorder characterized by exocrine gland dysfunction, remain unexplored. Herein, we leverage an integrative analysis combining public database resources and novel sequencing data to investigate the expression profiles of m6A regulatory genes in SS. Our cohort comprised 220 patients diagnosed with SS and 62 healthy individuals, enabling a comprehensive evaluation of peripheral blood at the transcriptomic level. We report a significant association between SS and altered expression of key m6A regulators, with these changes closely tied to the activation of CD4+ T cells. Employing a random forest (RF) algorithm, we identified crucial genes contributing to the disease phenotype, which facilitated the development of a robust diagnostic model via multivariate logistic regression analysis. Further, unsupervised clustering revealed two distinct m6A modification patterns, which were significantly associated with variations in immunocyte infiltration, immune response activity, and biological function enrichment in SS. Subsequently, we proceeded with a screening process aimed at identifying genes that were differentially expressed (DEGs) between the two groups distinguished by m6A modification. Leveraging these DEGs, we employed weight gene co-expression network analysis (WGCNA) to uncover sets of genes that exhibited strong co-variance and hub genes that were closely linked to m6A modification. Through rigorous analysis, we identified three critical m6A regulators - METTL3, ALKBH5, and YTHDF1 - alongside two m6A-related hub genes, COMMD8 and SRP9. These elements collectively underscore a complex but discernible pattern of m6A modification that appears to be integrally linked with SS's pathogenesis. Our findings not only illuminate the significant correlation between m6A modification and the immune microenvironment in SS but also lay the groundwork for a deeper understanding of m6A regulatory mechanisms. More importantly, the identification of these key regulators and hub genes opens new avenues for the diagnosis and treatment of SS, presenting potential targets for therapeutic intervention.

Background: Globally, gastric cancer (GC) is recognized as the third leading cause of cancer-related deaths and the fifth most prevalent malignant disease. Multiple studies have indicated that Hedyotis diffusa Willd, in pinyin, called Bai Hua She Cao (BHSSC), a traditional Chinese medicine (TCM) is an herbal remedy for cancer treatment. However, the specific mechanisms underlying its anti-tumor properties and mode of action are still unclear. Methods: To determine the role of BHSSC in GC, candidate target genes were selected from The Encyclopedia of Traditional Chinese Medicine (ETCM) and analyzed using network pharmacology, bioinformatics, and experimental validation. Differentially expressed genes (DEGs) associated with gastric cancer were obtained from RNA sequencing (RNA-seq) data sourced from The Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD). The Reactome Pathway was examined using Analysis Tools, while KEGG pathways were analyzed using KOBAS. Gene Ontology (GO) evaluations were performed using WebGestalt and DAVID. The relationships between proteins were investigated using the STRING database. Furthermore, cell viability, colony formation, and cell migration ability were conducted in gastric cancer cells, BGC-823 and MGC-803. Results: Network pharmacology and bioinformatics analyses revealed a significant association between BHSSC and metabolic pathways. In vitro experiments demonstrated that BHSSC effectively suppressed gastric cancer cell proliferation and colony formation, inhibited cell migration, and activated the endoplasmic reticulum (ER) stress. Furthermore, it was found that enhancement of the expression of IRE1α and BIP is the mechanism by which BHSSC activates ER stress. Conclusions: The findings suggest that BHSSC exerts its effects through modulation of metabolic pathways, leading to the suppression of cell proliferation, inhibition of cell migration, and activation of the endoplasmic reticulum. These results provide valuable insights into the mechanisms underlying the therapeutic effects of BHSSC in GC and support its potential as a novel treatment option.

Reperfusion stands as a pivotal intervention for ischemic heart disease. However, the restoration of blood flow to ischemic tissue always lead to further damage, which is known as myocardial ischemia/reperfusion injury (MIRI). Ramelteon is an orally administered drug used to improve sleep quality, which is famous for its high bioadaptability and absence of notable addictive characteristics. However, the specific mechanism by which it improves MIRI is still unclear. Sirtuin-3 (Sirt3), primarily located in mitochondria, is crucial in mitigating many cardiac diseases, including MIRI. Based on the structure of Sirt3, we simulated molecular docking and identified several potential amino acid binding sites between it and ramelteon. Therefore, we propose a hypothesis that ramelteon may exert cardioprotective effects by activating the Sirt3 signaling pathway. Our results showed that the activation levels and expression level of Sirt3 were significantly decreased in MIRI tissue and H2O2 stimulated H9C2 cells, while ramelteon treatment upregulated Sirt3 activity and expression. After treat with 3-TYP, a classic Sirt3 activity inhibitor, we constructed myocardial ischemia/reperfusion surgery in vivo and induced H9C2 cells with H2O2 in vitro. The results showed that the myocardial protection and anti-apoptotic effects of ramelteon were antagonized by 3-TYP, indicating that the activation of Sirt3 is a key mechanism for ramelteon to exert myocardial protection. In summary, our results confirm a novel mechanism by which ramelteon improves MIRI by activating Sirt3 signaling pathway, providing strong evidence for the treatment of MIRI with ramelteon.

