Tunable High-Performance Electromagnetic Interference Shielding of VO2 Nanowires-Based Composite.

The unique metal-insulator transition of VO2 is very suitable for dynamic electromagnetic (EM) regulation materials due to its sharp change in electrical conductivity. Here, we have developed an off/on switchable electromagnetic interference (EMI) shielding composite by interconnecting VO2 nanowires (NWs) in poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) to form conductive networks, resulting in outstanding performance at the X and Ku bands with maximum change values of 44.8 and 59.4 dB, respectively. The unique insulator-to-metal transition (IMT) of VO2 NWs has dominated the variation of polarization loss (εp″) and conductivity loss (εσ″) for the composites, which is the mechanism of EMI shielding switching between off and on states. Furthermore, the composite exhibits good cycling stability of the off/on switchable EMI shielding performance and has excellent mechanical properties, especially with 200 times abrasion resistance without obvious weight loss. This study provides a unique approach for dynamic switching of EM response with the potential to construct practical intelligent EM response systems for next-generation smart electromagnetic devices in various scenarios.

A Time Mode Pulse Interleaver in a Silicon-on-Insulator Platform for Optical Analog-to-Digital Converters.

We propose and demonstrate a novel on-chip optical sampling pulse interleaver based on time mode interleaving. The designed pulse interleaver was fabricated on a 220 nm silicon-on-insulator (SOI) platform, utilizing only one S-shaped delay waveguide. Interleaving is achieved by the relative time delay between different optical modes in the waveguide, eliminating the need for any active tuning. The total length of the delay waveguide is 5620.5 µm, which is reduced by a factor of 46.3% compared with previously reported time-wavelength interleaver schemes. The experimental results indicate that the device can convert an optical pulse into a 40 GHz pulse sequence composed of four pulses with a root mean square (RMS) timing error of 0.9 ps, making it well suited for generating high-frequency sampling pulses for optical analog-to-digital converters.

Unprecedented Spatial Manipulation and Transformation of Dynamic Thermal Radiation Based on Vanadium Dioxide.

Reconfigurable infrared (IR) materials have widespread applications in thermal management and smart IR concealment. Although various reconfigurable IR materials can be customized by positive or negative differential VO2-based resonators, their insightful mechanism remains unknown. Here, we comprehensively investigate the fundamental design rule of reconfigurable thermal radiation between positive and negative differential thermal radiation properties for the first time. Importantly, the skin depth of VO2 film in the metal state is investigated to clarify the transformation from positive to negative differential thermal radiation properties, and the critical thickness is further derived, providing important guidance in designing the reconfigurable thermal radiation regulator. Furthermore, the reconfigurable multistate thermal images had been presented into one plate. The resulting emittance variation (△ε8-14 µm) of the VO2-based resonator can change from 0.61 to -0.53, which consummates the ability for diverse demands such as infrared concealment, thermal illusion, and thermal management. This work constitutes a promising and universal route toward designing whole smart devices and may create new scientific and technological opportunities for platforms that can benefit from reconfigurable electromagnetic manipulation.

γ-Secretase inhibitor alleviates lipopolysaccharide-induced myocardial injury through regulating JAK2/STAT3 signaling.

BACKGROUND: Septic myocardial injury is one of the most life-threatening organ dysfunction. The γ-secretase-based approaches have been developed as potential strategies for diverse diseases management. Unfortunately, the role of γ-secretase inhibitor in septic myocardial injury is unclarified. The present study aims to investigate the effect of γ-secretase inhibitor in septic myocardial injury and reveal its mechanism. METHODS: The mouse model of septic myocardial injury was established by intraperitoneally injection of lipopolysaccharide (LPS), and γ-secretase inhibitor MW167 was applied in this model. RNA-sequencing analysis and further bioinformatics analyses were used to screen differential expressed genes (DEGs) and potentially enriched pathways between LPS and LPS + MW167 mice. Pathological examination was performed using haematoxylin and eosin (HE) staining. SD-1029 was used to block JAK2/STAT3 signaling in H9C2 cells and western blot analysis quantified JAK2/STAT3-related proteins. RESULTS: LPS induced myocardial injury accompanied with significant inflammatory infiltration and more apoptotic cells. Transcriptome sequencing screened 36 DEGs and bioinformatics identified JAK2/STAT3 signaling pathway was significantly enriched. Further in vitro experiments showed that γ-secretase inhibitor MW167 activated JAK2/STAT3 pathway. Additionally, MW167 restored cell viability, decreased myocardial injury markers including cardiac troponin I (cTnI) and brain natriuretic peptide (BNP), inhibited pro-inflammatory cytokines such as interleukin (IL)-1ß and tumor necrosis factor-α (TNF-α) and reduced nitric oxide (NO), cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) release. Application of SD-1029 reversely deteriorated LPS-induced myocardial injury and inflammatory response in γ-secretase inhibitor-treated myocardial cells. CONCLUSION: The results demonstrate that γ-secretase inhibitor alleviates septic myocardial injury via activating JAK2/STAT3 signaling, and provide novel therapeutic direction for septic myocardial injury.

