Icaritin exhibits potential drug-drug interactions through the inhibition of human UDP-glucuronosyltransferase in vitro.

Icaritin is a prenylflavonoid derivative of the genus Epimedium (Berberidaceae) and has a variety of pharmacological actions. Icaritin is approved by the National Medical Products Administration as an anticancer drug that exhibits efficacy and safety advantages in patients with hepatocellular carcinoma cells. This study aimed to evaluate the inhibitory effects of icaritin on UDP-glucuronosyltransferase (UGT) isoforms. 4-Methylumbelliferone (4-MU) was employed as a probe drug for all the tested UGT isoforms using in vitro human liver microsomes (HLM). The inhibition potentials of UGT1A1 and 1A9 in HLM were further tested by employing 17ß-estradiol (E2) and propofol (PRO) as probe substrates, respectively. The results showed that icaritin inhibits UGT1A1, 1A3, 1A4, 1A7, 1A8, 1A10, 2B7, and 2B15. Furthermore, icaritin exhibited a mixed inhibition of UGT1A1, 1A3, and 1A9, and the inhibition kinetic parameters (Ki) were calculated to be 3.538, 2.117, and 0.306 (µM), respectively. The inhibition of human liver microsomal UGT1A1 and 1A9 both followed mixed mechanism, with Ki values of 2.694 and 1.431 (µM). This study provides supporting information for understanding the drug-drug interaction (DDI) potential of the flavonoid icaritin and other UGT-metabolized drugs in clinical settings. In addition, the findings provide safety evidence for DDI when liver cancer patients receive a combination therapy including icaritin.

Immune-Related Molecules CD3G and FERMT3: Novel Biomarkers Associated with Sepsis.

Sepsis ranks among the most common health problems worldwide, characterized by organ dysfunction resulting from infection. Excessive inflammatory responses, cytokine storms, and immune-induced microthrombosis are pivotal factors influencing the progression of sepsis. Our objective was to identify novel immune-related hub genes for sepsis through bioinformatic analysis, subsequently validating their specificity and potential as diagnostic and prognostic biomarkers in an animal experiment involving a sepsis mice model. Gene expression profiles of healthy controls and patients with sepsis were obtained from the Gene Expression Omnibus (GEO) and analysis of differentially expressed genes (DEGs) was conducted. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to analyze genes within crucial modules. The functional annotated DEGs which related to the immune signal pathways were used for constructing protein-protein interaction (PPI) analysis. Following this, two hub genes, FERMT3 and CD3G, were identified through correlation analyses associated with sequential organ failure assessment (SOFA) scores. These two hub genes were associated with cell adhesion, migration, thrombosis, and T-cell activation. Furthermore, immune infiltration analysis was conducted to investigate the inflammation microenvironment influenced by the hub genes. The efficacy and specificity of the two hub genes were validated through a mice sepsis model study. Concurrently, we observed a significant negative correlation between the expression of CD3G and IL-1ß and GRO/KC. These findings suggest that these two genes probably play important roles in the pathogenesis and progression of sepsis, presenting the potential to serve as more stable biomarkers for sepsis diagnosis and prognosis, deserving further study.

Structural and Functional Abnormalities of Olfactory-Related Regions in Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

