Mechanism of Cnidii Fructus in the Treatment of Infertility Based on Network Pharmacology and Molecular Docking Analysis Technology.

Infertility is a condition characterized by a low fertility rate, which significantly affects the physical and mental health of women of reproductive age. Typically, the treatment duration is prolonged, and the therapeutic outcomes are often unsatisfactory. Professor Cheng-yao He, a renowned expert in traditional Chinese medicine, commonly uses the herb Cnidii Fructus (SCZ) for the treatment of infertility. However, the exact mechanism remains unclear, and there is limited research available on this topic. The active ingredients of SCZ were obtained from the traditional chinese medicine system pharmacology (TCMSP) database and screened for pharmacokinetics (PK), involving absorption, distribution, metabolism, and excretion (ADME). Target prediction was performed by SwissTargetPrediction database, and infertility-related disease targets were searched in GeneCards, TTD, DrugBank, and OMIM database. The protein-protein interaction (PPI) network was constructed using the STRING database (Version 11.5) and analyzed by Cytoscape software (Version 3.9.1). Additionally, the target genes were subjected to biological enrichment analysis in the Metascape database, including gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and the "Disease-Ingredient-pathway-target" network was constructed using Cytoscape software. With the assistance of AutoDockVina, Ligplot, and PyMOL software, a validation of Molecular docking results and a visualization of the results were performed. This study identified 11 retained active ingredients of SCZ, 447 drug targets, 233 of which were related to infertility, and 5393 disease targets. GO enrichment analysis mainly involved 221 biological processes such as cellular response to chemical stress and gland development. KEGG enrichment analysis mainly involved 68 pathways such as thyroid hormone signaling pathway, estrogen signaling pathway, FOXO signaling pathway, and PI3K/Akt signaling pathway. Molecular docking showed that the core active ingredients of SCZ, including Ammidin, Diosmetin, Xanthoxylin N, and Prangenidin, had strong binding abilities with core targets such as MDM2, MTOR, CCND1, EGFR, and AKT1. This study preliminarily demonstrated that SCZ may act on the PI3K/Akt signaling pathway, exerting its therapeutic effects on infertility by improving energy metabolism disorders and endometrial receptivity, inducing primordial follicle activation, regulating oocyte proliferation, differentiation, and apoptosis, and promoting the release of dominant follicles.

Efficacy of adalimumab combined with Tripterygium wilfordii Hook F in the treatment of patient with rheumatoid arthritis: A multicenter, open-label, randomized-controlled trial.

OBJECTIVES: To evaluate the efficacy and safety of adalimumab (ADA) combined with Tripterygium wilfordii Hook F (TwHF) in the treatment of methotrexate (MTX)-inadequate response patients with rheumatoid arthritis (RA). METHODS: In this multicenter, open-label, randomized controlled clinical trial, 64 RA patients with inadequate response to MTX were 1:1 randomly assigned into treatment or control groups. The treatment group was treated with ADA in combination with TwHF, and the control group was treated with ADA in combination with MTX for 24 weeks. The primary endpoint was the percentage of patients having low disease activity (2.6 ≤ DAS28-ESR < 3.2) and remission rates (DAS28-ESR < 2.6) at week 24. RESULTS: In total, 53 of the 64 patients (82.8%) completed this 24-week clinical trial. By intent-to-treat (ITT) analysis, a comparable outcome was observed between the two groups. The percentage of patients achieving low disease activity in the treatment group and control group were 43.8% and 46.9% (95% CI, 21.28 to 27.48, p = .802). Percentage of patients achieving low disease activity rates were respectively 28.1% and 31.3% in the treatment group and control group (95% CI, 19.18 to 25.58, p = .784). In per-protocol (PP) analysis, the results were consistent with the ITT model. The incidence of adverse events was comparable between the two groups. CONCLUSIONS: There were no significant differences in efficacy and safety between ADA combined with TwHF versus ADA combined with MTX in the treatment of RA. TwHF might be an alternative treatment for RA patients who are intolerant to MTX.

Low-Potential Iodide Oxidation Enables Dual-Atom CoFe─N─C Catalysts for Ultra-Stable and High-Energy-Efficiency Zn-Air Batteries.