Monolithically integrated 128-channel hybrid mode/polarization/wavelength (de)multiplexer on silicon-on-insulator.

In this paper, we proposed a 128-channel hybrid mode/polarization/wavelength (de)multiplexer by monolithically integrating four 16-wavelength-channel (de)multiplexers based on bi-directional MRRs arrays and an 8-channel hybrid mode/polarization (de)multiplexer. The hybrid mode/polarization (de)multiplexer consists of a polarization beam splitter (PBS) and cascaded six asymmetric directional couplers (ADCs). The present 128-channel hybrid (de)multiplexer utilizes four modes, dual polarizations, and sixteen wavelengths to improve the data transmission capacity of optical communication systems. For the fabricated hybrid (de)multiplexer, the channel spacing is 1.4 nm, and we used thermal tuning electrodes with a tuning efficiency of 0.45 nm/mW to calibrate resonance wavelengths. The measurement results show the insertion loss is 3∼8.5 dB, the inter-mode crosstalk is -7∼-23 dB, and the inter-wavelength crosstalk is-8∼-20 dB. The proposed (de)multiplexer is a promising approach to enhance the transmission capacity and has great potential in high-speed data transmission.

Genome-wide CRISPR off-target prediction and optimization using RNA-DNA interaction fingerprints.

The powerful CRISPR genome editing system is hindered by its off-target effects, and existing computational tools achieved limited performance in genome-wide off-target prediction due to the lack of deep understanding of the CRISPR molecular mechanism. In this study, we propose to incorporate molecular dynamics (MD) simulations in the computational analysis of CRISPR system, and present CRISOT, an integrated tool suite containing four related modules, i.e., CRISOT-FP, CRISOT-Score, CRISOT-Spec, CRISORT-Opti for RNA-DNA molecular interaction fingerprint generation, genome-wide CRISPR off-target prediction, sgRNA specificity evaluation and sgRNA optimization of Cas9 system respectively. Our comprehensive computational and experimental tests reveal that CRISOT outperforms existing tools with extensive in silico validations and proof-of-concept experimental validations. In addition, CRISOT shows potential in accurately predicting off-target effects of the base editors and prime editors, indicating that the derived RNA-DNA molecular interaction fingerprint captures the underlying mechanisms of RNA-DNA interaction among distinct CRISPR systems. Collectively, CRISOT provides an efficient and generalizable framework for genome-wide CRISPR off-target prediction, evaluation and sgRNA optimization for improved targeting specificity in CRISPR genome editing.

A Novel Silicon Forward-Biased PIN Mach-Zehnder Modulator with Two Operating States.

In this paper, we demonstrate a silicon forward-biased positive intrinsic negative (PIN) Mach-Zehnder modulator (MZM), which has two operating states of high efficiency and high speed. The two operating states are switched by changing the position where the electric signal is loaded. The modulator incorporates a PIN phase shifter integrated with the passive resistance and capacitance (RC) equalizer (PIN-RC), which expands the electro-optic (E-O) bandwidth by equalizing it with modulation efficiency. The fabricated modulator exhibits a low insertion loss of 1.29 dB in two operating states and a compact design with a phase shifter length of 500 µm. The modulation efficiencies are 0.0088 V·cm and 1.43 V·cm, and the corresponding 3 dB E-O bandwidths are 200 MHz and 7 GHz, respectively. The high-speed modulation performance of the modulator is confirmed by non-return-to-zero (NRZ) modulation with a data rate of 15 Gbps without any pre-emphasis or post-processing. The presented modulator shows functional flexibility, low insertion loss, and a compact footprint, and it can be suitable for applications like optical switch arrays and analog signal processing.