A functionalized ethylene–vinyl-alcohol (EVOH) nanofibrous membrane (NFM) was fabricated via co-electrospinning H4SiW12O40 (SiW12) and EVOH first, and then grafting citric acid (CCA) on the electrospun SiW12@EVOH NFM. Characterization with FT-IR, EDX, and XPS confirmed that CCA was introduced to the surface of SiW12@EVOH NFM and the Keggin structure of SiW12 was maintained well in the composite fibers. Due to a number of carboxyl groups introduced by CCA, the as-prepared SiW12@EVOH-CCA NFM can form a high number of hydrogen bonds with CR, and thus can be used to selectively absorb congo red (CR) in aqueous solutions. More importantly, the CR enriched in the NFM can be rapidly degraded via photocatalysis. SiW12 in the NFM acted as a photocatalyst, and the hydroxyl groups in the NFM acted as an electron donor to accelerate the photodegradation rate of CR. Meanwhile, the SiW12@EVOH-CCA NFM was regenerated and then exhibited a relatively stable adsorption capacity in five cycles of filtration–regeneration. The bifunctional nanofibrous membrane filter showed potential for use in the thorough purification of dye wastewater.

Teleseismic traveltime tomography is an important tool for investigating the crust and mantle structure of the Earth. The imaging quality of teleseismic traveltime tomography is affected by many factors, such as mantle heterogeneities, source uncertainties and random noise. Many previous studies have investigated these factors separately. An integral study of these factors is absent. To provide some guidelines for teleseismic traveltime tomography, we discussed four main influencing factors: the method for measuring relative traveltime differences, the presence of mantle heterogeneities outside the imaging domain, station spacing and uncertainties in teleseismic event hypocenters. Four conclusions can be drawn based on our analysis. (1) Comparing two methods, i.e., measuring the traveltime difference between two adjacent stations (M1) and subtracting the average traveltime of all stations from the traveltime of one station (M2), reveals that both M1 and M2 can well image the main structures; while M1 is able to achieve a slightly higher resolution than M2; M2 has the advantage of imaging long wavelength structures. In practical teleseismic traveltime tomography, better tomography results can be achieved by a two-step inversion method. (2) Global mantle heterogeneities can cause large traveltime residuals (up to about 0.55 s), which leads to evident imaging artifacts. (3) The tomographic accuracy and resolution of M1 decrease with increasing station spacing when measuring the relative traveltime difference between two adjacent stations. (4) The traveltime anomalies caused by the source uncertainties are generally less than 0.2 s, and the impact of source uncertainties is negligible.

With the development of medical diagnosis and treatment, knowing the mechanical properties of living tissues becomes critical. The aim of this study was to investigation material properties of the fresh porcine kidney and the parametric characterization of its viscoelastic material behavior. The material investigation included uniaxial tension tests in different strain rates, relaxation tests, as well as hydrostatic compression tests on the samples extracted from the fresh porcine kidney cortex. Tension tests and relaxation tests were performed by a planar dog-bone specimen with a micron loading testing machine. Hydrostatic compression tests were performed on the kidney cylinder sample which was placed in a compression chamber. Furthermore, a nonlinear viscoelastic model recently proposed by us was employed to characterize the tension data at different strain rates and relaxation test data. The the experimental and numerical results show that the stress-strain relations of the porcine kidney cortex at different strain rates in tension are presented for the first time and a higher strain rate results in higher ultimate strength and initial Young modulus but a lower rupture strain. A damage-dependent visco-elastic model is employed to model the tension data at different strain rates and relaxation data and exhibits a good agreement with the experimental data, which also demonstrates that the damage has an obvious influence on the stress-strain relation. Through comparison with the existing reference covering the uniaxial compression data, it seems that the mechanical behavior of the porcine kidney cortex manifests a stress state-dependent mechanical behavior. The ultimate strength and rupture strain are larger in compression than that in tension.