BACKGROUND: Odor identification (OI) dysfunction is an early marker of Alzheimer's disease (AD), but it remains unclear how olfactory-related regions change from stages of subjective cognitive decline (SCD) and mild cognitive impairment (MCI) to AD dementia. METHODS: Two hundred and sixty-nine individuals were recruited in the present study. The olfactory-related regions were defined as the regions of interest, and the grey matter volume (GMV), low-frequency fluctuation, regional homogeneity (ReHo), and functional connectivity (FC) were compared for exploring the changing pattern of structural and functional abnormalities across AD, MCI, SCD, and normal controls. RESULTS: From the SCD, MCI to AD groups, the reduced GMV, increased low-frequency fluctuation, increased ReHo, and reduced FC of olfactory-related regions became increasingly severe, and only the degree of reduced GMV of hippocampus and caudate nucleus clearly distinguished the 3 groups. SCD participants exhibited reduced GMV (hippocampus, etc.), increased ReHo (caudate nucleus), and reduced FC (hippocampus-hippocampus and hippocampus-parahippocampus) in olfactory-related regions compared with normal controls. Additionally, reduced GMV of the bilateral hippocampus and increased ReHo of the right caudate nucleus were associated with OI dysfunction and global cognitive impairment, and they exhibited partially mediated effects on the relationships between OI and global cognition across all participants. CONCLUSION: Structural and functional abnormalities of olfactory-related regions present early with SCD and deepen with disease severity in the AD spectrum. The hippocampus and caudate nucleus may be the hub joining OI and cognitive function in the AD spectrum.

Diagnostic value of Lipoarabinomannan antigen for detecting Mycobacterium tuberculosis in adults and children with or without HIV infection.

OBJECTIVES: Even today, tuberculosis (TB) remains a leading public health problem; yet, the current diagnostic methods still have a few shortcomings. Lipoarabinomannan (LAM) provides an opportunity for TB diagnosis, and urine LAM detection seems to have a promising and widely applicable prospect. DESIGN OR METHODS: Four databases were systematically searched for eligible studies, and the quality of the studies was evaluated using the quality assessment of diagnostic accuracy studies-2 (QUADAS-2). Graphs and tables were created to show sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), the area under the curve (AUC), and so on. RESULTS: Based on the included 67 studies, the pooled sensitivity of urine LAM was 48% and specificity was 89%. In the subgroup analyses, the FujiLAM test had higher sensitivity (69%) and specificity (92%). Furthermore, among patients infected with human immunodeficiency virus (HIV), 50% of TB patients were diagnosed using a urine LAM test. Besides, the CD4+ cell count was inversely proportional to the sensitivity. CONCLUSIONS: Urine LAM is a promising diagnostic test for TB, particularly using the FujiLAM in HIV-infected adults whose CD4+ cell count is ≤100 per µl. Besides, the urine LAM test shows various sensitivities and specificities in different subgroups in terms of age, HIV infection status, CD4+ cell count, and testing method.

Tailorable infrared emission of microelectromechanical system-based thermal emitters with NiO films for gas sensing.

Infrared gas sensors hold great promise in the internet of things and artificial intelligence. Making infrared light sources with miniaturized size, reliable and tunable emission is essential but remains challenging. Herein, we present the tailorability of radiant power and the emergence of new emission wavelength of microelectromechanical system (MEMS)-based thermal emitters with nickel oxide (NiO) films. The coating of NiO on emitters increases top surface emissivity and induces the appearance of new wavelengths between 15 and 19 µm, all of which have been justified by spectroscopic methods. Furthermore, a sensor array is assembled for simultaneous monitoring of concentrations of carbon dioxide (CO2), methane (CH4), humidity, and temperature. The platform shows selective and sensitive detection at room temperature toward CO2 and CH4 with detection limits of around 50 and 1750 ppm, respectively, and also shows fast response/recovery and good recyclability. The demonstrated emission tailorability of MEMS emitters and their usage in sensor array provide novel insights for designing and fabricating optical sensors with good performance, which is promising for mass production and commercialization.

Pooled analysis of LAMP assay for the diagnosis of norovirus infection.

