Arbitrary fabrication of complex lithium niobate three-dimensional microstructures for second harmonic generation enhancement.

Lithium niobate (LN) crystal plays important roles in future integrated photonics, but it is still a great challenge to efficiently fabricate three-dimensional micro-/nanostructures on it. Here, a femtosecond laser direct writing-assisted liquid back-etching technology (FsLDW-LBE) is proposed to achieve the three-dimensional (3D) microfabrication of lithium niobate (LN) with high surface quality (Ra = 0.422 nm). Various 3D structures, such as snowflakes, graphic arrays, criss-cross arrays, and helix arrays, have been successfully fabricated on the surface of LN crystals. As an example, a microcone array was fabricated on LN crystals, which showed a strong second harmonic signal enhancement with up to 12 times bigger than the flat lithium niobate. The results indicate that the method provides a new approach for the microfabrication of lithium niobate crystals for nonlinear optics.

Effectiveness and safety of community-led assisted partner service among HIV-diagnosed men who have sex with men: a multicentre, randomized controlled trial in China.

Background: No randomized controlled trials have involved established HIV-diagnosed men who have sex with men (MSM) diagnosed for more than 6 months into the assisted partner service (aPS). We compared voluntary aPS involving community-based organizations (CBOs) and HIV self-testing (aPSST) with regular partner service (rPS) in HIV-diagnosed MSM irrespective of diagnosis time. Methods: In this unblinded, multicentre trial, we enrolled HIV-diagnosed MSM irrespective of diagnosis time in three cities in northern China. Index patients were randomly assigned to aPSST or rPS. Index patients in the aPSST group were additionally provided a comprehensive intervention package including HIV self-testing and CBO-based aPS compared with rPS group. The primary outcome was the number of index patients whose any sexual partner tested for HIV during the 6-month study. Completion of HIV testing was defined as sexual partners taking a clinic-based HIV test or HIV self-testing. Safety was assessed preliminary at the end of the 6-month follow-up. This study has been registered at chictr.org.cn (ChiCTR2000038784). Findings: From March to December 2021, 325 of HIV-diagnosed MSM were enrolled (90⋅2% were established HIV-diagnosed MSM) and randomly assigned to receive aPSST (n = 167) or rPS (n = 158). At 6 months, 110 (65⋅9%) index patients in the aPSST group had at least one sexual partner tested for HIV compared with 50 (31⋅6%) in the rPS group (hazard ratio 2⋅86; 95% confidence interval 2⋅03-4⋅03; p < 0⋅001). No significant difference was observed in effects of aPSST on HIV testing promotion between established and newly HIV-diagnosed MSM. Self-reported harms were infrequently observed in both groups (approximately 2⋅0%). Interpretation: Among HIV-diagnosed MSM regardless of diagnosis time, voluntary aPS involving CBOs and HIV self-testing was effective and safe for promoting partner HIV testing. Funding: This work was supported by the Mega-Projects of National Science Research, the National Natural Science Foundation of China and the Liaoning Revitalization Talents Program, China.

Chuanxiong improves angiogenesis via the PI3K/AKT/Ras/MAPK pathway based on network pharmacology and DESI-MSI metabolomics.

Introduction: Chuanxiong, a traditional Chinese medicine, has been proved to treat a variety of cardiovascular and cerebrovascular diseases by promoting angiogenesis. However, the mechanisms of Chuanxiong's pro-angiogenesis is currently unknown. This study aimed to uncover the effect and mechanisms of Chuanxiong promoting angiogenesis in vivo and in vitro. Methods: First, potential targets were predicted by network pharmacology analysis, and PPI network was established and the pathways were enriched. Then, the chorioallantoic membrane test on quails was applied to assess the proangiogenic effects in vivo. As well, to evaluate the effects in vitro, real-time PCR, western blot analysis, the scratch test, and the tube formation experiment were used. Subsequently, the major metabolic pathways were analyzed using non-targeted metabolomics. Results: As a result of network pharmacological analysis, 51 collective targets of Chuanxiong and angiogenesis were identified, which are mainly associated with PI3K/AKT/Ras/MAPK pathway. And the biological verification results showed that Chuanxiong could increase the vessel numbers and vessel area in qCAM models. Meanwhile, Chuanxiong contributed to HUVEC proliferation, tube formation, migration, by encouraging scratch healing rates and boosting tube branch points. In addition, the levels of VEGFR2, MAPK and PI3K were elevated compared to the control group. The western blot analysis also confirmed Chuanxiong could promote an increase in AKT, FOXO1 and Ras. Furtheremore, metabolomic results showed that the proangiogenic effect of Chuanxiong is associated with glycine, serine and threonine metabolism. Discussion: In conclusion, this study clarified that Chuanxiong could promote angiogenesis in vivo and in vitro via regulating PI3K/AKT/Ras/MAPK pathway.