Xp21 DNA microdeletion syndrome is a very rare disease characterized by retinitis pigmentosa (RP), chronic granulomatous disease (CGD), and McLeod syndrome (MLS). Due to the complex and diverse clinical manifestations, early diagnosis remains a challenge for many physicians. In this study, for the purpose of determining the pathogenic gene variants and definitive diagnosis in a patient medically backgrounded with RP and CGD from a normal Chinese family, whole-exome sequencing (WES) was performed in this proband and copy number variation (CNV) was further verified in other family members by qPCR. A genetic evaluation revealed that the short arm of the X chromosome in the proband had a deletion CNV Xp21.1p11.4 (37431123–38186681) of approximately 0.755 Mb in size, and contained three contiguous OMIM genes as X-linked Kx blood group antigen (XK), cytochrome b-245 beta chain (CYBB), and RP GTPase regulator (RPGR). The qPCR results confirmed the copy number loss in Xp21.1p11.4 present in the proband and his unaffected mother. According to the American College of Medical Genetics and Genomics (ACMG) guidelines for the CNV interpretation, the deletion of this segment was a pathogenic variant. Our results provided evidence that CNV deletion of Xp21.1p11.4 in the short arm of the X chromosome was a pathogenic variant in such Chinese RP and CGD family, and the McLeod phenotype was not yet available. This study suggests that genetic testing is essential for a definitive diagnosis, which should better assist physicians in prediction, diagnosis, genetic counseling, and guidance for Xp21 DNA microdeletion syndrome.

Abstract Gram-positive (G+) bacterial infection is a great burden to both healthcare and community medical resources. As a result of the increasing prevalence of multidrug-resistant G+ bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), novel antimicrobial agents must urgently be developed for the treatment of infections caused by G+ bacteria. Endolysins are bacteriophage (phage)-encoded enzymes that can specifically hydrolyze the bacterial cell wall and quickly kill bacteria. Bacterial resistance to endolysins is low. Therefore, endolysins are considered promising alternatives for solving the mounting resistance problem. In this review, endolysins derived from phages targeting G+ bacteria were classified based on their structural characteristics. The active mechanisms, efficacy, and advantages of endolysins as antibacterial drug candidates were summarized. Moreover, the remarkable potential of phage endolysins in the treatment of G+ bacterial infections was described. In addition, the safety of endolysins, challenges, and possible solutions were addressed. Notwithstanding the limitations of endolysins, the trends in development indicate that endolysin-based drugs will be approved in the near future. Overall, this review presents crucial information of the current progress involving endolysins as potential therapeutic agents, and it provides a guideline for biomaterial researchers who are devoting themselves to fighting against bacterial infections.

Herein, novel microcapsules were designed and synthesized by emulsion polymerization and used for self-healing coating for magnesium alloy. Polyaniline (PANI) was used directly as a capsule shell, and thermoplastic acrylic resin was used as the core material. Polymerization processes of microcapsules were observed by optical microscopy, and some key polymerization parameters were discussed. Composite microcapsules were analyzed by scanning electron microscopy, infrared spectroscopy, and thermogravimetric analysis. The corrosion protection performance of microcapsule and epoxy varnish coatings with defect was tested by electrochemical impedance spectroscopy. Results showed that the microcapsule coating had a higher corrosion protection than epoxy varnish coating because capsule core acrylic resin could significantly improve the shield performance of the defect coating and capsule shell PANI could inhibit the corrosion reaction of magnesium alloy.

Abstract Background Protein arginine methyltransferase 5 (PRMT5) is upregulated in multiple tumors and plays a pivotal role in cancer cell proliferation. However, the role of PRMT5 in colorectal cancer remains poorly understood. Methods We detected the expression level of PRMT5 and glycolytic enzymes using online databases and colorectal cancer cell lines by immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. And MTT and colony formation assays were conducted to investigate cell proliferation. Then, we evaluated ECAR and OCR levels using a biological energy analyzer to investigate the energy status of colorectal cancer, and the transcriptional regulation was detected by dual luciferase reporter assay and ChIP assay. Finally, the efficacy of combined treatment of tadalafil and 5-FU was verified. Results PRMT5 was highly expressed in colorectal cancer tissues compared with their normal counterparts and correlated with poor prognosis in CRC patients. Then, we demonstrated that PRMT5 knockdown or loss of function attenuated the viability of CRC cells, while overexpression of PRMT5 promoted cell proliferation. Mechanistically, PRMT5 enhanced glycolysis through transcriptionally activating LDHA expression. In addition, the PRMT5 inhibitor, tadalafil, rendered CRC cells sensitive to antitumor agent 5-FU in vitro and in vivo. Conclusions Our data indicates that PRMT5 promoted colorectal cancer proliferation partially through activating glycolysis and may be a potential target for colorectal cancer therapy.

Selective hydrogenation of quinolines with easy-to-handle hydrogen donors and cost-effective catalysts is desirable. Here electrocatalytic quinoline hydrogenation to 1,2,3,4-tetrahydroquinolines is reported with water over a fluorine-modified cobalt.

