RNA helicase DEAD-box protein 5 alleviates nonalcoholic steatohepatitis progression via tethering TSC complex and suppressing mTORC1 signaling.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease and its progressive form, nonalcoholic steatohepatitis (NASH), are rapidly becoming the top causes of hepatocellular carcinoma (HCC). Currently, there are no approved therapies for the treatment of NASH. DEAD-box protein 5 (DDX5) plays important roles in different cellular processes. However, the precise role of DDX5 in NASH remains unclear. APPROACH AND RESULTS: DDX5 expression was downregulated in patients with NASH, mouse models with diet-induced NASH (high-fat diet [HFD], methionine- and choline-deficient diet, and choline-deficient HFD), mouse models with NASH-HCC (diethylnitrosamine with HFD), and palmitic acid-stimulated hepatocytes. Adeno-associated virus-mediated DDX5 overexpression ameliorates hepatic steatosis and inflammation, whereas its deletion worsens such pathology. The untargeted metabolomics analysis was carried out to investigate the mechanism of DDX5 in NASH and NASH-HCC, which suggested the regulatory effect of DDX5 on lipid metabolism. DDX5 inhibits mechanistic target of rapamycin complex 1 (mTORC1) activation by recruiting the tuberous sclerosis complex (TSC)1/2 complex to mTORC1, thus improving lipid metabolism and attenuating the NACHT-, leucine-rich-repeat (LRR)-, and pyrin domain (PYD)-containing protein 3  inflammasome activation. We further identified that the phytochemical compound hyperforcinol K directly interacted with DDX5 and prevented its ubiquitinated degradation mediated by ubiquitin ligase (E3) tripartite motif protein 5, thereby significantly reducing lipid accumulation and inflammation in a NASH mouse model. CONCLUSIONS: These findings provide mechanistic insight into the role of DDX5 in mTORC1 regulation and NASH progression, as well as suggest a number of targets and a promising lead compound for therapeutic interventions against NASH.

After 50 Years of Hepatic Clearance Models, Where Should We Go from Here? Improvements and Implications for Physiologically Based Pharmacokinetic Modeling.

There is overwhelming preference for application of the unphysiologic, well-stirred model (WSM) over the parallel tube model (PTM) and dispersion model (DM) to predict hepatic drug clearance, CLH , despite that liver blood flow is dispersive and closer to the DM in nature. The reasoning is the ease in computation relating the hepatic intrinsic clearance ( CLint ), hepatic blood flow ( QH ), unbound fraction in blood ( fub ) and the transmembrane clearances ( CLin and CLef ) to CLH for the WSM. However, the WSM, being the least efficient liver model, predicts a lower EH that is associated with the in vitro CLint ( Vmax / Km ), therefore requiring scale-up to predict CLH in vivo. By contrast, the miniPTM, a three-subcompartment tank-in-series model of uniform enzymes, closely mimics the DM and yielded similar patterns for CLint versus EH , substrate concentration [S] , and KL / B , the tissue to outflow blood concentration ratio. We placed these liver models nested within physiologically based pharmacokinetic models to describe the kinetics of the flow-limited, phenolic substrate, harmol, using the WSM (single compartment) and the miniPTM and zonal liver models (ZLMs) of evenly and unevenly distributed glucuronidation and sulfation activities, respectively, to predict CLH For the same, given CLint ( Vmax and Km ), the WSM again furnished the lowest extraction ratio ( EH,WSM = 0.5) compared with the miniPTM and ZLM (>0.68). Values of EH,WSM were elevated to those for EH, PTM and EH, ZLM when the Vmax s for sulfation and glucuronidation were raised 5.7- to 1.15-fold. The miniPTM is easily manageable mathematically and should be the new normal for liver/physiologic modeling. SIGNIFICANCE STATEMENT: Selection of the proper liver clearance model impacts strongly on CLH predictions. The authors recommend use of the tank-in-series miniPTM (3 compartments mini-parallel tube model), which displays similar properties as the dispersion model (DM) in relating CLint and [ S ] to CLH as a stand-in for the DM, which best describes the liver microcirculation. The miniPTM is readily modified to accommodate enzyme and transporter zonation.

Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

Genomic and Transcriptional Profiles of Kelch-like (klhl) Gene Family in Polyploid Carassius Complex.

