MRI and CT compatible asymmetric bilayer hydrogel electrodes for EEG-based brain activity monitoring.

The exploration of multi-dimensional brain activity with high temporal and spatial resolution is of great significance in the diagnosis of neurological disease and the study of brain science. Although the integration of electroencephalogram (EEG) with magnetic resonance imaging (MRI) and computed tomography (CT) provides a potential solution to achieve a brain-functional image with high spatiotemporal resolution, the critical issues of interface stability and magnetic compatibility remain challenging. Therefore, in this research, we proposed a conductive hydrogel EEG electrode with an asymmetrical bilayer structure, which shows the potential to overcome the challenges. Benefiting from the bilayer structure with different moduli, the hydrogel electrode exhibits high biological and mechanical compatibility with the heterogeneous brain-electrode interface. As a result, the impedance can be reduced compared with conventional metal electrodes. In addition, the hydrogel-based ionic conductive electrodes, which are free from metal conductors, are compatible with MRI and CT. Therefore, they can obtain high spatiotemporal resolution multi-dimensional brain information in clinical settings. The research outcome provides a new approach for establishing a platform for early diagnosis of brain diseases and the study of brain science.

A Janus hydrogel that enables wet tissue adhesion and resists abdominal adhesions.

Hydrogels have indeed achieved significant advancements, yet their clinical translation has been hampered by their inherent limitations in wet adhesion properties. Furthermore, the design of adhesive hydrogels that can resist postoperative adhesions remains an intricate challenge. In this study, we introduce a Janus hydrogel (JGP) that offers a novel approach to address these challenges. The JGP hydrogel has two asymmetrical sides, consisting of an adhesion layer (AL) and an anti-adhesion layer (AAL). Specifically, the AL incorporates three key components: N-[tris(hydroxymethyl)methyl]acrylamide (THMA), acrylic acid (AAc), and the acrylic acid N-hydroxysuccinimide ester (AAc-NHS). By drying the AL, it has a rapid water absorption capability. The abundance of hydroxyl and carboxyl groups in the AL enables the formation of robust hydrogen bonds with tissues, thereby achieving superior adhesive properties. Additionally, the synergistic effect of THMA's tridentate hydrogen bonding and the covalent bonding formed by AAc-NHS with tissue ensures long-lasting wet adhesion. To realize the anti-adhesion function, one side of the AL was immersed in a solution of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), which undergoes crosslinking to form the AAL. A comprehensive series of tests have confirmed that the JGP hydrogel exhibits exceptional mechanical properties, efficient and enduring adhesion, excellent biocompatibility, and degradability. Moreover, it possesses remarkable hemostatic properties and robust anti-abdominal adhesion characteristics.

Novel insights into the mechanisms of seasonal cyclicity of testicles by proteomics and transcriptomics analyses in goose breeder lines.

Spermatogenesis is a crucial indicator of geese reproduction performance and production. The testis is the main organ responsible for sperm production, and the egg-laying cycle in geese is a complex physiological process that demands precise orchestration of hormonal cues and cellular events within the testes, however, the seasonal changes in the transcriptomic and proteomic profiles of goose testicles remain unclear. To explore various aspects of the mechanisms of the seasonal cyclicity of testicles in different goose breeds, in this study, we used an integrative transcriptomic and proteomic approach to screen the key genes and proteins in the testes of 2 goose males, the Hungarian white goose and the Wanxi white goose, at 3 different periods of the laying cycle: beginning of laying cycle (BLC), peak of laying cycle (PLC), and end of laying cycle (ELC). The results showed that a total of 9,273 differentially expressed genes and 4,543 differentially expressed proteins were identified in the geese testicles among the comparison groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that the DEGs, in the comparison groups, were mainly enrichment in metabolic pathways, neuroactive ligand-receptor interaction, cyctokine-cyctokine receptor interaction, calcium signaling pathway, apelin signaling pathway, ether lipid metabolism, cysteine, and methionine metabolism. While the DEPs, in the 3 comparison groups, were mainly involved in the ribosome, metabolic pathways, carbon metabolism, proteasome, endocytosis, lysosome, regulation of actin cytoskeleton, oxidative phosphorylation, nucleocytoplasmic transport, and tight junction. The protein-protein interaction network analysis (PPI) indicated that selected DEPs, such as CHD1L, RAB18, FANCM, TAF5, TSC1/2, PHLDB2, DNAJA2, NCOA5, DEPTOR, TJP1, and RAPGEF2, were highly associated with male reproductive regulation. Further, the expression trends of 4 identified DEGs were validated by qRT-PCR. In conclusion, this work offers a new perspective on comprehending the molecular mechanisms and pathways involved in the seasonal cyclicity of testicles in the Hungarian white goose and the Wanxi white goose, as well as contributing to improving goose reproductive performance.