Silicon nitride assisted tri-layer edge coupler on lithium niobate-on-insulator platform.

Lithium niobate-on-insulator (LNOI) is a promising integration platform for various applications, such as optical communication, microwave photonics, and nonlinear optics. To make Lithium niobate (LN) photonic integrated circuits (PICs) more practical, low-loss fiber-chip coupling is essential. In this Letter, we propose and experimentally demonstrate a silicon nitride (SiN) assisted tri-layer edge coupler on LNOI platform. The edge coupler consists of a bilayer LN taper and an interlayer coupling structure composed of an 80 nm-thick SiN waveguide and an LN strip waveguide. The measured fiber-chip coupling loss for the TE mode is 0.75 dB/facet at 1550 nm. Transition loss between the SiN waveguide and LN strip waveguide is ∼0.15 dB. In addition, the fabrication tolerance of the SiN waveguide in the tri-layer edge coupler is high.

[Effects of Fusobacterium nucleus derived outer membrane vesicles on claudin-4 expression in oral epithelial cells].

PURPOSE: To investigate the effect of outer membrane vesicles (OMVs) secreted by Fusobacterium nucleatum (F.n) on Claudin-4 of human oral keratinocytes (HOK) and oral epithelial barrier function. METHODS: Fusobacterium nucleatum was cultured under anaerobic conditions. The OMVs were extracted by dialysis and characterized by nanosight and transmission electron microscopy (TEM). HOK were stimulated with OMVs at different mass concentrations(0-100 µg/mL) for 12 h, and stimulated with 100 µg/mL OMVs for 6 h and 12 h respectively. The expression of Claudin-4 at gene and protein level was analyzed by RT-qPCR and Western blotting. Inverted fluorescence microscope was used to observe co-localization of HOK and OMVs and localization and distribution of Claudin-4 protein. Human oral epithelial barrier was constructed by Transwell apical chamber. Transepithelial electrical resistance(TER) of barrier was measured with a transmembrane resistance measuring instrument(EVOM2), and the permeability of the barrier was evaluated by transmittance of fluorescein isothiocyanate-dextran(FD-4). Statistical analysis was performed with GraphPad Prism 8.0 software package. RESULTS: Compared with the control group, the expression of Claudin-4 at protein and gene level in the HOK of OMVs stimulated group was significantly reduced (P＜0.05), and immunofluorescence showed that the continuity of Claudin-4 fluorescence among cells was destroyed. OMVs stimulation decreased TER value of oral epithelial barrier(P＜0.05) and increased the transmittance of FD-4(P＜0.05). CONCLUSIONS: OMVs derived from Fusobacterium nucleatum may damage oral mucosal epithelial barrier function through inhibiting the expression of Claudin-4.

Amelioration effects of α-viniferin on hyperuricemia and hyperuricemia-induced kidney injury in mice.

