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Selenium (Se) is an essential trace element known for its significant role in maintaining human health and mitigating disease progression. Selenium and its compounds exhibit high selective cytotoxicity against tumor cells. However, their anti-cervical cancer (CC) effects and underlying mechanisms have not been fully explored. This study found that sodium selenite (SS) inhibits the viability of HeLa and SiHa cells in a dose- and time-dependent manner. Intraperitoneal injection of 3 and 6 mg/kg SS for 14 days in female nude mice significantly inhibited the growth of HeLa cell xenografts without evident hepatotoxicity or nephrotoxicity. RNA sequencing results indicated that the AMP-activated protein kinase (AMPK), Forkhead box protein O (FOXO), and apoptosis signaling pathways are key regulatory pathways in SS's anti-CC effects, and SS's inhibition of HeLa cell proliferation may be related to autophagy and ROS-induced apoptosis. Further research has revealed that SS induces cell autophagy and apoptosis through the AMPK/mTOR/FOXO3a pathway, characterized by the upregulation of p-AMPK/AMPK, FOXO3a, LC3-II, cleaved-caspase3, and cleaved-PARP and the downregulation of p-mTOR/mTOR and p62. Additionally, SS impaired mitochondrial function, including decreased mitochondrial membrane potential, mitochondrial Ca2+ overload, and accumulation of mitochondrial reactive oxygen species (mtROS). Pretreatment with Mitoquinone mesylate (Mito Q) and compound C partially reversed SS-induced apoptosis, autophagy, and proliferation inhibition. Pretreatment with 3-methyladenine (3-MA) enhances SS-induced apoptosis and proliferation inhibition in HeLa cells but reverses these effects in SiHa cells. In summary, SS induces apoptosis, autophagy, and proliferation inhibition in HeLa and SiHa cells through the activation of the AMPK/mTOR/FOXO3a signaling pathway via mtROS. Autophagy activation may be a major risk factor for SS-induced apoptosis in SiHa cells but can protect HeLa cells from SS-induced apoptosis. These findings provide new evidence for understanding the molecular mechanisms underlying SS in potential new drug development for CC. [ABSTRACT FROM AUTHOR]

Self-accelerating beams show considerable captivating phenomena and applications owing to their transverse acceleration, diffraction-free and self-healing properties in free space. Metasurfaces consisting of dielectric or metallic subwavelength structures attract enormous attention to acquire self-accelerating beams, owing to their extraordinary capabilities in the arbitrary control of electromagnetic waves. However, because the self-accelerating beam generator possesses a large phase gradient, traditional discrete metasurfaces suffer from insufficient phase sampling, leading to a low efficiency and narrow spectral band. To overcome this limitation, a versatile platform of catenary-inspired dielectric metasurfaces is proposed to endow arbitrary continuous wavefronts. A high diffraction efficiency approaching 100% is obtained in a wide spectral range from 9 to 13 μm. As a proof-of-concept demonstration, the broadband, high-efficiency and high-quality self-accelerating beam generation is experimentally verified in the infrared band. Furthermore, the chiral response of the proposed metasurfaces enables the spin-controlled beam acceleration. Considering these superior performances, this design methodology may find wide applications in particle manipulation, high-resolution imaging, optical vortex generation, and so forth.

Background: Extramammary Paget's disease (EMPD) is a rare cutaneous malignant tumor with a high recurrence rate after surgery. However, the genetic and epigenetic alterations underlying its pathogenesis remain unknown. DNA methylation is an important epigenetic modification involved in many biological processes. Methods: In this study, enzymatic methyl‐sequencing (EM‐seq) technique was used to investigate the landscape of genome‐wide DNA methylation from three pairs of tumor tissues and adjacent tissues of patients with EMPD. Additionally, we conducted histopathological examinations to assess the expression of fatty acid‐binding protein 5 (FABP5) in another three paired samples from EMPD patients. Results: The cluster analysis showed the good quality of the samples. A differential methylation region (DMR) heat map was used to quantitatively characterize genome‐wide methylation differences between tumors and controls. Global DNA methylation level is lower in EMPD tissue compared to matched controls, indicating that DNA methylation discriminates between tumor and normal skin. And the top hypomethylation gene on the promoter region in tumor tissues was FABP5 on chromosome 8 with 38.44% decreased median methylation. We next identified the expression of FABP5 in paired tumors and adjacent tissues in three additional patients with EMPD. Immunofluorescence results showed FABP5 highly expressed in tumor tissues and co‐located with CK7, CK20 and EMA. GO and KEGG enrichment analysis showed DMR genes on promoter are mainly enriched in the calcium ion transport, GTPase mediated signal transduction, Rap1 signaling pathway and GnRH signaling pathway. Conclusion: Taken together, our findings provide the first description of the whole genome methylation map of EMPD and identify FABP5 as a pathogenic target of EMPD. [ABSTRACT FROM AUTHOR]