The combination of RNA-seq transcriptomics and data-independent acquisition proteomics reveal the mechanisms and function of different gooses testicular development at different stages of laying cycle.

Egg production performance is an important economic trait in the poultry industry. In previous studies, attention has often been paid to the growth and development of the ovaries, while there has been less research on the testicular tissue of male goose. Due to various factors, there are usually significant differences in the process of testicular spermatogenesis among different goose breeds. The Jilin white goose (JL) is a high-production local goose species in China, domesticated from Anser cygnoides, which has a high egg-laying performance and the egg-laying period can last from February to July. In the production of goose within Jilin Province, the female goose of Jilin White goose is considered as an important maternal parent of synthetic lines, and ganders from Hungarian white goose (HU), Wanxi white goose (WX) and Jilin white goose are the main male parents. Each year, all 3 gander species begin to exhibit breeding capacity in February and reach the peak of reproductive capacity by April, marked by high fertilization rates. With the gradual increase in temperature, the testicular tissue of Hungarian and Wanxi goose gradually diminishes in its ability to produce sperm. the testicular tissue undergoes significant shrinkage by the end of June, resulting in a near loss of sperm production capability, thereby yielding low fertilization rates. However, the Jilin White goose demonstrates the ability to maintain a stable sperm production capacity. Individuals with low sperm motility contribute to increased seed production costs and pose constraints on the industrial development of livestock and poultry varieties. In this study, transcriptomics and proteomics data from gooses testicular of 3 different goose breeds inclouding Jilin white goose, Wanxi white gooseand Hungary white goose sampled in 2 stages, peak of laying cycle (PLC) and end of laying cycle (ELC). In a comparative analysis between PLC and ELC groups (ELC vs. PLC) of 3 breeds, we identified 401,340,6651 differentially expressed genes (DEGs) and 18,225,323 differentially expressed proteins (DEPs), respectively. Differentially expressed genes and proteins were significantly enriched in Gene Ontology (GO) terms such as phosphotransferase activity, cytoskeletal protein binding, microtubule motor activity, channel activity and carbohydrate metabolic process. The KEGG enrichment analysis of the DEGs in testicular showed that most differentially expressed mRNAs participate in the KEGG pathways, including ECM-receptor interaction, MAPK signaling pathway, carbon metabolism, Cell cycle, VEGF signaling pathway, Lipoic acid metabolism and p53 signaling pathway. The differential expression of 4 selected DEGs (SPAG6, NEK2, HSPA4L, SERF1A) was verified by qRT-PCR, and the results were consistent with RNA-seq data. In conclusion, this study reveals the differences in gene expression regulation in testicular tissues of different goose species, and screening candidate genes and proteins related to spermatogenesis.

A bioinspired switchable adhesive patch with adhesion and suction mechanisms for laparoscopic surgeries.

Medical adhesives play an important role in clinical medicine because of their flexibility and convenient operation. However, they are still limited to laparoscopic surgeries, which have demonstrated urgent demand for liver retraction with minimal damage to the human body. Here, inspired by the suction cup structure of octopus, an adhesive patch with excellent mechanical properties, robust and switchable adhesiveness, and biocompatibility is proposed. The adhesive patch is combined by the attachment body mainly made of poly(acrylic acid) grafted with N-hydroxysuccinimide ester, crosslinked biodegradable gelatin methacrylate and biodegradable biopolymer gelatin to mimic the adhesive sucker rim, and the temperature-sensitive telescopic layer of microgel-crosslinked poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) to shrink and form internal cavity with reduced pressure. Through mechanical tests, adhesion evaluation, and biocompatibility analysis, the bioinspired adhesive patch has demonstrated its capacity not only in adhesion to tissues but also in potential treatment for medical applications, especially laparoscopic technology. The bioinspired adhesive patch can break through the limitations of traditional retraction methods, and become an ideal candidate for liver retraction in laparoscopic surgery and related clinical medicine.

