HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma.

BACKGROUND AND AIMS: The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC. APPROACH AND RESULTS: Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n  = 106) and an independent validation cohort ( n  = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99). CONCLUSION: HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.

Grating-assisted hot-electron photodetectors for S- and C-band telecommunication.

Although outstanding detectivities, InGaAs photodetectors for optic fiber communication are often costly due to the need for cooling. Therefore, cryogen-free and cost-effective alternatives working in telecommunication bands are highly desired. Here, we present a design of hot-electron photodetectors (HE PDs) with attributes of room-temperature operation and strong optical absorption over S and C bands (from 1460 to 1565 nm). The designed HE PD consists of a metal-semiconductor-metal hot-electron stack integrated with a front grating. Optical simulations reveal that mode hybridizations between Fabry-Pérot resonance and grating-induced surface plasmon excitation lead to high absorption efficiencies (≥0.9) covering S and C bands. Probability-based electrical calculations clarify that device responsivity is mainly determined by working wavelength on the premise of broadband strong absorption. Moreover, through comparison studies between the grating-assisted HE PD and purely planar microcavity system that serves as a reference, we highlight the design superiorities in average absorption and average responsivity with optimized values of 0.97 and 0.73 mA W-1, respectively. The upgraded peformances of the designed device are promising for efficient photoelectric conversion in optic fiber communication systems.

High sensitivity Sagnac interferometric temperature sensor using stress region refractive index modulation.

An all-fiber temperature sensor employing intentional refractive index modulation is experimentally demonstrated. The sensor consists of four sections of polarization maintaining fiber (FPMF) sandwiched between multi-mode fiber (MMF). The stress region of two sections of polarization maintaining fibers (PMFs) is aligned and then anti-clockwise rotates one PMF in 10 deg angles while the other keeps still. Finally, the discharge proceeds. The remaining two PMFs are fusion spliced with the same method. Then the prepared FPMF-MMF structure is connected to the 3 dB coupler to construct a Sagnac loop. The temperature sensitivity reaches 1.49 nm/°C for a temperature range from 16°C to 55°C. The proposed temperature sensor with easy fabrication and good linearity in measuring temperature can be a promising candidate for various applications in environmental monitoring and industrial production.

Laser-Based Mobile Visible Light Communication System.

Mobile visible light communication (VLC) is key for integrating lighting and communication applications in the 6G era, yet there exists a notable gap in experimental research on mobile VLC. In this study, we introduce a mobile VLC system and investigate the impact of mobility speed on communication performance. Leveraging a laser-based light transmitter with a wide coverage, we enable a light fidelity (LiFi) system with a mobile receiving end. The system is capable of supporting distances from 1 m to 4 m without a lens and could maintain a transmission rate of 500 Mbps. The transmission is stable at distances of 1 m and 2 m, but an increase in distance and speed introduces interference to the system, leading to a rise in the Bit Error Rate (BER). The mobile VLC experimental system provides a viable solution to the issue of mobile access in the integration of lighting and communication applications, establishing a solid practical foundation for future research.

Planar hot-electron photodetection with polarity-switchable photocurrents controlled by the working wavelength.

Hot-electron photodetection is attracting increasing interests. Based on internal photoemission mechanism, hot-electron photodetectors (HE PDs) convert incident photon energy into measurable photocurrent. To obtain polarity-switchable photocurrent, one often applies electric bias to reverse the hot-electron flow. However, the employment of bias reduces the device flexibility and increasing the bias voltage degrades the detectivity of the device. Herein, we design a planar HE PD with the polarity-switchable photocurrent controlled by the working wavelength. Optical simulations show that the device exhibits two absorption peaks due to the resonances of two Tamm plasmons (TPs). Electrical calculations predict two corresponding TP-assisted responsivity peaks, but with opposite photocurrent polarities, which are determined by the hot-electron flows with opposite directions. We find that the hot-electron flows are closely related with the population differences of TP-induced hot electrons in two electrodes. We further demonstrate that the photocurrent polarity of the HE PD can be switched by altering working wavelength from one TP wavelength to the other. We believe that this approach paves a route to achieve flexible hot-electron photodetection for extensive applications.

Topological edge and corner states in honeycomb-kagome photonic crystals.