BACKGROUND: α-Viniferin, the major constituent of the roots of Caragana sinica (Buc'hoz) Rehder with a trimeric resveratrol oligostilbenoid skeleton, was demonstrated to possess a strong inhibitory effect on xanthine oxidase in vitro, suggesting it to be a potential anti-hyperuricemia agent. However, the in vivo anti-hyperuricemia effect and its underlying mechanism were still unknown. PURPOSE: The current study aimed to evaluate the anti-hyperuricemia effect of α-viniferin in a mouse model and to assess its safety profile with emphasis on its protective effect on hyperuricemia-induced renal injury. METHODS: The effects were assessed in a potassium oxonate (PO)- and hypoxanthine (HX)-induced hyperuricemia mice model by analyzing the levels of serum uric acid (SUA), urine uric acid (UUA), serum creatinine (SCRE), serum urea nitrogen (SBUN), and histological changes. Western blotting and transcriptomic analysis were used to identify the genes, proteins, and signaling pathways involved. RESULTS: α-Viniferin treatment significantly reduced SUA levels and markedly mitigated hyperuricemia-induced kidney injury in the hyperuricemia mice. Besides, α-viniferin did not show any obvious toxicity in mice. Research into the mechanism of action of α-viniferin revealed that it not only inhibited uric acid formation by acting as an XOD inhibitor, but also reduced uric acid absorption by acting as a GLUT9 and URAT1 dual inhibitor as well as promoted uric acid excretion by acting as a ABCG2 and OAT1 dual activator. Then, 54 differentially expressed (log2 FPKM ≥ 1.5, p ≤ 0.01) genes (DEGs) repressed by the treatment of α-viniferin in the hyperuricemia mice were identified in the kidney. Finally, gene annotation results revealed that downregulation of S100A9 in the IL-17 pathway, of CCR5 and PIK3R5 in the chemokine signaling pathway, and of TLR2, ITGA4, and PIK3R5 in the PI3K-AKT signaling pathway were involved in the protective effect of α-viniferin on the hyperuricemia-induced renal injury. CONCLUSIONS: α-Viniferin inhibited the production of uric acid through down-regulation of XOD in hyperuricemia mice. Besides, it also down-regulated the expressions of URAT1 and GLUT9 and up-regulated the expressions of ABCG2 and OAT1 to promote the excretion of uric acid. α-Viniferin could prevent hyperuricemia mice from renal damage by regulating the IL-17, chemokine, and PI3K-AKT signaling pathways. Collectively, α-viniferin was a promising antihyperuricemia agent with desirable safety profile. This is the first report of α-viniferin as an antihyperuricemia agent.

Comparative transcriptome analysis of Saposhnikovia divaricata to reveal drought and rehydration adaption strategies.

BACKGROUND: Water scarcity has become one of the most prevalent environmental factors adversely affecting plant growth and development. Different species have developed multiple ways of drought resistance. Saposhnikovia divaricata is a commonly used traditional herb in East Asia. However, limited information is available on the drought response of this herb and further clarification of underlying molecular mechanism remains a challenge. METHODS AND RESULTS: In this study, a comparative transcriptome analysis was firstly conducted to identify the major pathways and candidate genes involved in the drought adaptive response of S. divaricata. The seedlings of S. divaricata were subjected to progressive drought by withholding water for 16 days followed by 8 days of rehydration. Transcriptome analysis identified a total of 89,784 annotated unigenes. The number of differentially expressed genes (DEGs) gradually increased with the deepening of drought and decreased after rehydration. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested genes related to oxidoreductase activity, carbohydrate metabolism, plant hormone signaling pathway and secondary metabolism were important in drought response of S. divaricata. Specific genes involved in reactive oxygen species scavenging system (POD, Cu/Zn-SOD, APX), abscisic acid and jasmonic acid signaling pathway (PYL4, PP2Cs, JAR1, JAZ) and phenylpropanoid biosynthesis (4CL, CCR, CAD) underwent dynamic alterations under drought and rehydration. Finally, the expression pattern of 12 selected DEGs from the transcriptomic profiling was validated by real-time quantitative PCR. CONCLUSION: Our study laid a foundation for understanding the stress response of S. divaricata and other Apiaceae family plant at molecular level.

The expression and biological effect of NR2F6 in non-small cell lung cancer.