Wafer-scale high aspect-ratio sapphire periodic nanostructures fabricated by self-modulated femtosecond laser hybrid technology.

Sapphire nanostructures with a high aspect-ratio have broad applications in photoelectronic devices, which are difficult to be fabricated due to the properties of high transparency and hardness, remarkable thermal and chemical stability. Although the phenomenon of laser-induced periodic surface structures (LIPSS) provides an extraordinary idea for surface nanotexturing, it suffers from the limitation of the small depth of the nanostructures. Here, a high-efficiency self-modulated femtosecond laser hybrid technology was proposed to fabricate nanostructures with high aspect-ratios on the sapphire surface, which was combined backside laser modification and subsequent wet etching. Due to the refractive index mismatch, the focal length of the laser could be elongated when focused inside sapphire. Thus, periodic nanostructures with high-quality aspect ratios of more than 55 were prepared on the sapphire surface by using this hybrid fabrication method. As a proof-of-concept, wafer-scale (∼2 inches) periodic nanostripes with a high aspect-ratio were realized on a sapphire surface, which possesses unique diffractive properties compared to typical shallow gratings. The results indicate that the self-modulated femtosecond laser hybrid technology is an efficient and versatile technique for producing high aspect-ratio nanostructures on hard and transparent materials, which would propel the potential applications in optics and surface engineering, sensing, etc.

Integration of Multifocal Microlens Array on Silicon Microcantilever via Femtosecond-Laser-Assisted Etching Technology.

Micro-opto-electromechanical systems (MOEMSs) are a new class of integrated and miniaturized optical systems that have significant applications in modern optics. However, the integration of micro-optical elements with complex morphologies on existing micro-electromechanical systems is difficult. Herein, we propose a femtosecond-laser-assisted dry etching technology to realize the fabrication of silicon microlenses. The size of the microlens can be controlled by the femtosecond laser pulse energy and the number of pulses. To verify the applicability of this method, multifocal microlens arrays (focal lengths of 7-9 µm) were integrated into a silicon microcantilever using this method. The proposed technology would broaden the application scope of MOEMSs in three-dimensional imaging systems.

Smart Diffraction Gratings Based on the Shape Memory Effect.

The shape memory effect is the capability of a structure or a material that can be deformed into a certain temporary shape under external stimulus, and the shape will be fixed without the stimulus. The recovery process can be triggered by the same stimulus. The intelligent tunable device based on the shape memory effect has a wide range of applications in many fields. In the optical field, smart diffraction gratings can accomplish in situ optical diffractions according to requirements, meeting the high demand in the next generation of smart optical systems. However, it is essential to construct high-precision grating structures based on shape memory materials. Here, a smart diffraction grating based on UV-curable shape memory polymers (SMPs) via two-beam interference is reported, with nano-scale precision, excellent deformability and recovery ability, and adjustable spectroscopic performance. More importantly, based on the shape memory effect, grating structures that surpass the precision of the fabrication system can be obtained. The smart grating exhibits rapid deformation and recovery upon heating and long-term storage capability, which facilitates them to be applied in optics, electronics, and integrated sensing.

Rapid Fabrication of Smooth Micro-Optical Components on Glass by Etching-Assisted Femtosecond Laser Modification.

