Reversal of gentamicin sulfate resistance in avian pathogenic Escherichia coli by matrine combined with berberine hydrochloride.

In recent years, the evolution of antibiotic resistance has led to the inefficacy of several antibiotics, and the reverse of resistance was a novel method to solve this problem. We previously demonstrated that matrine (Mat) and berberine hydrochloride (Ber) had a synergistic effect against multidrug-resistant Escherichia coli (MDREC). This study aimed to demonstrate the effect of Mat combined with Ber in reversing the resistance of MDREC. The MDREC was sequenced passaged in the presence of Mat, Ber, and a combination of Mat and Ber, which did not affect its growth. The reverse rate was up to 39.67% after MDREC exposed to Mat + Ber for 15 days. The strain that reversed resistance was named drug resistance reversed E. coli (DRREC) and its resistance to ampicillin, streptomycin, gentamicin, and tetracycline was reversed. The MIC of Gentamicin Sulfate (GS) against DRREC decreased 128-fold to 0.63 µg/mL, and it was stable within 20 generations. Furthermore, the susceptible phenotype of DRREC remained stable within 20 generations, as well. The LD50 of DRREC for chickens was 8.69 × 109 CFU/mL. qRT-PCR assays revealed that the transcript levels of antibiotic-resistant genes and virulence genes in the DRREC strain were significantly lower than that in the MDREC strain (P < 0.05). In addition, GS decreased the death, decreased the bacterial loading in organs, alleviated the injury of the spleen and liver, and decreased the cytokine levels in the chickens infected by the DRREC strain. In contrast, the therapeutic effect of GS in chickens infected with MDREC was not as evident. These findings suggest that the combination of Mat and Ber has potential for reversing resistance to MDREC.

Relationship between intervertebral disc height and post operative dysphagia secondary to single-level anterior cervical discectomy and fusion- a retrospective study.

BACKGROUND: One goal of Anterior Cervical Discectomy and Fusion (ACDF) is to restore the loss of intervertebral disc height (IDH) results from the degenerative process. However, the effects of IDH on postoperative dysphagia after ACDF remain unclear. METHODS: Based on the results of a one-year telephone follow-up, A total of 217 consecutive patients after single-level ACDF were enrolled. They were divided into dysphagia and non-dysphagia groups. The age, BMI, operation time and blood loss of all patients were collected from the medical record system and compared between patients with and without dysphagia. Radiologically, IDH, spinous process distance (SP) of the operated segment, and C2-7 angle (C2-7 A) were measured preoperatively and postoperatively. The relationship between changes in these radiological parameters and the development of dysphagia was analyzed. RESULTS: Sixty-three (29%) cases exhibited postoperative dysphagia. The mean changes in IDH, SP, and C2-7 A were 2.84 mm, -1.54 mm, and 4.82 degrees, respectively. Changes in IDH (P = 0.001) and changes in C2-7 A (P = 0.000) showed significant differences between dysphagia and non-dysphagia patients. Increased IDH and increased C2-7 A (P = 0.037 and 0.003, respectively) significantly and independently influenced the incidence of postoperative dysphagia. When the change in IDH was ≥ 3 mm, the chance of developing postoperative dysphagia for this patient was significantly greater. No significant relationship was observed between the change in spinous process distance (SP) and the incidence of dysphagia. The age, BMI, operation time and blood loss did not significantly influence the incidence of postoperative dysphagia. CONCLUSION: The change in IDH could be regarded as a predictive factor for postoperative dysphagia after single-level ACDF.

A quantitative proteomic study reveals oxidative stress and synapse-related proteins contributed to TDCIPP exposure induced neurotoxicity.

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) has been consistently identified in various environmental media and biological specimens. Current understanding of the in vivo toxicities of TDCIPP is limited, especially for potential for neurotoxic and cognitive impairment effects. To better evaluate the potential adverse effect of the chemical on learning and memory, Sprague Dawley (SD) rats were administered TDCIPP via gavage at doses of 40, 120, and 360 mg/kg/day for a period of 90 days. Quantitative proteomic analysis, immunohistochemistry, and Western blotting were employed to assess alterations in proteins following exposure to TDCIPP. An open field test and the Morris Water Maze were used to assess anxiety and spatial learning memory capacity. Administration of TDCIPP induced anxiety and cognitive impairments in rats. Additionally, a noteworthy decrease in the number of neurons was observed in the hippocampal CA3 and dentate gyrus (DG) regions. Proteomic and bioinformatic analyses revealed dysregulation of numerous hippocampal proteins, particularly those associated with synapses (PKN1) or oxidative stress (GSTM4, NQO1, and BMAL1), which was further confirmed by Western blot analysis. In sum, the cognitive impairment of rats caused by TDCIPP exposure was associated with dysregulation of synaptic and oxidative stress-related proteins.