Unraveling the assembly mechanism of SADS-CoV virus nucleocapsid protein: insights from RNA binding, dimerization, and epitope diversity profiling.

The swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused significant disruptions in porcine breeding and raised concerns about potential human infection. The nucleocapsid (N) protein of SADS-CoV plays a vital role in viral assembly and replication, but its structure and functions remain poorly understood. This study utilized biochemistry, X-ray crystallography, and immunization techniques to investigate the N protein's structure and function in SADS-CoV. Our findings revealed distinct domains within the N protein, including an RNA-binding domain, two disordered domains, and a dimerization domain. Through biochemical assays, we confirmed that the N-terminal domain functions as an RNA-binding domain, and the C-terminal domain is involved in dimerization, with the crystal structure analysis providing visual evidence of dimer formation. Immunization experiments demonstrated that the disordered domain 2 elicited a significant antibody response. These identified domains and their interactions are crucial for viral assembly. This comprehensive understanding of the N protein in SADS-CoV enhances our knowledge of its assembly and replication mechanisms, enabling the development of targeted interventions and therapeutic strategies. IMPORTANCE: SADS-CoV is a porcine coronavirus that originated from a bat HKU2-related coronavirus. It causes devastating swine diseases and poses a high risk of spillover to humans. The coronavirus N protein, as the most abundant viral protein in infected cells, likely plays a key role in viral assembly and replication. However, the structure and function of this protein remain unclear. Therefore, this study employed a combination of biochemistry and X-ray crystallography to uncover distinct structural domains in the N protein, including RNA-binding domains, two disordered domains, and dimerization domains. Additionally, we made the novel discovery that the disordered domain elicited a significant antibody response. These findings provide new insights into the structure and functions of the SADS-CoV N protein, which have important implications for future studies on SADS-CoV diagnosis, as well as the development of vaccines and anti-viral drugs.

Secretory Nogo-B regulates Th2 differentiation in the lung cancer microenvironment.

Nogo-B, a ubiquitously expressed member of the reticulon family, plays an important role in maintaining endoplasmic reticulum (ER) structure, regulating protein folding, and calcium homeostasis. In this study, we demonstrate that Nogo-B expression and secretion are upregulated in lung cancer and correlate to overall survival. Nogo-B is secreted by various cells, particularly lung cancer cells. ER stress and phosphorylation at serine 107 can induce Nogo-B secretion. Secretory Nogo-B suppresses the differentiation of Th2 cells and the release of type 2 cytokines, thus influencing the anti-tumor effects of Th2-related immune cells, including IgE+B cell class switching and eosinophil activation.

Chromosome-level genome sequencing and multi-omics of the Hungarian White Goose (Anser anser domesticus) reveals novel miRNA-mRNA regulation mechanism of waterfowl feather follicle development.

The Hungarian White Goose (Anser anser domesticus) is an excellent European goose breed, with high feather and meat production. Despite its importance in the poultry industry, no available genome assembly information has been published. This study aimed to present Chromosome-level and functional genome sequencing of the Hungarian White Goose. The results showed that the genome assembly has a total length of 1115.82 Mb, 39 pairs of chromosomes, 92.98% of the BUSCO index, and contig N50 and scaffold N50 were up to 2.32 Mb and 60.69 Mb, respectively. Annotation of the genome assembly revealed 19550 genes, 286 miRNAs, etc. We identified 235 expanded and 1,167 contracted gene families in this breed compared with the other 16 species. We performed a positive selection analysis between this breed and four species of Anatidae to uncover the genetic information underlying feather follicle development. Further, we detected the function of miR-199-x, miR-143-y, and miR-23-z on goose embryonic skin fibroblast. In summary, we have successfully generated a highly complete genome sequence of the Hungarian white goose, which will provide a great resource to improve our understanding of gene functions and enhance the studies on feather follicle development at the genomic level.