Genome duplication supplies raw genetic materials and has been thought to be essential for evolutionary innovation and ecological adaptation. Here, we select Kelch-like (klhl) genes to study the evolution of the duplicated genes in the polyploid Carassius complex, including amphidiploid C. auratus and amphitriploid C. gibelio. Phylogenetic, chromosomal location and read coverage analyses indicate that most of Carassius klhl genes exhibit a 2:1 relationship with zebrafish orthologs and confirm two rounds of polyploidy, an allotetraploidy followed by an autotriploidy, occurred during Carassius evolution. The lineage-specific expansion and biased retention/loss of klhl genes are also found in Carassius. Transcriptome analyses across eight adult tissues and seven embryogenesis stages reveal varied expression dominance and divergence between the two species. The expression of klhls in response to Carassius herpesvirus 2 infection shows different expression changes corresponding to distinct herpesvirus resistances in three C. gibelio gynogenetic clones. Finally, we find that most C. gibelio klhl genes possess three alleles except eight genes that have lost one or two alleles due to genome rearrangement. The allele expression bias is prosperous for Cgklhl genes and varies during embryogenesis owning to the sequential expression manner of the alleles. The current study provides global insights into the genomic and transcriptional evolution of duplicated genes in a given superfamily resulting from multiple rounds of polyploidization.

Diverse polycyclic polyprenylated acylphloroglucinols with anti-neuroinflammatory activity from Hypericum beanii.

A phytochemical investigation on the roots of Hypericum beanii resulted in the isolation of six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperberlones A-F, along with fourteen known analogues. The structural characterization of these compounds was carried out by analyzing the HRESIMS data, 1D and 2D NMR spectroscopic data, electronic circular dichroism (ECD) calculations, and gauge-independent atomic orbital (GIAO) NMR calculations. Hyperberlone A (1) was a caged PPAP with a rare tricyclo[4.3.1.03,8]decane carbon skeleton. It was deduced to be biosynthetically generated from hyperbeanol C (8) through key Paternò-Büchi reaction, radical cascade cyclizations, and retro-aldol reaction. Compounds 4, 6, 7, 9, 14, and 16 exhibited significant nitric oxide (NO) production inhibitory effects in lipopolysaccharide (LPS)-induced BV-2 microglial cells with IC50 values of 6.11-25.28 µM. Moreover, compound 4 significantly decreased the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in LPS-induced BV-2 microglia, as well as the phosphorylation of JNK.

Comparative transcriptomic analysis reveals an association of gibel carp fatty liver with ferroptosis pathway.

BACKGROUND: Fatty liver has become a main problem that causes huge economic losses in many aquaculture modes. It is a common physiological or pathological phenomenon in aquaculture, but the causes and occurring mechanism are remaining enigmatic. METHODS: Each three liver samples from the control group of allogynogenetic gibel carp with normal liver and the overfeeding group with fatty liver were collected randomly for the detailed comparison of histological structure, lipid accumulation, transcriptomic profile, latent pathway identification analysis (LPIA), marker gene expression, and hepatocyte mitochondria analyses. RESULTS: Compared to normal liver, larger hepatocytes and more lipid accumulation were observed in fatty liver. Transcriptomic analysis between fatty liver and normal liver showed a totally different transcriptional trajectory. GO terms and KEGG pathways analyses revealed several enriched pathways in fatty liver, such as lipid biosynthesis, degradation accumulation, peroxidation, or metabolism and redox balance activities. LPIA identified an activated ferroptosis pathway in the fatty liver. qPCR analysis confirmed that gpx4, a negative regulator of ferroptosis, was significantly downregulated while the other three positively regulated marker genes, such as acsl4, tfr1 and gcl, were upregulated in fatty liver. Moreover, the hepatocytes of fatty liver had more condensed mitochondria and some of their outer membranes were almost ruptured. CONCLUSIONS: We reveal an association between ferroptosis and fish fatty liver for the first time, suggesting that ferroptosis might be activated in liver fatty. Therefore, the current study provides a clue for future studies on fish fatty liver problems.

Diverse Polycyclic Polyprenylated Acylphloroglucinol Congeners with Anti-Nonalcoholic Steatohepatitis Activity from Hypericum forrestii.