Intramedullary spinal cord metastasis from esophageal squamous cell carcinoma: case report and literature review.

BACKGROUND: Intramedullary spinal cord metastasis (ISCM) of malignant tumors rarely happens. To the best of our knowledge, only five cases of ISCM from esophageal cancer have been reported in literature. We here report the sixth descripted case of ISCM from esophageal cancer. CASE PRESENTATION: A 68-year-old male presented with weakness of right limbs and localized neck pain two years after diagnosed esophageal squamous cell carcinoma. The gadolinium enhanced Magnetic resonance imaging (MRI) of cervical spine showed a mixed-intense intramedullary tumor with typical more intense thin rim of peripheral enhancement in C4-C5. The patient died fifteen days after diagnosis of irreversible respiratory and circulatory failures. An autopsy was refused by his family. CONCLUSIONS: This case highlights the importance of gadolinium enhanced MRI for diagnosis in ISCM. We believe that early diagnosis and surgery for selected patients shows helpfulness to save their neurologic function and improve quality of life.

Percutaneous versus open posterior stabilization and decompression in AOSpine-type A3 thoracolumbar fractures with neurological deficit.

BACKGROUND: This retrospective cohort study aimed to compare the clinical and radiological outcomes between two treatment strategies focusing on non-osteoporotic AOSpine-type A3 fractures of the thoracolumbar spine with neurological deficits at levels T11 to L2. METHODS: In total, 67 patients between 18 and 60 years of age who were treated operatively with either of the two treatment strategies were included. One treatment strategy included open posterior stabilization and decompression, whereas the other was based on percutaneous posterior stabilization and decompression via a tubular retraction system. Demographic data, surgical variables, and further parameters were assessed. Patient-reported outcomes (PROs), including the Visual Analog Scale (VAS), the Oswestry Disability Index (ODI), and the American Spinal Injury Association (ASIA) impairment score, were measured to assess functional outcomes. The regional Cobb angle (CA), the anterior height ratio of the fractured vertebrae (AHRV), and the degree of canal encroachment (DCE) were assessed. The ASIA score was used to assess neurological function recovery. The follow-up period was at least 12 months. RESULTS: Surgical time and postoperative hospital stay were significantly shorter in the minimally invasive surgery (MIS) group. Intraoperative blood loss was significantly less in the MIS group. Regarding radiological outcome, CA and AHRV at the time of follow-up did not show a significant difference. DCE at the time of follow-up was significantly improved in the MIS group. Lower VAS scores and better ODIs were observed in the MIS group at the 6-month follow-up, but similar outcomes were observed at the 12-month follow-up. The ASIA score was similar between both groups at the 12-month follow-up. CONCLUSIONS: Both treatment strategies are safe and effective; however, MIS could provide earlier pain relief and better functional outcomes compared with OS.

Serum antioxidant enzymes in spinal stenosis patients with lumbar disc herniation: correlation with degeneration severity and spinal fusion rate.

OBJECTIVE: To determine whether superoxide dismutase (SOD) and glutathione reductase (GR) correlated with the intervertebral disc degeneration (IDD) severity and the postoperative spinal fusion rate in lumbar spinal stenosis patients accompanied with lumbar disc herniation. METHODS: This retrospective study investigated 310 cases of posterior lumbar decompression and fusion. The cumulative grade was calculated by adding the pfirrmann grades of all the lumbar discs. Subjects were grouped based on the median cumulative grade. Logistic regression was used to determine the associations among the demographical, clinical, and laboratory indexes and severe degeneration and fusion. The receiver operating characteristic (ROC) curve was performed to measure model discrimination, and Hosmer-Lemeshow (H-L) test was used to measure calibration. RESULTS: SOD and GR levels were significantly lower in the severe degeneration group (cumulative grade > 18) than in the mild to moderate degeneration group (cumulative grade ≤ 18). Furthermore, the SOD and GR concentrations of the fusion group were significantly higher than that of the non-fusion group (p < 0.001 and p = 0.006). The multivariate binary logistic models revealed that SOD and GR were independently influencing factors of the severe degeneration (OR: 0.966, 95%CI: 0.950-0.982, and OR: 0.946, 95%CI: 0.915-0.978, respectively) and non-fusion (OR: 0.962; 95% CI: 0.947-0.978; OR: 0.963; 95% CI: 0.933-0.994). The models showed excellent discrimination and calibration. Trend analysis indicated that the levels of SOD and GR tended to decrease with increasing severity (p for trend < 0.001 and 0.003). In addition, it also revealed that SOD provided protection from non-fusion in a concentration-dependent manner (p for trend < 0.001). However, GR concentration-dependent effects were not apparent (p for trend = 0.301). CONCLUSION: High serum SOD and GR levels are associated with a better fusion prognosis and a relief in degeneration severity.

