NIPBL-mediated RAD21 facilitates tumorigenicity by the PI3K pathway in non-small-cell lung cancer.

It is urgent to identify novel early diagnostic markers and therapeutic targets for non-small-cell lung cancer (NSCLC), which accounts for 85% of lung cancer cases and has a 5-year survival rate of 4-17%. Here, chromatin immunoprecipitation (ChIP) was used to identify DNA‒protein interactions, RNA methylation was determined by methylated RNA immunoprecipitation (MeRIP), RNA stability was tested by an RNA decay assay. We showed that RAD21, a member of the cohesin complex, is upregulated in NSCLC tissues and cell lines and found to be an independent prognostic factor for overall survival (OS) of NSCLC patients. Mechanistically, the cohesin loading factor Nipped-B-Like Protein (NIPBL) promoted RAD21 gene transcription by enhancing histone H3 lysine 27 (H3K27) demethylation via recruiting lysine demethylase 6B (KDM6B) to the RAD21 gene promoter. RAD21 enhanced phosphatidylinositol 3-kinase (PI3K) gene transcription, and NIPBL reversed the effect of enhancer of zeste 2; catalytic subunit of polycomb repressive complex 2 (EZH2) on RAD21-mediated PI3K gene transcription by disrupting the association between EZH2 and RAD21. Moreover, NIPBL level was increased by stabilization of its transcripts through mRNA methylation. These findings highlight the oncogenic role of RAD21 in NSCLC and suggest its use as a potential diagnostic marker and therapeutic target for NSCLC.

Comprehensive study of clinicopathological and immune cell infiltration and lactate dehydrogenase expression in patients with thymic epithelial tumours.

BACKGROUND: Lactate dehydrogenase (LDH) has emerged as a promising biomarker for cancer. However, the current understanding of LDH and circulating LDH expression in thymic epithelial tumour (TET) is lacking. METHODS: A comprehensive literature review and meta-analysis were performed to evaluate the clinical significance of circulating LDH levels in patients with TET. Circulating LDH levels were measured using a laboratory analyser (Cobas8000, Roche, Basel, Switzerland). The maximum standardised uptake value (SUVmax) was determined in patients who underwent whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Multiplex immunohistochemistry (IHC) was performed using a commercially available kit (Opal 6-plex Detection Kit, Akoya Biosciences, Marlborough, MA, USA) and slide scanner (Slideview VS200, Olympus, Tokyo, Japan). All statistical analyses were performed using SPSS (IBM Corp., Armonk, NY, USA) and Prism version 9.0 (GraphPad Inc., San Diego, CA, USA). Differences with p < 0.05 were considered to be statistically significant. RESULTS: Meta-analysis revealed that elevated circulating serum levels of LDH predicted poor prognosis in patients with TET. Circulating levels of LDH were analysed in the serum of 313 patients with TET and 87 with benign mediastinal mass. The mean circulating LDH level in patients with thymic carcinoma (TC) was significantly higher than that in those with thymoma (TM) and the benign group (p < 0.001). Expression levels of circulating LDH were significantly reduced in postoperative samples compared with that in preoperative samples (p < 0.05). Receiver operating characteristic (ROC) curve analysis for diagnosing TC yielded an area under the curve of 0.74, with a sensitivity of 54 % and specificity of 86 %. Furthermore, patients with TC exhibited higher 18F-FDG PET/CT SUVmax values compared to those with TM. Correlation analysis demonstrated a positive association between SUVmax values and circulating LDH levels. In addition, the percentages of LDH-positive cells in TC and type B1 TM tissues were higher than those in other subtypes of TM, and a significant positive correlation between the percentages of LDH-positive and CD20-positive cells was detected in patients with TET (p < 0.05). CONCLUSION: Circulating serum LDH level may serve as a non-invasive biomarker for the diagnosis and prognosis of TET. The relationship between LDH expression and immune cell infiltration merits further regarding its application in companion diagnosis for immunotherapy.

The combination of etoposide and platinum for the treatment of thymic neuroendocrine neoplasms: A retrospective analysis.

