Enhancement of the Water Affinity of Histidine by Zinc and Copper Ions.

Histidine (His) is widely involved in the structure and function of biomolecules. Transition-metal ions, such as Zn2+ and Cu2+, widely exist in biological environments, and they are crucial to many life-sustaining physiological processes. Herein, by employing density function calculations, we theoretically show that the water affinity of His can be enhanced by the strong cation-π interaction between His and Zn2+ and Cu2+. Further, the solubility of His is experimentally demonstrated to be greatly enhanced in ZnCl2 and CuCl2 solutions. The existence of cation-π interaction is demonstrated by fluorescence, ultraviolet (UV) spectroscopy and nuclear magnetic resonance (NMR) experiments. These findings are of great importance for the bioavailability of aromatic drugs and provide new insight for understanding the physiological functions of transition metal ions.

Bottom-Up Synthesis of MoS2 /CNTs Hollow Polyhedron with 1T/2H Hybrid Phase for Superior Potassium-Ion Storage.

Enslaved to the large-size K-ions, the construction of suitable anode materials with superior and stable potassium-ion storage properties is a major challenge. 1T phase MoS2 possesses higher conductivity, bigger interlayer distance, and more electrochemically active sites than the 2H phase, which offers intriguing benefits for energy-related applications. In this work, the 1T/2H-phase hybrid MoS2 nanosheets are successfully anchored in the N-doped carbon nanotube hollow polyhedron (1T/2H-MoS2 /NCNHP) by a bottom-up solvothermal method. For the synthesized 1T/2H-MoS2 /NCNHP, the fewer-layer 1T/2H-MoS2 nanosheets are embedded in an N-doped carbon nanotube hollow polyhedron, with an enlarged interlayer spacing of 0.96 nm. When evaluated as anode material for potassium-ion batteries, the 1T/2H-MoS2 /NCNHP hybrid presents outstanding potassium storage performance. It delivers a high-specific capacity of 519.2 mAh g-1 at 50 mA g-1 and maintains 281.2 mAh g-1 at 1 A g-1 over 500 cycles. The good potassium-ion electrochemical performance is attributed to the rational structural design and the synergistic effect of the components. Moreover, the 1T-MoS2 nanosheet has excellent electrical conductivity and its enlarged interlayer spacing reduces the barrier for the embedding and stripping of K ions. Finally, the practical application of the 1T/2H-MoS2 /NCNHP electrode material is also evaluated by assembled K-ion full cells.

Anti-inflammatory effects of Aureusidin in LPS-stimulated RAW264.7 macrophages via suppressing NF-κB and activating ROS- and MAPKs-dependent Nrf2/HO-1 signaling pathways.

Aureusidin, a naturally-occurring flavonoid, is found in various plants of Cyperaceae such as Heleocharis dulcis (Burm. f.) Trin., but its pharmacological effect and active mechanism are rarely reported. This study aimed to investigate the anti-inflammatory effect and action mechanism of Aureusidin in LPS-induced mouse macrophage RAW264.7 cells. The results suggested that lipopolysaccharide (LPS)-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) production were obviously inhibited by Aureusidin. Moreover, Aureusidin also significantly decreased the mRNA expression of various inflammatory factors in LPS-stimulated RAW264.7 cells. Furthermore, mechanistic studies showed that Aureusidin significantly inhibited nuclear transfer of nuclear factor-κB (NF-κB), while increasing the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) as well as expression of Nrf2 target genes such as heme oxygenase (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1), but the addition of the HO-1 inhibitor Sn-protoporphyrin (Snpp) significantly abolished the anti-inflammatory effect of Aureusidin in LPS-stimulated RAW264.7 cells, confirming the view that HO-1 was involved in the anti-inflammatory effect. In addition, Aureusidin increased the levels of reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) phosphorylation in RAW264.7 cells. Antioxidant N-acetylcysteine (NAC) or three MAPK inhibitors blocked the nuclear translocation of Nrf2 and HO-1 expression induced by Aureusidin, indicating that Aureusidin activated the Nrf2/HO-1 signaling pathway through ROS and MAPKs pathways. At the same time, co-treatment with the NAC blocked the phosphorylation of MAPKs. Results from molecular docking indicated that Aureusidin inhibited the NF-κB pathway by covalently binding to NF-κB. Thus, Aureusidin exerted the anti-inflammatory activity through blocking the NF-κB signaling pathways and activating the MAPKs and Nrf2/HO-1 signaling pathways. Based on the above results, Aureusidin may be an attractive therapeutic candidate for the inflammation-related diseases.

CADM + : Confusion-Based Learning Framework With Drift Detection and Adaptation for Real-Time Safety Assessment.