The low energy efficiency and limited cycling life of rechargeable Zn-air batteries (ZABs) arising from the sluggish oxygen reduction/evolution reactions (ORR/OERs) severely hinder their commercial deployment. Herein, a zeolitic imidazolate framework (ZIF)-derived strategy associated with subsequent thermal fixing treatment is proposed to fabricate dual-atom CoFe─N─C nanorods (Co1 Fe1 ─N─C NRs) containing atomically dispersed bimetallic Co/Fe sites, which can promote the energy efficiency and cyclability of ZABs simultaneously by introducing the low-potential oxidation redox reactions. Compared to the mono-metallic nanorods, Co1 Fe1 ─N─C NRs exhibit remarkable ORR performance including a positive half-wave potential of 0.933 V versus reversible hydrogen electrode (RHE) in alkaline electrolyte. Surprisingly, after introducing the potassium iodide (KI) additive, the oxidation overpotential of Co1 Fe1 ─N─C NRs to reach 10 mA cm-2 can be significantly reduced by 395 mV compared to the conventional destructive OER. Theoretical calculations show that the markedly decreased overpotential of iodide oxidation can be ascribed to the synergistic effects of neighboring Co─Fe diatomic sites as the unique adsorption sites. Overall, aqueous ZABs assembled with Co1 Fe1 ─N─C NRs and KI as the air-cathode catalyst and electrolyte additive, respectively, can deliver a low charging voltage of 1.76 V and ultralong cycling stability of over 230 h with a high energy efficiency of ≈68%.

Formulating N-Doped Carbon Hollow Nanospheres with Highly Accessible Through-Pores to Isolate Fe Single-Atoms for Efficient Oxygen Reduction.

It is challenging yet promising to design highly accessible N-doped carbon skeletons to fully expose the active sites inside single-atom catalysts. Herein, mesoporous N-doped carbon hollow spheres with regulatable through-pore size can be formulated by a simple sequential synthesis procedure, in which the condensed SiO2 is acted as removable dual-templates to produce both hollow interiors and through-pores, meanwhile, the co-condensed polydopamine shell is served as N-doped carbon precursor. After that, Fe─N─C hollow spheres (HSs) with highly accessible active sites can be obtained after rationally implanting Fe single-atoms. Microstructural analysis and X-ray absorption fine structure analysis reveal that high-density Fe─N4 active sites together with tiny Fe clusters are uniformly distributed on the mesoporous carbon skeleton with abundant through-pores. Benefitted from the highly accessible Fe─N4 active sites arising from the unique through-pore architecture, the Fe─N─C HSs demonstrate excellent oxygen reduction reaction (ORR) performance in alkaline media with a half-wave potential up to 0.90 V versus RHE and remarkable stability, both exceeding the commercial Pt/C. When employing Fe─N─C HSs as the air-cathode catalysts, the assembled Zn-air batteries deliver a high peak power density of 204 mW cm-2 and stable discharging voltage plateau over 140 h.

Self-Sacrificing Template Synthesis of Carbon Nanosheets Assembled Hollow Spheres with Abundant Active Fe-N4 O1 Moieties for Electrocatalytic Oxygen Reduction.

Single-atom Fe-N-C (Fe1 -N-C) materials represent the benchmarked electrocatalysts for oxygen reduction reaction (ORR). However, single Fe atoms in the carbon skeletons cannot be fully utilized due to the mass transfer limitation, severely restricting their intrinsic ORR properties. Herein, a self-sacrificing template strategy is developed to fabricate ultrathin nanosheets assembled Fe1 -N-C hollow microspheres (denoted as Fe1 /N-HCMs) by rational carbonization of Fe3+ chelating polydopamine coated melamine cyanuric acid complex. The shell of Fe1 /N-HCMs is constructed by ultrathin nanosheets with thickness of only 2 nm, which is supposed to be an ideal platform to isolate and fully expose single metal atoms. Benefiting from unique hierarchical hollow architecture with highly open porous structure, 2 nm-thick ultrathin nanosheet subunits and abundant Fe-N4 O1 active sites revealed by X-ray absorption fine structure analysis, the Fe1 /N-HCMs exhibit high ORR performance with a positive half-wave potential of 0.88 V versus the reversible hydrogen electrode and robust stability. When served as air-cathode catalysts with ultralow loading mass of 0.25 mg cm-2 , Fe1 /N-HCMs based Zn-air batteries present a maximum power density of 187 mW cm-2 and discharge specific capacity of 806 mA h gZn -1 in primary Zn-air batteries, all exceeding those of commercial Pt/C.

Isolating Fe Atoms in N-Doped Carbon Hollow Nanorods through a ZIF-Phase-Transition Strategy for Efficient Oxygen Reduction.