Femtosecond laser (fs-laser) is unfavorable in applications for the fabrication of micro-optical devices on hard materials owing to the problems of low fabrication efficiency and high surface roughness. Herein, a hybrid method combining fs-laser scanning, subsequent etching, and annealing was proposed to realize micro-optical devices with low roughness on glass. Compared to traditional laser ablation, the fabrication efficiency in this work was improved by one order of magnitude, and the surface roughness was decreased to 15 nm. Using this method, aspherical convex microlenses and spherical concave microlenses that possess excellent focusing and imaging properties are realized on photosensitive glass. The diameter and height of the microlenses were controlled by adjusting the fabrication parameters. These results indicate that the fs-laser-based hybrid method will open new opportunities for fabricating micro-optical components on hard materials.

Luteolin relieves lung cancer-induced bone pain by inhibiting NLRP3 inflammasomes and glial activation in the spinal dorsal horn in mice.

BACKGROUND: Bone cancer pain (BCP) is one of the most severe complications in cancer patients. However, the pharmacological therapeutic approaches are limited. Luteolin, a major component of flavones, is widely distributed in plants and plays a critical role in the antinociceptive effects, but whether luteolin could alleviate cancer pain and its underlying mechanisms are not known. HYPOTHESIS/PURPOSE: This study investigated the molecular mechanisms by which luteolin reduced BCP. METHODS: Behavioral, pharmacological, immunohistochemical, and biochemical approaches were used to investigate the effect of luteolin on BCP. RESULTS: Luteolin treatment ameliorated Lewis lung cancer (LLC)-induced bone pain in mice in a dose-dependent manner. Luteolin treatment could inhibit the activation of neurons, glial cells, and NOD-like receptor protein 3 (NLRP3) inflammasomes in the dorsal spinal cord in the BCP mouse model. Furthermore, phosphorylated p-38 mitogen-activated protein kinase (MAPK) in the spinal dorsal horn (SDH) was suppressed by luteolin treatment that could influence the analgesic and glial inhibition effects of luteolin. CONCLUSION: Our results demonstrated that luteolin inhibited neuroinflammation by obstructing glial cell and NLRP3 inflammasome activation via modulating p38 MAPK activity in SDH, ultimately improving LLC-induced BCP.

Immunometabolism at the service of traditional Chinese medicine.

To enhance therapeutic efficacy and reduce adverse effects, ancient practitioners of traditional Chinese medicine (TCM) prescribe combinations of plant species/animal species and minerals designated "TCM formulae" developed based on TCM theory and clinical experience. TCM formulae have been shown to exert curative effects on complex diseases via immune regulation but the underlying mechanisms remain unknown at present. Considerable progress in the field of immunometabolism, referring to alterations in the intracellular metabolism of immune cells that regulate their function, has been made over the past decade. The core context of immunometabolism is regulation of the allocation of metabolic resources supporting host defense and survival, which provides a critical additional dimension and emerging insights into how the immune system and metabolism influence each other during disease progression. This review summarizes research findings on the significant association between the immune function and metabolic remodeling in health and disease as well as the therapeutic modulatory effects of TCM formulae on immunometabolism. Progressive elucidation of the immunometabolic mechanisms involved during the course of TCM treatment continues to aid in the identification of novel potential targets against pathogenicity. In this report, we have provided a comprehensive overview of the benefits of TCM based on regulation of immunometabolism that are potentially applicable for the treatment of modern diseases.

Regular Aerobic Exercise Attenuates Pain and Anxiety in Mice by Restoring Serotonin-Modulated Synaptic Plasticity in the Anterior Cingulate Cortex.

PURPOSE: Clinical studies found that regular aerobic exercise has analgesic and antianxiety effects; however, the underlying neural mechanisms remain unclear. Multiple studies have suggested that regular aerobic exercise may exert brain-protective effects by promoting the release of serotonin, which may be a pain modulator. Anterior cingulate cortex (ACC) is a key brain area for pain information processing, receiving dense serotonergic innervation. As a result, we hypothesized that exercise may increase the release of serotonin in the ACC, thus improving pain and anxiety behaviors. METHODS: Integrative methods were used, including behavioral, electrophysiological, pharmacological, biochemical, and genetic approaches, to explore the effects of regular aerobic exercise and the underlying neural mechanisms. RESULTS: Regular aerobic exercise in the form of voluntary wheel running for 30 min daily for 15 d showed significant effectiveness in relieving pain and concomitant anxiety in complete Freund's adjuvant-induced chronic inflammation pain models. c-Fos staining and multielectrode array recordings revealed alterations in neuronal activities and synaptic plasticity in the ACC. Moreover, systemic pharmacological treatment with 4-chloro-dl-phenylalanine (PCPA) to deplete endogenous serotonin and local delivery of serotonin to the ACC revealed that exercise-related serotonin release in the ACC bidirectionally modulates pain sensitization and anxiety behaviors by modulating synaptic plasticity in the ACC. Furthermore, we found that 5-HT1A and 5-HT7 receptors mediated the serotonin modulation effects under conditions of regular aerobic exercise through local infusion of a selective antagonist and shRNA in the ACC. CONCLUSIONS: Our results reveal that regular aerobic exercise can increase serotonin release and modulate synaptic plasticity in the ACC, ultimately improving pain and concomitant anxiety behaviors through the functions of the 5-HT1A and 5-HT7 receptors.