BACKGROUND: Rapid laboratory detection is essential to diagnose norovirus infection. LAMP has many advantages compared with RT-PCR for detecting norovirus, including high sensitivity, high specificity, rapidity, low cost, and intuitive results, which can be easily read with the naked eye with the help of color-based reporters. In this study, we intend to analyze the accuracy of LAMP methods for the diagnosis of norovirus infection. METHODS: Two researchers independently retrieved relevant literature up to January 2021 (PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wan Fang, and VIP). The researchers screened all articles and extracted their research data for meta-analysis. QUADAS-2 tool was used to evaluate the quality of the included studies by Review Manager 5.3. Forest plots were performed by Meta-DiSc 1.4 to evaluate the accuracy of the test. Deeks' funnel plot symmetry tests were conducted by Stata 15.0 to check the potential publication bias. RESULTS: Eleven sets of data extracted from the eight included studies were included for meta-analysis. For the detection of norovirus, the pooled sensitivity, specificity, positive LR, negative LR, diagnostic OR, and their 95% CI were 0.96 (0.95-0.97), 0.99 (0.99-1.00), 91.14 (31.88-260.56), 0.06 (0.04-0.09), and 1473.68 (562.96-3857.70), respectively. Besides, AUC in the SROC curve was 0.9920. CONCLUSION: LAMP had high sensitivity and specificity in terms of the diagnosis of norovirus infection. However, further extension of this approach should be researched to ensure the accuracy and practicability of this hopeful test in the future.

Effects on the complexation of heavy metals onto biochar-derived WEOM extracted from low-temperature pyrolysis.

Biochar-derived water-extractable organic matter (WEOM) was obtained under low-temperature pyrolysis (300 °C) using corncob as raw material. WEOM may affect the mobility and bioavailability of soil heavy metals (HMs) through complexation when biochar was used for soil HM remediation. Herein, the characteristics of complexation between HMs (Cr(III) and Cu(II)) and biochar-derived WEOM were investigated by using spectroscopic techniques in conjunction with parallel factor (PARAFAC) analysis and two-dimensional correlation spectroscopy (2D-COS). Six components were identified by PARAFAC modeling, in which protein-, fulvic- and humic-like components accounted for 48.86%, 25.63% and 25.51%, respectively. A nonlinear model was employed to determine the conditional stability constant (KM) and total ligand concentration (CL) of WEOM-HM complexes. The log KM values were in the range of 4.02-5.04 for WEOM-Cr(III) and 4.04-6.58 for WEOM-Cu(II). The 2D-COS in conjunction with log-transformed synchronous fluorescence spectroscopy (SFS) suggested that WEOM components were preferentially complexed with HMs in the following order: 433/270, 433/335, 496/270, 496/335, 370/335, 433/402, 496/402, 335/290, 402/290 for Cr(III), and 290/280, 390/280, 433/280, 496/280, 433/335, 496/335, 390/335, 433/420, 496/402, 335/290, 316/290 for Cu(II). The results of 2D-FTIR-COS suggested a preferential bonding of Cr(III) to the C-N group of alkyl, and Cu(II) to the CO group of alcohols, ethers and esters. Meanwhile, the CO group of ethers and the CN group of alkyl indicated preferential susceptibilities for the addition of Cr(III) and Cu(II) at different concentrations. In addition, protein-like components had remarkably higher total ligand concentration (CL) than fulvic- or humic-like components.

Supercontinuum generation in varying dispersion and birefringent silicon waveguide.

Ability to selectively enhance the amplitude and maintain high coherence of the supercontinuum signal with long pulses is gaining significance. In this work, an extra degree of freedom afforded by varying the dispersion profile of a waveguide is utilized to selectively enhance supercontinuum. As much as 16 dB signal enhancement in the telecom window and 100 nm of wavelength extension is achieved with a cascaded waveguide, compared to a fixed dispersion waveguide. Waveguide tapering, in particular with increasing width, is determined to have a flatter and more coherent supercontinuum than a fixed dispersion waveguide when longer input pulses are used. Furthermore, due to the strong birefringence of an asymmetric silicon waveguide the supercontinuum signal is broadened by pumping simultaneously with both quasi-transverse electric (TE) and quasi-transverse magnetic (TM) mode in the anomalous dispersion regime. Thus, selective signal generation is obtained by controlling the dispersion for the two modes. Such waveguides offer several advantages over optical fiber as the variation in dispersion can be controlled with greater flexibility in an integrated platform. This work paves the way forward for various applications in fields ranging from medicine to telecom where specific wavelength windows need to be targeted.