TMPRSS13 promotes the cell entry of swine acute diarrhea syndrome coronavirus.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused severe intestinal diseases in pigs. It originates from bat coronaviruses HKU2 and has a potential risk of cross-species transmission, raising concerns about its zoonotic potential. Viral entry-related host factors are critical determinants of susceptibility to cells, tissues, or species, and remain to be elucidated for SADS-CoV. Type II transmembrane serine proteases (TTSPs) family is involved in many coronavirus infections and has trypsin-like catalytic activity. Here we examine all 18 members of the TTSPs family through CRISPR-based activation of endogenous protein expression in cells, and find that, in addition to TMPRSS2 and TMPRSS4, TMPRSS13 significantly facilitates SADS-CoV infection. This is confirmed by ectopic expression of TMPRSS13, and specific to trypsin-dependent SADS-CoV. Infection with pseudovirus bearing SADS-CoV spike protein indicates that TMPRSS13 acts at the entry step and is sensitive to serine protease inhibitor Camostat. Moreover, both human and pig TMPRSS13 are able to enhance the cell-cell membrane fusion and cleavage of spike protein. Overall, we demonstrate that TMPRSS13 is another host serine protease promoting the membrane-fusion entry of SADS-CoV, which may expand its host tropism by using diverse TTSPs.

Evaluation of nanoparticle albumin-bound paclitaxel loaded macrophages for glioblastoma treatment based on a microfluidic chip.

Introduction: Glioblastoma (GBM) is a primary brain malignancy with a dismal prognosis and remains incurable at present. In this study, macrophages (MΦ) were developed to carry nanoparticle albumin-bound paclitaxel (nab-PTX) to form nab-PTX/MΦ. The aim of this study is to use a GBM-on-a-chip to evaluate the anti-GBM effects of nab-PTX/MΦ. Methods: In this study, we constructed nab-PTX/MΦ by incubating live MΦ with nab-PTX. We developed a microfluidic chip to co-culture GBM cells and human umbilical vein endothelial cells, mimicking the simplified blood-brain barrier and GBM. Using a syringe pump, we perform sustainable perfusion of nutrient media. To evaluate the anti-GBM effects nab-PTX/MΦ, we treated the GBM-on-a-chip model with nab-PTX/MΦ and investigated GBM cell proliferation, migration, and spheroid formation. Results: At the chosen concentration, nab-PTX did not significantly affect the viability, chemotaxis and migration of MΦ. The uptake of nab-PTX by MΦ occurred within 1 h of incubation and almost reached saturation at 6 h. Additionally, nab-PTX/MΦ exhibited the M1 phenotype, which inhibits tumor progression. Following phagocytosis, MΦ were able to release nab-PTX, and the release of nab-PTX by MΦ had nearly reached its limit at 48 h. Compared with control group and blank MΦ group, individual nab-PTX group and nab-PTX/MΦ group could inhibit tumor proliferation, invasion and spheroid formation. Meanwhile, the anti-GBM effect of nab-PTX/MΦ was more significant than nab-PTX. Discussion: Our findings demonstrate that nab-PTX/MΦ has a significant anti-GBM effect compared to individual nab-PTX or MΦ administration, suggesting MΦ as potential drug delivery vectors for GBM therapy. Furthermore, the developed GBM-on-a-chip model provides a potential ex vivo platform for innovative cell-based therapies and tailored therapeutic strategies for GBM.

Protein profile analysis of Jilin white goose testicles at different stages of the laying cycle by DIA strategy.

BACKGROUND: Jilin white goose is an excellent local breed in China, with a high annual egg production and laying eggs mainly from February to July each year. The testis, as the only organ that can produce sperm, can affect the sexual maturity and fecundity of male animals. Its growth and development are affected and regulated by a variety of factors. Proteomics is generally applied to identify and quantify proteins in cells and tissues in order to understand the physiological or pathological changes that occur in tissues or cells under specific conditions. Currently, the female poultry reproductive system has been extensively studied, while few related studies focusing on the regulatory mechanism of the reproductive system of male poultry have been conducted. RESULTS: A total of 1753 differentially expressed proteins (DEPs) were generated in which there were 594, 391 and 768 different proteins showing differential expression in three stages, Initial of Laying Cycle (ILC), Peak of Laying Cycle (PLC) and End of Laying Cycle (ELC). Furthermore, bioinformatics was used to analyze the DEPs. Gene ontology (GO) enrichment, Clusters of Orthologous Groups (COG), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis were adopted. All DEPs were found to be implicated in multiple biological processes and pathways associated with testicular development, such as renin secretion, Lysosomes, SNARE interactions in vesicle trafficking, the p53 signaling pathway and pathways related to metabolism. Additionally, the reliability of transcriptome results was verified by real-time quantitative PCR by selecting the transcript abundance of 6 selected DEPs at the three stages of the laying cycle. CONCLUSIONS: The funding in this study will provide critical insight into the complex molecular mechanisms and breeding practices underlying the developmental characteristics of testicles in Jilin white goose.