Periodic Microstructures Fabricated by Laser Interference with Subsequent Etching.

Periodic nanostructures have wide applications in micro-optics, bionics, and optoelectronics. Here, a laser interference with subsequent etching technology is proposed to fabricate uniform periodic nanostructures with controllable morphologies and smooth surfaces on hard materials. One-dimensional microgratings with controllable periods (1, 2, and 3 µm) and heights, from dozens to hundreds of nanometers, and high surface smoothness are realized on GaAs by the method. The surface roughness of the periodic microstructures is significantly reduced from 120 nm to 40 nm with a subsequent inductively coupled plasma (ICP) etching. By using laser interference with angle-multiplexed exposures, two-dimensional square- and hexagonal-patterned microstructures are realized on the surface of GaAs. Compared with samples without etching, the diffraction efficiency can be significantly enhanced for samples with dry etching, due to the improvement of surface quality.

Functional and structural properties of spirulina phycocyanin modified by ultra-high-pressure composite glycation.

Phycocyanin (PC), a plant-based protein with interesting biological activity, is rarely directly applied in the food industry because it has structural and functional limitations. This study combined ultra-high-pressure (UHP) treatment with glycation to improve PC functionality and explored resulting structural changes using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, scanning electron microscopy, Fourier-transform infrared spectroscopy, circular dichroism, and UV-visible spectroscopy. The UHP treatment obviously improved the speed and degree of glycation and the composite-modified PC (CM-PC) showed high solubility and good emulsifying and foaming performance. Scanning electron microscopy images showed the CM-PC surface was loose and fluffy. Gel electrophoresis, Fourier-transform infrared spectroscopy, and circular dichroism results demonstrated that the content of α-helix decreased from 78.1% in PC to 26.6% in CM-PC, and hydroxyl groups were introduced. UV-visible spectroscopy showed that the mechanism of composite modification involved stretching of the PC and promotion of binding with sugars.

Crosstalk between apoptosis and autophagy in prostate epithelial cells under androgen deprivation.

The present study investigated the molecular mechanism of apoptosis and autophagy in prostate epithelial cells under androgen deprivation (AD). BPH-1 cells were divided into four groups as follows: Control (Cont), AD, autophagy inhibition (AI) and AD + AI groups. Cells in the four groups were treated accordingly, and the level of apoptosis was subsequently measured via flow cytometry. The expression of the microtubule-associated proteins 1A/1B light chain 3 (LC3), caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1) and Beclin-1 proteins of BPH-1 cells was detected at different time points following culture in androgen-deprived medium. Western blotting revealed that the basal levels of the LC3-II protein were detected at 0 h. At 4 h, LC3-II was significantly increased compared with 0 h (P<0.05). Beginning at 20 h, the expression level of the LC3-II protein decreased significantly (P<0.05). Western blotting revealed that beginning at 24 h, the expression level of the PARP-1 protein decreased significantly (P<0.001) and the cleavage fragments of the PARP-1 protein appeared. These results further imply that autophagy serves a cell protective function by mutual inhibition with apoptosis in BPH-1 cells in the removal of androgen conditions. Furthermore, the fragments of the cleaved Beclin-1 protein appeared as 35 and 37 kDa bands. Flow cytometry analysis demonstrated that the rate of cell apoptosis in the AD, AI and AD + AI groups was significantly increased compared with the Cont group (P<0.01). Compared with the AD or the AI groups individually, the rate of cell apoptosis in the AD + AI group was significantly increased (P<0.001). These findings suggest that in the early stage of AD, autophagy has a compensatory function in the cell, whereas in the whole process, autophagy and apoptosis share a mutual antagonism. The Beclin-1-C protein fragment contributed positive feedback to the process of apoptosis, which may be a potential mechanism of AD therapy. Therefore, AD and AI exhibit a synergistic effect to further improve the level of apoptosis.