Development a high-throughput zebrafish embryo acute toxicity testing method based on OECD TG 236.

The Organization for Economic Co-operation and Development (OECD）Test Guideline (TG) 236 for zebrafish embryo acute toxicity testing was adopted for chemical toxicity assessment in 2013. Due to the increasing demand for prediction and evaluation of the acute toxicity using zebrafish embryos, we developed a method based on OECD 236 test guideline with the aim to improve the testing efficiency. We used 4-128 cell stage zebrafish embryos and performed an exposure assay in a 96-well microtiter plate, observing the lethality endpoints of embryos at 48-h postexposure. A total of 32 chemicals (two batches) were used in the comparison study. Our results indicated that the logarithmic LC50 (half lethal concentration) obtained by the modified method exhibited good correlation with that obtained by the OECD 236 testing method, and the R2 of the linear regression analysis was 0.9717 (0.9621 and 0.9936 for the two batches, respectively). Additionally, the intra- and inter-laboratory coefficient of variation (CVs) for the LC50 from the testing chemicals (17 chemicals in second batch) was less than 30%, except for CuSO4. Therefore, the developed method was less time-consuming and demonstrated a higher throughput for toxicity testing compared to the prior method. We argue the developed method could be used as an additional choice for high-throughput zebrafish embryo acute toxicity test.

Inhibition of miR-130b-3p restores autophagy and attenuates intervertebral disc degeneration through mediating ATG14 and PRKAA1.

Oxidative stress-induced autophagy dysfunction is involved in the pathogenesis of intervertebral disc degeneration (IVDD). MicroRNAs (miRNAs) not only have been regarded as important regulators of IVDD but also reported to be related to autophagy. This research was aimed to explore the role of miR-130b-3p in IVDD and its regulation on autophagy mechanism. The miR-130b-3p expression in the patient's degenerative nucleus pulposus (NP) samples and rat NP tissues was detected by qRT-PCR and FISH assay. The miR-130b-3p was knocked down or overexpressed in the human NP cells by lentivirus transfection. TBHP was used to induce oxidative stress in the human NP cells. Apoptosis, senescence, and autophagy were evaluated by flow cytometry, ß-gal staining, immunofluorescence, electron microscopy, and Western blot in the miR-130b-3p knocked down human NP cells under TBHP treatment. The relationship between the miR-130b-3p and ATG14 or PRKAA1 was confirmed by luciferase assay. The siRNA transfection was used to knock down the ATG14 and PRKAA1 expression, and then the human NP cells functions were further determined. In the in vivo experiment, the IVDD rat model was constructed and an adeno-associated virus (AAV)-miR-130b-3p inhibitor was intradiscally injected. After that, MRI and histological staining were conducted to evaluate the role of miR-130b-3p inhibition in the IVDD rat model. We found that the miR-130b-3p was upregulated in the degenerative NP samples from humans and rats. Interestingly, the inhibition of miR-130b-3p rescued oxidative stress-induced dysfunction of the human NP cells, and miR-130b-3p inhibition upregulated autophagy. Mechanistically, we confirmed that the miR-130b-3p regulated the ATG14 and PRKAA1 directly and the knockdown of the ATG14 or PRKAA1 as well as the treatment of autophagy inhibitor blockaded the autophagic flux and reversed the protective effects of miR-130b-3p inhibition in the TBHP-induced human NP cells. Furthermore, the inhibition of the miR-130b-3p via AAV- miR-130b-3p injection ameliorated the IVDD in a rat model. These data demonstrated that the miR-130b-3p inhibition could upregulate the autophagic flux and alleviate the IVDD via targeting ATG14 and PRKAA1.The translational potential of this article: The suppression of miR-130b-3p may become an effective therapeutic strategy for IVDD.

