Neurobionic material is an emerging field in material and translational science. For material design, much focus has already been transferred from von Neumann architecture to the neuromorphic framework. As it is impractical to reconstruct the real neural tissue solely from materials, it is necessary to develop a feasible neurobionics framework to realize advanced brain function. In this study, we proposed a mathematical neurobionic material model, and attempted to explore advanced function only by simple and feasible structures. Here an equivalent simplified framework was used to describe the dynamics expressed in an equation set, while in vivo study was performed to verify simulation results. In neural tissue, the output of neurobionic material was characterized by spike frequency, and the stability is based on the excitatory/inhibitory proportion. Spike frequency in mathematical neurobionic material model can spontaneously meet the solution of a nonlinear equation set. Assembly can also evolve into a certain distribution under different stimulations, closely related to decision making. Short-term memory can be formed by coupling neurobionic material assemblies. In vivo experiments further confirmed predictions in our mathematical neurobionic material model. The property of this neural biomimetic material model demonstrates its intrinsic neuromorphic computational ability, which should offer promises for implementable neurobionic device design.

Lung adenocarcinoma accounts for half of all lung cancer cases in most countries. Mounting evidence has demonstrated that microRNAs play important roles in cancer progression, and some of them can be identified as potential biomarkers. This study aimed to explore the role of miR-550a-5p, a lung adenocarcinoma-associated mature microRNA screened out from the TCGA database via R-studio and Perl, with abundant expression in samples and with 5-year survival prognosis difference, as well as having not been studied in lung cancer yet. Potential target genes were predicted by the online database. Gene ontology enrichment, pathway enrichment, protein-protein interaction network, and hub genes-microRNA network were constructed by FunRich, STRING database, and Cytoscape. Then, LIMD1, a known tumor suppressor gene reported by multiple articles, was found to have a negative correlation with miR-550a-5p. The expression of miR-550a-5p was up-regulated in tumor samples and tumor-associated cell lines. Its high expression was also correlated with tumor size. Cell line A549 treated with miR-550a-5p overexpression promoted tumor proliferation, while H1299 treated with miR-550a-5p knockdown showed the opposite result. Mechanically, miR-550a-5p negatively regulated LIMD1 by directly binding to its 3'-UTR validated by dual luciferase assay. In summary, a new potential prognostic and therapeutic biomarker, miR-550a-5p, has been identified by bioinformatics analysis and experimental validation in vitro and in vivo, which promotes lung adenocarcinoma by silencing a known suppressor oncogene LIMD1.

Drought-tolerance ensures a crop to maintain life activities and protect cell from damages under dehydration. It refers to diverse mechanisms temporally activated when the crop adapts to drought. However, knowledge about the temporal dynamics of rice transcriptome under drought is limited.

Directly observing intracellular nanostructure formation remains challenging. In this work, using a rationally designed small-molecule 4-nitrobenzyl carbamate-Cys(SEt)-Asp-Asp-Phe(iodine)-2-cyano-benzothiazole (NBC-Iod-CBT), we directly observed intracellular nanoparticle formation with nanocomputed tomography (nano-CT). In vitro, upon glutathione reduction and nitroreductase (NTR) cleavage, NBC-Iod-CBT undergoes a CBT-Cys click condensation reaction to self-assemble nanoparticles Iod-CBT-NPs with an average linear absorption coefficient (LAC) value of 0.182 ± 0.078 μm-1 to x-ray. Nano-CT imaging of the NBC-Iod-CBT-treated, NTR-overexpressing HeLa cells showed the existence of Iod-CBT-NPs in their cytoplasm with an average LAC value of 0.172 ± 0.032 μm-1 We anticipate that our strategy could help people to deeply understand the formation mechanism of intracellular nanostructures in the near future.