Fast Diffusion of O2 on Nitrogen-Doped Graphene to Enhance Oxygen Reduction and Its Application for High-Rate Zn-Air Batteries.

N-doped graphene (NDG) was investigated for oxygen reduction reaction (ORR) and used as air-electrode catalyst for Zn-air batteries. Electrochemical results revealed a slightly lower kinetic activity but a much larger rate capability for the NDG than commercial 20% Pt/C catalyst. The maximum power density for a Zn-air cell with NDG air cathode reached up to 218 mW cm-2, which is nearly 1.5 times that of its counterpart with the Pt/C (155 mW cm-2). The equivalent diffusion coefficient (DE) of oxygen from electrolyte solution to the reactive sites of NDG was evaluated as about 1.5 times the liquid-phase diffusion coefficient (DL) of oxygen within bulk electrolyte solution. Combined with experiments and ab initio calculations, this seems counterintuitive reverse ORR of NDG versus Pt/C can be rationalized by a spontaneous adsorption and fast solid-state diffusion of O2 on ultralarge graphene surface of NDG to enhance effective ORR on N-doped-catalytic-centers and to achieve high-rate performance for Zn-air batteries.

Clinical efficacy of digital flexible reteroscope and modular flexible ureteroscope combined with holmium laser lithotripsy for subrenal calyx calculus / 中国内镜杂志

Objective To evaluate the efficacy of flexible ureteroscopy combined with holmium laser lithotripsy for the treatment of subrenal calyx calculus, and comparing with digital flexible ureteroscope and modular flexible ureteroscope with holmium lithotripsy for the difference of the efficacy of the treatment of subrenal calyx calculus. Methods Review of the clinical data of 93 patients with subrenal calyx calculus, of which 48 cases were treated with digital flexible ureteroscope (digital flexible ureteroscope group, DFU group), 45 cases with modular flexible ureteroscope treatment (modular flexible ureteroscope group, MFU group), lithotripsy effect and complications were compared between the two groups. Results The mean operation time, one-session stone-free rate were significantly different between the two groups (P < 0.05). No significant differences in hospital stay, the success rate of looking for calculus, complication and hospitalization expense (P > 0.05). Conclusion With digital flexible ureteroscope and modular flexible ureteroscope treatment of subrenal calyx calculus all are safe and effective. The use of DFU than the use of MFU in the treatment of subrenal calyx calculus operation time is shorter, stone-free rateis higher, the effect is better. There is little difference between their hospitalization expenses, but the use of MFU can reduce the cost of the department.

Clinical efficacy of digital flexible reteroscope and modular flexible ureteroscope combined with holmium laser lithotripsy for subrenal calyx calculus / 中国内镜杂志

Objective To evaluate the efficacy of flexible ureteroscopy combined with holmium laser lithotripsy for the treatment of subrenal calyx calculus, and comparing with digital flexible ureteroscope and modular flexible ureteroscope with holmium lithotripsy for the difference of the efficacy of the treatment of subrenal calyx calculus. Methods Review of the clinical data of 93 patients with subrenal calyx calculus, of which 48 cases were treated with digital flexible ureteroscope (digital flexible ureteroscope group, DFU group), 45 cases with modular flexible ureteroscope treatment (modular flexible ureteroscope group, MFU group), lithotripsy effect and complications were compared between the two groups. Results The mean operation time, one-session stone-free rate were significantly different between the two groups (P < 0.05). No significant differences in hospital stay, the success rate of looking for calculus, complication and hospitalization expense (P > 0.05). Conclusion With digital flexible ureteroscope and modular flexible ureteroscope treatment of subrenal calyx calculus all are safe and effective. The use of DFU than the use of MFU in the treatment of subrenal calyx calculus operation time is shorter, stone-free rateis higher, the effect is better. There is little difference between their hospitalization expenses, but the use of MFU can reduce the cost of the department.