BACKGROUND: To provide real-world outcomes for the combination of etoposide and platinum as a first-line treatment for advanced thymic neuroendocrine neoplasms (TNENs). METHODS: Retrospective analysis was performed on patients with advanced TNENs confirmed by pathology who received etoposide combined with platinum as a first-line chemotherapy in our institution between 2010 and 2022. RESULTS: A total of 16 patients were included in this study. Twelve patients (75%) received etoposide combined with cisplatin, and four patients (25%) received etoposide combined with carboplatin. Efficacy was evaluated in all patients, with an objective response rate of 31.3%. One patient achieved a complete response, four achieved a partial response, and in eight patients the disease remained stable; the disease control rate was 81.3%. The median progression-free survival (PFS) was 7.2 months with a 95% confidence interval (CI) of 2.1-12.3 months. The median overall survival (OS) was 50.4 months with a 95% CI of 32.1-68.8 months. No significant difference in efficacy was observed between the treatment groups with regards to PFS (p = 0.095) and OS (p = 0.061). Treatment-related adverse events were observed in all 12 patients when evaluated for toxicity, manifesting as hematologic toxicity. Grade 3-4 bone marrow suppression occurred in six patients (50%). No treatment-related deaths were recorded. CONCLUSION: This retrospective analysis, conducted in a real-life setting, suggests that the combination of etoposide and platinum has a promising anti-tumor activity in advanced TNENs, with a clinically significant overall response rate.

Nanobionics-Driven Synthesis of Molybdenum Oxide Nanosheets with Tunable Plasmonic Resonances in Visible Light Regions.

Nanobionics-driven synthesis offers a process of designing and synthesizing functional materials on a nanoscale based on the structures and functions of biological systems. An approach such as this is environmentally friendly and sustainable, providing a viable option for synthesizing functional nanomaterials for catalysis and nanoelectronic components. In this work, we present a facile and green nanobionics approach to synthesize plasmonic HxMoO3 by interacting chloroplasts extracted from spinach with two-dimensional (2D) MoO3 nanoflakes. The generated plasmon resonances can be modulated in the visible wavelength ranges, and the efficiency to form the plasmonic materials is enhanced by 90% within 45 min of light excitation compared to reactions without chloroplast involvement. Such a characteristic is ascribed to the interfacial carrier dynamics between the two entities in the reactions, in which highly doped metal oxides with quasi-metallic properties can be formed to generate optical absorptions in the visible light region. The green synthesized plasmonic materials show high photocatalytic activities without the coupling of semiconductors, providing a promising nanoelectronics unit, based on the nanobionics-driven synthesized plasmonic materials.

Terahertz cavity optomechanics using a topological nanophononic superlattice.

Cavity optomechanical systems operating at the quantum ground state provide a novel way for the ultrasensitive measurement of mass and displacement and provide a new toolbox for emerging quantum information technologies. The high-frequency optomechanical devices could reach the quantum ground state at a high temperature because the access to high frequency is favorable for the cavity optomechanical devices to decouple from the thermal environment. However, reaching ultra-high frequency (THz) is extremely difficult due to the structure of cavity optomechanical devices and properties of materials. In this paper, by introducing acoustic topological interface states, we designed a THz mechanical frequency semiconductor pillar microcavity optomechanical device based on a GaAs/AlAs nanophononic superlattice. In the optomechanical system, multi-optical cavity modes are obtained and the frequency separation between adjacent optical modes is equal to the frequency of the mechanical mode (optomechanical frequency matching). By detuning the laser pump to a lower (higher) energy-resolved sideband to make a spontaneously scattering photon doubly resonate with optical cavity modes at an anti-Stokes (Stokes) frequency and pump frequency, we can achieve an anti-Stokes (Stokes) scattering efficiency 2600 (1800) times larger than that of Stokes (anti-Stokes) scattering, which provides potential for laser cooling and low threshold phonon lasing in the optomechanical system.

Hexagonal metal oxide monolayers derived from the metal-gas interface.