A quantitative proteomic analysis reveals the potential roles of PRDX3 in neurite outgrowth in N2a-APPswe cells.

Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles accompanied by progressive neurite loss. Mitochondria play pivotal roles in AD development. PRDX3 is a mitochondrial peroxide reductase critical for H2O2 scavenging and signal transduction. In this study, we found that PRDX3 knockdown (KD) in the N2a-APPswe cell line promoted retinoic acid (RA)-induced neurite outgrowth but did not reduce the viability of cells damaged by tert-butyl hydroperoxide (TBHP). We found that knocking down PRDX3 expression induced dysregulation of more than one hundred proteins, as determined by tandem mass tag (TMT)-labeled proteomics. A Gene Ontology (GO) analysis revealed that the dysregulated proteins were enriched in protein localization to the plasma membrane, the lipid catabolic process, and intermediate filament cytoskeleton organization. A STRING analysis showed close protein-protein interactions among dysregulated proteins. The expression of Annexin A1 (ANXA1), serine (Ser)-/threonine (Thr)-protein phosphatase 2A catalytic subunit alpha isoform (PP2A) and glutathione S-transferase Mu 2 (GSTM2) was significantly upregulated in PRDX3-KD N2a-APPswe cell lines, as verified by western blotting. Our study revealed, for the first time, that PRDX3 may play important roles in neurite outgrowth and AD development.

Human Umbilical Cord Wharton Jelly Cells Treatment Prevents Osteoporosis Induced by D-Galactose.

Methods: Sixteen male mice were randomly divided into 4 groups: control (ordinary feeding), D-gal (D-galactose) group, D-gal + MSC (human umbilical cord Wharton jelly cells), and D-gal + MSC-TNFα groups. Except for the control group (fed with same amount of saline solution), other mice received gastric feeding of 250 mg/kg D-galactose every day for 8 weeks. TNFα (10 ng/mL for 24 h) cocultured or noncocultured HUCWJCs (5 × 105) were suspended in 0.1 ml of sterile PBS and injected into tail veins every other week in D-gal + MSC-TNFα and D-gal + MSC groups, respectively, and only 0.1 ml of sterile PBS for control and D-gal groups. The bone mass was detected by qPCR, ELISA, microcomputed tomography (µCT), and hematoxylin-eosin staining. Proliferation, apoptosis, and differentiation of periosteal-derived osteoblasts (POB) were assessed. Transwell assay and scratch healing were performed to detect POB migration and invasion ability. The effect of HUCWJCs on POB signaling pathway expression was evaluated by immunoblotting. Results: The malondialdehyde (MDA) in serum was higher and superoxide dismutase (SOD) was lower in the D-gal group compared to the other groups (p < 0.05). Mice in D-gal group showed significantly decreased bone mass when compared to the control group, while HUCWJCs treatment partially rescued the phenotype, as demonstrated by µCT and histology (p < 0.05). Mechanically, HUCWJCs treatment partially promoted proliferation and migration and decreased apoptosis of POB induced by oxidative stress via activating the mitogen-activated protein kinase (MAPK) signaling pathway. Conclusion: HUCWJCs can prevent the progression of osteoporosis by inhibiting oxidative stress, which may act by regulating osteoblasts fate through the MAPK signaling pathway.

Is intervertebral disc degeneration associated with reduction in serum ferritin?

OBJECTIVE: Ferritin autophagy is characterized by intracellular ferroptosis and selective ferritin degradation. However, the role of ferritin in the development of intervertebral disc degeneration (IDD) has not been elucidated. The study aimed to investigate the role of serum iron metabolism markers, especially serum ferritin (SF), in IDD. METHODS: 217 patients who came to the spine surgery department of our hospital for low back pain were recruited, and blood samples were collected for routine examination after admission. The cumulative grade was also calculated by summing up the Pfirrmann grade of all lumbar discs. RESULTS: Correlation analysis showed that cumulative grade was correlated with SF (r = - 0.185, p = 0.006), not with serum iron (SI), transferrin saturation (TS), unsaturated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC) (all p > 0.05). In addition, SF levels in the low severity IDD were significantly higher than high severity IDD in cumulative grade (p = 0.003) and single disc grade. No statistically significant difference was found in the other four indicators. A statistically significant difference was observed between the high (cumulative grade > 17) and low score (cumulative grade ≤ 17) groups in terms of age. According to the ROC curve, the cut-off value of SF levels was 170.5. Patients with SF < 170.5 ng/mL had severe disc degeneration. The sensitivity and specificity were 0.635 and 0.602, respectively. CONCLUSION: This study preliminarily showed that SF was negatively correlated with the degree of IDD and can be used to predict IDD severity.