Integrated CMOS-compatible Q-switched mode-locked lasers at 1900nm with an on-chip artificial saturable absorber.

We present a CMOS-compatible, Q-switched mode-locked integrated laser operating at 1.9 µm with a compact footprint of 23.6 × 0.6 × 0.78mm. The Q-switching rate is 720 kHz, the mode-locking rate is 1.2 GHz, and the optical bandwidth is 17nm, which is sufficient to support pulses as short as 215 fs. The laser is fabricated using a silicon nitride on silicon dioxide 300-mm wafer platform, with thulium-doped Al2O3 glass as a gain material deposited over the silicon photonics chip. An integrated Kerr-nonlinearity-based artificial saturable absorber is implemented in silicon nitride. A broadband (over 100 nm) dispersion-compensating grating in silicon nitride provides sufficient anomalous dispersion to compensate for the normal dispersion of the other laser components, enabling femtosecond-level pulses. The laser has no off-chip components with the exception of the optical pump, allowing for easy co-integration of numerous other photonic devices such as supercontinuum generation and frequency doublers which together potentially enable fully on-chip frequency comb generation.

CMOS-compatible all-Si metasurface polarizing bandpass filters on 12-inch wafers.

The implementation of polarization controlling components enables additional functionalities of short-wave infrared (SWIR) imagers. The high-performance and mass-producible polarization controller based on Si metasurface is in high demand for the next-generation SWIR imaging system. In this work, we report the first demonstration of all-Si metasurface based polarizing bandpass filters (PBFs) on 12-inch wafers. The PBF achieves a polarization extinction ratio of above 10 dB in power within the passbands. Using the complementary metal-oxide-semiconductor (CMOS) compatible 193nm ArF deep ultra-violet (DUV) immersion lithography and inductively coupled plasma (ICP) etch processing line, a device yield of 82% is achieved.

On-Chip Tailorability of Capacitive Gas Sensors Integrated with Metal-Organic Framework Films.

Gas sensing technologies for smart cities require miniaturization, cost-effectiveness, low power consumption, and outstanding sensitivity and selectivity. On-chip, tailorable capacitive sensors integrated with metal-organic framework (MOF) films are presented, in which abundant coordinatively unsaturated metal sites are available for gas detection. The in situ growth of homogeneous Mg-MOF-74 films is realized with an appropriate metal-to-ligand ratio. The resultant sensors exhibit selective detection for benzene vapor and carbon dioxide (CO2 ) at room temperature. Postsynthetic modification of Mg-MOF-74 films with ethylenediamine decreases sensitivity toward benzene but increases selectivity to CO2 . The reduced porosity and blocked open metal sites caused by amine coordination account for a deterioration in the sensing performance for benzene (by ca. 60 %). The enhanced sensitivity for CO2 (by ca. 25 %) stems from a tailored amine-CO2 interaction. This study demonstrates the feasibility of tuning gas sensing properties by adjusting MOF-analyte interactions, thereby offering new perspectives for the development of MOF-based sensors.

Monolithically integrated erbium-doped tunable laser on a CMOS-compatible silicon photonics platform.

A tunable laser source is a crucial photonic component for many applications, such as spectroscopic measurements, wavelength division multiplexing (WDM), frequency-modulated light detection and ranging (LIDAR), and optical coherence tomography (OCT). In this article, we demonstrate the first monolithically integrated erbium-doped tunable laser on a complementary-metal-oxide-semiconductor (CMOS)-compatible silicon photonics platform. Erbium-doped Al2O3 sputtered on top is used as a gain medium to achieve lasing. The laser achieves a tunability from 1527 nm to 1573 nm, with a >40 dB side mode suppression ratio (SMSR). The wide tuning range (46 nm) is realized with a Vernier cavity, formed by two Si3N4 microring resonators. With 107 mW on-chip 980 nm pump power, up to 1.6 mW output lasing power is obtained with a 2.2% slope efficiency. The maximum output power is limited by pump power. Fine tuning of the laser wavelength is demonstrated by using the gain cavity phase shifter. Signal response times are measured to be around 200 µs and 35 µs for the heaters used to tune the Vernier rings and gain cavity longitudinal mode, respectively. The linewidth of the laser is 340 kHz, measured via a self-delay heterodyne detection method. Furthermore, the laser signal is stabilized by continuous locking to a mode-locked laser (MLL) over 4900 seconds with a measured peak-to-peak frequency deviation below 10 Hz.