Transition metal-nitrogen-carbon (TM-N-C) catalysts have been intensely investigated to tackle the sluggish oxygen reduction reactions (ORRs), but insufficient accessibility of the active sites limits their performance. Here, by using solid ZIF-L nanorods as self-sacrifice templates, a ZIF-phase-transition strategy is developed to fabricate ZIF-8 hollow nanorods with open cavities, which can be subsequently converted to atomically dispersed Fe-N-C hollow nanorods (denoted as Fe1 -N-C HNRs) through rational carbonization and following fixation of iron atoms. The microstructure observation and X-ray absorption fine structure analysis confirm abundant Fe-N4 active sites are evenly distributed in the carbon skeleton. Thanks to the highly accessible Fe-N4 active sites provided by the highly porous and open carbon hollow architecture, the Fe1 -N-C HNRs exhibit superior ORR activity and stability in alkaline and acidic electrolytes with very positive half-wave potentials of 0.91 and 0.8 V versus RHE, respectively, both of which surpass those of commercial Pt/C. Remarkably, the dynamic current density (JK ) of Fe1 -N-C HNRs at 0.85 V versus RHE in alkaline media delivers a record value of 148 mA cm-2 , 21 times higher than that of Pt/C. The assembled Zn-air battery using Fe1 -N-C HNRs as cathode catalyst exhibits a high peak power density of 208 mW cm-2 .

Si nano-cavity enabled surface-enhanced Raman scattering signal amplification.

Surface-enhanced Raman scattering (SERS) detection technique has gained much attention as a powerful analytical tool in recent years. Nevertheless, the attention was mainly focused on the efficient scattering platform by structuring metals themselves, leading to more complex platforms and higher costs. Herein, a new and simple strategy to prepare large-area, low-cost, high-performance SERS substrate is introduced. Ultra-thin semiconductor silicon (Si) film is used as the functional layer for the metallic nano-particles based meta-surface. During the SERS sensing process, the emergence of a Si layer is observed to provide three key contributions: (1) to produce a maximal enhancement factor (EF) ∼470% compared to that of the bare meta-surface, (2) to keep a higher spectral stability for the Raman signal, and (3) to physically interdict the contact between the metal and the molecule. Moreover, the Si film's thickness is down to the scale of an electron's Bohr radius, indicating efficient electronic oscillations for the semiconductor material under electromagnetic excitation. The charge transfer behaviors between the molecules and the Si layer and metal nano-particles can also emerge. These findings could pave new insights on the surface-enhanced spectroscopy and lead to applications for the high-performance, large-area, low-cost SERS sensing process.

Protective effects of total flavonoids in Caragana against hypoxia/reoxygenation-induced injury in human brain microvascular endothelial cells.

This study aimed to explore the protective effect of total flavonoids in Caragana against hypoxia/reoxygenation (H/R)-induced injury in human brain microvascular endothelial cells (BMECs). Human BMECs were selected and assigned into control, H/R, H/R+NMP, H/R+Low dose, H/R+Moderate dose, H/R+High dose groups. MTT and Transwell assays were used to detect cell viability and migration, respectively. Cell adhesion rate and tube formation were also detected. Real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to test HIF-1α, VEGF and Notch1 mRNA and protein expressions. Compared with the H/R group, the cell viability rates in the H/R+NMP, H/R+Moderate dose and H/R+High dose groups were increased. The cell adhesion rates in the H/R+NMP, H/R+Moderate dose and H/R+High dose groups were significantly different from those in the H/R group. As compared to the H/R group, the cell migration abilities in the H/R+NMP, H/R+Moderate dose and H/R+High dose groups were enhanced. Compared with the H/R group, the number and length of tubes of BMECs in the H/R+NMP, H/R+High dose and H/R+Moderate dose groups were increased. HIF-1α, VEGF and Notch1 mRNA and protein expressions were higher in the H/R+Low dose, H/R+Moderate dose and H/R+High dose groups than in the H/R group. These findings revealed that total flavonoids in Caragana can protect BMECs from H/R-induced injury in a dose-dependent manner and it also may promote angiogenesis in BMECs by activating HIF- 1α-VEGF-Notch 1 signaling pathway.

One-process fabrication of metal hierarchical nanostructures with rich nanogaps for highly-sensitive surface-enhanced Raman scattering.

