A novel mixed frequency sampling discrete grey model for forecasting hard disk drive failure.

The mixed data sampling (MIDAS) model has attracted increasing attention due to its outstanding performance in dealing with mixed frequency data. However, most MIDAS model extension studies are based on statistical methods or machine learning models, which suffer from insufficient prediction performance and stability in small sample environments. To solve this problem, this paper proposes a novel mixed frequency sampling discrete grey model (MDGM(1, N)), which is a coupled form of the MIDAS model and discrete grey multivariate model. By adjusting the structure parameters, the model can be adapted to different sampling frequencies data, and degenerate into several types of grey models. Then, the unbiasedness and stability of the model are proved using the mathematical analysis method and numerical random experiment. The meta-heuristic algorithm is introduced to obtain the optimal weight parameters and the maximum lag order, improving the model's fitting ability to mixed frequency data. To demonstrate the effectiveness of the new model, a model evaluation system consisting of traditional evaluation metrics and a monotonicity test is established. Taking four hard disk drive failure datasets as research cases, the performance of the proposed model is compared with seven mainstream benchmark models. The results show that the proposed model has excellent applicability and outperforms other competition models in terms of validity, stability, and robustness. Furthermore, it is observed that the reported uncorrectable errors and the command timeout have a greater impact on hard disk drive failure. Finally, the new model is employed to forecast the failure of four hard disk drives. The forecasting results indicate that in the next four time points with a cycle of 21 days beginning in April 2023, the failure of the smaller capacity hard disk drives (0055 and 0086, corresponding to 8TB and 10TB) show a decreasing trend, reaching 67.442% and 89.7683%, respectively. The failure of the other larger capacity hard disk drives (0007 and 0138, corresponding to 12TB and 14TB) has increased, with a growth rate of 17.1016% and 123.7899%.

Catalpol Exerts Antidepressant-Like Effects by Enhancing Anti-oxidation and Neurotrophy and Inhibiting Neuroinflammation via Activation of HO-1.

Catalpol is an iridoid glycoside with rich content, rich nutrition, and numerous biological activities in Rehmanniae Radix contained in classic antidepressant prescriptions in Chinese clinical medicine. Catalpol has been confirmed previously its exact antidepressant-like effect involved heme oxygenase (HO)-1, but its antidepressant molecular targets and mechanism are still unclear. Here, catalpol's antidepressant-like molecular target was diagnosed and confirmed by ZnPP intervention [the antagonist of HO-1, (10 µg/rat), intracerebroventricular] for the first time, and its molecule mechanism network was determined through HO-1 related pathway and molecules in the hippocampus. Results showed that ZnPP significantly abolished catalpol's (10 mg/kg) reversal on depressive-like behaviors of chronic unpredictable mild stress rats, abolished catalpol's up-regulation on the phosphorylation level of extracellular regulated protein kinases (ERK)1/2 and brain-derived neurotrophic factor (BDNF)'s receptor tropomyosin-related kinase B (TrkB), the nuclear expression level of nuclear factor E 2-related factor 2 (Nrf2), the levels of anti-oxidant factors (such as HO-1, SOD, GPX, GST, GSH) and BDNF, and abolished catalpol's down-regulation on the levels of peroxide and neuroinflammation factors [cyclooxygenase-2 (COX-2), induced nitrogen monoxide synthase (iNOS), nitric oxide (NO)]. Thus, HO-1 could serve as an important potential molecular target for catalpol's antidepressant-like process, and the antidepressant-like mechanism of catalpol could at least involve the activation of HO-1 triggering the up-regulation of the ERK1/2/Nrf2/HO-1 pathway-related factors to enhance the anti-oxidant defense, triggering the down-regulation of the COX-2/iNOS/NO pathway-related factors to inhibit neuroinflammation, and triggering the up-regulation of the BDNF/TrkB pathway to enhance neurotrophy.

Moxifloxacin Derivatives with Potential Antibacterial Activity against Methicillin- Resistant Staphylococcus Aureus (MRSA).

