Auxiliary two-filter particle smoothing for one generalized hidden Markov model.

This paper develops two-filter particle smoothing (TFPS) algorithms for the nonlinear fixed-interval smoothing problem of one generalized hidden Markov model (GHMM), where the current observation depends not only on the current state, but also on one-step previous state. Firstly, by Bayesian approach, the two-filter smoothing (TFS) formula for GHMM is established to calculate smoothing densities. In this TFS formula, the backward information prediction density is generally not a density of the state. This results in a difficulty that the normal sequential Monte Carlo (SMC) sampling technique cannot be directly applied to design corresponding TFPS algorithms based on the TFS formula. To solve this difficulty, a generalized TFS formula for GHMM is then proposed by introducing a sequence of artificial densities. By combining this generalized TFS formula, SMC, and the auxiliary variable sampling technique, a basic auxiliary TFPS (ATFPS) algorithm with quadratic computational complexity is proposed, and a simplified ATFPS algorithm with linear computational complexity is further developed. Finally, the effectiveness and superiority of the two proposed ATFPS algorithms for GHMM are verified via simulation examples and real experimental data.

Characterization and expression profiles of the ZmLBD gene family in Zea mays.

BACKGROUND: The Lateral Organ Boundaries Domain (LBD) gene family is a family of plant-specific transcription factors (TFs) that are widely involved in processes such as lateral organ formation, stress response, and nutrient metabolism. However, the function of LBD genes in maize remains poorly understood. METHODS AND RESULTS: In this study, a total of 49 ZmLBD genes were identified at the genome-wide level of maize, they were classified into nine branches based on phylogenetic relationships, and all of them were predicted to be nuclear localized. The 49 ZmLBD genes formed eight pairs of segmental duplicates, and members of the same branches' members had similar gene structure and conserved motif composition. The promoters of ZmLBD genes contain multiple types of cis-acting elements. In addition, by constructing the regulatory network of ZmLBD and other genes and miRNAs, 12 and 22 ZmLBDs were found to be involved in the gene regulatory network and miRNA regulatory network, respectively. The expression pattern analysis suggests that ZmLBD genes may be involved in different biological pathways, and drought stress induced the expressions of two inbred lines. CONCLUSIONS: The findings enhance our comprehension of the potential roles of the ZmLBD gene family in maize growth and development, which is pivotal for genetic enhancement and breeding efforts pertaining to this significant crop.

ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways. / ELABELA衍生肽ELA13通过抑制Smad和ERK信号通路减轻肾纤维化.

Kidney fibrosis is an inevitable result of various chronic kidney diseases (CKDs) and significantly contributes to end-stage renal failure. Currently, there is no specific treatment available for renal fibrosis. ELA13 (amino acid sequence: RRCMPLHSRVPFP) is a conserved region of ELABELA in all vertebrates; however, its biological activity has been very little studied. In the present study, we evaluated the therapeutic effect of ELA13 on transforming growth factor-ß1 (TGF-ß1)-treated NRK-52E cells and unilateral ureteral occlusion (UUO) mice. Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum, and reduce the expression of fibrosis biomarkers confirmed by Masson staining, immunohistochemistry, real-time polymerase chain reaction (RT-PCR), and western blot. Inflammation biomarkers were increased after UUO and decreased by administration of ELA13. Furthermore, we found that the levels of essential molecules in the mothers against decapentaplegic (Smad) and extracellular signal-regulated kinase (ERK) pathways were reduced by ELA13 treatment in vivo and in vitro. In conclusion, ELA13 protected against kidney fibrosis through inhibiting the Smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.

Facial Expression Realization of Humanoid Robot Head and Strain-Based Anthropomorphic Evaluation of Robot Facial Expressions.

The facial expressions of humanoid robots play a crucial role in human-computer information interactions. However, there is a lack of quantitative evaluation methods for the anthropomorphism of robot facial expressions. In this study, we designed and manufactured a humanoid robot head that was capable of successfully realizing six basic facial expressions. The driving force behind the mechanism was efficiently transmitted to the silicone skin through a rigid linkage drive and snap button connection, which improves both the driving efficiency and the lifespan of the silicone skin. We used human facial expressions as a basis for simulating and acquiring the movement parameters. Subsequently, we designed a control system for the humanoid robot head in order to achieve these facial expressions. Moreover, we used a flexible vertical graphene sensor to measure strain on both the human face and the silicone skin of the humanoid robot head. We then proposed a method to evaluate the anthropomorphic degree of the robot's facial expressions by using the difference rate of strain. The feasibility of this method was confirmed through experiments in facial expression recognition. The evaluation results indicated a high degree of anthropomorphism for the six basic facial expressions which were achieved by the humanoid robot head. Moreover, this study also investigates factors affecting the reproduction of expressions. Finally, the impulse was calculated based on the strain curves of the energy consumption of the humanoid robot head to complete different facial expressions. This offers a reference for fellow researchers when designing humanoid robot heads, based on energy consumption ratios. To conclude, this paper offers data references for optimizing the mechanisms and selecting the drive components of the humanoid robot head. This was realized by considering the anthropomorphic degree and energy consumption of each part. Additionally, a new method for evaluating robot facial expressions is proposed.