One-process fabrication of highly active and reproducible surface-enhanced Raman scattering (SERS) substrates via ion beam deposition is reported. The fabricated metal-dielectric-metal (MDM) hierarchical nanostructure possesses rich nanogaps and a tunable resonant cavity. Raman scattering signals of analytes are dramatically strengthened due to the strong near-field coupling of localized surface plasmon resonances (LSPRs) and the strong interaction of LSPRs of metal NPs with surface plasmon polaritons (SPPs) on the underlying metal film by crossing over the dielectric spacer. The maximum Raman enhancement for the highest Raman peak at 1650 cm(-1) is 13.5 times greater than that of a single metal nanoparticle (NP) array. Moreover, the SERS activity can be efficiently tailored by varying the size and number of voids between adjacent metal NPs and the thickness of the dielectric spacer. These findings may broaden the scope of SERS applications of MDM hierarchical nanostructures in biomedical and analytical chemistry.

Robust multispectral transparency in continuous metal film structures via multiple near-field plasmon coupling by a finite-difference time-domain method.

We propose a robust multispectral transparent plasmonic structure and calculate its transparency response by using the three-dimensional finite-difference time-domain (FDTD) method. The proposed structure is composed of a continuous ultrathin metal film sandwiched by double two-dimensional (2D) hexagonal non-close-packed metal-dielectric multilayer core-shell nanoparticle arrays. The top and bottom plasmonic arrays in such a structure, respectively, act as the light input and output couplers to carry out the efficient trapping and release of light. Near-perfect multispectral optical transparency in the visible and near-infrared regions is achieved theoretically. The calculated electric field distribution patterns show that the near-perfect multispectral optical transparency mainly originates from the excitation and hybridization of shell and core plasmon modes, strong near-field coupling of dipole plasmon modes between adjacent nanoparticles as well as the excitation of surface plasmon waves of the metal film. The robust transparency bands can be efficiently tuned in a large range by varying the structural parameters and the surrounding dielectric environment. The proposed structure also shows additional merits such as a deep sub-wavelength size and fully retained electrical and mechanical properties of the natural metal. These features might provide promising applications in highly integrated optoelectronic devices including plasmonic filters, nanoscale multiplexers, and non-linear optics.

Fluid-structure interaction analysis of pulsatile flow within a layered and stenotic aorta.

In this paper, the hemodynamic characteristics of blood flow and stress distribution in a layered and stenotic aorta are investigated. By introducing symmetrical and unsymmetrical stenosis, the influence of stenosis morphology and stenotic ratio on the coupled dynamic responses of aorta is clarified. In the analysis, the in-vivo pulsatile waveforms and fully fluid-structure interaction (FSI) between the layered elastic aorta and the blood are considered. The results show that the fluid domain is abnormal in the stenotic aorta, and the whirlpool forms at the obstructed and downstream unobstructed regions. The maximum wall shear stresses appear at the throat of the stenosis. Downstream region appears low and oscillated shear stresses. In addition, along with the increase of the stenotic ratio, the amplitude of the maximum shear stress will be intensively increased and localized, and the sensitivity is also increased. In the aorta with unsymmetrical stenosis, the Von Mises stresses reach the peak value at the side with the surface protuberance, but they are reduced at the side with no protuberance. The sign variation of the layer interface shear stresses near the throat indicates the variation of the shear direction which increases the opportunity of shear damage at the transition plane. Moreover, the shear stress levels at the fluid-solid and intima-media interfaces are higher than that at the media-adventitia interface. The unsymmetrical stenosis causes higher stresses at the side with the surface protuberance than symmetrical one, but lower at the side with no protuberance. These results provide an insight in the influence of the stenosis, as well as its morphology, on the pathogenesis and pathological evolution of some diseases, such as arteriosclerosis and aortic dissection.

Near-unity transparency of a continuous metal film via cooperative effects of double plasmonic arrays.

Metal structures with high optical transparency and conductivity are of great importance for practical applications in optoelectronic devices. Here we investigate the transparency response of a continuous metal film sandwiched by double plasmonic nanoparticle arrays. The upper nanoparticle array shows efficient light trapping of the incident field, acting as a light input coupler, and the lower nanoparticle array shows a light release gate opening at the other side, acting as the light output coupler. The strong near-field light-matter interactions of the nano-scale separated plasmonic nanoparticles, the excitation of surface plasmon waves of the metal film, and their cooperative coupling effects result in broadband scattering cancellation and near-unity transparency (up to 96%) in the optical regime. The transparency response in such a structure can be efficiently modified by varying the gap distance of adjacent nanoparticles, dielectric environments, and the distance between the plasmonic array and the metal film. This motif may provide a new alternative approach to obtain transparent and highly conducting metal structures with potential applications in transparent conductors, plasmonic filters, and highly integrated light input and output components.