The new polycyclic polyprenylated acylphloroglucinols, hyperforcinols A-J (1-10), were isolated from the fruits of Hypericum forrestii, together with 30 biogenetic congeners of known structures. The structures of hyperforcinols A-J were determined by HRESIMS and 1D/2D NMR spectroscopic analysis, and their absolute configurations were determined by a combination of the electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis. A selection of 25 isolates, possessing seven types of carbon skeletons, were assessed for their in vitro effects against nonalcoholic steatohepatitis (NASH) using a free fatty acid-induced L02 cell model. Compounds 20 and 40 significantly decreased intracellular lipid accumulation. QRT-PCR analyses revealed that compounds 20 and 40 regulate the expression of lipid metabolism-related genes, including CD36, FASN, PPARα, and ACOX1.

Dimethylated acylphloroglucinol meroterpenoids with anti-oral-bacterial and anti-inflammatory activities from Hypericum elodeoides.

Acylphloroglucinol meroterpenoids are adducts of the acylphloroglucinol unit and polyprenylated fragments (terpenoids) with attractive structures and bioactivities. During study of the medicinal molecules of the genus Hypericum, the first example of dimethylated acylphloroglucinol meroterpenoids with pyran-fused 6/6/6 tricyclic skeletons ((+)/(-)-elodeoidols A-F (1-6)), along with three biogenetical homologues (7-9) were isolated from the herbaceous plant of Hypericum elodeoides. Their structures including absolute configurations were then identified by nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HRESIMS), electronic circular dichroism (ECD) analysis and calculations. The monoterpene moiety of 1-6 were cyclized as two cyclohexanes and fused with a dimethylated acylphloroglucinol unit through an additional ether linkage, which led to an interesting pyran-fused linear or angle type 6/6/6 tricyclic skeleton. Compounds 5, 8 and 9 showed preferable antibacterial activities against three oral bacteria, among the MIC value of (+)-5 was 6.25 µg/ml; Compounds 3, 7 and 8 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells (IC50: 10.39 ± 0.49 ~ 34.25 ± 2.32 µM).

A retrospective survey of influencing factors on patient survival without local recurrence and total survival in patients with early cervical cancer.

OBJECTIVE: The article is based on the results of a retrospective review to observe the survival without local recurrence and the influencing factors of overall survival in patients with early cervical cancer. METHODS: Retrospective analysis was performed on clinical and pathological data of 247 cases of early cervical cancer treated by radical resection in the period January 2011 to January 2018. Univariate and multivariate Logistic Regression Models were used to evaluate the survival without local recurrence and independent factors affecting overall survival. RESULTS: All patients were classified by the FIGO(Federation International of Gynecology and Obstetrics) stage. The difference between adjuvant chemotherapy and brachytherapy was statistically significant (p<0.05). The median local relapse-free survival time of 247 patients was 45.0 months, and the postoperative follow-up for 2 years, 5 years and 10 years was 4.45% (11/247), 6.88% (17/247) and 8.50% (21/247), respectively. Influencing factors were, presence or absence of lymphatic vascular space infiltration, tumour diameter, whether treated with external pelvic irradiation, adjuvant chemotherapy and proximal treatment were related to local recurrence and survival of patients with early cervical cancer (p<0.05). CONCLUSIONS: Patients with a smaller tumour size, no lymph node metastasis and external pelvic irradiation had a better overall survival. Patients with early cervical cancer should be treated with a combination of extracavitatry irradiation and brachytherapy to reduce the risk of local recurrence.

Differential expression of innate and adaptive immune genes in the survivors of three gibel carp gynogenetic clones after herpesvirus challenge.

BACKGROUND: Accompanied with rapid growth and high density aquaculture, gibel carp has been seriously threatened by Carassius auratus herpesvirus (CaHV) since 2012. In previous study, distinct CaHV resistances and immune responses were revealed in the diseased individuals of three gibel carp gynogenetic clones (A+, F and H). However, little is known about the gene expression changes in the survivors after CaHV challenge, particularly their differences of innate and adaptive immune system between susceptible clone and resistant clone. RESULTS: We firstly confirmed the CaHV carrier state in the survivors of three gibel carp clones after CaHV challenge by evaluating the abundances of five CaHV genes. The assay of viral loads indicated the resistant clone H possessed not only stronger resistance but also higher tolerance to CaHV. Then, 2818, 4047 and 3323 differentially expressed unigenes (DEUs) were screened from the head-kidney transcriptome profiles of survivors compared with controls from clone A+, F and H. GO and KEGG analysis suggested that a persistent immune response might sustain in resistant clone H and F, while susceptible clone A+ had a long-term impact on the circulatory system which was consistent with the major symptoms of bleeding caused by CaHV. Among the top 30 enriched pathways of specifically up-regulated DEUs in respective clones, 26, 7 and 15 pathways in clone H, F and A+ were associated with infections, diseases, or immune-related pathways respectively. In addition, 20 pathways in clone F belonged to "metabolism" or "biogenesis", and 7 pathways involved in "circulatory system" were enriched in clone A+. Significantly, we revealed the differential expression changes of IFN system genes and immunoglobulin (Ig) genes among the survivors of three clones. Finally, myosins and Igs were identified as co-expression modules which were positively or negatively correlated to CaHV viral loads respectively. CONCLUSIONS: Our results revealed the common and distinct gene expression changes in immune and circulatory system in the survivors of three gibel carp gynogenetic clones with different CaHV resistances. The current study represents a paradigm of differential innate and adaptive immune reactions in teleost, and will be beneficial to the disease-resistance breeding of gibel carp.