Real-time safety assessment (RTSA) of dynamic systems holds substantial implications across diverse fields, including industrial and electronic applications. However, the complexity and rapid flow nature of data streams, coupled with the expensive label cost and pose significant challenges. To address these issues, a novel confusion-based learning framework, termed confusion-and-detection method plus (CADM + ), is proposed in this article. When drift occurs, the model is updated with uncertain samples, which may cause confusion between existing and new concepts, resulting in performance differences. The cosine similarity is used to measure the degree of such conceptual confusion in the model. Furthermore, the change of standard deviation within a fixed-size cosine similarity window is introduced as an indicator for drift detection. Theoretical demonstrations show the asymptotic increase of cosine similarity. In addition, the approximate independence of the change in standard deviation with the number of trained samples is indicated. Finally, the extreme value theory (EVT) is applied to determine the threshold of judging drifts. Several experiments are conducted to verify its effectiveness. Experimental results prove that the proposed framework is more suitable for RTSA tasks compared with state-of-the-art algorithms. The source code is available at https://github.com/THUFDD/CADM-plus.

Aureusidin ameliorates 6-OHDA-induced neurotoxicity via activating Nrf2/HO-1 signaling pathway and preventing mitochondria-dependent apoptosis pathway in SH-SY5Y cells and Caenorhabditis elegans.

Movement disorder Parkinson's disease (PD) is the second most common neurodegenerative disease in the world after Alzheimer's disease, which severely affects the quality of patients' lives and imposes an increasingly heavy socioeconomic burden. Aureusidin is a kind of natural flavonoid compound with anti-inflammatory and anti-oxidant activities, while its pharmacological action and mechanism are rarely reported in PD. This study aimed to explore the neuroprotective effects and potential mechanisms of Aureusidin in PD. The present study demonstrated that Aureusidin protected SH-SY5Y cells from cell damage induced by 6-hydroxydopamine (6-OHDA) via inhibiting the mitochondria-dependent apoptosis and activating the Nrf2/HO-1 antioxidant signaling pathway. Additionally, Aureusidin diminished dopaminergic (DA) neuron degeneration induced by 6-OHDA and reduced the aggregation toxicity of α-synuclein (α-Syn) in Caenorhabditis elegans (C. elegans.) In conclusion, Aureusidin showed a neuroprotective effect in the 6-OHDA-induced PD model via activating Nrf2/HO-1 signaling pathway and prevented mitochondria-dependent apoptosis pathway, and these findings suggested that Aureusidin may be an effective drug for the treatment of PD.

The effectiveness of postoperative exercise based on gait analysis compared with conventional exercise in patients with lumbar spinal stenosis: A randomized clinical trial.

BACKGROUND: Despite being used as a program of postoperative rehabilitation, few randomized controlled trials have compared the effectiveness of postoperative exercise based on gait analysis in patients with lumbar spinal stenosis (LSS). OBJECTIVE: To investigate the effectiveness of postoperative exercise based on gait analysis in patients with LSS and to compare it with the effectiveness of conventional exercise. METHODS: This was a double-blind, randomized clinical trial. Sixty-eight participants with LSS were randomly assigned to one of two groups. After receiving a standardized surgical procedure, the observation group received exercises based on 3-D gait analysis, and the control group received empirical physiotherapy containing 4 basic interventions. Both groups took a one-hour session twice daily for 2 weeks. The Oswestry Disability Index (ODI) scale and the Visual Analog Scale (VAS) were measured before and 2 weeks and 6 months after intervention. The gait indicators were measured before and 6 months after intervention. RESULTS: At baseline, there were no significant differences in the ODI, VAS or absolute symmetry index (ASI) of the gait variables between the observation group and the control group. However, at 6 months, pain intensity, walking, standing, social life and summary scores of ODI and VAS of the leg demonstrated significant differences (p< 0.05, respectively) between groups, and the observation group had greater reductions in ASI of stride length, hip flexion, knee flexion and ankle dorsiflexion compared with the control group (p< 0.05, respectively). CONCLUSIONS: The postoperative rehabilitation scheme based on gait analysis resulted in significant short- to medium-term improvements in pain intensity, walking, standing, social life and the summary score of ODI, VAS of leg and symmetry of stride length, hip flexion, knee flexion and ankle dorsiflexion compared with empirical exercise in patients with LSS.

Amphetamine-type stimulants use and socio-economic factors associated with hepatitis C antibody positivity among border drug users in South of China.

Background: Amphetamine-type stimulants (ATS) use has become popular in China. This study explored ATS use status and related risk factors of hepatitis C virus (HCV) infection among ATS users in Jinghong City, Xishuangbanna Prefecture, Yunnan Province, China. Methods: A cross-sectional study was conducted by questionnaires from January to July 2021 in border area in Yunnan. Respondent driving sampling and consecutive sampling was carried out among border drug users, and blood samples were tested for HCV antibodies. HCV infection and related risk factors among ATS users were measured. Descriptive, univariate and multivariate analysis were conducted separately by Software SPSS 26.0. Results: The ATS users accounted for 85.82% (345/402) among drug users, while anti-HCV antibody prevalence was 6.38% (22/345) among ATS users. The combined use of other types of drugs (OR = 7.29, 95%CI: 1.982-26.81, P = 0.003), injection drug use (OR = 6.823, 95%CI: 1.898-24.525, P = 0.003), average monthly income (OR = 4.825, 95%CI: 1.325-17.566, P = 0.017) might increase the risk of HCV infection among ATS users. ATS users with high school or above had higher HCV infection rates than those with primary school or below (OR = 5.718, 95%CI: 1.172-27.908, P = 0.031). Conclusion: Taken together, among drug users using ATS in Jinghong City, Xishuangbanna Autonomous Prefecture, Yunnan Province, combined use of multiple drugs and intravenous drug use was the high risk factor for HCV infection. Therefore, corresponding education and intervention measures should be taken.