A Comprehensive View on the Protein Functions of Porcine Epidemic Diarrhea Virus.

Porcine epidemic diarrhea (PED) virus (PEDV) is one of the main pathogens causing diarrhea in piglets and fattening pigs. The clinical signs of PED are vomiting, acute diarrhea, dehydration, and mortality resulting in significant economic losses and becoming a major challenge in the pig industry. PEDV possesses various crucial structural and functional proteins, which play important roles in viral structure, infection, replication, assembly, and release, as well as in escaping host innate immunity. Over the past few years, there has been progress in the study of PEDV pathogenesis, revealing the crucial role of the interaction between PEDV viral proteins and host cytokines in PEDV infection. At present, the main control measure against PEDV is vaccine immunization of sows, but the protective effect for emerging virus strains is still insufficient, and there is no ideal safe and efficient vaccine. Although scientists have persistently delved their research into the intricate structure and functionalities of the PEDV genome and viral proteins for years, the pathogenic mechanism of PEDV remains incompletely elucidated. Here, we focus on reviewing the research progress of PEDV structural and nonstructural proteins to facilitate the understanding of biological processes such as PEDV infection and pathogenesis.

TRIM28 promotes porcine epidemic diarrhea virus replication by mitophagy-mediated inhibition of the JAK-STAT1 pathway.

Porcine epidemic diarrhea virus (PEDV) infection causes immunosuppression and clinical symptoms such as vomiting, watery diarrhea, dehydration, and even death in piglets. TRIM28, an E3 ubiquitin ligase, is involved in the regulation of autophagy. However, the role of TRIM28 in PEDV infection is unknown. This study aimed to determine whether TRIM28 acts as a host factor for PEDV immune escape. We found that depletion of TRIM28 inhibited PEDV replication, whereas overexpression of TRIM28 promoted the viral replication in host cells. Furthermore, knockdown of TRIM28 reversed PEDV-induced downregulation of the JAK/STAT1 pathway. Treatment with the mitophagic activator carbonyl cyanide 3-chlorophenylhydrazone (CCCP) attenuated the activating effect of TRIM28 depletion on the expression of the STAT1 pathway-related proteins. Treatment with CCCP also reduced the nuclear translocation of pSTAT1. Moreover, TRIM28, via its RING domain, interacted with PEDV N. Overexpression of TRIM28 induced mitophagy, which could be enhanced by co-expression with PEDV N. The results indicate that PEDV infection upregulates the expression of TRIM28, which induces mitophagy, leading to inhibition of the JAK-STAT1 pathway. This research unveils a new mechanism by which PEDV can hijack host cellular TRIM28 to promote its own replication.

Evolution and distribution of rabies viruses from a panorama view.

Rabies kills more than 59,000 people annually, mainly in developing countries. Previous studies on the evolution and distribution of rabies viruses (RABVs) were scattered. Here, we explore the evolution and distribution of this deadly virus from a novel panorama view. Multiple bioinformatic software tools were employed to analyze the phylogenetic diversity, evolution, spatiotemporal, and distribution of RABVs. The analyses were based on 1,202 qualified full-length genomes of RABVs and numerous literatures. Of the 10 distinct phylogenetic clades of RABV that we identified, more frequent intra- and inter-clade recombination occurs in the sequences of Asian-SEA, Arctic, and Cosmopolitan clades isolated from China, while according to existing sequence information, RABV might originate from bats (posterior probability, PP = 0.75, PP = 0.60 inferred from N and L genes, separately) in North America (PP = 0.57, PP = 0.62 inferred from N and L genes, separately). Due to the difference in evolutionary rate of N (2.22 × 10-4 subs/site/year, 95% HPD 1.99-2.47 × 10-4 subs/site/year) and L genes (1.67 × 10-4 subs/site/year, 95% HPD 1.59-1.74 × 10-4 subs/site/year), the root age was 1,406.6 (95% HPD 1,291.2-1,518.2) and 1,122.7 (95% HPD 1,052.4-1,193.9) inferred from N and L genes, separately. Among other findings, Mephitidae plays an important role in the interspecific transmission and communication of RABV, which we found tends to spread to populations genetically proximate to the host. We also identified amino acids under positive selection in different genes of different clades as well as single nucleotide variation sites important for different lineages. IMPORTANCE Rabies virus is widely distributed all over the world, and wild animals are its largest potential reservoir. Our study offers a panorama view about evolution and distribution of rabies viruses and emphasizes the need to monitor the transmission dynamics of animal rabies.