The intermetallic PtBi/MgO/Mg monolithic catalyst was first prepared using non-equilibrium plasma electrolytic oxidation (PEO) technology. Spherical aberration-corrected transmission electron microscope (ACTEM) observation confirms the successful synthesis of the PtBi intermetallic structure. The efficiency of PtBi/Mg/MgO catalysts in catalyzing the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of NaBH4 was demonstrated. The activity factor for the catalyst is 31.8 s−1 g−1, which is much higher than reported values. In addition, the resultant catalyst also exhibits excellent catalytic activity in the organic pollutant reaction of p-nitrobenzoic acid (p-NBA) and methyl orange (MO). Moreover, benefiting from ordered atomic structures and the half-embedded PtBi nanoparticles (NPs), the catalyst demonstrates excellent stability and reproducibility in the degradation of 4-NP. This study provides an example of a simple method for the preparation of intermetallic structures as catalysts for organic pollutant degradation.

α-amylase inhibitors (α-AI) are a kind of active substances which show inhibitory activities to human, insect pancreas and saliva. α-AI can reduce blood glucose index in human body and kill insects, thus widely used in medicine and agriculture. This review summarizes the source, structure and action mechanisms of protein and non-protein-based α-AI, focuses on the mechanisms from the view of structure-function relationship. The applications of α-AI in disease prevention, agricultural production and plant protection are also summarized. This review may provide new insights into the comprehensive exploitation and application of α-AI from different sources.

Abstract Background Pachychoroid pigment epitheliopathy (PPE), a retinal disorder that falls into the pachychoroid spectrum, is characterized by retinal pigment epithelium changes in pachychoroid eyes without existing or previous subretinal fluid or soft drusen. Previous reports have indicated that PPE may share some pathophysiologic component with other pachychoroid spectrum diseases and could transform into central serous chorioretinopathy (CSC) during follow-up. CSC transformation to PNV and PCV has also been reported, but PPE transformation to PCV has not been reported. Case presentation Seven eyes of seven patients (four male three female, aged 62.7 ± 8.4 years) who presented with PPE at baseline transformed to PCV during follow-up. All study eyes had baseline contralateral eye diagnoses of PCV. All PPE eyes reported no symptoms at baseline and were followed up regularly for the treatment of their contralateral eyes. All PPE presented as pigment epithelium detachment (PED) at baseline. The mean central macular thickness (CMT) was 217.6 ± 14.6 µm, the mean subfoveal choroidal thickness (SFCT) was 354.9 ± 94.9 µm, and the mean sub-PPE choroidal thickness was 332.3 ± 84.6 µm. The mean PPE width and height were 1326.4 ± 791.4 µm and 58.7 ± 23.6 µm, respectively, at baseline. Disruption of the ellipsoid zone (EZ) was noted in 3 eyes, while choroidal vascular hyperpermeability (CVH) was noted in 5 eyes at baseline. The follow-up period was 75.0 ± 41.1 months, and the mean transformation time was 49.6 ± 24.8 months. All study eyes received no intervention before transformation. Conclusions PPE could transform to PCV after a long follow-up period. Regular follow-ups for a long time should be recommended for patients with PPE.

The oxygen evolution reaction (OER) is a slow step in electrocatalytic water splitting. NiFe layered double hydroxides (LDH) have shown promise as affordable OER electrocatalysts, but their performance is hindered by poor charge transfer and sluggish kinetics. To address this, we doped NiFe LDH with sulfur (S) using an in situ electrodeposition method. By growing S-doped NiFe LDH on Cu nanoarrays, we created core–shell structures that improved both the thermodynamics and kinetics of OER. The resulting S-NiFe LDH@Cu core–shell nanoarrays exhibited enhanced activity in water oxidation, with a low potential of 236 mV (at 50 mA cm−2) and a small Tafel slope of 50.64 mV dec−1. Moreover, our alkaline electrolyzer, based on these materials, demonstrated remarkable activity, with a low voltage of 1.56 V at 100 mA cm−2 and excellent durability. The core–shell nanoarray structures provided a larger electroactive surface area, facilitated fast electron transport, and allowed for effective gas release. These findings highlight the potential of S-NiFe LDH@Cu core–shell nanoarrays as efficient OER electrocatalysts.