Broadband 2-µm emission on silicon chips: monolithically integrated Holmium lasers.

Laser sources in the mid-infrared are of great interest due to their wide applications in detection, sensing, communication and medicine. Silicon photonics is a promising technology which enables these laser devices to be fabricated in a standard CMOS foundry, with the advantages of reliability, compactness, low cost and large-scale production. In this paper, we demonstrate a holmium-doped distributed feedback laser monolithically integrated on a silicon photonics platform. The Al2O3:Ho3+ glass is used as gain medium, which provides broadband emission around 2 µm. By varying the distributed feedback grating period and Al2O3:Ho3+ gain layer thickness, we show single mode laser emission at wavelengths ranging from 2.02 to 2.10 µm. Using a 1950 nm pump, we measure a maximum output power of 15 mW, a slope efficiency of 2.3% and a side-mode suppression ratio in excess of 50 dB. The introduction of a scalable monolithic light source emitting at > 2 µm is a significant step for silicon photonic microsystems operating in this highly promising wavelength region.

High-Q-factor Al2O3 micro-trench cavities integrated with silicon nitride waveguides on silicon.

We report on the design and performance of high-Q integrated optical micro-trench cavities on silicon. The microcavities are co-integrated with silicon nitride bus waveguides and fabricated using wafer-scale silicon-photonics-compatible processing steps. The amorphous aluminum oxide resonator material is deposited via sputtering in a single straightforward post-processing step. We examine the theoretical and experimental optical properties of the aluminum oxide micro-trench cavities for different bend radii, film thicknesses and near-infrared wavelengths and demonstrate experimental Q factors of > 106. We propose that this high-Q micro-trench cavity design can be applied to incorporate a wide variety of novel microcavity materials, including rare-earth-doped films for microlasers, into wafer-scale silicon photonics platforms.

Ultra-narrow-linewidth Al2O3:Er3+ lasers with a wavelength-insensitive waveguide design on a wafer-scale silicon nitride platform.

We report ultra-narrow-linewidth erbium-doped aluminum oxide (Al2O3:Er3+) distributed feedback (DFB) lasers with a wavelength-insensitive silicon-compatible waveguide design. The waveguide consists of five silicon nitride (SiNx) segments buried under silicon dioxide (SiO2) with a layer Al2O3:Er3+ deposited on top. This design has a high confinement factor (> 85%) and a near perfect (> 98%) intensity overlap for an octave-spanning range across near infra-red wavelengths (950-2000 nm). We compare the performance of DFB lasers in discrete quarter phase shifted (QPS) cavity and distributed phase shifted (DPS) cavity. Using QPS-DFB configuration, we obtain maximum output powers of 0.41 mW, 0.76 mW, and 0.47 mW at widely spaced wavelengths within both the C and L bands of the erbium gain spectrum (1536 nm, 1566 nm, and 1596 nm). In a DPS cavity, we achieve an order of magnitude improvement in maximum output power (5.43 mW) and a side mode suppression ratio (SMSR) of > 59.4 dB at an emission wavelength of 1565 nm. We observe an ultra-narrow linewidth of ΔνDPS = 5.3 ± 0.3 kHz for the DPS-DFB laser, as compared to ΔνQPS = 30.4 ± 1.1 kHz for the QPS-DFB laser, measured by a recirculating self-heterodyne delayed interferometer (R-SHDI).