A universal all-in-one RPA-Cas12a strategy with de novo autodesigner and its application in on-site ultrasensitive detection of DNA and RNA viruses.

Revolutionary all-in-one RPA-CRISPR assays are rapidly becoming the most sought-after tools for point-of-care testing (POCT) due to their high sensitivity and ease of use. Despite the availability of one-pot methods for specific targets, the development of more efficient methods for new targets remains a significant challenge. In this study, we present a rapid and universal approach to establishing an all-in-one RPA-Cas12a method CORDSv2 based on rational balancing amplification and Cas12a cleavage, which achieves ultrasensitive detection of several targets, including SARS-CoV-2, ASFV, HPV16, and HPV18. CORDSv2 demonstrates a limit of detection (LOD) of 0.6 cp/µL and 100% sensitivity for SARS-CoV-2, comparable to qPCR. Combining with our portable device(hippo-CORDS), it has a visual detection LOD of 6 cp/µL and a sensitivity up to 100% for SARS-CoV-2 and 97% for Ct<35 ASFV samples, surpassing most one-pot visual methods. To simplify and accelerate the process for new targets, we also develop a de novo autodesigner by which the optimal couples of primers and crRNA can be selected rapidly. As a universal all-in-one RPA-CRISPR method for on-site testing, CORDSv2 becomes an attractive choice for rapid and accurate diagnosis in resource-limited settings.

Replaceable Dielectric Film for Low-Voltage and High-Performance Electrowetting-Based Digital Microfluidics.

Electrowetting-on-dielectric (EWOD) technology has been considered as a promising candidate for digital microfluidic (DMF) applications due to its outstanding flexibility and integrability. The dielectric layer with a hydrophobic surface is the key element of an EWOD device, determining its driving voltage, reliability, and lifetime. Hereby, inspired by the ionic-liquid-filled structuring polymer with high capacitance independent on thickness, namely ion gel (IG), we develop a polymer (P)-ion gel-amorphous fluoropolymer, namely, PIGAF, composite film as a replaceable hydrophobic dielectric layer for fabrication of a high-efficiency and stable EWOD-DMF device at relatively low voltage. The results show that the proposed EWOD devices using the PIGAF-based dielectric layer can achieve a large contact angle (θ) change of ∼50° and excellent reversibility with a contact angle hysteresis of ≤5° at a relatively low voltage of 30 Vrms. More importantly, the EWOD actuation voltage did not change obviously with the PIGAF film thickness in the range of several to tens of microns, enabling the thickness of the film to be adjusted according to the demand within a certain range while keeping the actuation voltage low. An EWOD-DMF device can be prepared by simply stacking a PIGAF film onto a PCB board, demonstrating stable droplet actuation (motion) at 30 Vrms and 1 kHz as well as a maximum moving velocity of 69 mm/s at 140 Vrms and 1 kHz. The PIGAF film was highly stable and reliable, maintaining excellent EWOD performance after multiple droplet manipulations (≥50 cycles) or long-term storage of 1 year. The proposed EWOD-DMF device has been demonstrated for digital chemical reactions and biomedical sensing applications.

Surface Modification of Cyclic-Olefin-Copolymer (COC)-Based Microchannels for the Large-Scale Industrial Production of Droplet Microfluidic Devices.

The copolymers of cycloolefin (COC), a type of thermoplastic material, have been widely used for the large-scale industrial fabrication of droplet microfluidic devices, which is often performed using hot-embossing or injection-molding techniques. The generation of droplets and the uniformity of droplet sizes are significantly affected by the surface wettability of COC during fabrication and the pressure stability of the employed fluid pump during operation. In order to alleviate the effects of undesirable surface wettability and pressure variation on the generation of droplets in COC-based devices, a simple surface modification procedure was applied to hydrophobically modify the surfaces of COC-based microchannels for large-scale industrial production. The surface modification procedure consisted of an oxygen plasma treatment of the polymer surface followed by a solution-phase reaction in fluorocarbon solvent. The experimental results demonstrate that following the proposed surface modification, the COC droplet microfluidic devices could stably generate microvolume water droplets with a small coefficient of variation, even if the pressure of the dispersed phase (water) fluctuated. The durability test results regarding the modified surfaces show that the hydrophobicity of the modified COC surfaces could be sustained for up to four months, deteriorating with time thereafter. Our study can provide a potential solution useful in and guidance for the large-scale industrial production of droplet microfluidic devices for various applications, including polymerase chain reaction and single-cell analysis.