Divergent Expression Patterns and Function of Two cxcr4 Paralogs in Hermaphroditic Epinephelus coioides.

Chemokine receptor Cxcr4 evolved two paralogs in the teleost lineage. However, cxcr4a and cxcr4b have been characterized only in a few species. In this study, we identified two cxcr4 paralogs from the orange-spotted grouper, Epinephelus coioides. The phylogenetic relationship and gene structure and synteny suggest that the duplicated cxcr4a/b should result from the teleost-specific genome duplication (Ts3R). The teleost cxcr4 gene clusters in two paralogous chromosomes exhibit a complementary gene loss/retention pattern. Ec_cxcr4a and Ec_cxcr4b show differential and biased expression patterns in grouper adult tissue, gonads, and embryos at different stages. During embryogenesis, Ec_cxcr4a/b are abundantly transcribed from the neurula stage and mainly expressed in the neural plate and sensory organs, indicating their roles in neurogenesis. Ec_Cxcr4a and Ec_Cxcr4b possess different chemotactic migratory abilities from the human SDF-1α, Ec_Cxcl12a, and Ec_Cxcl12b. Moreover, we uncovered the N-terminus and TM5 domain as the key elements for specific ligand⁻receptor recognition of Ec_Cxcr4a-Ec_Cxcl12b and Ec_Cxcr4b-Ec_Cxcl12a. Based on the biased and divergent expression patterns of Eccxcr4a/b, and specific ligand⁻receptor recognition of Ec_Cxcl12a/b⁻Ec_Cxcr4b/a, the current study provides a paradigm of sub-functionalization of two teleost paralogs after Ts3R.

The influence of locally applied granulocyte-colony stimulating factor on osteoporotic bone.

OBJECTIVES: The compromised capacity of bone healing in osteoporotic population renders a serious concern of patients and clinicians. This study aimed to investigate the influence of G-CSF on bone reconstruction using an osteoporotic animal model. MATERIALS AND METHODS: Sixty skeletal mature female Spraque-Dawley rats underwent bilateral ovariectomy (OVX) and were assigned into three groups (n = 20). Three months after OVX, defects of 5 mm in cranial and 2 mm in femur were surgically created on all the animals. The defects were left unfilled, filled with gelatin sponge (GS), or filled with granulocyte-colony stimulating factor (G-CSF) infused GS. Specimens were retrieved for histomorphometric and micro-CT analyses at weeks 1, 4, 8, and 12 after surgery. RESULTS: At early stage of week 1 to week 8, the histomorphometric and micro-CT analysis demonstrated more advanced bone formation in femur in the control group; by week 12, all groups achieved cortical closure. In cranial bone, more advanced bone formation was exhibited in G-CSF-treated group at both early and late stages, although this observation was not statistically significant. CONCLUSIONS: The results indicated that in osteoporotic bone, G-CSF may advance bone healing in cranial bone where spontaneous bone formation was insufficient.

Divergent Expression Patterns and Function Implications of Four nanos Genes in a Hermaphroditic Fish, Epinephelus coioides.