Objective: This study aimed to explore the expression and effect of the nuclear receptor subfamily 2 group F member 6 (NR2F6) gene in non-small cell lung cancer (NSCLC) and provide an experimental basis for the targeted therapy of NSCLC. Method: First, the expression of NR2F6 in lung cancer tissues was analyzed using the Gene Expression Omnibus and the Cancer Genome Atlas (TCGA) databases, and the expression of NR2F6 in lung cancer tissues and cells was verified by Western blotting and quantitative polymerase chain reaction. Next, the relationship between NR2F6 expression and the clinicopathological features of lung cancer was analyzed via immunohistochemistry, and the relationship between NR2F6 expression and prognosis was analyzed using the Kaplan-Meier Plotter. The influence of NR2F6 knockdown on the proliferation capacity of lung cancer cells was then verified at cell level. Finally, the expression of heterogeneous nuclear ribonucleoprotein D (HNRNPD) in lung cancer tissue was analyzed using the TCGA database and immunohistochemistry. The impact of HNRNPD knockdown on the proliferation capacity of lung cancer cells was verified at cell level, and the relationship between NR2F6 and HNRNPD was verified by co-immunoprecipitation. Results: NR2F6 was highly expressed in lung cancer tissues and cells, and its expression was positively correlated with the depth of invasion, lymphatic metastasis, and clinical stage of lung cancer. High expression of NR2F6 in lung cancer was also significantly associated with poor prognosis. At cell level, NR2F6 knockdown was found to inhibit the proliferation of H460 and H358 in lung cancer cells. Furthermore, the TCGA database and immunohistochemical results showed that HNRNPD was highly expressed in lung cancer tissues and was highly consistent with NR2F6 expression in these tissues. Knockdown of HNRNPD also inhibited the proliferation of lung cancer cells. The co-immunoprecipitation experiment verified that NR2F6 interacted with HNRNPD. Conclusion: NR2F6 may interact with HNRNPD to jointly regulate the progression of lung cancer, and this conclusion provides a new experimental basis for the study of the molecular targeted therapy of NSCLC.

PALD encoding a lipid droplet-associated protein is critical for the accumulation of lipid droplets and pollen longevity in Arabidopsis.

Pollen longevity is critical for plant pollination and hybrid seed production, but few studies have focused on pollen longevity. In this study, we identified an Arabidopsis thaliana gene, Protein associated with lipid droplets (PALD), which is strongly expressed in pollen and critical for the regulation of pollen longevity. PALD was expressed specifically in mature pollen grains and the pollen tube, and its expression was upregulated under dry conditions. PALD encoded a lipid droplet (LD)-associated protein and its N terminus was critical for the LD localization of PALD. The number of LDs and diameter were reduced in pollen grains of the loss-of-function PALD mutants. The viability and germination of the mature pollen grains of the pald mutants were comparable with those of the wild-type, but after the pollen grains were stored under dry conditions, pollen germination and male transmission of the mutant were compromised compared with those of the wild-type. Our study suggests that PALD was required for the maintenance of LD quality in mature pollen grains and regulation of pollen longevity.

VO2-Based Infrared Radiation Regulator with Excellent Dynamic Thermal Management Performance.

Dynamic thermal management materials attract fast-increasing interest due to their adaptability to changing environments and greater energy savings as compared to static materials. However, the high transition temperature and the low emittance tunability of the vanadium dioxide (VO2)-based infrared radiation regulators limit their practical applications. This study addresses these issues by proposing a smart infrared radiation regulator based on a Fabry-Pérot cavity structure (VO2/HfO2/Al), which is prepared by high-power impulse magnetron sputtering (HiPIMS) and has the potential for large-scale production. Remarkably, the outstanding emittance tunability reaches 0.51, and the phase transition temperature is lowered to near a room temperature of 27.5 °C by tungsten (W) doping. In addition, a numerical thermal management power of 196.3 W/m2 (at 8-14 µm band) can be obtained from 0 to 60 °C. As a proof-of-concept, the demonstrated capabilities of the VO2 infrared radiation regulator show great potentials in a wide range of applications for the thermal management of buildings and vehicles.

Intralesional and peripheral plasma of oral lichenoid reactions exhibit different cytokine profiles: A preliminary study.

BACKGROUND/PURPOSE: Oral lichenoid reactions (OLRs) are commonly characterized by the infiltration and activation of inflammatory cells at the interface of the oral mucosa. This study aimed to compare the cytokine profiles between intralesional and peripheral plasma from patients with OLRs and elucidate the cytokine profile in the OLR microenvironment. MATERIALS AND METHODS: A total of 26 paired intralesional and peripheral plasma samples were collected from patients with OLRs. A panel of 15 cytokines was measured using a Luminex assay. The reticular, erythema, and ulcerative score was used to evaluate the degree of OLR severity. RESULTS: IL-10 was detected in a fewer number of intralesional samples (19/26) compared to peripheral samples (26/26, p = 0.01). The intralesional plasma exhibited significantly elevated levels of granzyme B (median 108.94 vs. 16.00), TGF-ß1 (mean 30448.92 vs. 10199.04), TGF-ß2 (mean 1659.73 vs. 1308.49), and TGF-ß3 (mean 914.33 vs. 573.13) compared to the peripheral plasma (p = 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). The levels of intralesional IL-2 (median 2.84 vs. 3.45, p = 0.019) and TNF-α (median 7.66 vs. 10.34, p = 0.048) were significantly lower in the intralesional plasma compared to the peripheral plasma. CONCLUSION: The intralesional concentrations of granzyme B and TGF-ß were elevated, whereas IL-2 and TNF-α were decreased in the OLR microenvironment compared to the peripheral plasma. These findings may contribute to establishing a panel of biomarkers that can be used to monitor the disease activity of OLRs in a large cohort study in future.