We systematically study the first- and second-order band topologies, which are tied to the pseudospin and valley degree of freedoms (DOFs), in honeycomb-kagome photonic crystals (HKPCs). We first demonstrate the quantum spin Hall phase as the first-order pseudospin-induced topology in HKPCs by observing the partial pseudospin-momentum locked edge states. By employing the topological crystalline index, we also discover the multiple corner states emerging in the hexagon-shaped supercell as the manifestation of the second-order pseudospin-induced topology in HKPCs. Next, by gapping the Dirac points, a lower band gap associated with the valley DOF emerges, in which the valley-momentum locked edge states are observed as the first-order valley-induced topology. Such HKPCs without inversion symmetry are proved to be Wannier-type second-order topological insulators, which manifested with valley-selective corner states. Additionally, we also discuss the symmetry breaking effect on pseudospin-momentum locked edge states. Our work realizes both pseudospin-induced and valley-induced topologies in a higher-order manner and thus provides more flexibility in manipulating electromagnetic waves, which may find potential applications in topological routings.

Large dynamic strain measurement via slope-assisted Brillouin optical time domain reflectometry using a frequency equalizer.

In this Letter, a method for measuring large dynamic strain via slope-assisted Brillouin optical time domain reflectometry (SA-BOTDR) is proposed. A linear artificial slope created by a frequency equalizer is used instead of the traditional slope of the Brillouin gain spectrum (BGS) as the linear response region between the Brillouin frequency shift (BFS) and signal intensity. This method makes the strain measurement range independent of the bandwidth of the BGS. The large dynamic strain with a maximum value of 3108 µÎµ and the spatial resolution of 5 m along the ∼1.94-km single-mode fiber (SMF) are obtained by means of the proposed technique. Meanwhile, a strong linear relationship is also established between the signal strength and strain at the vibration frequencies of 10.3 and 13.1 Hz. The maximum measured errors of vibration frequency are 0.5 Hz@10.3 Hz and 0.8 Hz@13.1 Hz.

Directional Torsion Sensor Based on a Two-Core Fiber with a Helical Structure.

A fiber-optic torsion sensor based on a helical two-core fiber (HTCF) is proposed and experimentally demonstrated for simultaneously measuring torsion angle and torsion direction. The sensor consists of a segment of HTCF and two single-mode fibers (SMFs) forming a Mach-Zehnder interferometer (MZI). The helical structure is implemented by pre-twisting a 1 cm long two-core fiber (TCF). The performance of the sensor with pre-twisted angles of 180°, 360°, and 540° is experimentally analyzed. The results show that the sensor can realize the angular measurement and effectively distinguish the torsion direction. It is worth noting that the sensor has maximum sensitivity when the pre-twist angle is 180 degrees. The obtained wavelength sensitivities of torsion and temperature are 0.242 nm/(rad/m) and 32 pm/°C, respectively. The sensor has the advantages of easy fabrication, low cost, compact structure, and high sensitivity, which is expected to yield potential applications in fields where both torsion angle and direction measurements are required.

VHL L169P Variant Does Not Alter Cellular Hypoxia Tension in Clear Cell Renal Cell Carcinoma.

In the current era of tumor genome sequencing, single amino acid missense variants in the von Hippel-Lindau (VHL) tumor suppressor gene are frequently identified in clear cell renal carcinoma (ccRCC). Due to the incomplete knowledge of the structural architecture of VHL protein, the functional significance of many missense mutations cannot be assigned. L169P is one such missense mutation identified in the case of aggressive, metastatic ccRCC. Here, we characterized the biochemical activity, transcriptomic hypoxia signature and biological functions of the L169P variant. Lentiviral vector expressing either wildtype (WT) or L169P VHL were used to transduce two VHL-deficient human ccRCC cell lines, 786-O and RCC4. The stability of the VHL protein and the expression level of VHL, HIF1α and HIF2α were analyzed. The impact of restoring L169P or WT VHL on the hypoxia gene expression program in 786-O cells was assessed by mRNA sequencing (RNAseq) and computed hypoxic scores. The impact of restoring VHL expression on the growth of ccRCC models was assessed in cell cultures and in chorioallantoic membrane (CAM) xenografts. In the 786-O cells, the protein stability of L169P VHL was comparable to WT VHL. No obvious difference in the capability of degrading HIF1α and HIF2α was observed between WT and L169P VHL in the 786-O or RCC4 cells. The hypoxic scores were not significantly different in the 786-O cells expressing either wildtype or L169P VHL. From the cellular function perspective, both WT and L169P VHL slowed cell proliferation in vitro and in vivo. The L169P VHL variant is comparable to WT VHL in terms of protein stability, ability to degrade HIF1α factors and ability to regulate hypoxia gene expression, as well as in the suppression of ccRCC tumor cell growth. Taken together, our data indicate that the L169P VHL variant alone is unlikely to drive the oncogenesis of sporadic ccRCC.