This study aims to investigate functional brain reorganization brought about by the loss of physical movement and sensory feedback in lower limbs in chronic spinal cord injury (SCI). Eleven paraplegia patients with SCI and 13 healthy controls (HCs) were recruited. The experimental task used was a visuomotor imagery task requiring subjects to engage in visualization of repetitive tapping movements of the upper or lower limbs. Blood oxygen level-dependent (BOLD) responses were captured during the experimental task, along with the accuracy rate and the response time. The SCI patients performed worse in the Rey Auditory Verbal Learning Test (RAVLT) and the Trail Making Test. SCI patients had a larger BOLD signal in the left lingual gyrus and right external globus pallidus (GPe) when imagining lower-limb movements. For the upper-limb task, SCI patients showed stronger BOLD responses than the HCs in extensive areas over the brain, including the bilateral precentral gyrus (preCG), bilateral inferior parietal gyrus, right GPe, right thalamus, left postcentral gyrus, and right superior temporal gyrus. In contrast, the HCs displayed stronger BOLD responses in the medial frontal gyrus and anterior cingulate gyrus for both upper- and lower-limb tasks than the SCI patients. In the SCI group, for the upper-limb condition, the amplitudes of BOLD responses in the left preCG were negatively correlated with the time since injury (r = -0.72, p = 0.012). For the lower-limb condition, the amplitudes of BOLD responses in the left lingual gyrus were negatively correlated with the scores on the Short Delay task of the RAVLT (r = -0.73, p = 0.011). Our study provided imaging evidence for abnormal changes in brain function and worsened cognitive test performance in SCI patients. These findings suggested possible compensatory strategies adopted by the SCI patients for the loss of sensorimotor function from the lower limbs when performing a limb imagery task.

Cancer immune plays a critical role in cancer progression. Tumour immunology and immunotherapy are one of the exciting areas in bladder cancer research. In this study, we aimed to develop an immune-related gene signature to improve the prognostic prediction of bladder cancer. Firstly, we identified 392 differentially expressed immune-related genes (IRGs) based on TCGA and ImmPort databases. Functional enrichment analysis revealed that these genes were enriched in inflammatory and immune-related pathways, including in 'regulation of signaling receptor activity', 'cytokine-cytokine receptor interaction' and 'GPCR ligand binding'. Then, we separated all samples in TCGA data set into the training cohort and the testing cohort in a ratio of 3:1 randomly. Data set GSE13507 was set as the validation cohort. We constructed a prognostic six-IRG signature with LASSO Cox regression in the training cohort, including AHNAK, OAS1, APOBEC3H, SCG2, CTSE and KIR2DS4. Six IRGs reflected the microenvironment of bladder cancer, especially immune cell infiltration. The prognostic value of six-IRG signature was further validated in the testing cohort and the validation cohort. The results of multivariable Cox regression and subgroup analysis revealed that six-IRG signature was a clinically independent prognostic factor for bladder cancer patients. Further, we constructed a nomogram based on six-IRG signature and other clinicopathological risk factors, and it performed well in predict patients' survival. Finally, we found six-IRG signature showed significant difference in different molecular subtypes of bladder cancer. In conclusions, our research provided a novel immune-related gene signature to estimate prognosis for patients' survival with bladder cancer.

Salmonella spp. are a major cause of foodborne illness throughout the world. Traditional serotyping by antisera agglutination has been used as a standard identification method for many years but newer nucleic acid-based tests have become available that may provide advantages in workflow and test turnaround time. In this study, we evaluated the Luminex® xMAP® Salmonella Serotyping Assay (SSA), a multiplex nucleic acid test capable of identifying 85% of the most common Salmonella serotypes, in comparison to the traditional serum agglutination test (SAT) on 4 standard strains and 255 isolates from human (224), environmental, and food (31) samples. Of the total of 259 isolates, 256 could be typed by the SSA. Of these, 197 (77.0%) were fully typed and 59 (23.0%) were partially typed. By SAT, 246 of the 259 isolates (95%) were successfully typed. Sixty isolates had discrepant results between SAT and SSA and were resolved using whole genome sequencing (WGS). By SAT, 80.0% (48/60) of the isolates were consistent with WGS while by SSA 91.7% (55/60) were partially consistent with WGS. By serovar, all 30 serovars except one tested were fully or partially typable. The workflow comparison showed that SSA provided advantages over SAT with a hands-on time (HOT) of 3.5 min and total turnaround time (TAT) of 6 h, as compared to 1 h HOT and 2-6 days TAT for SAT. Overall, this study showed that molecular serotyping is promising as a rapid method for Salmonella serotyping with good accuracy for typing most common Salmonella serovars circulating in China.