miR-140-y targets TCF4 to regulate the Wnt signaling pathway and promote embryonic feather follicle development in Hungarian white goose.

Goose down feather has become one of the most important economical products in the goose breeding industry and it provides several essential physiological roles in birds. Therefore, understanding and regulating the development of skin and feather follicles during embryogenesis is critical for avian biology and the poultry industry. MicroRNAs are known to play an important role in controlling gene expression during skin and feather follicle development. In this study, bioinformatics analysis was conducted to select miR-140-y as a potential miRNA involved in skin and feather follicle development and to predict TCF4 as its target gene. This gene was expressed at significant levels during embryonic feather follicle development, as identified by qPCR and Western blot. The targeting relationship was confirmed by a dual-luciferase assay in 293T cells. Then, the miR-140-y/TCF4 function in dermal fibroblast cells was explored. The results showed that miR-140-y could suppress the proliferation of goose embryonic dermal fibroblast cells (GEDFs) by suppressing the activity of some Wingless-types (Wnt) pathway related genes and proliferation marker genes, while miR-140-y inhibition led to the opposite effect. Similarly, the inhibition of the TCF4 gene results in blocking the proliferation of GEDFs by reducing the activity of some Wnt pathway-related genes. Finally, the co-transfection of miR-140-y inhibitor and siRNA-TCF4 results in a rescue of the TCF4 function and an increase of the Wnt signaling pathway and GEDFs proliferation. In conclusion, these results demonstrated that the miR-140-y-TCF4 axis influences the activity of the Wnt signaling pathway and works as a dynamic regulator during skin and feather follicle development.

An early warning indicator of mortality risk in patients with COVID-19: the neutrophil extracellular traps/neutrophilic segmented granulocyte ratio.

Background: Neutrophil extracellular traps (NETs) play a key role in thrombus formation in patients with coronavirus disease 2019 (COVID-19). However, the existing detection and observation methods for NETs are limited in their ability to provide quantitative, convenient, and accurate descriptions of in situ NETs. Therefore, establishing a quantitative description of the relationship between NETs and thrombosis remains a challenge. Objective: We employed morphological observations of blood cells and statistical analyses to investigate the correlation between the NETs/neutrophilic segmented granulocyte ratio and mortality risk in patients with COVID-19. Methods: Peripheral blood samples were collected from 117 hospitalized patients with COVID-19 between November 2022 and February 2023, and various blood cell parameters were measured. Two types of smudge cells were observed in the blood and counted: lymphatic and neutral smudge cells. Statistical data analysis was used to establish COVID-19 mortality risk assessment indicators. Results: Morphological observations of neutrophilic smudge cells revealed swelling, eruption, and NETs formation in the neutrophil nuclei. Subsequently, the NETs/neutrophilic segmented granulocyte ratio (NNSR) was calculated. A high concentration of NETs poses a fatal risk for thrombus formation in patients. Statistical analysis indicated that a high NNSR was more suitable for evaluating the risk of death in patients with COVID-19 compared to elevated fibrinogen (FIB) and D-dimer (DD) levels. Conclusion: Observing blood cell morphology is an effective method for the detection of NETs, NNSR are important markers for revealing the mortality risk of patients with COVID-19.

Recent research advances on polysaccharide-, peptide-, and protein-based hemostatic materials: A review.