Three-dimensional digital measurement of the facet joint in normal individual and lumbar intervertebral disc herniation patients aged 13 - 18 years.

BACKGROUND: Lumbar facet joint is an important element of spinal "three-joint complex". Whether there is a relationship between strange structure of facet joint and adolescent lumbar disc herniation (ALDH) is nonetheless controversial, and the current research is mainly centered on adults. OBJECTIVE: To find out the normal lumbar facet joints between 13 and 18 years old to provide anatomical basis for early diagnosis and therapy of lumbar disc herniation. METHODS: CT imaging information of 32 sufferers with lumbar disc herniation aged from 13 to 18 years old in Inner Mongolia have been collected as the ALDH group, and 62 wholesome subjects in the equal period had been chosen as the normal group. Uncooked records of continuous scanning lumbar tomography pix were imported into MIMICS 21.0 for evaluation and size in DICOM format. The parameters include facet joint height, facet joint width, et al. RESULTS: 1. The left and right transverse angle of L5S1 segment in the ALDH group were (52.41 ± 9.2) ° and (55.99 ± 10.91) ° (P < 0.05), and the differences were statistically significant. The right side is larger than the left side. 2. Facet joint thickness in L3-L5 segment of the normal group was significantly higher than that of male (1.63 ± 0.32) mm than that of female (1.38 ± 0.25) mm; In 16-18 years old group, comparison of facet joint cross-sectional area was statistically significant (22.1 ± 3.04) mm2 in male than (18.92 ± 3.71) mm2 in female. 3. In comparison between normal and ALDH group, there was significant difference in L3-4 transverse angle (P < 0.05), L4-5 facet joint height and facet joint thickness (P < 0.05), L5S1 facet joint thickness and transverse angle (P < 0.05). CONCLUSION: When ALDH occurs in the L5S1 segment, there is a substantial difference between the left and right sides of the transverse angle, and there is a difference in the thickness and the facet joint cross-sectional area between males and females, which is generally larger in males than in females. Facet joint height is larger, transverse angle of left and right is asymmetric, inferior articular process is larger, and facet joint thickness is smaller can indicate that lumbar disc herniation is effortless to occur.

C-band four-channel CWDM (de-)multiplexers on a thin film lithium niobate-silicon rich nitride hybrid platform.

A four-channel coarse wavelength division multiplexing (CWDM) (de)multiplexer on a thin film lithium niobate-silicon rich nitride hybrid platform has been designed, fabricated, and experimentally measured. Enabled by cascaded multimode waveguide Bragg gratings, the (de)multiplexer has a box-like spectral response, wide 1-dB bandwidth (10 nm), low excess loss (<1.08dB), and low channel cross talk (<-18dB). The central wavelengths of the (de-)multiplexer are 1531/1551/1571/1591 nm, which align to the wavelength grids stipulated by the standard ITU-T G.694.2.

Antihyperuricemia and antigouty arthritis effects of Persicaria capitata herba in mice.