Abstract Background One of the primary obstacles to measure clinical quality is the lack of configurable solutions to make computers understand and compute clinical quality indicators. The paper presents a solution that can help clinical staff develop clinical quality measurement more easily and generate the corresponding data reports and visualization by a configurable method based on openEHR and Clinical Quality Language (CQL). Methods First, expression logic adopted from CQL was combined with openEHR to express clinical quality indicators. Archetype binding provides the clinical information models used in expression logic, terminology binding makes the medical concepts consistent used in clinical quality artifacts and metadata is regarded as the essential component for sharing and management. Then, a systematic approach was put forward to facilitate the development of clinical quality indicators and the generation of corresponding data reports and visualization. Finally, clinical physicians were invited to test our system and give their opinions. Results With the combination of openEHR and CQL, 64 indicators from Centers for Medicare & Medicaid Services (CMS) were expressed for verification and a complicated indicator was shown as an example. 68 indicators from 17 different scenes in the local environment were also expressed and computed in our system. A platform was built to support the development of indicators in a unified way. Also, an execution engine can parse and compute these indicators. Based on a clinical data repository (CDR), indicators were used to generate data reports and visualization and shown in a dashboard. Conclusion Our method is capable of expressing clinical quality indicators formally. With the computer-interpretable indicators, a systematic approach can make it more easily to define clinical indicators and generate medical data reports and visualization, and facilitate the adoption of clinical quality measurements.

Abstract Increasing domestic solid waste (DSW) is becoming one of the most serious challenges for city and regional environment. As an epitome of the society, the investigation on the influencing factors and reduction of DSW of university students can not only provide policy suggestions for the waste management in the university campus, but also can achieve demonstration effect to other communities due to its high social status and wide impacts. This research combined direct weighing, questionnaire surveys, and regression analysis to quantify the influencing factors of DSW at East China Normal University’s dormitory in Shanghai. Direct weighting and questionnaire survey were conducted in 112 randomly selected dormitory rooms. Totally 523 valid questionnaires were collected. It is found that the average waste generation was 0.275 kg/day/cap, in which residual waste accounted for 64% of total, followed by household food waste (29%), and recyclable waste (7%). Regressions based on ordinary least square method suggested that students’ attitude towards waste played the most important role in affecting the waste reduction with its elasticity − 0.195. Lower educational level and better financial condition would lead to more waste generation, whose elasticity was 0.148 and 0.098 respectively. The influences of gender and major varied from waste types. Policies implications for university administration departments for sustainable waste and resource management include developing personalized and humanized waste management policies, enhancing environmental awareness through diverse educational activities, and expanding the publicity role of campus cultural activities on waste reduction.

In our previous study, we have isolated Lactoplantibacillus plantarum L3 (GenBank accession No. MT781360) which can secret bacteriocin L3 with broad-spectrum antibacterial activities. This work aimed to illustrate the antibacterial mechanism of bacteriocin L3 and predict the functionalities of the L. plantarum L3 strain through whole genome analysis. Preliminary exploration of the bacteriostatic mechanism showed that bacteriocin L3 destroyed the cell membrane integrity and led to the extravasation of the cell contents, leading to cell death. The sequencing results showed that the genome of Lactobacillus plantarum L3 was 3 187 020 bp in size, with a GC content of 44.57%. Overall, 3 024 encoding genes were annotated, with a sequence length of 2 679 162 bp, accounting for 84.06% of the total genome length. The strain has strong reproductive and metabolic abilities and high safety. The bacteriocin gene cluster analysis showed that the bacteriocins L3 belonged to the class IIb bacteriocins. This work might provide a theoretical basis for the application of this strain in the food industry, especially its potential use in dairy products.

Abstract Electrodynamic therapy (EDT) has recently emerged as a potential external field responsive approach for tumor treatment. While it presents a number of clear superiorities, EDT inherits the intrinsic challenges of current reactive oxygen species (ROS) based therapeutic treatments owing to the complex tumor microenvironment, including glutathione (GSH) overexpression, acidity and others. Herein for the first time, iron oxide nanoparticles are decorated using platinum nanocrystals (Fe3O4@Pt NPs) to integrate the current EDT with chemodynamic phenomenon and GSH depletion. Fe3O4@Pt NPs can effectively induce ROS generation based on the catalytic reaction on the surface of Pt nanoparticles triggered by electric field (E), and meanwhile it may catalyze intracellular H2O2 into ROS via Fenton reaction. In addition, Fe3+ ions released from Fe3O4@Pt NPs under the acidic condition in tumor cells consume GSH in a rapid fashion, inhibiting ROS clearance to enhance its antitumor efficacy. As a result, considerable in vitro and in vivo tumor inhibition phenomena are observed. This study has demonstrated an alternative concept of combinational therapeutic modality with superior efficacy.