Background and Aims: Non-invasive evaluation of liver necroinflammation in patients with chronic liver disease is an unmet need in clinical practice. The diagnostic accuracy of transient elastography-based liver stiffness measurement (LSM) for liver fibrosis could be affected by liver necroinflammation, the latter of which could intensify stiffness of the liver. Such results have prompted us to explore the diagnosis potential of LSM for liver inflammation. Methods: Three cross-sectional cohorts of liver biopsy-proven chronic liver disease patients were enrolled, including 1417 chronic hepatitis B (CHB) patients from 10 different medical centers, 106 non-alcoholic steatohepatitis patients, and 143 patients with autoimmune-related liver diseases. Another longitudinal cohort of 14 entecavir treatment patients was also included. The receiver operating characteristic (ROC) curve was employed to explore the diagnostic value of LSM. Results: In CHB patients, LSM value ascended with the increased severity of liver necroinflammation in patients with the same fibrosis stage. Such positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoimmune-related liver diseases populations. Furthermore, the ROC curve exhibited that LSM could identify moderate and severe inflammation in CHB patients (area under the ROC curve as 0.779 and 0.838) and in non-alcoholic steatohepatitis patients (area under the ROC curve as 0.826 and 0.871), respectively. Such moderate diagnostic value was also found in autoimmune-related liver diseases patients. In addition, in the longitudinal entecavir treated CHB cohort, a decline of LSM values was observed in parallel with the control of inflammatory activity in liver. Conclusions: Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.

Drug-resistant Mycobacterium tuberculosis (M. tuberculosis) has become an increasingly serious public health problem and has complicated tuberculosis (TB) treatment. Levofloxacin (LOF) is an ideal anti-tuberculosis drug in clinical applications. However, the detailed molecular mechanisms of LOF-resistant M. tuberculosis in TB treatment have not been revealed. Our study performed transcriptome and methylome sequencing to investigate the potential biological characteristics of LOF resistance in M. tuberculosis H37Rv. In the transcriptome analysis, 953 differentially expressed genes (DEGs) were identified; 514 and 439 DEGs were significantly downregulated and upregulated in the LOF-resistant group and control group, respectively. The KEGG pathway analysis revealed that 97 pathways were enriched in this study. In the methylome analysis, 239 differentially methylated genes (DMGs) were identified; 150 and 89 DMGs were hypomethylated and hypermethylated in the LOF-resistant group and control group, respectively. The KEGG pathway analysis revealed that 74 pathways were enriched in this study. The overlap study suggested that 25 genes were obtained. It was notable that nine genes expressed downregulated mRNA and upregulated methylated levels, including pgi, fadE4, php, cyp132, pckA, rpmB1, pfkB, acg, and ctpF, especially cyp132, pckA, and pfkB, which were vital in LOF-resistant M. tuberculosis H37Rv. The overlapping genes between transcriptome and methylome could be essential for studying the molecular mechanisms of LOF-resistant M. tuberculosis H37Rv. These results may provide informative evidence for TB treatment with LOF.

The periosteum plays a vital role in both development and injury healing process of bone. However, few researches have focused on artificial periosteum, which was also limited by the complexity on its construction and biological risks for clinical practice. In order to tackle this issue, inspired by the structural development of periosteum, we put forward a hierarchical micro/nanofibrous bionic periosteum with sustained releasing of VEGF as exogenous vascularized fibrous layer of periosteum to induce endogenous cambium layer in vivo for complete regeneration of periosteal and bone tissue, through collagen self-assembly and micro-sol electrospinning technologies. The VEGF encapsulated in hyaluronan-PLLA core-shell structure was demonstrated to be released in a durable way for angiogenesis in fibrous layer and bone defect area. Meanwhile, the self-assembly of collagen together with electrospun fibers contributed to a hierarchical micro/nanostructure which greatly mimicked the microenvironment of extracellular matrix to provide structural and biochemical cues for cell adhesion, proliferation and differentiation, and lead to the formation of cambium layer which mimicked the in-situ ossification manner as intramembranous ossification. As the motif of this study, the periosteal regeneration was characterized both by osteoblasts and periostin, which represented structural and molecular mechanisms respectively. Furthermore, the periosteal biomaterial proposed here possessed the superior abilities of scar inhibition, angiogenesis, osteogenesis to repair the bone defect in a uniform and rapid manner by inherent periosteal ossific mechanism involved in both intramembranous and endochondral ossification. Thus, the endogenous-exogenous combined bionic periosteum proved to be efficient and versatile in triggering periosteal and bone regeneration and hopefully supply a promising strategy for solving clinical issue.

Epulis has a tumor-like appearance but is considered to be a massive reactive lesion rather than a true neoplasia. Limited information about the pathogenesis of epulis is available. The purpose of our study was to identify potential signaling pathways in fibrous epulis through transcriptome profiling.

To investigate the genetic causes and clinical characteristics of dominant optic atrophy (DOA) in a Chinese family.