BACKGROUND: Hyperuricemia (HUA) is an important risk factor for gout, renal dysfunction and cardiovascular diseases. The whole plant of Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, namely Persicaria capitata herba, is a well-known ethnic herb with potent therapeutic effects on urinary tract infections and urinary calculus, yet previous reports have only focused on its effect on urinary tract infections. PURPOSE: To evaluate the therapeutic potential of P. capitata herba against gout by investigating its antihyperuricemia and antigouty arthritis effects and possible mechanisms. METHODS: The ethanol extract (EP) and water extract (WP) of P. capitata herba were prepared by extracting dried and ground whole plants of P. capitata with 75% ethanol and water, respectively, followed by removal of solvents and characterization by UHPLC-Q-TOF/MS. The antihyperuricemia and antigouty arthritis effects of the two extracts were evaluated in a potassium oxonate- and hypoxanthine-induced hyperuricemia mouse model and a monosodium urate crystal (MSUC)-induced acute gouty arthritis mouse model, respectively. The mechanisms were investigated by testing their effects on the expression of correlated proteins (by Western blot) and mRNAs (by RT-PCR). RESULTS: UHPLC-HRMS fingerprinting and two chemical markers (i.e., quercetin and quercitrin) determination were used for the characterization of the WP and EP extracts. Both WP and EP extracts showed pronounced antihyperuricemia activities, with a remarkable decline in serum uric acid and a marked increase in urine uric acid in hyperuricemic mice. Unlike the clinical xanthine oxidase (XOD) inhibitor allopurinol, WP and EP did not show any distinct renal toxicities. The underlying antihyperuricemia mechanism involves the inhibition of the activity and expression of XOD and the downregulation of the mRNA and protein expression of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1). The extracts of P. capitata herba also demonstrated remarkable anti-inflammatory activity in MSUC-induced acute gouty arthritis mice. The mechanism might involve inhibitory effects on the expression of proinflammatory factors. CONCLUSIONS: The extracts of P. capitata herba possessed pronounced antihyperuricemia and antigouty arthritis effects and were, therefore, promising natural medicines for hyperuricemia-related disorders and gouty arthritis. The use of P. capitata herba for the treatment of urinary calculus may be, at least to some degree, related to its potential as an antihyperuricemia and antigouty arthritis drug.

On-chip four-mode (de-)multiplexer on thin film lithium niobate-silicon rich nitride hybrid platform.

A four-mode (de-)multiplexer with transverse electric field light (TE0-TE3) is experimentally demonstrated on a thin film lithium niobate-silicon rich nitride hybrid platform. Enabled by cascaded asymmetrical directional couplers, a (de-)multiplexer with low insertion loss (0.38 dB to 1.6 dB) and low cross talk (-18.46dB to -20.43dB) is obtained at 1550 nm. All channels have cross talk <-16dB from 1480 nm to 1580 nm. The transmission of 4×50 Gbps on-off keying signals is experimentally achieved on the proposed (de-)multiplexer. Experimental results show that the proposed (de-)multiplexer is a promising approach to enhance the transmission capacity in thin film lithium niobate based photonics integrated circuits.

Design, synthesis, and biological evaluation of 2,4-diamino pyrimidine derivatives as potent FAK inhibitors with anti-cancer and anti-angiogenesis activities.

A series of 2,4-diamino pyrimidine (DAPY) derivatives were designed, synthesized, and evaluated as inhibitors of focal adhesion kinase (FAK) with antitumor and anti-angiogenesis activities. Most compounds effectively suppressed the enzymatic activities of FAK, and the IC50s of 11b and 12f were 2.75 and 1.87 nM, respectively. 11b and 12f exhibited strong antiproliferative effects against seven human cancer cells, with IC50 values against two FAK-overexpressing pancreatic cancer cells (PANC-1 and BxPC-3) of 0.98 µM, 0.55 µM, and 0.11 µM, 0.15 µM, respectively. Moreover, 11b and 12f obviously suppressed the colony formation, migration, and invasion of PANC-1 cells in a dose-dependent manner. Meanwhile, these two compounds could induce the apoptosis of PANC-1 cells and arrest the cell cycle in G2/M phase according to the flow cytometry assay. Western blot revealed that 11b and 12f effectively inhibited the FAK/PI3K/Akt signal pathway and significantly decreased the expression of cyclin D1 and Bcl-2. In addition, compounds 11b and 12f potently inhibited the antiproliferative of HUVECs and obviously altered the cell morphology. 11b and 12f also significantly inhibited the migration, tube formation of HUVECs and severely impaired the angiogenesis in the zebrafish model. Overall, these results revealed the potential of compounds 11b and 12f as promising candidates for further preclinical studies.