Association between human herpesvirus 6 (HHV-6) and cognitive function in the elderly population in Shenzhen, China.

AIM: Human herpesvirus 6 (HHV-6) is neurophilic, and its relationship with Alzheimer's disease (AD) remains controversial. This study aimed to examine the relationships between HHV-6 and cognitive abilities in elderly people aged 60 years or above from communities in Shenzhen. METHODS: We recruited participants from 10 community health service centers in Shenzhen. Participants were divided into case and control groups according to Mini-Mental State Examination (MMSE) scale standards and were included in this study with 1:1 matching based on sex and age (± 3 years). The HHV-6 gene was detected by real-time fluorescent quantitative PCR, and the HHV-6 copy number was quantified. RESULTS: A total of 580 participants (cases, n = 290; controls, n = 290), matched for gender and age was included in this study. A positive HHV-6 test was not associated with a significant difference in global cognitive performance (ORadjusted = 1.651, 95% CI = 0.671-4.062). After adjusting for gender, age, education, Pittsburgh Sleep Quality Index (PSQI) score, homocysteine (Hcy) and glycosylated hemoglobin (HbA1c), the results of multiple linear regression showed that there was a statistically negative correlation between HHV-6 copy number and orientation (ßadjusted = -0.974, p = 0.013), attention and calculation (ßadjusted = -1.840, p < 0.001), and language (ßadjusted = -2.267, p < 0.001). The restricted cubic spline (RCS) model results showed that there was a nonlinear dose-response relationship between HHV-6 log10-transformed copies and orientation (poverall = 0.003, pnonliner = 0.045), attention and calculation (poverall < 0.001, pnonliner < 0.001), and language (poverall < 0.001, pnonliner = 0.016). CONCLUSIONS: HHV-6 infection significantly associated with orientation, attention and calculation, and language in elderly individuals.

Nutritional deficiency induces nucleus pulposus cell apoptosis via the ATF4-PKM2-AKT signal axis.

BACKGROUND: The intervertebral disc is the largest avascular tissue in the human body. The nucleus pulposus (NP) consumes glucose and oxygen to generate energy to maintain cellular metabolism via nutrients that diffuse from the cartilage endplate. The microenvironment in the intervertebral disc becomes nutritionally deficient during degeneration, and nutritional deficiency has been shown to inhibit the viability and proliferation of NP cells. METHODS: To investigate the molecular mechanism by which nutritional deficiency reduces viability and decreases proliferation, we created an in vitro model by using decreasing serum concentration percentages. RESULTS: In this study, we found that nutritional deficiency reduced NP cell viability and increased cell apoptosis and that the upregulation of ATF4 expression and the downregulation of PKM2 expression were involved in this process. Moreover, we found that PKM2 inhibition can reduce the cell apoptosis induced by ATF4 silence under nutritional deficiency. CONCLUSION: Our findings revealed that PKM2 inhibition reduces the cell apoptosis induced by ATF4 silence under nutritional deficiency by inhibiting AKT phosphate. Revealing the function and mechanism of NP cell development under nutritional deficiency will provide new insights into the etiology, diagnosis, and treatment of intervertebral disc and related diseases.