Glioma is the most common brain tumor with high mortality. However, there are still challenges for the timely and accurate diagnosis and effective treatment of the tumor. One hundred and twenty-one samples with grades II, III and IV from the Gene Expression Omnibus database were used to construct gene co-expression networks to identify hub modules closely related to glioma grade, and performed pathway enrichment analysis on genes from significant modules. In gene co-expression network constructed by 2345 differentially expressed genes from 121 gene expression profiles for glioma, we identified the black and blue modules that associated with grading. The module preservation analysis based on 118 samples indicates that the two modules were replicable. Enrichment analysis showed that the extracellular matrix genes were enriched for blue module, while cell division genes were enriched for black module. According to survival analysis, 21 hub genes were significantly up-regulated and one gene was significantly down-regulated. What's more, IKBIP, SEC24D, and FAM46A are the genes with little attention among the 22 hub genes. In this study, IKBIP, SEC24D, and FAM46A related to glioma were mentioned for the first time to the current knowledge, which might provide a new idea for us to study the disease in the future. IKBIP, SEC24D and FAM46A among the 22 hub genes identified that are related to the malignancy degree of glioma might be used as new biomarkers to improve the diagnosis, treatment and prognosis of glioma.

Hepatocyte apoptosis is the main pathophysiological process underlying liver ischemia/reperfusion (I/R) injury. Mitochondrial abnormalities have a vital role in hepatocellular damage. The hepatoprotective effects of mesenchymal stem cells (MSCs) have been previously demonstrated. In this study, we aim to investigate the effect and potential mechanism of MSCs against liver I/R injury. Effects of MSCs were studied in mice liver I/R injury model and in a hypoxia/reoxygenation (H/R) model of L02 hepatocytes. The potential mechanisms of MSCs on these in vivo and in vitro I/R-induced hepatocellular apoptosis models were studies. Accompanied by the improvement of hepatic damage, MSCs exhibited capabilities of controlling mitochondrial quality, shown by reduced mitochondrial reactive oxygen species (mtROS) overproduction, decreased the accumulation of mitochondrial fragmentation, restored ATP generation and upregulated mitophagy. Furthermore, we descripted a potential mechanism of MSCs on upregulating mitophagy and found that the reduced Parkin and PINK1 expression and inactivated AMPKα pathway were observed in the liver tissue in I/R model. These effects were reversed by MSCs treatment. In vitro study showed that MSC-conditioned medium (MSC-CM) suppressed hepatocellular apoptosis and inhibited mtROS accumulation in the H/R environment. And these effects of MSC-CM were partially blocked after the cells were transfected with PINK1 siRNA or added with dorsomorphin. Collectively, our findings provide a novel pharmacological mechanism that MSCs exert hepatoprotective effect in liver I/R injury via upregulating PINK1-dependent mitophagy. In addition, this effect might be attributed to the modulation of AMPKα activation.

Long non-coding RNAs (lncRNAs), which have little or no ability to encode proteins, have attracted special attention due to their potential role in cancer disease. In this study we aimed to establish a lncRNAs classifier to improve the accuracy of recurrence prediction for thymic epithelial tumors (TETs).

The kidney function of patients with chronic kidney disease (CKD) is impaired irreversibly. Organ transplantation is the only treatment to restore kidney function in CKD patients. The assessment of new potential therapeutic procedures relies heavily on experimental animal models, but it is limited by its human predictive capacity. In addition, the frequently used two-dimensional in vitro human renal cell models cannot replicate all the features of the in vivo situation. In this study, we developed a three-dimensional (3D) in vitro human renal organoid model from whole kidney cells as a promising drug screening tool. At present, the renal tissue generated from human pluripotent stem cells (hPSCs) exhibits intrinsic tumorigenicity properties. Here we first developed a 3D renal organoid culture system that originated from adult differentiated cells without gene modification. Renal organoids composed of multiple cell types were created under optimal experimental conditions and evaluated for morphology, viability and erythropoietin production. As a novel screening tool for renal toxicity, 3D organoids were exposed to three widely used drugs: aspirin, penicillin G and cisplatin. The study results showed this 3D renal organoid model can be used as a drug screening tool, a new in vitro 3D human kidney model, and provide hope for potential regenerative therapies for CKD.

