Low-noise mode-locking in a GHz repetition rate Tm3+-doped fiber laser.

We demonstrate a GHz repetition rate mode-locked Tm3+-doped fiber laser with low noise. Based on a home-made Tm3+-doped barium gallo-germanate fiber with reduced dispersion, a broad optical spectrum of mode-locking is achieved, and its amplified spontaneous emission quantum-limited timing jitter is largely suppressed. Besides, we carefully investigate the influence of the intracavity pump strength on the noise performance of the mode-locked pulses and find that manipulating the intracavity pump power can be an effective method for optimizing the timing jitter and relative intensity noise (RIN). Particularly, RIN, which originated from the relaxation oscillation, can be effectively suppressed by 33 dB at offset frequencies of >1 MHz. The integrated timing jitter and RIN are only 7.9 fs (10 kHz-10 MHz) and 0.05% (10 Hz-10 MHz), respectively.

Lutein inhibits tumor progression through the ATR/Chk1/p53 signaling pathway in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related death. In particular, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Due to tumor resistance and the toxicity of chemotherapeutic agents, it is increasingly critical to discover novel, potent antitumorigenic drugs for treating NSCLC. Lutein, a carotenoid, has been reported to exert toxic effects on cells in several tumor types. However, the detailed functions and underlying mechanisms of lutein in NSCLC remain elusive. The present study showed that lutein significantly and dose-dependently inhibited cell proliferation, arrested the cell cycle at the G0/G1 phase, and induced apoptosis in NSCLC cells. RNA-sequencing analysis revealed that the p53 signaling pathway was the most significantly upregulated in lutein-treated A549 cells. Mechanistically, lutein exerted antitumorigenic effects by inducing DNA damage and subsequently activating the ATR/Chk1/p53 signaling pathway in A549 cells. In vivo, lutein impeded tumor growth in mice and prolonged their survival. In conclusion, our findings demonstrate the antitumorigenic potential of lutein and reveal its molecular mechanism of action, suggesting that lutein is a promising candidate for clinical NSCLC treatment.

Doxazosin oral intake therapy to relieve stent - related urinary symptoms and pain: a prospective, randomized, controlled study.

OBJECTIVE: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. RESULTS: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. CONCLUSIONS: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL.

The protective effects of icariin against testicular dysfunction in type 1 diabetic mice Via AMPK-mediated Nrf2 activation and NF-κB p65 inhibition.

BACKGROUND: Owing to the early suffering age and the rising incidence of type 1 diabetes (T1D), the resulting male reproductive dysfunction and fertility decline have become a disturbing reality worldwide, with no effective strategy being available. Icariin (ICA), a flavonoid extracted from Herba Epimedium, has been proved its promising application in improving diabetes-related complications including diabetic nephropathy, endothelial dysfunction and erectile dysfunction. Ensuring the future reproductive health of children and adolescents with T1D is crucial to improve global fertility. However, its roles in the treatment of T1D-induced testicular dysfunction and the potential mechanisms remain elusive. PURPOSE: The purpose of this present study was to investigate whether ICA ameliorates T1D-induced testicular dysfunction as well as its potential mechanisms. METHODS: T1D murine model was established by intraperitoneal injection of STZ with or without treated with ICA for eleven weeks. Morphological, pathological and serological experiments were used to determine the efficacy of ICA on male reproductive function of T1D mice. Western blotting, Immunohistochemistry analysis, qRT-PCR and kit determination were performed to investigated the underlying mechanisms. RESULTS: We found that replenishment of ICA alleviated testicular damage, promoted testosterone production and spermatogenesis, ameliorated apoptosis and blood testis barrier impairment in streptozotocin-induced T1D mice. Functionally, ICA treatment triggered adenosine monophosphate protein kinase (AMPK) activation, which in turn inhibited the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) to reduce inflammatory responses in the testis and activated nuclear factor erythroid 2-related factor 2(Nrf2), thereby enhancing testicular antioxidant capacity. Further studies revealed that supplementation with the AMPK antagonist Compound C or depletion of Nrf2 weakened the beneficial effects of ICA on testicular dysfunction of T1D mice. CONCLUSION: Collectively, these results demonstrate the feasibility of ICA in the treatment of T1D-induced testicular dysfunction, and reveal the important role of AMPK-mediated Nrf2 activation and NF-κB p65 inhibition in ICA-associated testicular protection during T1D.

Does the construction of network infrastructure reduce environmental pollution?-evidence from a quasi-natural experiment in "Broadband China".