Monolithically-integrated distributed feedback laser compatible with CMOS processing.

An optically-pumped, integrated distributed feedback laser is demonstrated using a CMOS compatible process, where a record-low-temperature deposited gain medium enables integration with active devices such as modulators and detectors. A pump threshold of 24.9 mW and a slope efficiency of 1.3 % is demonstrated at the lasing wavelength of 1552.98 nm. The rare-earth-doped aluminum oxide, used as the gain medium in this laser, is deposited by a substrate-bias-assisted reactive sputtering process. This process yields optical quality films with 0.1 dB/cm background loss at the deposition temperature of 250 °C, and therefore is fully compatible as a back-end-of-line CMOS process. The aforementioned laser's performance is comparable to previous lasers having gain media fabricated at much higher temperatures (> 550 °C). This work marks a crucial step towards monolithic integration of amplifiers and lasers in silicon microphotonic systems.

Wavelength division multiplexed light source monolithically integrated on a silicon photonics platform.

We demonstrate monolithic integration of a wavelength division multiplexed light source for silicon photonics by a cascade of erbium-doped aluminum oxide (Al2O3:Er3+) distributed feedback (DFB) lasers. Four DFB lasers with uniformly spaced emission wavelengths are cascaded in a series to simultaneously operate with no additional tuning required. A total output power of -10.9 dBm is obtained from the four DFBs with an average side mode suppression ratio of 38.1±2.5 dB. We characterize the temperature-dependent wavelength shift of the cascaded DFBs and observe a uniform dλ/dT of 0.02 nm/°C across all four lasers.

Large-scale silicon nitride nanophotonic phased arrays at infrared and visible wavelengths.

We demonstrate passive large-scale nanophotonic phased arrays in a CMOS-compatible silicon photonic platform. Silicon nitride waveguides are used to allow for higher input power and lower phase variation compared to a silicon-based distribution network. A phased array at an infrared wavelength of 1550 nm is demonstrated with an ultra-large aperture size of 4 mm×4 mm, achieving a record small and near diffraction-limited spot size of 0.021°×0.021° with a side lobe suppression of 10 dB. A main beam power of 400 mW is observed. Using the same silicon nitride platform and phased array architecture, we also demonstrate, to the best of our knowledge, the first large-aperture visible nanophotonic phased array at 635 nm with an aperture size of 0.5 mm×0.5 mm and a spot size of 0.064°×0.074°.

High-power thulium lasers on a silicon photonics platform.

Mid-infrared laser sources are of great interest for various applications, including light detection and ranging, spectroscopy, communication, trace-gas detection, and medical sensing. Silicon photonics is a promising platform that enables these applications to be integrated on a single chip with low cost and compact size. Silicon-based high-power lasers have been demonstrated at 1.55 µm wavelength, while in the 2 µm region, to the best of our knowledge, high-power, high-efficiency, and monolithic light sources have been minimally investigated. In this Letter, we report on high-power CMOS-compatible thulium-doped distributed feedback and distributed Bragg reflector lasers with single-mode output powers up to 267 and 387 mW, and slope efficiencies of 14% and 23%, respectively. More than 70 dB side-mode suppression ratio is achieved for both lasers. This work extends the applicability of silicon photonic microsystems in the 2 µm region.

Mid-IR supercontinuum pumped by femtosecond pulses from thulium doped all-fiber amplifier.

We present a mid-infrared (mid-IR) supercontinuum (SC) light source pumped by femtosecond pulses from a thulium doped fiber amplifier (TDFA) at 2 µm. An octave-spanning spectrum from 1.1 to 3.7 µm with an average power of 253 mW has been obtained from a single mode ZBLAN fiber. Spectral flatness of 10 dB over a 1390 nm range has been obtained in the mid-IR region from 1940 - 3330 nm. It is resulted from the enhanced self phase modulation process in femtosecond regime. The all-fiber configuration makes such broadband coherent source a compact candidate for various applications.