Multiple nanos genes have been characterized in several fishes, but the functional implications of their various expression patterns remain unclear. In this study, we identified and characterized four nanos genes from a hermaphroditic fish orange-spotted grouper, Epinephelus coioides. Ecnanos1a and Ecnanos1b show divergent expression patterns, and the dynamic expression change of Ecnanos1a in pituitaries during sex change is associated with testis differentiation and spermatogenesis. Ecnanos2 and Ecnanos3 might be germline stem cells (GSCs) and primordial germ cells (PGCs)-specific markers, respectively. Significantly, Ecnanos3 3'-untranslated region (UTR) is necessary for PGC specific expression, where a non-canonical "GCACGTTT" sequence is required for miR-430-mediated repression of Ecnanos3 RNA. Furthermore, grouper Dead end (Dnd) can relieve miR-430 repression in PGCs by associating with a 23 bp U-rich region (URR) in Ecnanos3 3'-UTR. The current study revealed the functional association of multiple nanos genes with PGC formation and germ cell development in orange-spotted grouper, and opened up new possibilities for developing biotechnologies through utilizing the associations between Ecnanos3 and PGCs or between Ecnanos2 and GSCs in the hermaphroditic fish.

Role of periodontal disease in bisphosphonate-related osteonecrosis of the jaws in ovariectomized rats.

OBJECTIVE: This study aimed to investigate the role of progressive periodontal disease in inducing bisphosphonate-related osteonecrosis of the jaws (BRONJ) using an ovariectomized (OVX) rat model mimicking human intracortical remodeling process. MATERIALS AND METHODS: Thirty 12-week-old Spraque-Dawly (SD) female rats were randomly assigned into two groups. All rats underwent bilateral ovariectomy. Six weeks after surgery, zoledronic acid (ZA) or vehicle control was administered intraperitoneally for 12 weeks. On the same day of injection, a cotton ligature was placed subgingivally around the first left lower molar to induce periodontitis. All animals were sacrificed 12 weeks after injection. The entire mandibles were harvested for micro-computed tomography (micro-CT) and histological examinations. RESULTS: Micro-CT examination showed that ligature placement caused significant alveolar bone loss both in ZA (0.63 ± 0.13 vs. 0.38 ± 0.06 mm, P < 0.001) and in control (0.88 ± 0.19 vs. 0.40 ± 0.06 mm, P < 0.001) groups. Whereas in the ZA group, bone loss was attenuated compared with the control group (P < 0.01); the bone mineral density in the ZA group (1.00 ± 0.02 g/cm(3)) was significantly higher than that in vehicle control group (0.96 ± 0.03 g/cm(3), P < 0.001). Histological examination found necrotic bone tissue with extensive, empty lacunae in two of 15 rats in ZA group, but in none of the control group. CONCLUSION: Bisphosphonates inhibit alveolar bone resorption in progressive periodontal disease, which might benefit the management of periodontitis, but increase the risk of developing BRONJ.

Skeletal site-specific response to ovariectomy in a rat model: change in bone density and microarchitecture.

OBJECTIVES: Ovariectomized (OVX) rat model has been widely used in osteoporosis-related studies. However, the discrepancies in age and skeletal sites being investigated make it difficult to compare the results from different studies. The purpose of this study was to provide information of systemic skeletal site-specific changes in a stable OVX rat model. MATERIAL AND METHODS: Thirty-three 6-month Spraque-Dawley female rats were used. Fifteen rats underwent ovariectomy, and fifteen received sham surgery. Three animals without any surgery were sacrificed at week 0 to serve as baseline. Three animals in the OVX and sham group, respectively, were euthanized at week 2, 4, 12, 24 and 36 post-surgery. Ten bone sites, including parietal bone, interparietal bone, maxilla, mandible, humerus, ulna, femur, tibia, lumber vertebra, and ilium, were subjected to micro-CT. RESULTS: Overall, long bones, lumber vertebra, and ilium showed similar trend of bone loss post-OVX, with tibia and femur suffered the most bone loss and spine the least (decreased by 75.0%, 70.4% and 36.6% in bone mineral density BMD at week 36 from base line, respectively). Upon OVX, jaw bones and cranial bones only showed a minor reduction in BMD (decreased by 1~3% from baseline) at week 36. Significant deterioration of trabecular structure was detected in long bones, lumber vertebra, and ilium post-OVX, while jaw bones remained relatively stable. CONCLUSIONS: This study for the first time assessed the systemic site-specific bone loss and microarchitecture changes in OVX rat model. It provided valuable information for selecting bone site and observation time in osteoporosis-related study.

A Deep-Learning Model for Diagnosing Fresh Vertebral Fractures on Magnetic Resonance Images.