Therapeutic potential for targeting Annexin A1 in fibrotic diseases.

Annexin A1, a well-known endogenous anti-inflammatory mediator, plays a critical role in a variety of pathological processes. Fibrosis is described by a failure of tissue regeneration and contributes to the development of many diseases. Accumulating evidence supports that Annexin A1 participates in the progression of tissue fibrosis. However, the fundamental mechanisms by which Annexin A1 regulates fibrosis remain elusive, and even the functions of Annexin A1 in fibrotic diseases are still paradoxical. This review focuses on the roles of Annexin A1 in the development of fibrosis of lung, liver, heart, and other tissues, with emphasis on the therapy potential of Annexin A1 in fibrosis, and presents future research interests and directions in fibrotic diseases.

Effect of Pre-Anodized Film on Micro-Arc Oxidation Process of 6063 Aluminum Alloy.

In the current investigation, micro-arc oxidation (MAO) ceramic coatings on aluminum are galvanostatically synthesized at various processing stages in an alkaline silicate system. The resultant coatings are systematically investigated in terms of the following respects: The working voltage and surface sparking evolution over the studied course of MAO are recorded by the signal acquisition system and the real-time imaging, respectively; the phase composition, the surface morphology, and the polished cross-section of the coatings are characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM) assisted with an energy-dispersive X-ray spectrometer (EDS), respectively. In particular, with the help of a low-rate increase in working voltage, the evolution of the sparks, the energy consumption, and the microstructure development of aluminum in alkaline silicate electrolyte by pre-anodizing are systematically investigated. The results show that the pre-anodized film can accelerate the evolution process of MAO spark and shorten the reaction process in the early stage of MAO reaction, reducing energy consumption and improving the corrosion resistance of the MAO coating. The γ-Al2O3 phase content after pre-anodized is significantly increased in MAO coatings. In particular, the thicker the pre-anodized film (beyond 8 µm) was broken down and fragmentation thinning in the early stage of the MAO process with the presence of micro discharges. This is due to the fact that the electron transition will be released by the emission of radiative recombination and reveals obvious galvanoluminescence (GL) behavior on the surface of the pre-anodized film. Further, based on the present MAO coating microstructure, a model of coating growth after pre-anodized that evolves over time is proposed.

Design of a highly potent GLP-1R and GCGR dual-agonist for recovering hepatic fibrosis.

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl4, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-ß expression as well as downstream Smad signaling pathways particularly in CCl4-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl4-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

Enhancing signals of microfluidic impedance cytometry through optimization of microelectrode array.

Microfluidic impedance cytometry shows a great value in biomedical diagnosis. However, the crosstalk between neighboring microelectrodes strongly weakens the impedance signal. Hereby, we demonstrate a novel microfluidic impedance cytometer consisted of sensing electrodes and ground electrodes (GNDs). The simulation reveals a signal enhancement by more than five times with GNDs compared to that without ones. We also found that the linear correlation between the impedance at a high frequency and that at a low frequency varies as microparticle size changes, which can be used for microparticle classification. The study can help with microelectrode optimization and signal processing for microfluidic impedance analysis.

Therapeutic peptides: current applications and future directions.

Peptide drug development has made great progress in the last decade thanks to new production, modification, and analytic technologies. Peptides have been produced and modified using both chemical and biological methods, together with novel design and delivery strategies, which have helped to overcome the inherent drawbacks of peptides and have allowed the continued advancement of this field. A wide variety of natural and modified peptides have been obtained and studied, covering multiple therapeutic areas. This review summarizes the efforts and achievements in peptide drug discovery, production, and modification, and their current applications. We also discuss the value and challenges associated with future developments in therapeutic peptides.

A Novel Mechanism of Endoplasmic Reticulum Stress- and c-Myc-Degradation-Mediated Therapeutic Benefits of Antineurokinin-1 Receptor Drugs in Colorectal Cancer.