This paper discusses the effect of network infrastructure on environmental pollution reduction and the realization mechanism behind it. Based on the panel data of 285 cities in China from 2005 to 2019, this study regards the "Broadband China" pilot policy as a quasi-natural experiment to clarify the pollution emission reduction effect of network infrastructure construction through differences-in-differences method and other methods. The research results show the following: (1) The Broadband China pilot policy has reduced environmental pollution, that is, the construction of network infrastructure has the effect of environmental pollution reduction. The conclusion is still established after a series of robustness tests such as parallel trend test, placebo test, and instrumental variable method. Through the heterogeneity test, it is found that the pollution reduction effect of network infrastructure construction is more obvious in non-resource-based cities, first and second tier cities, and cities in the eastern region (2). The construction of network infrastructure plays a restraining role on local environmental pollution. Due to the insufficient level of regional linkage and the siphon effect of pilot cities, the spatial spillover characteristics of the pollution reduction effect are not obvious (3). The mechanism of action shows that green innovation is an important mediating effect mechanism for network infrastructure construction to reduce environmental pollution. Cities in regions with high degree of marketization and environmental regulation can strengthen the effect of network infrastructure construction on environmental pollution reduction. The research conclusions are conducive to accelerating the development of the digital economy represented by the construction of network infrastructure and provide a useful reference for promoting the level of environmental pollution reduction and achieving high-quality development.

Fostering sustainability: unveiling the impact of Internet development on carbon emissions in China.

The rapid development of the Internet has significantly impacted various socio-economic activities. Using Chinese Industrial Enterprise database and Industrial Enterprise Pollution database, this research examines the impact and mechanisms of Internet development on CO2 emissions. The key findings are as follows: (1) Internet development has substantially reduced the CO2 intensity of enterprises, and this conclusion remains robust even after performing a series of robustness analyses. (2) The major mechanisms responsible for the reduction in CO2 emissions are productivity improvement, technological innovation, and energy structure adjustment. (3) The analysis of heterogeneity reveals that the effect of Internet development on CO2 reduction is more pronounced in coastal areas, areas with a high share of secondary industry, low-carbon industries, clean industries, small-scale enterprises, and export enterprises. This study provides empirical evidence supporting China's "Internet+" strategy and its progress towards achieving the "Carbon Peaking and Carbon Neutrality Goals."

Targeting CXCL9/10/11-CXCR3 axis: an important component of tumor-promoting and antitumor immunity.

Chemokines are chemotactic-competent molecules composed of a family of small cytokines, playing a key role in regulating tumor progression. The roles of chemokines in antitumor immune responses are of great interest. CXCL9, CXCL10, and CXCL11 are important members of chemokines. It has been widely investigated that these three chemokines can bind to their common receptor CXCR3 and regulate the differentiation, migration, and tumor infiltration of immune cells, directly or indirectly affecting tumor growth and metastasis. Here, we summarize the mechanism of how the CXCL9/10/11-CXCR3 axis affects the tumor microenvironment, and list the latest researches to find out how this axis predicts the prognosis of different cancers. In addition, immunotherapy improves the survival of tumor patients, but some patients show drug resistance. Studies have found that the regulation of CXCL9/10/11-CXCR3 on the tumor microenvironment is involved in the process of changing immunotherapy resistance. Here we also describe new approaches to restoring sensitivity to immune checkpoint inhibitors through the CXCL9/10/11-CXCR3 axis.

miR-152-3p Inhibits Proliferation, Invasion and Autophagy in UMUC3 and TCCSUP Bladder Cancer Cell Lines via Suppressing HMGA2 Expression.

OBJECTIVE: MicroRNAs have been reported to be involved in the regulation of tumor progression. This study investigated the role of miR-152-3p in bladder cancer development. METHODS: A total of 67 bladder cancer cases were enrolled. miR-152-3p expression in bladder cancer tissues and cells were detected using quantitative reverse transcriptase polymerase chain reaction. Bladder cancer cells were transfected by miR-152-3p mimic and inhibitor to up-regulate and down-regulate miR-152-3p expression. After transfection, cell counting kit-8 assay, flow cytometry, Brdu staining assay, transwell experiment and wound healing assay were conducted to research the effect of miR-152-3p up-regulation/down-regulation on bladder cancer cell viability, apoptosis, proliferation, invasion and migration abilities. The expression of high-mobility group protein A2 (HMGA2) and autophagy-related proteins was researched using Western blot. The interaction between miR-152-3p and HMGA2 was explored by dual luciferase reporter gene assay. RESULTS: Low miR-152-3p expression in tumor tissues bladder cancer patients was associated with poor prognosis. miR-152-3p expression was abnormally down-regulated in bladder cancer cells. miR-152-3p up-regulation inhibited viability, proliferation, invasion, migration but promoted apoptosis of bladder cancer cells. miR-152-3p down-regulation showed the opposite effects. miR-152-3p up-regulation suppressed the expression of Beclin 1 and LC3II/LC3I proteins in bladder cancer cells, but miR-152-3p down-regulation increased them. HMGA2 was target of miR-152-3p, which could be directly inhibited by miR-152-3p. HMGA2 up-regulation reversed the inhibitory effect of miR-152-3p on bladder cancer cell malignant phenotype. CONCLUSION: miR-152-3p inhibited malignant phenotype of bladder cancer cell lines via suppressing HMGA2 expression.