BACKGROUND: Methicillin-resistant S. aureus (MRSA) has already tormented humanity and the environment for a long time and is responsible for many difficult-to-treat infections. Unfortunately, there are limited therapeutic options, and MRSA isolates with complete resistance to vancomycin, the first-line drug for the treatment of MRSA infections, have already emerged in recent years. Moxifloxacin retained activity against mutant bacterial strains with various levels of fluoroquinolones resistance and had a lower potential to select for resistant mutants. Isatin is a versatile structure, and its derivatives are potent inhibitors of many enzymes and receptors. The fluoroquinolone- isatin derivatives demonstrated excellent antibacterial activity against both drug-sensitive and drug-resistant organisms. The structure-activity relationship elucidated that incorporation of 1,2,3-triazole moiety into the C-7 position of fluoroquinolone skeleton was favorable to the antibacterial activity. Accordingly, fluoroquinolone derivatives with isatin and 1,2,3-triazole fragments at the side chain on the C-7 position are promising candidates to fight against drug-resistant bacteria. OBJECTIVE: To explore more active moxifloxacin derivatives to fight against MRSA and enrich the structure-activity relationships. METHODS: The synthesized moxifloxacin derivatives 7a-i and 14a-f were evaluated for their antibacterial activity against a panel of MRSA strains by means of standard two-fold serial dilution method. RESULTS: The majority of the synthesized moxifloxacin derivatives were active against most of the tested MRSA strains with MIC values in a range of 1 to 64 µg/mL. The mechanistic investigations revealed that topoisomerase IV was one of the targets for antibacterial activity. CONCLUSION: These derivatives are useful scaffolds for the development of novel topoisomerase IV inhibitors.

Antidepressant mechanism of catalpol: Involvement of the PI3K/Akt/Nrf2/HO-1 signaling pathway in rat hippocampus.

Catalpol is a major compound in Rehmanniae Radix with outstanding medicinal and nutritional values. Our previous studies have demonstrated catalpol's antidepressant effect, but its mechanisms remain unclear. This study aimed to explore the antidepressant mechanisms of catalpol via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1 (HO-1) pathway. Results demonstrated that chronic unpredictable mild stress (CUMS) for 5 consecutive weeks caused significant decreases in the sucrose preference and the horizontal and vertical scores of open-field test, as well as a significant increase in the swimming-immobility time of rats; catalpol administration significantly reversed the abnormality of these indicators. Further real-time fluorescent quantitative polymerase chain reaction and Western blotting results together showed that CUMS significantly downregulated the expression levels of hippocampal genes and proteins, including PI3K, Akt, Nrf2, HO-1, tropomyosin-related kinase B (TrkB), and brain-derived neurotrophic factor; catalpol administration significantly reversed the abnormal expression of these genes and proteins. CUMS also caused a significant decrease in the hippocampal superoxide dismutase, catalase, glutathione peroxidase, glutathione-s transferase, and reduced glutathione levels, as well as a significant increase in thiobarbituric acid reactive substances level in rats; catalpol administration significantly reversed the abnormality of these indicators. Taken together, this study confirmed for the first time that the antidepressant effect of catalpol on CUMS-induced depression involved the upregulation of the PI3K/Akt/Nrf2/HO-1 signaling pathway, thereby improving the hippocampal neurotrophic, neuroprotective, and antioxidant levels. The PI3K/Akt/Nrf2/HO-1 pathway-related molecules may serve as potential new biomarkers and candidate molecular targets for catalpol's antidepressant effects.

Pregnancy complicated with hepatitis B virus infection and preterm birth: a retrospective cohort study.