BACKGROUND: The accurate diagnosis of fresh vertebral fractures (VFs) was critical to optimizing treatment outcomes. Existing studies, however, demonstrated insufficient accuracy, sensitivity, and specificity in detecting fresh fractures using magnetic resonance imaging (MRI), and fall short in localizing the fracture sites. METHODS: This prospective study comprised 716 patients with fresh VFs. We obtained 849 Short TI Inversion Recovery (STIR) image slices for training and validation of the AI model. The AI models employed were yolov7 and resnet50, to detect fresh VFs. RESULTS: The AI model demonstrated a diagnostic accuracy of 97.6% for fresh VFs, with a sensitivity of 98% and a specificity of 97%. The performance of the model displayed a high degree of consistency when compared to the evaluations by spine surgeons. In the external testing dataset, the model exhibited a classification accuracy of 92.4%, a sensitivity of 93%, and a specificity of 92%. CONCLUSIONS: Our findings highlighted the potential of AI in diagnosing fresh VFs, offering an accurate and efficient way to aid physicians with diagnosis and treatment decisions.

Application of Entity-BERT model based on neuroscience and brain-like cognition in electronic medical record entity recognition.

Introduction: In the medical field, electronic medical records contain a large amount of textual information, and the unstructured nature of this information makes data extraction and analysis challenging. Therefore, automatic extraction of entity information from electronic medical records has become a significant issue in the healthcare domain. Methods: To address this problem, this paper proposes a deep learning-based entity information extraction model called Entity-BERT. The model aims to leverage the powerful feature extraction capabilities of deep learning and the pre-training language representation learning of BERT(Bidirectional Encoder Representations from Transformers), enabling it to automatically learn and recognize various entity types in medical electronic records, including medical terminologies, disease names, drug information, and more, providing more effective support for medical research and clinical practices. The Entity-BERT model utilizes a multi-layer neural network and cross-attention mechanism to process and fuse information at different levels and types, resembling the hierarchical and distributed processing of the human brain. Additionally, the model employs pre-trained language and sequence models to process and learn textual data, sharing similarities with the language processing and semantic understanding of the human brain. Furthermore, the Entity-BERT model can capture contextual information and long-term dependencies, combining the cross-attention mechanism to handle the complex and diverse language expressions in electronic medical records, resembling the information processing method of the human brain in many aspects. Additionally, exploring how to utilize competitive learning, adaptive regulation, and synaptic plasticity to optimize the model's prediction results, automatically adjust its parameters, and achieve adaptive learning and dynamic adjustments from the perspective of neuroscience and brain-like cognition is of interest. Results and discussion: Experimental results demonstrate that the Entity-BERT model achieves outstanding performance in entity recognition tasks within electronic medical records, surpassing other existing entity recognition models. This research not only provides more efficient and accurate natural language processing technology for the medical and health field but also introduces new ideas and directions for the design and optimization of deep learning models.

[Near-infrared excited graphene oxide/silver nitrate/chitosan coating for improving antibacterial properties of titanium implants].

Objective: To design and construct a graphene oxide (GO)/silver nitrate (Ag3PO4)/chitosan (CS) composite coating for rapidly killing bacteria and preventing postoperative infection in implant surgery. Methods: GO/Ag3PO4 composites were prepared by ion exchange method, and CS and GO/Ag3PO4 composites were deposited on medical titanium (Ti) sheets successively. The morphology, physical image, photothermal and photocatalytic ability, antibacterial ability, and adhesion to the matrix of the materials were characterized. Results: The GO/Ag3PO4 composites were successfully prepared by ion exchange method and the heterogeneous structure of GO/Ag3PO4 was proved by morphology phase test. The heterogeneous structure formed by Ag3PO4 and GO reduced the band gap from 1.79 eV to 1.39 eV which could be excited by 808 nm near-infrared light. The photothermal and photocatalytic experiments proved that the GO/Ag3PO4/CS coating had excellent photothermal and photodynamic properties. In vitro antibacterial experiments showed that the antibacterial rate of the GO/Ag3PO4/CS composite coating against Staphylococcus aureus reached 99.81% after 20 minutes irradiation with 808 nm near-infrared light. At the same time, the composite coating had excellent light stability, which could provide stable and sustained antibacterial effect. Conclusion: GO/Ag3PO4/CS coating can be excited by 808 nm near infrared light to produce reactive oxygen species, which has excellent antibacterial activity under light.