A preoperative magnetic resonance imaging-based model to predict biochemical failure after radical prostatectomy.

To investigate if a magnetic resonance imaging (MRI)-based model reduced postoperative biochemical failure (BF) incidence in patients with prostate cancer (PCa). From June 2018 to January 2020, we retrospectively analyzed 967 patients who underwent prostate bi-parametric MRI and radical prostatectomy (RP). After inclusion criteria were applied, 446 patients were randomized into research (n = 335) and validation cohorts (n = 111) at a 3:1 ratio. In addition to clinical variables, MRI models also included MRI parameters. The area under the curve (AUC) of receiver operating characteristic and decision curves were analyzed. The risk of postoperative BF, defined as persistently high or re-elevated prostate serum antigen (PSA) levels in patients with PCa with no clinical recurrence. In the research (age 69 [63-74] years) and validation cohorts (age 69 [64-74] years), the postoperative BF incidence was 22.39% and 27.02%, respectively. In the research cohort, the AUC of baseline and MRI models was 0.780 and 0.857, respectively, with a significant difference (P < 0.05). Validation cohort results were consistent (0.753 vs. 0.865, P < 0.05). At a 20% risk threshold, the false positive rate in the MRI model was lower when compared with the baseline model (31% [95% confidence interval (CI): 9-39%] vs. 44% [95% CI: 15-64%]), with the true positive rate only decreasing by a little (83% [95% CI: 63-94%] vs. 87% [95% CI: 75-100%]). 32 of 100 RPs can been performed, with no raise in quantity of patients with missed BF. We developed and verified a MRI-based model to predict BF incidence in patients after RP using preoperative clinical and MRI-related variables. This model could be used in clinical settings.

Plumbagin-loaded aptamer-targeted poly D,L-lactic-co-glycolic acid-b-polyethylene glycol nanoparticles for prostate cancer therapy.

Plumbagin inhibits the growth, metastasis, and invasion of prostate cancer (PCa). However, its lower bioavailability limits biopharmaceutical properties due to insolubility in water. Prostate-specific membrane antigen (PSMA) aptamer-targeted nanoparticles (NPs) significantly enhanced cytotoxicity in prostate epithelial cells. This study aimed to investigate the effects of plumbagin-loaded prostate-specific membrane antigen (PSMA) aptamer-targeted poly D,L-lactic-co-glycolic acid-b-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) on prostate cancer (PCa) in vitro.PLGA-PEG with a terminal carboxylic acid group (PLGA-PEG-COOH) was synthesized, and plumbagin was loaded on PLGA-PEG-COOH NPs using the nanoprecipitation method and characterized by field emission scanning electron microscopy (SEM), transmission electron microscopy (TEM), and laser light scattering. The uptake and distribution of plumbagin-NPs in human PCa LNCaP cells were investigated by fluorescent labeling. Subsequently, PSMA antibody-targeted PLGA-PEG-COOH NPs (targeted NPs) were prepared by covalent binding and characterized by x-ray photoelectron spectroscopy. Furthermore, the anticancer activity of plumbagin-loaded, targeted NPs was compared with that of nontargeted NPs in LNCaP cells in vitro.Plumbagin-NPs (diameter of 189.4 ±â€Š30.6 nm and zeta potential of -17.1 ±â€Š3.7 mV) were optimized based on theoretical drug loading of 5% and a ratio of water:acetone of 3:1. During the first 2 hours, the cumulative release rate of the drug was 66.4 ±â€Š8.56%. Moreover, plumbagin-targeted NPs with nitrogen atoms were prepared. The uptake rate was 90% at 0.5 hours for targeted and nontargeted NPs. The IC50 of targeted NPs and nontargeted NPs was 32.59 ±â€Š8.03 µM and 39.02 ±â€Š7.64 µM, respectively.Plumbagin-loaded PSMA aptamer-targeted NPs can be used in targeted chemotherapy against PCa.