Construction of a circular RNA-based competing endogenous RNA network to screen biomarkers related to intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IDD) is a leading cause of disability with limited treatment strategies. A better understanding of the mechanism of IDD might enable less invasive and more targeted treatments. This study aimed to identify the circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) regulatory mechanisms in IDD. METHODS : The GSE67567 microarray dataset was downloaded from the Gene Expression Omnibus database. After data preprocessing, differentially expressed circRNAs, miRNAs and mRNAs between IDD and controls were identified. A ceRNA network was constructed on the basis of the interaction between circRNAs and miRNAs, and miRNAs and mRNAs. Pathway enrichment analysis was performed on the mRNAs in the ceRNA network. Then, with 'intervertebral disc degeneration' as keywords, IDD-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were searched for in the Comparative Toxicogenomics Database. RESULTS: A total of 105 differentially expressed circRNAs, 84 miRNAs and 967 mRNAs were identified. After analysis, 86 circRNA-miRNA, and 126 miRNA-mRNA regulatory relationship pairs were obtained to construct a ceRNA network. The mRNAs were enriched in six KEGG signalling pathways, and four were associated with IDD: the hsa04350: TGF-beta signalling pathway, hsa04068: FoxO signalling pathway, hsa05142: Chagas disease (American trypanosomiasis) and hsa04380: Osteoclast differentiation. An IDD-related ceRNA network was constructed involving four circRNAs, three miRNAs and 11 mRNAs. Auxiliary validation showed that the expression levels of miR-185-5p, miR-486-5p, ACVR1B, FOXO1, SMAD2 and TGFB1 were consistent in different databases. CONCLUSIONS: Our study identified some circRNA-miRNA-mRNA interaction axes potentially associated with the progression of IDD, viz.: circRNA_100086-miR-509-3p-MAPK1, circRNA_000200-miR-185-5p-TGFB1, circRNA_104308-miR-185-5p-TGFB1, circRNA_400090-miR-486-5p-FOXO1 and circRNA_400090-miR-486-5p-SMAD2.

Global systemic risk and resilience for novel coronavirus in postpandemic era.

The ongoing pandemic has evolved and is posing diverse challenges for the world. Countermeasures for risks are needed to address both direct and indirect effects of disease on the healthcare system, economic and industrial sectors, governance, environment, transportation, energy, and communication systems. There are indicators of a forthcoming postpandemic era. The rethinking and reevaluation of policies adopted throughout the pandemic are ongoing to address cascading threats of emerging and reemerging infectious diseases. The first Special Issue introduced the topic. This second Special Issue describes international collaboration and innovation for pandemic risk and resilience, with a focus on future policy and operations of global systems toward a postandemic era.

Natural Dietary Compound Xanthohumol Regulates the Gut Microbiota and Its Metabolic Profile in a Mouse Model of Alzheimer's Disease.

Discovering new and effective drugs for the treatment of Alzheimer's disease (AD) is a major clinical challenge. This study focuses on chemical modulation of the gut microbiome in an established murine AD model. We used the 16S rDNA sequencing technique to investigate the effect of xanthohumol (Xn) on the diversity of intestinal microflora in 2-month- and 6-month-old APP/PS1 mice, respectively. APP/PS1 and wild-type mice were treated by gavage with corn oil with or without Xn every other day for 90 days. Prior to and following treatment, animals were tested for spatial learning, cognitive and memory function. We found Xn reduced cognitive dysfunction in APP/PS1 mice and significantly regulated the composition and abundance of gut microbiota both in prevention experiments (with younger mice) and therapeutic experiments (with older mice). Differential microflora Gammaproteobacteria were significantly enriched in APP/PS1 mice treated with Xn. Nodosilineaceae and Rikenellaceae may be the specific microflora modulated by Xn. The penicillin and cephalosporin biosynthesis pathway and the atrazine degradation pathway may be the principal modulation pathways. Taken together, oral treatment with Xn may have a neuroprotective role by regulating the composition of intestinal microflora, a result that contributes to the scientific basis for a novel prophylactic and therapeutic approach to AD.

Financial distress prediction using integrated Z-score and multilayer perceptron neural networks.

The COVID-19 pandemic led to a great deal of financial uncertainty in the stock market. An initial drop in March 2020 was followed by unexpected rapid growth over 2021. Therefore, financial risk forecasting continues to be a central issue in financial planning, dealing with new types of uncertainty. This paper presents a stock market forecasting model combining a multi-layer perceptron artificial neural network (MLP-ANN) with the traditional Altman Z-Score model. The contribution of the paper is presentation of a new hybrid enterprise crisis warning model combining Z-score and MLP-ANN models. The new hybrid default prediction model is demonstrated using Chinese data. The results of empirical analysis show that the average correct classification rate of thew hybrid neural network model (99.40%) is higher than that of the Altman Z-score model (86.54%) and of the pure neural network method (98.26%). Our model can provide early warning signals of a company's deteriorating financial situation to managers and other related personnel, investors and creditors, government regulators, financial institutions and analysts and others so that they can take timely measures to avoid losses.