BACKGROUND: We aimed to investigate whether maternal chronic hepatitis B virus (HBV) infection affects preterm birth (PTB) in pregnant women. METHODS: We retrospectively analyzed HBV-infected and non-infected pregnant women attending antenatal care at Fujian Maternity and Child Health Hospital, Fuzhou, China between January 1, 2016 to December 31, 2018. Participants were divided into HBV infection (n = 1302) and control (n = 12,813) groups. We compared baseline data, pregnancy and perinatal complications, and preterm delivery outcomes between groups. Performed multiple logistics regression analysis to adjust for confounding factors. Finally, we compared early PTB outcome between different HBV DNA level groups. RESULTS: The incidence of preterm birth (gestation less than 37 weeks) was similar between the groups, early preterm birth (gestation less than 34 weeks) were significantly more among the HBV infection group than among the controls (1.6% VS. 0.8%; P = 0.003). After adjusting for confounding factors through logistics regression, HBV infection was found to be an independent early PTB risk factor gestation (adjusted odds ratio 1.770; 95% confidence interval [1.046-2.997]). The incidence of early PTB in < 500 group, 500 ~ 2.0 × 10e5 group and > 2.0 × 10e5 group was not statistically significant (P = 0.417). CONCLUSION: HBV infection is an independent risk factor for early PTB, and the risk did not seem to be influenced by the levels of HBV DNA. Comprehensive programs focusing on pregnant women with HBV infection would reduce the incidence of adverse outcomes.

Ciprofloxacin-1,2,3-triazole-isatin hybrids tethered via amide: Design, synthesis, and in vitro anti-mycobacterial activity evaluation.

The purpose of this study was to prepare various novel amide tethered ciprofloxacin-1,2,3-triazole-isatin hybrids 7a-l, and evaluate their in vitro anti-mycobacterial activity as well as cytotoxicity in VERO cells. The synthesized hybrids showed considerable in vitro activity against both MTB H37Rv and MDR-MTB with MIC of 0.12 to 32 µg/mL, and acceptable cytotoxicity in VERO cells (CC50: 8.0->128.0 µg/mL). In particular, the most active hybrid 7a (MICMTB H37Rv: 0.5 µg/mL and MICMDR-MTB: 0.12 µg/mL) had the activity in the same level with the first-line anti-tubercular agents isoniazid (MIC: 0.12 µg/mL) and rifampicin (MIC: 0.25 µg/mL), and it was 2-fold more active than the parent ciprofloxacin (MIC: 1.0 µg/mL) against MTB H37Rv, and ≥16 folds more potent than ciprofloxacin (MIC: 2.0 µg/mL), isoniazid (MIC: >64 µg/mL) and rifampicin (MIC: >64 µg/mL) against MDR-MTB. Moreover, hybrid 7a (CC50: 16.0 µg/mL) also displayed considerable cytotoxicity towards VERO cells. Thus, hybrid 7a could act as a platform for further investigations.

Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology.

Context: Radix Tripterygium wilfordii Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. Objective: To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower Lonicera japonica Thunb. (Caprifoliaceae) (JYH), Radix Paeonia lactiflora Pall. (Ranunculaceae) (BS), Herba Lysimachia christinae Hance (Primulaceae) (JQC), Radix et Rhizoma Glycyrrhiza uralensis Fisch. (Fabaceae) (GC) and Seed Phaseolus radiatus L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Materials and methods: LGT raw and processed products were orally administered at 60 mg/kg to KM male mice inoculated with S180 tumour cells for 14 consecutive days, and blood, tumour, liver and kidney were taken to observe the detoxifying effects and biological mechanisms. Results: Herbal-processing technology significantly weakened hepatotoxicity and nephrotoxicity evoked by LGT with ED50 of the converted triptolide in each processed-herb product for serum alanine transaminase, aspartate transaminase, creatinine and urea nitrogen of 9.3, 16.6, 2.5 and 4.2 µg/kg, for liver glutathione, glutathione S-transferase, catalase, tumour necrosis factor-α and interleukin-10 of 114.9, 67.8, 134.1, 7.7, 4171.6 µg/kg, and for kidney 21.9, 20.5, 145.0, 529.7, 19.4 µg/kg, respectively. Moreover, herbal-processing technology promoted the accumulation of Nrf2 into the nucleus, and upregulated mRNA expression of Nrf2 and heme oxygenase-1. Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED50 12.2 µg/kg. Discussion and conclusions: Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules.

Sodium carbonate promoted [3 + 2] annulation of α-halohydroxamates and isocyanates.

A new [3 + 2] annulation of readily available α-halohydroxamates and isocyanates has been developed. This protocol allows a rapid assembly of various hydantoins in good to high yields as well as a broad substrate scope and good functional group tolerance.