Two-dimensional (2D) crystals are promising materials for developing future nano-enabled technologies1-6. The cleavage of weak, interlayer van der Waals bonds in layered bulk crystals enables the production of high-quality 2D, atomically thin monolayers7-10. Nonetheless, as earth-abundant compounds, metal oxides are rarely accessible as pure and fully stoichiometric monolayers owing to their ion-stabilized 'lamellar' bulk structure11-14. Here, we report the discovery of a layered planar hexagonal phase of oxides from elements across the transition metals, post-transition metals, lanthanides and metalloids, derived from strictly controlled oxidation at the metal-gas interface. The highly crystalline monolayers, without the support of ionic dopants or vacancies, can easily be mechanically exfoliated by stamping them onto substrates. Monolayer and few-layered hexagonal TiO2 are characterized as examples, showing p-type semiconducting properties with hole mobilities of up to 950 cm2 V-1 s-1 at room temperature. The strategy can be readily extended to a variety of elements, possibly expanding the exploration of metal oxides in the 2D quantum regime.

Unsaturated fatty acid-enriched extract from Hippophae rhamnoides seed reduces skin dryness through up-regulating aquaporins 3 and hyaluronan synthetases 2 expressions.

BACKGROUND: Seed oil of sea buckthorn (SBT) is well known to contain high amount of polyunsaturated fatty acid (PUFA), and PUFA is generally acknowledged to promote skin hydration by reducing trans-epidermal water loss (TEWL). AIMS: The present study is aimed to investigate that skin hydration offered by SBT seed oil is whether through up-regulating AQP3 or HAS2 expression. METHODS: MTT assay was performed to detect cytotoxicity of SBT seed oil, and then, PCR was carried out to explore whether SBT seed oil can increase AQP3 mRNA expression in normal human epidermis keratinocytes (NHEK) cells or not. Immunofluorescence (IF) and Western blot analysis were used to test the protein level expression of AQP3 and HAS2 influenced by SBT seed oil in NHEK cells or in reconstructed epidermis skin model. RESULTS: According to the result of MTT assay, all test concentration of SBT seed oil showed no cytotoxicity to cells. 10 µg/mL SBT seed oil treatment evidently increased AQP3 mRNA level compared to negative control (NC). IF and Western blot analysis results demonstrated that AQP3 and HAS2 protein levels in NHEK cells treated with 10 µg/mL SBT seed oil were much higher than that of NC. Finally, treatment with 10 µg/mL SBT seed oil substantially up-regulated expression of AQP3 and HAS2 protein in reconstructed epidermis skin model in comparison to NC. CONCLUSIONS: In summary, our study first proved that SBT seed oil can improve skin hydration through increasing AQP3 and HAS2 expressions.

Laparoscopy versus laparotomy approach of a radical resection for gallbladder cancer: a retrospective comparative study.

BACKGROUND: Laparoscopic approach for gallbladder cancer (GBC) has long been contraindicated, but few recent studies have demonstrated the oncologic outcomes of this treatment. The purpose of this study was to compare the perioperative outcomes and long-term survival for laparoscopic surgery versus traditional open surgery of GBC. METHOD: Between January 2014 and December 2018, 63 GBC patients who received radical resection were enrolled in this study, with 32 patients in laparoscopic group and 31 cases in laparotomy group. Perioperative data and postoperative survival were retrospectively evaluated. RESULTS: Laparoscopic approach was associated with less intraoperative bleeding (267.20 ± 47.07 vs. 502.60 ± 69.70, P = 0.007), fewer postoperative days of oral diet recovery (2.34 ± 0.31 vs. 3.32 ± 0.35, P = 0.041), and hospital stay (11.03 ± 0.99 vs. 14.35 ± 1.11, P = 0.028). There were no significant differences between two groups regarding other perioperative outcomes. Patients in laparoscopic group showed better 1-year overall survival than those in laparotomy group (72.91% vs. 47.82%, P = 0.086). Subgroup analysis for GBC patients in T3 stages revealed that laparoscopic approach was associated with less intraoperative bleeding (268.00 ± 57.19 vs. 541.50 ± 101.30, P = 0.009), fewer postoperative days of hospital stay (9.87 ± 1.10 vs. 14.90 ± 1.53, P = 0.017), and improved 1-year overall survival (P = 0.023). Subgroup analysis for GBCs in TNM III and TNM IV stages showed comparable intraoperative parameters and postoperative survival between two groups. CONCLUSION: Laparoscopic surgery for GBCs may offer the comparable perioperative outcomes as conventional laparotomy procedure, and tend to be associated with less intraoperative bleeding, faster oral diet recovery, shorter hospital stay, and improved 1-year overall survival.