The response mechanism and interaction patterns of HIF-1α and p53 in animals in an hypoxic environment are crucial for their hypoxic tolerance and adaptation. Many studies have shown that underground rodents have better hypoxic adaptation characteristics. However, the mechanism by which HIF-1α and p53 in underground rodents respond to hypoxic environments compared with in ground rodents remains unclear. Further, whether a synergy between HIF-1α and p53 enables animals tolerate extremely hypoxic environments is unclear. We studied HIF-1α and p53 expression in the brain tissue and cell apoptosis in the hippocampal CA1 region during 6 hours of acute hypoxia (5% oxygen) in Lasiopodomys mandarinus (Milne-Edwards, 1871) and Lasiopodomys brandtii (Radde, 1861), two closely related small rodents with different life characteristics (underground and aboveground, respectively), using a comparative biology method to determine the mechanisms underlying their adaptation to this environment. Our results indicate that HIF-1α and p53 expression is more rapid in L. mandarinus than in L. brandtii under acute hypoxic environments, resulting in a significant synergistic effect in L. mandarinus. Correlation analysis revealed that HIF-1α expression and the apoptotic index of the hippocampal CA1 regions of the brain tissues of L. mandarinus and L. brandtii, both under hypoxia, were significantly negatively and positively correlated, respectively. Long-term existence in underground burrow systems could enable better adaptation to hypoxia in L. mandarinus than in L. brandtii. We speculate that L. mandarinus can quickly eliminate resulting damage via the synergistic effect of p53 and HIF-1α in response to acute hypoxic environments, helping the organism quickly return to a normal state after the stress.

N6-methyladenosine (m6A) is the most abundant inner RNA modification in eukaryotes. Due to the development of RNA sequencing technology, the distribution pattern of m6A in the transcriptome has been uncovered. Dynamically, the reversible N6-methylation is mediated by two types of proteins, which are classified as “writers” and “erasers”. Under the association of specific co-factors, writers show spatiotemporal N6-methyltransferase activity. Mechanically, m6A can be recognized by “reader” proteins or can directly modify RNA conformation, and it widely affects gene expression by mediating RNA stability, translation, splicing and export. m6A is involved in a series of physiology processes. Dysregulation of m6A is gradually defined as the pathogenesis of some diseases, e.g., cancer and cardiovascular disease. Therefore, a good understanding of m6A is essential for molecular biology and pathology research. In this article we systemically present an overview of the functions and mechanisms of identified m6A regulators. The discovered biological and pathological processes affected by m6A are also summarized. We hope that readers with related research interests benefit from our review.

The potential role of tadalafil, a PDE5 inhibitor, in anticancer activity and prolonged survival has been proposed. However, the systematic effects of tadalafil in colorectal cancer were not fully understood. In this study, we assessed the anti-tumor activity of tadalafil in human colorectal cancer cells. A systematic perspective of the tadalafil-induced anti-tumor mechanism was provided by the integration of transcriptomics and metabolomics. We found that differentially expressed genes (DEGs) were mainly involved in microRNAs in cancer, purine metabolism, glycosphingolipid biosynthesis, arginine biosynthesis, and amino acid metabolism. Amino acid metabolism, especially alanine, aspartate, and glutamate metabolism was the most of the differentially accumulated metabolites (DAMs) through the analysis of metabolomics. The conjoint analysis of DEGs and DAMs presented that they were also mainly involved in alanine, aspartate, and glutamate metabolism. Amino acid metabolism-related genes, GPT, GGT5, and TAT, were significantly decreased after tadalafil treatment. In particular, the disturbance of alanine, aspartate, and glutamate metabolism may be the explanation for the major mechanism resulting from tadalafil anti-tumor activity.

Inspired by the 3D hierarchical porous structure and abundant hydroxyl groups of wood, we used basswood as a biological template to synthesize NiFe/porous carbon (C) through an impregnation and pyrolysis strategy. The optimized NiFe/C composite exhibited an impressive low overpotential of 259 mV at 10 mA cm−2 for oxygen evolution reaction (OER) in 1.0 M KOH. More importantly, the catalyst had an extremely good durability. This study provides an alternative strategy to utilize green wood-based materials to design highly efficient OER electrocatalysts.

Abstract Two new fused‐ring electron acceptor (FREA) isomers with nonlinear and linear molecular conformation, m‐BAIDIC and p‐BAIDIC, are designed and synthesized. Despite the similar light absorption range and energy levels, the two isomers exhibit distinct electron reorganization energies and molecular packing motifs, which are directly related to the molecular conformation. Compared with the nonlinear acceptor, the linear p‐BAIDIC shows more ordered molecular packing and higher crystallinity. Furthermore, p‐BAIDIC‐based devices exhibit reduced nonradiative energy loss and improved charge transport mobilities. It is beneficial to enhance the open‐circuit voltage (VOC) and short‐current current density (JSC) of the devices. Therefore, the linear FREA, p‐BAIDIC yields a relatively higher efficiency of 7.71% in the binary device with PM6, in comparison with the nonlinear m‐BAIDIC. When p‐BAIDIC is incorporated into the binary PM6/BO‐4Cl system to form a ternary system, synergistic enhancements in VOC, JSC, fill factor (FF), and ultimately a high efficiency of 17.6% are achieved.