Application of IRI Visualization to Terahertz Vibrational Spectroscopy of Hydroxybenzoic Acid Isomers.

The characteristic absorption spectra of three positional isomers of hydroxybenzoic acid are measured using a terahertz time-domain spectroscopy system (THz-TDS) in the 0.6-2.0 THz region at room temperature. Significant differences in their terahertz spectra are discovered, which indicates that THz-TDS is an effective means to identify positional isomers. In order to simulate their spectra, the seven molecular clusters of 2-, 3-, and 4-hydroxybenzoic acid (2-, 3-, and 4-HA) are calculated using the DFT-D3 method. Additionally, the potential energy distribution (PED) method is used to analyze their vibration modes. The analysis indicates that the vibration modes of 2-HA are mainly out-of-plane angle bending and bond angle bend in plane. The vibration modes of 3-HA are mainly bond length stretch and dihedral angle torsion. The vibration modes of 4-HA are mainly bond angle bend in plane and dihedral angle torsion. Interaction region indicator (IRI) analysis is used to visualize the location and type of intermolecular interactions in 2-, 3-, and 4-HA crystals. The results show that the weak interaction type of 2-, 3-, and 4-HA is dominated by van der Waals (vdW) interaction. Therefore, we can confirm that terahertz spectroscopy detection technology can be used as an effective means to identify structural isomers and detect the intermolecular interactions in these crystals. In addition, it can explain the absorption mechanism of terahertz waves interacting with matter.

Exosomes from Von Hippel-Lindau-Null Cancer Cells Promote Metastasis in Renal Cell Carcinoma.

Exosomes are extracellular vesicles that modulate essential physiological and pathological signals. Communication between cancer cells that express the von Hippel-Lindau (VHL) tumor suppressor gene and those that do not is instrumental to distant metastasis in renal cell carcinoma (RCC). In a novel metastasis model, VHL(-) cancer cells are the metastatic driver, while VHL(+) cells receive metastatic signals from VHL(-) cells and undergo aggressive transformation. This study investigates whether exosomes could be mediating metastatic crosstalk. Exosomes isolated from paired VHL(+) and VHL(-) cancer cell lines were assessed for physical, biochemical, and biological characteristics. Compared to the VHL(+) cells, VHL(-) cells produce significantly more exosomes that augment epithelial-to-mesenchymal transition (EMT) and migration of VHL(+) cells. Using a Cre-loxP exosome reporter system, the fluorescent color conversion and migration were correlated with dose-dependent delivery of VHL(-) exosomes. VHL(-) exosomes even induced a complete cascade of distant metastasis when added to VHL(+) tumor xenografts in a duck chorioallantoic membrane (dCAM) model, while VHL(+) exosomes did not. Therefore, this study supports that exosomes from VHL(-) cells could mediate critical cell-to-cell crosstalk to promote metastasis in RCC.

Bias voltage-tuned hot-electron optical sensing with planar Au-MoS2-Au junction.

Harvesting photoexcited hot electrons in metals promises a number of benefits in optical sensing. In practice, hot-electron optical sensors with tunable performance in electrical sensitivity are still absent. Herein, we propose a design to realize tunable hot-electron optical sensing. The proposed device consists of a one-dimensional grating deposited on a planar Au-MoS2-Au junction that is used for efficient hot-electron harvesting. Photoelectric simulations show that when grating-assisted plasmonic resonance is excited, bias voltage between two Au layers can be used to manipulate the magnitude and polarity of responsivity at the working wavelength. Therefore, the change in responsivity that originates from the change in refractive index of analyte in which the device is immersed can also be tuned by applied voltage. It is found that when bias voltage is 1 V, the electrical sensitivity doubled compared with that when applied voltage is absent. We believe the bias voltage-tuned strategy that is applied to planar hot-electron harvesting junctions facilitates the development of optical sensing.

Five-layer planar hot-electron photodetectors at telecommunication wavelength of 1550†nm.