Treatment with Docosahexaenoic Acid Improves Epidermal Keratinocyte Differentiation and Ameliorates Inflammation in Human Keratinocytes and Reconstructed Human Epidermis Models.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that can cause skin barrier function damage. Although co-incubation with docosahexaenoic acid (DHA) exerts a positive effect on deficient skin models, no studies have investigated the effects of topical treatment with DHA in an inflammatory reconstructed human epidermis (RHE) model. The effects of DHA on monolayer normal human epidermal keratinocyte (NHEK) cells were evaluated using cell counting kit-8 (CCK-8), real-time quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). The skin-related barrier function was assessed using hematoxylin-eosin (HE) staining, Western blot (WB), immunohistofluorescence (IF), and ELISA in normal and inflammatory RHE models. Docosahexaenoic acid upregulated filaggrin and loricrin expression at mRNA levels in addition to suppressing overexpression of tumor necrosis factor-α (TNF-α), interleukin-α (IL-1α), and interleukin-6 (IL-6) stimulated by polyinosinic-polycytidylic acid (poly I:C) plus lipopolysaccharide (LPS) (stimulation cocktail) in cultured NHEK cells. After topical treatment with DHA, cocktail-induced inflammatory characteristics of skin diseases, including barrier morphology, differentiation proteins, and thymic stromal lymphopoietin (TSLP) secretion, were alleviated in RHE models. Supplementation with DHA can improve related barrier function and have anti-inflammation effects in monolayer keratinocytes and RHE models, which indicates that DHA may have potential value for the treatment of inflammation-associated skin diseases.

Effects of Tea-Polysaccharide Conjugates and Metal Ions on Precipitate Formation by Epigallocatechin Gallate and Caffeine, the Key Components of Green Tea Infusion.

The mechanism of tea-infusion precipitation is not clear. Epigallocatechin gallate (EGCG) and caffeine (CAF) are the core components of green tea infusion precipitate. The critical precipitation concentration ( CCPC) of EGCG-CAF mixed aqueous solutions was assayed through a turbidity assay performed at 25 °C and verified by a differential-scanning calorimeter (DSC) for reliability. Different concentrations of the green tea polysaccharide conjugate fraction (gTPC-D), with a molecular weight of 2.32 × 105 Da, and of metal ions (K+, Mg2+, Ca2+, and Al3+) were respectively introduced into the mixed solution to study their effects on CCPC. On the basis of the changed CCPC, the clarification-precipitation phase diagrams of the mixed aqueous solutions were constructed. By calculating the integral area of the clarification phase, it was determined that the four metal ions and gTPC-D could accelerate precipitate formation with a dose-response relationship; among the metal ions, the effect of Al3+ is the strongest, followed by that of Ca2+.

An Ultrasensitive Silicon Photonic Ion Sensor Enabled by 2D Plasmonic Molybdenum Oxide.

Silicon photonics has demonstrated great potential in ultrasensitive biochemical sensing. However, it is challenging for such sensors to detect small ions which are also of great importance in many biochemical processes. A silicon photonic ion sensor enabled by an ionic dopant-driven plasmonic material is introduced here. The sensor consists of a microring resonator (MRR) coupled with a 2D restacked layer of near-infrared plasmonic molybdenum oxide. When the 2D plasmonic layer interacts with ions from the environment, a strong change in the refractive index results in a shift in the MRR resonance wavelength and simultaneously the alteration of plasmonic absorption leads to the modulation of MRR transmission power, hence generating dual sensing outputs which is unique to other optical ion sensors. Proof-of-concept via a pH sensing model is demonstrated, showing up to 7 orders improvement in sensitivity per unit area across the range from 1 to 13 compared to those of other optical pH sensors. This platform offers the unique potential for ultrasensitive and robust measurement of changes in ionic environment, generating new modalities for on-chip chemical sensors in the micro/nanoscale.

Some limit properties for a hidden inhomogeneous Markov chain.

This paper presents a general strong limit theorem for delayed sum of functions of random variables for a hidden time inhomogeneous Markov chain (HTIMC), and as corollaries, some strong laws of large numbers for HTIMC are established thereby.