The neurokinin-1 receptor (NK-1R) antagonists are approved as treatment for chemotherapy-associated nausea and vomiting in cancer patients. The emerging role of the substance P-NK-1R system in oncogenesis raises the possibility of repurposing well-tolerated NK-1R antagonists for cancer treatment. This study reports that human colorectal cancer (CRC) patients with high NK-1R expression have poor survival, and NK-1R antagonists SR140333 and aprepitant induce apoptotic cell death in CRC cells and inhibit CRC xenograft growth. This cytotoxicity induced by treatment with NK-1R antagonists is mediated by induction of endoplasmic reticulum (ER) stress. ER stress triggers calcium release, resulting in the suppression of prosurvival extracellular signal-regulated kinase (ERK)-c-Myc signaling. Along with ER calcium release, one ER stress pathway mediated by protein kinase RNA-like ER kinase (PERK) is specifically activated, leading to increased expression of proapoptotic C/EBP-homologous protein (CHOP). Moreover, NK-1R antagonists enhance the efficacy of chemotherapy by increasing the sensitivity and overcoming resistance to 5-fluorouracil in CRC cells through the induction of sustained ER stress and the consequent suppression of ERK-c-Myc signaling both in vitro and in vivo. Collectively, the findings provide novel mechanistic insights into the efficacy of NK-1R antagonists either as a single agent or in combination with chemotherapy for cancer treatment.

Antimicrobial peptides: mechanism of action, activity and clinical potential.

The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. As an excellent candidate to overcome antibiotic resistance, antimicrobial peptides (AMPs) that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity. These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action. This comprehensive review provides a broad overview of AMPs from the origin, structural characteristics, mechanisms of action, biological activities to clinical applications. We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.

Flow-Field-Assisted Dielectrophoretic Microchips for High-Efficiency Sheathless Particle/Cell Separation with Dual Mode.

Prefocusing of cell mixtures through sheath flow is a common technique used for continuous and high-efficiency dielectrophoretic (DEP) cell separation. However, it usually limits the separation flow velocity and requires a complex multichannel fluid control system that hinders the integration of a DEP separator with other microfluidic functionalities for comprehensive biomedical applications. Here, we propose and develop a high-efficiency, sheathless particle/cell separation method without prefocusing based on flow-field-assisted DEP by combining the effects of AC electric field (E-field) and flow field (F-field). A hollow lemon-shaped electrode array is designed to generate a long-range E-field gradient in the microchannel, which can effectively induce lateral displacements of particles/cells in a continuous flow. A series of arc-shaped protrusion structures is designed along the microchannel to form a F-field, which can effectively guide the particles/cells toward the targeted E-field region without prefocusing. By tuning the E-field, two distinct modes can be realized and switched in one single device, including the sheathless separation (ShLS) and the adjustable particle mixing ratio (AMR) modes. In the ShLS mode, we have achieved the continuous separation of breast cancer cells from erythrocytes with a recovery rate of 95.5% and the separation of polystyrene particles from yeast cells with a purity of 97.1% at flow velocities over 2.59 mm/s in a 2 cm channel under optimized conditions. The AMR mode provides a strategy for controlling the mixing ratio of different particles/cells as a well-defined pretreatment method for biomedical research studies. The proposed microchip is easy to use and displays high versatility for biological and medical applications.

Fabrication and Property Regulation of Small-Size Polyamine Microcapsules via Integrating Microfluidic T-Junction and Interfacial Polymerization.

The self-healing system based on microencapsulated epoxy-amine chemistry is currently the self-healing system with the most practical application potential. It can be widely used in many epoxy-based materials with a size restriction for the microcapsules, such as fiber-reinforced composites, anti-corrosion coatings, etc. Although epoxy microcapsules of different sizes can be fabricated using different techniques, the preparation of polyamine microcapsules with suitable sizes and good performance is the prerequisite for further developing this self-healing system. In this investigation, based on the novel microencapsulation technique via integrating microfluidic T-junction and interfacial polymerization, the feasibility of preparing small-size polyamine microcapsules and the process regulation to optimize the properties of the small-size microcapsules were studied. We show that polyamine microcapsules with sizes smaller than 100 µm can be obtained through the T-junction selection and the feeding rate control of the polyamine. To regulate the small-size microcapsules' quality, the effects of the concentration of the shell-forming monomer and the solvent with different polarity in the reaction solution and the reaction condition were studied. It shows that dry, free-flowing small-size microcapsules can still be obtained when the shell-forming monomer concentration is higher and the solvent's polarity is lower, compared with the preparation of larger polyamine microcapsules. Although the change of reaction conditions (reaction temperature and duration) has a certain effect on the microcapsules' effective core content, it is relatively small. The results of this investigation further promote the potential application of the self-healing systems based on microencapsulated epoxy-amine chemistry in materials with a size restriction for the microcapsules.