Summary: MicroRNAs (miRNAs) have been shown to play important roles in viral infections, but their associations with SARS-CoV-2 infection remain poorly understood. Here, we detected 85 differentially expressed miRNAs (DE-miRNAs) from 2,336 known and 361 novel miRNAs that were identified in 233 plasma samples from 61 healthy controls and 116 patients with COVID-19 using the high-throughput sequencing and computational analysis. These DE-miRNAs were associated with SASR-CoV-2 infection, disease severity, and viral persistence in the patients with COVID-19, respectively. Gene ontology and KEGG pathway analyses of the DE-miRNAs revealed their connections to viral infections, immune responses, and lung diseases. Finally, we established a machine learning model using the DE-miRNAs between various groups for classification of COVID-19 cases with different clinical presentations. Our findings may help understand the contribution of miRNAs to the pathogenesis of COVID-19 and identify potential biomarkers and molecular targets for diagnosis and treatment of SARS-CoV-2 infection.

The growth hormone/insulin-like growth factor (GH/IGF) system, also called the pituitary-liver axis, has a somatotrophic role in the body. Although the GH/IGF system has always been regarded as a vertebrate-specific endocrine system, its actual origin remained unknown for a long time. The basal chordate, amphioxus, occupies an evolutionary position between vertebrates and invertebrates. Impressively, most of the members of the GH/IGF system are present in the amphioxus. The GH-like molecule in the amphioxus is mainly expressed in Hatschek’s pit. It functions similarly to vertebrate GH and has a GH receptor-like binding partner. The amphioxus IGF-like peptide shows mitogenic activity and an expression pattern resembling that of vertebrate IGF-I. The receptor of IGF-like peptide and IGF binding protein (IGFBP) have also been demonstrated to exist in the amphioxus. These results reveal the origin of the gene families in the GH/IGF system, providing strong evidence that this system emerged in the amphioxus.

Diabetes is a systemic disease, and its progression involves multiple organ dysfunction. However, the exact mechanisms underlying pathological progression remain unclear. Small extracellular vesicles (sEVs) mediate physiological and pathological signaling communication between organs and have been shown to have important regulatory roles in diabetes and its complications in recent years. In particular, the majority of studies in the diabetes-related research field have focused on the noncoding RNAs carried by sEVs. Researchers found that noncoding RNA sorting into sEVs is not random but selective. Both tissue origin differences and environmental variations affect the cargo of sEVs. In addition, the function of sEVs differs according to the tissue they derive from; for example, sEVs derived from adipose tissue regulate insulin sensitivity in the periphery, while sEVs derived from bone marrow promote β-cell regeneration. Therefore, understanding the roles of sEVs from different tissues is important for elucidating their molecular mechanisms and is necessary for the application of sEVs as therapeutic agents for diabetes treatment in the future. In this review, we summarized current studies on the mechanisms of noncoding RNA sorting into sEVs, as well as the research progress on the effects of sEVs from different tissue origins and noncoding RNAs in diabetes and diabetic complications. The knowledge of noncoding RNAs in sEVs will help us better understand the role of sEVs in the diabetes progression.

The cell-mediated protective and pathogenic immune responses to SARS-CoV-2 infection remain largely elusive. Here we identified 76 distinct cell subsets in the PBMC samples that were associated with various clinical presentations of COVID-19 using scRNA-seq technology coupled with a deep and comprehensive analysis of unique cell surface markers and differentially expressed genes. We revealed that (TRAV1-2+CD8+)MAIT cells and (NCAM1hiCD160+)NK cells significantly enriched in the asymptomatic subjects whereas (LAG3+CD160+CD8+)NKT cells increased in the symptomatic patients. We also observed that (CD68-CSF1R-IL1BhiCD14+)classical monocytes were positively correlated with the disease severity. Moreover, (CD33-HLA-DMA-CD14+)classical monocytes and (CLEC10A-S100A9lo)pDC were associated with the viral persistence. The GO and KEGG analyses identified enriched pathways related to immune responses, inflammation, and apoptosis. These findings may enhance our understanding of the immunopathogenesis of COVID-19 and help develop novel strategies against SARS-CoV-2 infection.

Nowadays, the impact ionization coefficient in the avalanche breakdown theory is obtained using 1-D PN junctions or SBDs, and is considered to be a constant determined by the material itself only. In this paper, the impact ionization coefficient of silicon in a 2D lateral power device is found to be no longer a constant, but instead a function of the 2D coupling effects. The impact ionization coefficient of silicon that considers the 2D depletion effects in real-world devices is proposed and extracted in this paper. The extracted impact ionization coefficient indicates that the conventional empirical impact ionization in the Fulop equation is not suitable for the analysis of 2D lateral power devices. The veracity of the proposed impact ionization coefficient is validated by the simulations obtained from TCAD tools. Considering the complexity of direct modeling, a new prediction method using deep neural networks is proposed. The prediction method demonstrates 97.67% accuracy for breakdown location prediction and less than 6% average error for the impact ionization coefficient prediction compared with the TCAD simulation.