Cost-effective and high-responsivity photodetectors at a telecommunication wavelength of 1550 nm are highly desired in optical communication systems. Differing from conventional semiconductor-based photodetectors, several planar hot-electron photodetectors (HE PDs) that operate at 1550 nm have been reported. However, these devices were often comprised of many planar layers and exhibited relatively low responsivities. Herein, we propose a design of high-performance planar HE PDs consisting of five layers. Utilizing Fabry-Pérot (FP) resonance, the nearly perfect absorption of the proposed device can be achieved at the targeted wavelength of 1550 nm. Simulation results show that FP resonance orders are crucial for the optical absorption efficiencies, and then electrical responses. Analytical electrical calculations reveal that, benefiting from the strong absorption (>0.6) in the ultrathin Au layer with a thickness of 5 nm and the low Schottky barrier (0.5 eV) of Au-MoS2 contact, predicted responsivity of proposed HE PD at zero-order FP resonance is up to ∼10 mA/W. Our design provides a new approach to realize low-cost and efficient photodetection for optical communication technology.

In-line reflected fiber sensor for simultaneous measurement of temperature and liquid level based on tapered few-mode fiber.

An in-line reflective dual-parameters fiber-optic sensor is proposed in this work, whereas it is experimentally verified by measuring both the liquid level and the local temperature distribution simultaneously. The proposed sensor configuration comprises a single-mode fiber (SMF), a tapered few-mode fiber (TFMF), as well as a silver-coated capillary tube. The extracted experimental results indicate that the liquid level only affects the power of the resonant dips, while having little impact on the wavelength. On the other hand, both the wavelength and the power of the resonant dips vary with the temperature change. Therefore, the simultaneous measurement of the liquid level and temperature can be realized according to the different responses of the resonant dips to the liquid level and temperature. The obtained liquid level and temperature sensitivities can reach the values of 0.106 dB/mm and 0.029 dB/°C, 35 pm/°C, respectively. The sensor exhibits the advantages of high stability and low cost, the demodulation relates on only one wavelength which can shorten the scanning wavelength range during measurement. The proposed sensor can be potentially applied where accurate and simultaneous measurements of both temperature and liquid level are required.

46.4 Gbps visible light communication system utilizing a compact tricolor laser transmitter.

Visible light communication (VLC), combining wireless communication with white lighting, has many advantages. It is free of electromagnetic interference, is rich in spectrum resources, and has a gigabit-per-second (Gbps) data rate. Laser diodes (LDs) are emerging as promising light sources for high-speed VLC communication due to their high modulation bandwidth. In this paper, we demonstrate a red/green/blue (R/G/B) LDs based VLC system with a recorded data rate of 46.41 Gbps, employing discrete multitone (DMT) and adaptive bit-loading technology to achieve high spectral efficiency (SE). The emission characteristics and transmission performance of R/G/B-LDs are discussed. The optimal data rates of R/G/B-LDs channels are 17.168/14.652/14.590 Gbps, respectively. The bit-error-ratio (BER) of each channel satisfies the 7% forward-error-correction (FEC) threshold (3.8×10-3) and greatly approaches the channel Shannon limit.

Large dynamic strain range slope-assisted Brillouin optical time domain reflectometry based on a graded-index multi-mode fiber.

A slope-assisted Brillouin optical time domain reflectometry system with large dynamic strain range was proposed and demonstrated using graded-index multi-mode fiber (GI-MMF) as sensing fiber. Analysis of the simulated and experimental results indicated that the Brillouin gain spectrum in GI-MMF could be broadened by controlling the coupling efficiency of optical and acoustic modes. The coupling efficiency could be controlled by adjusting lateral offset between single mode fiber (SMF) and GI-MMF. The system realized the maximum strain dynamic measurement of 3000 µÉ› with the spatial resolution of 5 m along ∼1 km GI-MMF, and exhibited significant linear relationship between signal intensity and strain at vibrational frequency of 7.83 and 15.47 Hz. The measured error of vibration frequency was less than 0.2 and 1.5 Hz, respectively. The measured strain range of this system was more than three times that of traditional systems based on SMF and could be achieved at relatively low cost.

Rainbow trapping based on higher-order topological corner modes.