Penicillenols from a deep-sea fungus Aspergillus restrictus inhibit Candida albicans biofilm formation and hyphal growth.

Penicillenols (A1, A2, B1, B2, C1 and C2) were isolated from Aspergillus restrictus DFFSCS006, and could differentially inhibit biofilm formation and eradicate pre-developed biofilms of Candida albicans. Their structure-bioactivity relationships suggested that the saturation of hydrocarbon chain at C-8, R-configuration of C-5 and trans-configuration of the double bond between C-5 and C-6 of pyrrolidine-2,4-dione unit were important for their anti-biofilm activities. Penicillenols A2 and B1 slowed the hyphal growth and suppressed the transcripts of hypha specific genes HWP1, ALS1, ALS3, ECE1 and SAP4. Moreover, penicillenols A2 and B1 were found to act synergistically with amphotericin B against C. albicans biofilm formation.

Cytotoxic polyketides from the deep-sea-derived fungus Engyodontium album DFFSCS021.

Eight new chromones, engyodontiumones A-H (1-8), and three new phenol derivatives (9-11) together with eight known polyketides (12-19) were isolated from the deep-sea-derived fungus Engyodontium album DFFSCS021. Their structures were identified by extensive spectroscopic analysis. Compounds 8 and 16 showed significant selective cytotoxicity against human histiocytic lymphoma U937 cell line with IC50 values of 4.9 and 8.8 µM, respectively. In addition, this is the first time to report that 8, 15 and 16 had mild antibacterial activity against Escherichia coli and Bacillus subtilis, and 15 showed potent antilarval activity against barnacle Balanus amphitrite larval settlement.

Four-wavelength microdisk laser array laterally coupled with a bus waveguide.

A four-wavelength microdisk laser array laterally coupled with a bus waveguide is demonstrated numerically and experimentally. The coupled-mode characteristics as well as scattering loss in the bus waveguide caused by the connected microdisks are simulated by a 2D finite-difference time-domain technique. An AlGaInAs/InP microdisk laser array with circular radii of 10.1, 10.2, 10.3, and 10.4 µm is designed and fabricated by common photolithography and an inductively coupled-plasma etching technique. Continuous-wave electrically injected operation is realized at room temperature with the lowest threshold current of 3 mA. Four-wavelength lasing operation is realized with wavelength intervals of 3-4 nm and side mode suppression ratios larger than 25 dB. Finally, the influences of heating effect and thermal cross talk on lasing mode wavelength tuning are investigated experimentally.

Analysis of vertical radiation loss and far-field pattern for microcylinder lasers with an output waveguide.

Vertical radiation loss and far-field pattern are investigated for microcylinder lasers by 3D FDTD simulation and experimentally. The numerical results show that an output waveguide connected to the microcylinder resonator can result in additional vertical radiation loss for high Q coupled modes and affect the far field pattern. The vertical radiation loss can be controlled by adjusting the up cladding layer thickness. Furthermore, two lobes of vertical far-field patterns are observed for a 15-µm-radius microcylinder laser connected with an output waveguide, which confirms the vertical radiation loss.

High-Q modes in defected microcircular resonator confined by metal layer for unidirectional emission.

Defected circular resonators laterally confined by a metal layer with a flat side as an emitting window are numerically investigated based on the boundary element method for realizing unidirectional emission microlasers. The results indicate that Fabry-Pérot (FP) modes become high Q confined modes in the defected circular resonator with a metallic layer. The mode coupling between the FP mode and chaotic-like mode can result in high Q confined mode for unidirectional emission with a narrow far field pattern.

Wide-angle emission and single-mode deformed circular microlasers with a flat side.

We demonstrate wide-angle emission and single mode operation in deformed circular microlasers with a flat side. The mode characteristics of a metallic confined deformed circular resonator with a flat side are investigated by finite-difference time-domain simulation. The numerical results indicate that this structure is suitable to realize wide-angle emission. Furthermore, metallic confined deformed circular microlasers with a flat side are fabricated using common photolithography and inductively coupled-plasma etching techniques. A continuous-wave single-mode operation with a side mode suppression ratio of 25 dB is achieved at an injection current of 4 mA for an 8 µm radius microlaser with a flat side. Additionally, wide angle emission over 120° is observed from the far-field pattern.