Mitochondria are the energy production center in cells, which regulate aerobic metabolism, calcium balance, gene expression and cell death. Their homeostasis is crucial for cell viability. Although mitochondria own a nucleus-independent and self-replicating genome, most of the proteins, which fulfill mitochondrial functions and mitochondrial quality control, are encoded by the nuclear genome and are imported into mitochondria. Hence, the regulation of mitochondrial protein expression and translocation is considered essential for mitochondrial homeostasis. By means of high-throughput RNA sequencing and bioinformatic analysis, non-coding RNAs localized in mitochondria have been generally identified. They are either generated from the mitochondrial genome or the nuclear genome. The mitochondrial non-coding RNAs can directly interact with mitochondrial DNAs or transcripts to affect gene expression. They can also bind nuclear genome-encoded mitochondrial proteins to regulate their mitochondrial import, protein level and combination. Generally, mitochondrial non-coding RNAs act as regulators for mitochondrial processes including oxidative phosphorylation and metabolism. In this review, we would like to introduce the latest research progressions regarding mitochondrial non-coding RNAs and summarize their identification, biogenesis, translocation, molecular mechanism and function.

In recent years, with the rapid increase in coverage and lines, security maintenance has become one of the top concerns with regard to railway transportation in China. As the key transportation infrastructure, the railway turnout system (RTS) plays a vital role in transportation, which will cause incalculable losses when accidents occur. The traditional fault-diagnosis and maintenance methods of the RTS are no longer applicable to the growing amount of data, so intelligent fault diagnosis has become a research hotspot. However, the key challenge of RTS intelligent fault diagnosis is to effectively extract the deep features in the signal and accurately identify failure modes in the face of unbalanced datasets. To solve the above two problems, this paper focuses on unbalanced data and proposes a fault-diagnosis method based on an improved autoencoder and data augmentation, which realizes deep feature extraction and fault identification of unbalanced data. An improved autoencoder is proposed to smooth the noise and extract the deep features to overcome the noise fluctuation caused by the physical characteristics of the data. Then, synthetic minority oversampling technology (SMOTE) is utilized to effectively expand the fault types and solve the problem of unbalanced datasets. Furthermore, the health state is identified by the Softmax regression model that is trained with the balanced characteristics data, which improves the diagnosis precision and generalization ability. Finally, different experiments are conducted on a real dataset based on a railway station in China, and the average diagnostic accuracy reaches 99.13% superior to other methods, which indicates the effectiveness and feasibility of the proposed method.

BackgroundThe widespread adoption of electronic health records (EHRs) has facilitated the secondary use of EHR data for clinical research. However, screening eligible patients from EHRs is a challenging task. The concepts in eligibility criteria are not completely matched with EHRs, especially derived concepts. The lack of high-level expression of Structured Query Language (SQL) makes it difficult and time consuming to express them. The openEHR Expression Language (EL) as a domain-specific language based on clinical information models shows promise to represent complex eligibility criteria. ObjectiveThe study aims to develop a patient-screening tool based on EHRs for clinical research using openEHR to solve concept mismatch and improve query performance. MethodsA patient-screening tool based on EHRs using openEHR was proposed. It uses the advantages of information models and EL in openEHR to provide high-level expressions and improve query performance. First, openEHR archetypes and templates were chosen to define concepts called simple concepts directly from EHRs. Second, openEHR EL was used to generate derived concepts by combining simple concepts and constraints. Third, a hierarchical index corresponding to archetypes in Elasticsearch (ES) was generated to improve query performance for subqueries and join queries related to the derived concepts. Finally, we realized a patient-screening tool for clinical research. ResultsIn total, 500 sentences randomly selected from 4691 eligibility criteria in 389 clinical trials on stroke from the Chinese Clinical Trial Registry (ChiCTR) were evaluated. An openEHR-based clinical data repository (CDR) in a grade A tertiary hospital in China was considered as an experimental environment. Based on these, 589 medical concepts were found in the 500 sentences. Of them, 513 (87.1%) concepts could be represented, while the others could not be, because of a lack of information models and coarse-grained requirements. In addition, our case study on 6 queries demonstrated that our tool shows better query performance among 4 cases (66.67%). ConclusionsWe developed a patient-screening tool using openEHR. It not only helps solve concept mismatch but also improves query performance to reduce the burden on researchers. In addition, we demonstrated a promising solution for secondary use of EHR data using openEHR, which can be referenced by other researchers.