The recent advancements in higher-order topology have provided unprecedented opportunities in optical device designs and applications. Here, we propose a new, to the best of our knowledge, method to realize rainbow trapping based on higher-order topological corner modes (HOTCMs), which are constructed by two configurations of breathing kagome photonic crystals with distinct topological phases. Interestingly, the HOTCMs localized at corners with different geometric configurations are found to be frequency dispersive and thus initiate the possible application in realizing rainbow trapping. By designing a polygon structure containing several configurations of corners, we demonstrate that the HOTCMs can be excited with the frequency sequence locked to the corner order (clockwise/anticlockwise direction) in the polygon. The reported HOTCMs provide a new mechanism to realize multiple-frequency trapping, which may find potential applications in future integrated photonics.

Development of a Predictive Nomogram for Estimating Medication Nonadherence in Hemodialysis Patients.

BACKGROUND Medication compliance in hemodialysis patients affects the therapeutic effect of treatment and patient survival. Therefore, we aimed to explore the influencing factors of medication adherence in hemodialysis patients and develop a nomogram model to predict medication adherence. MATERIAL AND METHODS Data from questionnaires on medication adherence in hemodialysis patients were collected in Chengde from May 2020 to December 2020. The least absolute selection operator (LASSO) regression model and multivariable logistic regression analysis were used to analyze the risk factors for medication adherence in hemodialysis patients, and then a nomogram model was established. The bootstrap method was applied for internal validation. The concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), decision curve analysis (DCA), calibration curve, net reclassification improvement (NRI) index, and integrated discrimination improvement (IDI) index were used to evaluate the degree of differentiation and accuracy of the nomogram model, and clinical impact was used to investigate the potential clinical value of the nomogram model. RESULTS In total, 206 patients were included in this study, with a rate of medication nonadherence of 41.75%. Eight predictors were identified to build the nomogram model. The C-index, AUC, DCA, calibration curve, NRI, and IDI showed that the model had good discrimination and accuracy. The clinical impact plot showed that the nomogram of medication adherence in hemodialysis patients had clinical application value. CONCLUSIONS We developed and validated a nomogram model that is intuitive to apply for predicting medication adherence in hemodialysis patients.

The miRNA-21-5p Payload in Exosomes from M2 Macrophages Drives Tumor Cell Aggression via PTEN/Akt Signaling in Renal Cell Carcinoma.

M2 macrophages in the tumor microenvironment are important drivers of cancer metastasis. Exosomes play a critical role in the crosstalk between different cells by delivering microRNAs or other cargos. Whether exosomes derived from pro-tumorigenic M2 macrophages (M2-Exos) could modulate the metastatic behavior of renal cell carcinoma (RCC) is unclear. This study found that M2-Exos promotes migration and invasion in RCC cells. Inhibiting miR-21-5p in M2-Exos significantly reversed their pro-metastatic effects on RCC cells in vitro and in the avian embryo chorioallantoic membrane in vivo tumor model. We further found that the pro-metastatic mechanism of miR-21-5p in M2-Exos is by targeting PTEN-3'UTR to regulate PTEN/Akt signaling. Taken together, our results demonstrate that M2-Exos carries miR-21-5p promote metastatic features of RCC cells through PTEN/Akt signaling. Reversing this could serve as a novel approach to control RCC metastasis.

Interference fading suppression in φ-OTDR using space-division multiplexed probes.

We propose and experimentally demonstrate a novel interference fading suppression method for phase-sensitive optical time domain reflectometry (φ-OTDR) using space-division multiplexed (SDM) pulse probes in a few-mode fiber. The SDM probes consist of multiple different modes, and three spatial modes (LP01, LP11a, and LP11b) are used in this work for the proof of concept. Firstly, the Rayleigh backscattering light of different modes is experimentally characterized, and it turns out that the waveforms of the φ-OTDR traces for distinct modes are all different and independent. Thanks to the spatial difference of the fading positions for distinct modes, multiple probes from spatially multiplexed modes can be used to suppress the interference fading in φ-OTDR. Then, the performances of the φ-OTDR systems using a single probe and multiple probes are evaluated and compared. Specifically, the statistical analysis shows that the fading probabilities over both the fiber length and the time scale are reduced significantly by using multiple SDM probes, which verifies the significant performance improvement on fading suppression. By introducing the concept of SDM to φ-OTDR, the proposed novel interference fading suppression method avoids the complicated frequency or phase modulation, which has the advantages of simplicity, good effectiveness and high reliability.