Development and validation of a simple and sensitive HPLC method for the determination of related substances in regorafenib tablets.

Regorafenib as an oral multi-kinase inhibitor has displayed a promising future in the anticancer drug market. However, there are no articles reporting the method for the determination of related substances in regorafenib tablets. A quality standard was first included in the Ph. Eur. 10.4 until April 2021 but could not detect seven known impurities A, C, D, E, FP-A, FP-B, and FP-C simultaneously. In this paper, a simple and sensitive HPLC method was established for the determination of related substances in regorafenib tablets. The determination was performed on a Polar-RP column with dual wavelength detection set at 230 nm and 260 nm. This method was validated according to the ICH guidelines. Furthermore, the possible sources of impurities were analyzed and forced degradation tests were performed, which provided guidance for formulation development and storage conditions. The established method is simple, sensitive and accurate for the determination of related substances in regorafenib tablets. A specified and sensitive HPLC method for the determination of related substances in regorafenib tablets.

Meriolin1 induces cell cycle arrest, apoptosis, autophagy and targeting the Akt/MAPKs pathways in human neuroblastoma SH-SY5Y cells.

OBJECTIVES: Meriolins, a kind of chemical hybrid between meridianins and variolins, have lately been determined as kinase inhibitors and reportedly have antitumour activity. However, there is currently no in-depth study for the action mechanism. This study aimed to elucidate the potentially antitumour action mechanism of Meriolin1 on human neuroblastoma (SH-SY5Y) cells. METHODS: Firstly, cell viability was detected by MTT assay. Secondly, cell cycle, cell apoptosis, cell autophagy, reactive oxygen species and mitochondrial membrane potential (ΔΨm) were measured by flow cytometry. Then, cell cycle-associated proteins, Bcl-2 family proteins, Akt/MAPK proteins and autophagy-associated proteins expressions were evaluated by Western blot. Bcl-2 and Bax mRNA expressions were also evaluated by qRT-PCR. Furthermore, cell adhesion assay and Hoechst 33258 fluorescent staining were carried out to detect the effect of Meriolin1 on cell adhesion and morphology. Finally, to gain further insight into mechanism of action of Meriolin1 to CDK protein, the molecular docking study was performed by using the CDOCKER module of DS software. KEY FINDINGS: Meriolin1 could exert the antitumour activity on SH-SY5Y cells by inducing cell cycle arrest, cell autophagy, the mitochondrion-dependent cell apoptosis and targeting the Akt/MAPKs signalling pathway. CONCLUSIONS: Meriolin1 might be a promising therapeutic candidate for neuroblastoma.

The room temperature electron reduction for the preparation of silver nanoparticles on cotton with high antimicrobial activity.

Functionalization of cotton by fabricating Ag nanoparticles (NPs) on cotton surface has aroused great interest for its promising applications for chemical, electronic, photonic and many other devices. Herein, a simple and rapid room temperature electron reduction, which uses argon glow discharge as the electron source, was employed to fabricate Ag NPs on cotton without using any chemical reducing agent. The color of Ag NP loaded cotton changes from light yellow to black upon the increasing Ag loading amount, while the average size of Ag NPs on the cotton barely changes from 4.4 to 6.3nm. This indicates the color change is due to the size of Ag aggregates rather than the size of single Ag NP, as demonstrated by scanning electron microscope (SEM) and UV-vis absorption analyses. The functionalized fabric exhibits high antimicrobial activity against both Gram-negative bacterium E. coli and Gram-positive bacterium B. subtilis.

Three-dimensional printed acrylonitrile butadiene styrene framework coated with Cu-BTC metal-organic frameworks for the removal of methylene blue.

Three-dimensional (3D) printing was applied for the fabrication of acrylonitrile butadiene styrene (ABS) framework. Functionalization of the ABS framework was then performed by coating of porous Cu-BTC (BTC = benzene tricarboxylic acid) metal-organic frameworks on it using a step-by-step in-situ growth. The size of the Cu-BTC particles on ABS was ranged from 200 nm to 900 nm. The Cu-BTC/ABS framework can take up most of the space of the tubular reactor that makes the adsorption effective with no need of stirring. Methylene blue (MB) can be readily removed from aqueous solution by this Cu-BTC/ABS framework. The MB removal efficiency for solutions with concentrations of 10 and 5 mg/L was 93.3% and 98.3%, respectively, within 10 min. After MB adsorption, the Cu-BTC/ABS composite can easily be recovered without the need for centrifugation or filtration and the composite is reusable. In addition the ABS framework can be recovered for subsequent reuse. A significant advantage of 3D-printed frameworks is that different frameworks can be easily fabricated to meet the needs of different applications. This is a promising strategy to synthesize new frameworks using MOFs and polymers to develop materials for applications beyond adsorption.