Information regarding the impact of the coronavirus disease 2019 (COVID‐19) pandemic on cervical cancer in mainland China is lacking. We explored its impact on the hospital attendance of patients with primary cervical cancer. We included 1918 patients with primary cervical cancer who initially attended Harbin Medical University Cancer Hospital between January 23, 2019, and January 23, 2021. Attendance decreased by 31%, from 1135 in 2019 to 783 in 2020, mainly from January to June (휒2 = 73.362, P <.001). The percentage of patients detected by screening decreased from 12.1% in January‐June 2019 to 5.8% in January‐June 2020 (휒2 = 7.187, P =.007). Patients with stage I accounted for 28.4% in 2020 significantly lower than 36.6% in 2019 (휒2 = 14.085, P <.001), and patients with stage III accounted for 27.1% in 2020 significantly higher than 20.5% in 2019 (휒2 = 11.145, P <.001). Waiting time for treatment was extended from 8 days (median) in January‐June and July‐December 2019 to 16 days in January‐June (휒2 = 74.674, P <.001) and 12 days in July‐December 2020 (휒2 = 37.916, P <.001). Of the 179 patients who delayed treatment, 164 (91.6%) were for the reasons of the healthcare providers. Compared to 2019, the number of patients in Harbin or non‐Harbin in Heilongjiang Province and outside the province decreased, and cross‐regional medical treatment has been hindered. The COVID‐19 pandemic has negatively impacted cervical cancer patient attendance at the initial phase. These results are solid evidence that a strategy and mechanism for the effective attendance of cervical cancer patients in response to public health emergencies is urgently needed. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic inflammatory skin disease characterized by recurrent erythema, flushing, telangiectasia, papules, pustules, and phymatous changes in the central area of the face. Patients with this condition often experience a significant negative impact on their quality of life, self-esteem, and overall well-being. Despite its prevalence, the pathogenesis of rosacea is not yet fully understood. Recent research advances are reshaping our understanding of the underlying mechanisms of rosacea, and treatment options based on the pathophysiological perspective hold promise to improve patient outcomes and reduce incidence. In this comprehensive review, we investigate the pathogenesis of rosacea in depth, with a focus on emerging and novel mechanisms, and provide an up-to-date overview of therapeutic strategies that target the diverse pathogenic mechanisms of rosacea. Lastly, we discuss potential future research directions aimed at enhancing our understanding of the condition and developing effective treatments. [ABSTRACT FROM AUTHOR]

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo , and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ. [ABSTRACT FROM AUTHOR]

Reflective optical fiber current sensors have been widely used in electric power and metallurgy. However, the closing gaps between the λ / 4 wave plate and the reflector leads to a strong background current when they are used in strong magnetic fields. In this paper, a mathematical model of the background current was analyzed, and the relationship between the external magnetic field and the background current was identified through experiments. Therefore, a method to reduce the background current by magnetic shielding was proposed. A magnetic ring to shield the magnetic field effectively was designed, and the effects of the structure and relative permeability of the magnetic ring on its shielding rate were established by experiments and numerical simulations. The results showed that the shielding rate exceeded 95% when the length, thickness, and inner diameter of the magnetic ring were 50 mm, 2 mm, and 13 mm, respectively. Overall, this work provided a comprehensive framework that is useful for the analysis and optimization of magnetic shielding and improved the measurement accuracy of optical fiber current sensors in strong magnetic fields. [ABSTRACT FROM AUTHOR]

Acne vulgaris is a chronic inflammatory cutaneous disease. 5‐Aminolaevulinic acid photodynamic therapy (ALA‐PDT) is a novel and effective approach for severe acne vulgaris treatment. However, its specific treatment mechanism still remains unclear. In the present study, we investigated the potential mechanism of how ALA‐PDT regulated intense inflammatory response in acne vulgaris. It appeared that ALA‐PDT suppresses proliferation and lipid secretion of primary human sebocytes. Besides, ALA‐PDT could up‐regulate the expression of CXCL8 in vivo and in vitro, amplifying the inflammatory response by recruiting T cells, B cells, neutrophils and macrophages. We also found that ALA‐PDT elevated the expression of CXCL8 via p38 pathway. SB203580, a p38 pathway inhibitor, decreased the expression of CXCL8 in sebocytes after ALA‐PDT. These findings indicate that ALA‐PDT amplifies the intense inflammatory response in the treatment of acne vulgaris via CXCL8. Our data decipher the mechanism of intense inflammatory response after ALA‐PDT for acne vulgaris. [ABSTRACT FROM AUTHOR]

Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for actinic keratosis (AK). However, the pain during illumination usually caused patient to discontinue PDT treatment and resulted lower efficacy. Previous study showed modified painless PDT (M-PDT) with short ALA incubation time and longer irradiation time can reduce pain and preserve the efficacy. If M-PDT worked in AK still need to investigate. A splie-face controlled clinical study was conducted. Eleven patients with facial AK received C-PDT (conventional PDT) on the left and M-PDT in the contralateral area. The left area was illuminated by a red LED light (a total light dose of 140 J/cm2) after applying the ALA cream for 3 hours; the other had illumination for a total light dose of 288 J/cm2 after applying the ALA cream for 0.5 hours. The primary endpoint was the lesion clearance rate at 1 month. Secondary endpoints included pain scores, the incidence of adverse events, and cosmetic outcomes. At one month following 3 treatments, the lesion clearance rate of M-PDT was non-inferior to that of C-PDT (93.1% vs. 86.4%, respectively. The lesion clearance rate of M-PDT to reach 100% clearance earlier than C-PDT for grade I lesions and higher clearance rates for grade III lesions. Moreover, the pain score during illumination was significantly lower for M-PDT than for C-PDT (P < 0.01). Regarding photoaging, the Global Subjective Skin Aging Assessment (GS2A2) score showed that the total and atrophy scores of C-PDT and M-PDT were significantly improved, and M-PDT also reduced discoloration. There was no significant difference in adverse reactions between C-PDT and M-PDT. M-PDT is non-inferior to C-PDT in terms of efficacy for treating AK, resulting in much lower pain scores. [ABSTRACT FROM AUTHOR]

Solid-state nanopores have shown great potential in investigating salinity gradient energy generation as a renewable power generator. In this work, various diameter silicon nitride (Si3N 4) nanopores were fabricated to investigate the power generation between two potassium chloride solutions with different concentration gradient ratios by reverse electrodialysis. The maximal estimated power density of a Si3N4 nanopore measured experimentally can be high to 16 649Wm − 2 . To compare with the single Si3N4 nanopore, multiple nanopores array has also been investigated. The equivalent circuit model of multiple Si3N4 nanopores array generator is quantitatively constructed by massive reproducible experimental data and theoretical derivation. For nanopore array, the osmotic current basically keep a linear growth with the number of the nanopores at every concentration ratio. While, the osmotic voltage is basically independent on the number of nanopore. The power generation circuit of the nanopore array can be regarded as a parallel circuit of multiple nanopores. Power generation from concentration gradients in Si3N4 nanopores could be widely used in a variety of applications like ultra-low power devices and micro-nano electromechanical systems. Salinity gradient energy was obtained by reverse electrodialysis in silicon nitride nanopores. The maximal estimated power density of single Si3N4 nanopore measured experimentally can be high to 16649 Wm–2. The equivalent circuit model of multiple Si3N4 nanopores array generator is quantitatively constructed by massive reproducible experimental data and theoretical derivation. Power generation from concentration gradients in Si3N4 nanopores could be widely used in a variety of applications like ultra-low power devices and micro-nano electromechanical systems. [ABSTRACT FROM AUTHOR]

Meningiomas are one of the most prevalent primary brain tumors. Our study aims to obtain mechanistic insights of meningioma pathobiology using mass spectrometry-based label-free quantitative proteome analysis to identifying druggable targets and perturbed pathways for therapeutic intervention. Label-free based proteomics study was done from peptide samples of 21 patients and 8 non-tumor controls which were followed up with Phosphoproteomics to identify the kinases and phosphorylated components of the perturbed pathways. In silico approaches revealed perturbations in extracellular matrix remodeling and associated cascades. To assess the extent of influence of Integrin and PI3K-Akt pathways, we used an Integrin Linked Kinase inhibitor on patient-derived meningioma cell line and performed a transcriptomic analysis of the components. Furthermore, we designed a Targeted proteomics assay which to the best of our knowledge for very first-time enables identification of peptides from 54 meningioma patients via SRM assay to validate the key proteins emerging from our study. This resulted in the identification of peptides from CLIC1, ES8L2, and AHNK many of which are receptors and kinases and are difficult to be characterized using conventional approaches. Furthermore, we were also able to monitor transitions for proteins like NEK9 and CKAP4 which have been reported to be associated with meningioma pathobiology. We believe, this study can aid in designing peptide-based validation assays for meningioma patients as well as IHC studies for clinical applications. [ABSTRACT FROM AUTHOR]