Detoxication mechanisms of Radix Tripterygium wilfordii via compatibility with Herba Lysimachia christinae in S180-bearing mice by involving Nrf2.

The combined administration between Radix Tripterygium wilfordii Hook F (LGT) and Herba Lysimachia christinae Hance (JQC) belongs to mutual detoxication compatibility of seven emotions in traditional Chinese medicine (TCM) theory. However, until now, the compatibility detoxication mechanisms remain unknown. The present study was undertaken to observe detoxication mechanisms of LGT through compatibility with JQC in tumor-bearing mice by involving NF-E2-related factor 2 (Nrf2)-mediated antioxidant defenses. In addition, influence of compatibility on antitumor activity was also investigated here. Our results demonstrated that compatibility with JQC administration significantly reversed LGT-elevated serum alanine/aspartate transaminase (ALT/AST) levels and alleviated hepatocytes' swelling or degeneration damage, and at the ratio 2/1 (LGT/JQC) produced the strongest detoxication effect. Besides, compatibility with JQC administration reversed not only LGT-elevated hepatic malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) but also the LGT lowered GSH, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and interleukin (IL)-10 levels. Furthermore, compatibility with JQC administration significantly up-regulated protein expression of Nrf2 and mRNA expression of it regulated downstream antioxidant genes such as heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and glutamate cysteine ligase catalytic subunit (GCLC). In addition, compatibility with JQC further decreased LGT-decreased tumor weight and at the ratio 2/1 (LGT/JQC) also exerted the strongest synergistic effect. Collectively, through compatibility with JQC exerted detoxication effect on LGT-induced hepatotoxicity and the mechanisms could be at least partly attributed to up-regulation of Nrf2 and its downstream signals, thereby enhancing antioxidant defenses, and inhibiting lipid peroxidation, oxidative stress, and inflammation. Additionally, at the ratio 2/1 (LGT/JQC) exerted the strongest effects on both detoxication and synergism.

In vivo protective effects of chlorogenic acid against triptolide-induced hepatotoxicity and its mechanism.

CONTEXT: Triptolide (TP) has outstanding biological activities, but it induces toxicities, particular hepatotoxicity, severely limiting its clinical application. Chlorogenic acid (CGA) has prominently medicinal and nutritional values. However, until now, it is not known whether CGA could mitigate TP-induced hepatotoxicity. OBJECTIVE: This study explored the possible protection of CGA against TP-induced hepatotoxicity and its potential mechanisms, for the first time. MATERIAL AND METHODS: KM mice were treated orally with TP at a single dose of 1 mg/kg at 4 h after being treated with CGA (10, 20 and 40 mg/kg) for seven continuous days. Blood samples were collected at 24 h after TP administration for measurement of serum biomarkers, and hepatic tissues for analysis of potential mechanisms. RESULTS: TP treatment-induced acute hepatotoxicity manifested by the significant elevation in serum alanine transaminase (93.9 U/L), aspartate transaminase (185.8 U/L) and hepatic malondialdehyde (0.637 µmol/mg protein), and the remarkable reduction in hepatic glutathione (1.425 µg/mg protein), glutathione S-transferase, glutathione peroxidase, superoxide dismutase and catalase (91.7, 320.7, 360.6 and 140.7 U/mg protein, respectively). In contrast, pretreatment with CGA for 7 days effectively attenuated acute liver injury and oxidative stress caused by TP with each ED50 of 44.4, 57.1, 46.6, 22.2, 40.9, 58.1, 86.4 and 61.0 mg/kg, respectively. Furthermore, pretreatment with CGA promoted the accumulation of Nrf2 into the nucleus, and up-regulated mRNA expression of Nrf2-target downstream genes. DISCUSSION AND CONCLUSIONS: Combined CGA medication may probably reduce the risk of TP poisoning, and in-depth mechanisms can be developed around the signal molecules of Nrf2.

Fe-catalyzed esterification of amides via C-N bond activation.

An efficient Fe-catalyzed esterification of primary, secondary, and tertiary amides with various alcohols for the preparation of esters was performed. The esterification process was accomplished with FeCl3·6H2O, which is a stable, inexpensive, environmentally friendly catalyst with high functional group tolerance.