Glioma is the most common primary malignancy of the central nervous system and is associated with high mortality rates. Despite the available treatment options including surgery, radiotherapy and chemotherapy, the median patient survival rate is low. Therefore, the development of novel anticancer agents for the treatment of glioma is urgently required. Tanshinone I (TS I) is a tanshinone compound that is isolated from Danshen. Accumulating evidence indicates that TS I exhibits antiproliferative activity in a variety of cancer types. However, the role of TS I and its mechanism of action in human glioma remain to be elucidated. In the present study, the anticancer potential of TS I against human glioma U87 MG cells was investigated. The results indicated that TS I exerted a potential cytotoxic effect on human glioma U87 MG cells. TS I was found to induce cell proliferation, inhibition, cell cycle arrest, apoptosis and autophagy in U87 MG cells. Mechanistic experiments indicated that TS I activated endoplasmic reticulum (ER) stress and inhibited AKT signaling and apoptosis in human glioma U87 MG cells. Furthermore, the present study demonstrated that TS I induced protective autophagy in U87 MG cells. Additionally, ER stress and AKT signal‑mediated apoptosis and protective autophagy were found to be induced by TS I via intracellular reactive oxygen species accumulation. The results of the present study demonstrated that TS I may be a potential anticancer drug candidate that may be of value in the treatment of human glioma.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease exhibiting the poorest prognosis among solid tumors. The efficacy of conventional therapies has been hindered largely due to the insufficient chemotherapeutic delivery to the dense desmoplastic tumor stroma, and the extremely high or toxic dose needed for chemotherapy. Traditional Chinese Medicine (TCM) contains effective components that can effectively regulate tumor microenvironment and kill tumor cells, providing promising alternatives to PDAC chemotherapy. In this study, two active drug monomers of TCM were screened out and a sequentially targeting delivery regimen was developed to realize the optimized combinational therapy. Transforming growth factor-β (TGF-β) plays an indispensable role in promoting cancer-associated fibroblasts (CAFs) activation and proliferation, and CAFs have caused major physical barriers for chemotherapeutic drug delivery. Herein, CAFs-targeting biodegradable polymer nanoparticle (CRE-NP(α-M)) coated with CREKA peptide and loaded with TCM α-mangostin (α-M) was developed to modulate tumor microenvironment by interfering of TGF-β/Smad signaling pathway. Low pH-triggered micelle modified with CRPPR peptide and loaded with another TCM triptolide was constructed to increase the therapeutic effect of triptolide at the tumor sites and reduced its damage to main organs. As expected, CRE-NP(α-M) effectively inactived CAFs, reduced extracellular matrix production, promoted tumor vascular normalization and enhanced blood perfusion at the tumor site. The sequentially targeting drug delivery regimen, CRP-MC(Trip) following CRE-NP(α-M) pretreatment, exhibited strong tumor growth inhibition effect in the orthotopic tumor model. Hence, sequentially targeting delivery of nanoformulated TCM offers an efficient approach to overcome the permeation obstacles and improve the effect of chemotherapy on PDAC, and provides a novel option to treat desmoplastic tumors.

Catechins are the predominant products in tea plants and have essential functions for both plants and humans. Several genes encoding the enzymes regulating catechin biosynthesis have been identified, and the identification of single nucleotide polymorphisms (SNPs) resulting in nonsynonymous mutations within these genes can be used to establish a functional link to catechin content. Therefore, the transcriptomes of two parents and four filial offspring were sequenced using next-generation sequencing technology and aligned to the reference genome to enable SNP mining. Subsequently, 176 tea plant accessions were genotyped based on candidate SNPs using kompetitive allele-specific polymerase chain reaction (KASP). The catechin contents of these samples were characterized by high-performance liquid chromatography (HPLC), and analysis of variance (ANOVA) was subsequently performed to determine the relationship between genotypes and catechin content. As a result of these efforts, a SNP within the chalcone synthase (CHS) gene was shown to be functionally associated with catechin content. Furthermore, the geographical and interspecific distribution of this SNP was investigated. Collectively, these results will contribute to the early evaluation of tea plants and serve as a rapid tool for accelerating targeted efforts in tea breeding.

Congenital scoliosis (CS) is a complex genetic disorder characterized by vertebral malformations. The precise etiology of CS is not fully defined. Here, we identify that mutation in dual serine/threonine and tyrosine protein kinase (dstyk) lead to CS-like vertebral malformations in zebrafish. We demonstrate that the scoliosis in dstyk mutants is related to the wavy and malformed notochord sheath formation and abnormal axial skeleton segmentation due to dysregulated biogenesis of notochord vacuoles and notochord function. Further studies show that DSTYK is located in late endosomal/lysosomal compartments and is involved in the lysosome biogenesis in mammalian cells. Dstyk knockdown inhibits notochord vacuole and lysosome biogenesis through mTORC1-dependent repression of TFEB nuclear translocation. Inhibition of mTORC1 activity can rescue the defect in notochord vacuole biogenesis and scoliosis in dstyk mutants. Together, our findings reveal a key role of DSTYK in notochord vacuole biogenesis, notochord morphogenesis and spine development through mTORC1/TFEB pathway.