Hemorrhage is a potentially life-threatening emergency that can occur at any time or place. Whether traumatic, congenital, surgical, disease-related, or drug-induced, bleeding can lead to severe complications or death. Therefore, the development of efficient hemostatic materials is critical. However, the results and prognosis demonstrated by clinical means of hemostasis do not reach expectations. With the development of technology, novel hemostatic materials have been developed from polysaccharides (chitosan, hyaluronic acid, alginate, cellulose, cyclodextrins, starch, dextran, and carrageenan), peptides (self-assembling peptides), and proteins (silk fibroin, collagen, gelatin, keratin, and thrombin). These new materials exhibit high hemostatic efficacy due to the enhancement or interaction of various hemostatic mechanisms. The main forms include adhesives, sealants, bandages, hemostatic powders, and hemostatic sponges. This article introduces the clotting process and principles of hemostatic methods and reviews the research on polysaccharide-, peptide-, and protein-based hemostatic materials in the last five years. The design ideas and hemostatic principles of polysaccharide-, peptide-, and protein-based hemostatic materials are mainly introduced. Finally, we summarize material designs, advantages, disadvantages, and challenges regarding hemostatic materials.

Porcine delta coronavirus inhibits NHE3 activity of porcine intestinal epithelial cells through miR-361-3p/NHE3 regulatory axis.

Porcine deltacoronavirus (PDCoV) infection in piglets can cause small intestinal epithelial necrosis and atrophic enteritis, which leads to severe damages to host cells, and result in diarrhea. In this study, we investigated the relationship between miR-361, SLC9A3(Solute carrier family 9, subfamily A, member 3), and NHE3(sodium-hydrogen exchanger member 3) in in porcine intestinal epithelial cells (IPI-2I) cells after PDCoV infection. Our results showed that the ssc-miR-361-3p expression inhibits the mRNA level of SLC9A3 gene which lead to the descending of NHE3 protein expression, and the NHE3 activity was suppressed. NHE3 activity was suppressed via down-regulation expression of SLC9A3 mRNA by transfection with siRNA. Ssc-miR-361-3p mimics and inhibitors were used to change the expression of ssc-miR-361-3p in IPI-2I cells. Ssc-miR-361-3p overexpression reduced the mRNA level of SLC9A3 gene, the level of NHE3 protein expression and NHE3 activity in IPI-2I cells, while ssc-miR-361-3p inhibits NHE3. Furthermore, luciferase reporter assay showed that SLC9A3 gene was a direct target of ssc-miR-361-3p. Ssc-miR-361-3p inhibition restored NHE3 activity in PDCoV infected IPI-2I cells by up-regulating SLC9A3 mRNA expression and NHE3 protein expression. These results demonstrate that the PDCoV infection can inhibit NHE3 activity through miR-361-3p/SLC9A3 regulatory axis. The relevant research is reported for the first time in PDCoV, which has significance in exploring the pathogenic mechanism of PDCoV and can provide a theoretical basis for its prevention and control. suggesting that NHE3 and ssc-miR-361-3p may be potential therapeutic targets for diarrhea in infected piglets.

Circ_103809 Aggravates the Malignant Phenotype of Pancreatic Cancer Through Modulating miR-197-3p/TSPAN3 Axis.

Pancreatic cancer (PC) is a malignant tumor with insidious clinical manifestations and dismal prognosis. Emerging reports have demonstrated that circRNAs exert pivotal biological function in PC. Here, we investigated the crucial biological role and underlying regulatory mechanisms of differentially expressed circ_103809 in PC. In this study, hsa_circ_103809 (hsa_circ_0072088) was identified as the research object via analyzing and screening the aberrantly expressed circRNAs in PC by GSE69362 dataset. The levels of circ_103809 in PC tissues and cells were assessed via qRT-PCR. Functional assays were conducted to monitor the impacts of circ_103809 on PC cells. Additionally, the downstream molecular targets and regulatory networks of circ_103809 were predicted by bioinformatics and validated using luciferase assays and rescue experiments. We found that circ_103809 was substantially upregulated in PC tissues and cells. Silencing circ_103809 restrained the growth viability, clonogenic rate, migration, and invasion capabilities of PC cells. Further mechanistic exploration disclosed that miR-197-3p was the downstream gene of circ_103809, while Tetraspanin-3 (TSPAN3) was a direct target of miR-197-3p. The suppressive effect of circ_103809 knockdown on malignant processes of PC cells was eliminated by miR-197-3p downregulation or TSPAN3 upregulation. Our study demonstrated that circ_103809 served as an innovative positive regulator in the growth and metastasis of PC cells. Furthermore, circ_103809 mediated the miR-197-3p/TSPAN3 axis to modulate the malignant progression of PC cells, which was prospected to be a probable biomarker and an efficient therapeutic target for PC.