[Regulation of PARP-1 deficiency on epidermal growth factor receptor during lung injury of mice induced by benzo [a] pyrene inhalation exposure].

OBJECTIVE: To investigate the regulation of PARP-1 deficiency on epidermal growth factor receptor(EGFR) during lung injury of mice induced by benzo[a]pyrene(B[a]P) inhalation exposure. METHODS: PARP-1 knockout mice(PARP-1~(-/-)) and WT mice were selected as the object, and which were randomly assigned into either an intervention or a control group(n=40, half male and half female). The intervention group were individually treated with 10.0 µg/m~(3 )B[a]P for 180 days by dynamic inhalation exposure(6 h per day and 5 days per week), and the control group was given the solvent dimethyl sulfoxide(DMSO) during the same period. The expression of EGFR in lung tissues of animals were examined by RT-PCR, Western blot and immunofluorescence. RESULTS: In WT mice, the intervention manifested significant increase expression of EGFR in lung tissue, but no changes were found in the control. In PARP-1~(-/-) mice, the intervention manifested significant inhibition expression of EGFR, but the control group exhibited no changes. CONCLUSION: PARP-1 deficiency suppresses the abnormal activation of EGFR during lung injury of mice induced by B[a]P inhalation exposure.

ACTG1 regulates intervertebral disc degeneration via the NF-κB-p65 and Akt pathways.

ACTG1 is a member of the actin family but is not a muscle actin gene. The ACTG1 mutation leads to hearing loss in humans, and the knockdown of ACTG1 suppresses the proliferation and migration of tumor cells; however, its role in intervertebral disc degeneration (IDD) is yet unclear. Bioinformatics methods revealed that ACTG1 might be a hub gene in IDD. Furthermore, the expression ACTG1 in severely degenerated nucleus pulposus (NP) tissues (Pfirrmann grade IV and V) was low as compared to that in mildly degenerated samples (Pfirrmann grade II and III). Moreover, the ACTG1 level was negatively correlated with human disc degeneration grades. The low expression of ACTG1 is also found in degenerated NP tissues in the rat. To further explore the function of ACTG1 in IDD, the gene expression was depleted in human NP cells via siRNA transfection. The ablation of ACTG1 increased MMP3 expression but decreased the level of collagen II. Excessive apoptosis was observed in ACTG1 knockdown groups, indicating that the absence of ACTG1 exacerbated IDD. GO function and pathway enrichment analysis for differentially expressed genes (DEGs) of two microarray datasets (GSE56081 and GSE42611) indicated that inflammatory response plays a crucial role in IDD. Interestingly, in the protein-protein interaction (PPI) network, ACTG1 is connected to the proteins of inflammation-related pathways. Furthermore, ACTG1 knockdown upregulated P-P65 level but suppressed P-Akt expression. These data collectively demonstrated that ACTG1 regulated the development of IDD through the NF-κB-p65 and Akt pathways, and ACTG1 may be a novel marker and therapeutic target of IDD in the future.

Pre-validation of choriogenin H transgenic medaka eleutheroembryos as a quantitative estrogenic activity test method.

The choriogenin H - EGFP transgenic medaka (Oryzias melastigma) has been used to test estrogenic substances and quantify estrogenic activity into 17ß-estradiol (E2) equivalency (EEQ). The method uses 8 eleutheroembryos in 2 ml solution per well and 3 wells per treatment in 24-well plates at 26 ± 1 °C for 24 ± 2 h, with subsequent measurements of induced GFP signal intensity. EEQ measurements are calculated using a E2 probit regression model with a coefficient of determination (R2) > 0.90. The selectivity was confirmed evaluating 27 known estrogenic and 5 known non-estrogenic compounds. Limit of quantitation (LOQ), recovery rate and bias were calculated to be 1 ng/ml EEQ, 104% and 4% respectively. Robustness analysis revealed exposure temperature is a sensitive parameter that should be kept at 26 ± 1 °C. The repeatability of intra- and inter-laboratories achieved CV < 30% for most tested food and cosmetics samples. The lot-lot stability was confirmed by the stable EEQ qualitative control (QC, 1 ng/mL E2) and calibration curve results. The stability of standard reagents, samples and sample extracts was also investigated. These data demonstrated this method to be an accurate indicator of estrogenic activity for both chemicals and extracts.