Magnetic anisotropy and high-frequency property of flexible FeCoTa films obliquely deposited on a wrinkled topography.

We investigated the magnetic anisotropy and the high-frequency property of flexible Fe60Co26Ta14 (FeCoTa) thin films obtained by oblique sputtering onto a wrinkled surface. The sinuously wrinkled topography is produced by growing Ta layer on a pre-strained polydimethylsiloxane (PDMS) membrane. Due to the enhanced effect of shadowing, the oblique deposition of FeCoTa layer gives rise to a shift of wrinkle peak towards the incident atomic flux. With increasing the PDMS pre-strain or increasing the oblique sputtering angle, both the uniaxial magnetic anisotropy and the ferromagnetic resonance frequency of FeCoTa films are enhanced, but the initial permeability decreases. The magnetization reversal mechanism of wrinkled FeCoTa films can be interpreted by a two-phase model composed of both coherent rotation and domain wall nucleation. With the enhancement of uniaxial magnetic anisotropy, the domain wall nucleation becomes pronounced in FeCoTa films.

Development of a cell-seeded modified small intestinal submucosa for urethroplasty.

OBJECTIVE: To explore the feasibility of a modified 3D porous small intestinal submucosa (SIS) scaffold seeded with urothelial cells (UC) for surgical reconstruction in a rabbit model. MATERIAL AND METHODS: Eighteen New England white male rabbits were divided into three groups and a 0.8 × 1.5 cm(2) section of the anterior urethral mucosa was removed from each animal. Ventral onlay urethroplasty was performed with a 1.0 × 1.7 cm(2) SIS scaffold that was either cell-seeded and treated with 5% peracetic acid (PAA) (n = 6), or cell-seeded and untreated (n = 6), or unseeded and treated with 5% PAA (n = 6). Animals were sacrificed at 6 months post-repair and retrograde urethrography and histological analyses performed. RESULTS: In animals implanted with cell-seeded and PAA treated SIS scaffolds, urethrography showed wide-caliber urethra without any signs of stricture or fistulae, and histological analyses confirmed a complete urethral structure. In contrast, ulceration and fistula occurred in the reconstructed urethra of animals implanted with cell-seeded but untreated SIS scaffolds, and evident stricture was present in the unseeded, PAA treated group. Histological analyses demonstrated less urothelial coverage and smooth muscle in the cell-seeded and untreated SIS scaffold group, and serious fibrosis formation occurred in the unseeded, treated group. CONCLUSIONS: A modified 3D porous SIS scaffold seeded with UC and treated with PAA produces better urethroplasty results than cell-seeded untreated SIS scaffolds, or unseeded PAA treated SIS scaffolds.

Targeting CXCL9/10/11–CXCR3 axis: an important component of tumor-promoting and antitumor immunity

Chemokines are chemotactic-competent molecules composed of a family of small cytokines, playing a key role in regulating tumor progression. The roles of chemokines in antitumor immune responses are of great interest. CXCL9, CXCL10, and CXCL11 are important members of chemokines. It has been widely investigated that these three chemokines can bind to their common receptor CXCR3 and regulate the differentiation, migration, and tumor infiltration of immune cells, directly or indirectly affecting tumor growth and metastasis. Here, we summarize the mechanism of how the CXCL9/10/11–CXCR3 axis affects the tumor microenvironment, and list the latest researches to find out how this axis predicts the prognosis of different cancers. In addition, immunotherapy improves the survival of tumor patients, but some patients show drug resistance. Studies have found that the regulation of CXCL9/10/11–CXCR3 on the tumor microenvironment is involved in the process of changing immunotherapy resistance. Here we also describe new approaches to restoring sensitivity to immune checkpoint inhibitors through the CXCL9/10/11–CXCR3 axis (AU)

Doxazosin oral intake therapy to relieve stent - related urinary symptoms and pain: a prospective, randomized, controlled study

ABSTRACT Objective: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. Results: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. Conclusions: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL.

Intramolecular Fe(II)-catalyzed N-O or N-N bond formation from aryl azides.

Iron(II) bromide catalyzes the transformation of aryl and vinyl azides with ketone or methyl oxime substituents into 2,1-benzisoxazoles, indazoles, or pyrazoles through the formation of an N-O or N-N bond. This transformation tolerates a variety of different functional groups to facilitate access to a range of benzisoxazoles or indazoles. The unreactivity of the Z-methyloxime indicates that N-heterocycle formation occurs through a nucleophilic attack of the ketone or oxime onto an activated planar iron azide complex.