Nitrogen removal characteristics of heterotrophic nitrification-aerobic denitrification bacterium Acinetobacter ZQ-A1 and community characteristics analysis of its application in pig farm wastewater.

A heterotrophic nitrifying aerobic denitrifying (HN-AD) strain ZQ-A1 with excellent denitrification performance, identified as Acinetobacter, was isolated from simultaneous nitrification and denitrification (SND) craft. ZQ-A1 was capable of removing NH4+, NO2-, and NO3-; the 21-hour removal rates were 84.84%, 87.13%, and 92.63%. ZQ-A1 has the ability to treat mixed nitrogen sources. In addition, ZQ-A1 can be well applied to actual sewage. According to the analysis of microbial community characteristics, the relative abundance of Acinetobacter in the experimental group increased from 0.06% to 2.38%, which is an important reason for the removal rate of NH4+ exceeding 99% within 30 days. The results of KEGG function prediction showed that with the addition of ZQ-A1, the relative abundance of pathways related to bacterial metabolism, such as tricarboxylic acid cycle metabolism, was higher. The research expanded the thinking of HN-AD bacteria in actual production and laid a foundation for its application in sewage treatment.

Identification of a receptor tyrosine kinase inhibitor CP-724714 inhibits SADS-CoV related swine diarrhea coronaviruses infection in vitro.

The outbreak of the COVID-19 epidemic in 2020 has caused unprecedented panic among all mankind, pointing the major importance of effective treatment. Since the emergence of the swine acute diarrhea syndrome coronavirus (SADS-CoV) at the end of 2017, multiple reports have indicated that the bat-related SADS-CoV possesses a potential threat for cross-species transmission. Vaccines and antiviral drugs development deserve more attention. In this study, we found that the HER2 phosphorylation inhibitor (CP-724714) inhibited SADS-CoV infection in a dose-dependent manner. Further validation demonstrated that CP-724714 affected at the post-entry stage of SADS-CoV infection cycle. Also, efficient SADS-CoV infection required the activation of HER2 and its cascade Ras-Raf-Mek-Erk signaling pathway. In addition, CP-724714 has a broad-spectrum anti-swine diarrhea coronaviruses activity, and can dose-dependently combat SADS-CoV, porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV) and transmissible gastroenteritis virus (TGEV) infection in vitro with a specificity index of greater than 21.98, 9.38, 95.23 and 31.62, respectively. These results highlight the potential utility of CP-724714 or antiviral drugs targeting with HER2 and its cascade Ras-Raf-Mek-Erk signaling pathway as host-targeted SADS-CoV and other related coronaviruses therapeutics.

Glioblastoma-on-a-chip construction and therapeutic applications.

Glioblastoma (GBM) is the most malignant type of primary intracranial tumor with a median overall survival of only 14 months, a very poor prognosis and a recurrence rate of 90%. It is difficult to reflect the complex structure and function of the GBM microenvironment in vivo using traditional in vitro models. GBM-on-a-chip platforms can integrate biological or chemical functional units of a tumor into a chip, mimicking in vivo functions of GBM cells. This technology has shown great potential for applications in personalized precision medicine and GBM immunotherapy. In recent years, there have been efforts to construct GBM-on-a-chip models based on microfluidics and bioprinting. A number of research teams have begun to use GBM-on-a-chip models for the investigation of GBM progression mechanisms, drug candidates, and therapeutic approaches. This review first briefly discusses the use of microfluidics and bioprinting technologies for GBM-on-a-chip construction. Second, we classify non-surgical treatments for GBM in pre-clinical research into three categories (chemotherapy, immunotherapy and other therapies) and focus on the use of GBM-on-a-chip in research for each category. Last, we demonstrate that organ-on-a-chip technology in therapeutic field is still in its initial stage and provide future perspectives for research directions in the field.