Cascading Boost Effect on the Capacity of Nitrogen-Doped Graphene Sheets for Li- and Na-Ion Batteries.

Specific capacity and cyclic performance are critically important for the electrode materials of rechargeable batteries. Herein, a capacity boost effect of Li- and Na-ion batteries was presented and clarified by nitrogen-doped graphene sheets. The reversible capacities progressively increased from 637.4 to 1050.4 mAh g-1 (164.8% increase) in Li-ion cell tests from 20 to 185 cycles, and from 187.3 to 247.5 mAh g-1 (132.1% increase) in Na-ion cell tests from 50 to 500 cycles. The mechanism of the capacity boost is proposed as an electrochemical induced cascading evolution of graphitic N to pyridinic and/or pyrrolic N, during which only these graphitic N adjacent pyridinic or pyrrolic structures can be taken precedence. The original and new generated pyridinic and pyrrolic N have strengthened binding energies to Li/Na atoms, thus increased the Li/Na coverage and delivered a progressive capacity boost with cycles until the entire favorable graphitic N transform into pyridinic and pyrrolic N.

Eriodictyol attenuates cisplatin-induced kidney injury by inhibiting oxidative stress and inflammation.

Eriodictyol, a flavonoid present in citrus fruits, has been reported to have antioxidant and anti-inflammatory effects. In this study, the protective effects of eriodictyol on cisplatin (CP)-induced kidney injury were detected. CP-induced kidney injury model was established by administration of CP (20mg/kg). The results showed that treatment of eriodictyol inhibited the production of blood urea nitrogen (BUN), creatinine, MDA, TBARS, reactive oxygen species (ROS), as well as the production of TNF-α, and IL-1ß in kidney tissues induced by CP. Eriodictyol also up-regulated the activities of SOD, CAT, and GSH-PX decreased by CP. Furthermore, eriodictyol was found to up-regulate the expression of Nrf2/HO-1 and inhibited CP-induced NF-κB activation in kidney tissues. In conclusion, eriodictyol protected against CP-induced kidney injury through activating Nrf2 and inhibiting NF-κB activation.

γ-Fe2O3 Nanocrystalline Microspheres with Hybrid Behavior of Battery-Supercapacitor for Superior Lithium Storage.

Maghemite (γ-Fe2O3) nanocrystalline microspheres (MNMs) self-assembled with 52 nm nanocrystals bridged with FeOOH around grain boundaries were formed by solvothermal reaction and thermal oxidation. The unique architecture endows the MNMs with the lithium storage behavior of a hybrid battery-supercapacitor electrode: initial charge capacity of 1060 mAh g(-1) at the 100 mA g(-1) rate, stable cyclic capacity of 1077.9 mAh g(-1) at the same rate after 140 cycles, and rate capability of 538.8 mAh g(-1) at 2400 mA g(-1). This outstanding performance was attributed to the nanocrystal superiority, which shortens the Li(+) diffusion paths. The mechanism of this hybrid anode material was investigated with experimental measurements and structural analysis. The results indicate that at the first discharge, the MNM nanocrystal microsphere, whose structure can buffer the volume change that occurs during lithiation/delithiation, goes through four stages: Li(+) insertion in cation vacancies, spinel-to-rocksalt transformation, Li(+) intercalation of Li(1.75+x)Fe2O3 nanocrystals, and interfacial Li storage around nanocrystal boundaries. Only the latter two stages were reversible at and after the second charging/discharging cycle, exhibiting the hybrid behavior of a battery-supercapacitor with superior lithium storage.

Synthesis and biological evaluation of novel pyrimidine-benzimidazol hybrids as potential anticancer agents.

A series of pyrimidine-benzimidazol hybrids was synthesized and evaluated for anticancer activity on four human cancer cell lines including MCF-7, MGC-803, EC-9706 and SMMC-7721. Some of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 5a-b and 6a-b showed most effective activity. Compounds 5b and 6b were more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines, with IC50 values ranging from 2.03 to 10.55 µM and 1.06 to 12.89 µM, respectively. Flow cytometry analysis demonstrated that treatment of MGC-803 with 6b led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death.