Ligand binding initiates single-molecule integrin conformational activation.

Integrins link the extracellular environment to the actin cytoskeleton in cell migration and adhesiveness. Rapid coordination between events outside and inside the cell is essential. Single-molecule fluorescence dynamics show that ligand binding to the bent-closed integrin conformation, which predominates on cell surfaces, is followed within milliseconds by two concerted changes, leg extension and headpiece opening, to give the high-affinity integrin conformation. The extended-closed integrin conformation is not an intermediate but can be directly accessed from the extended-open conformation and provides a pathway for ligand dissociation. In contrast to ligand, talin, which links the integrin ß-subunit cytoplasmic domain to the actin cytoskeleton, modestly stabilizes but does not induce extension or opening. Integrin activation is thus initiated by outside-in signaling and followed by inside-out signaling. Our results further imply that talin binding is insufficient for inside-out integrin activation and that tensile force transmission through the ligand-integrin-talin-actin cytoskeleton complex is required.

Asymmetric-absorption-induced spectral redshift in a monolithic III-nitride on-chip system.

Integrating optoelectronic devices with various functions into a monolithic chip is a popular research frontier. The top-down integration scheme on silicon-based III-nitride wafers has unique advantages. A monolithic III-nitride on-chip system with lighting source, electrical absorption modulator, waveguide and photodetector with the same structure were designed and fabricated to discover the asymmetry of photon emission and absorption in quantum well diode. The characteristics of the chip were characterized in detail and three different spectral redshifts were observed in the experiment. Results revealed that the asymmetric absorption causes spectral redshift in a quantum well diode, and self-absorption is a fundamental and universal phenomenon in quantum wells. This work provides an important reference for future III-nitride optoelectronic integration.

Rotational angle and speed detection via a chip-scale GaN optoelectronic device.

In this paper, a new method for rotational angle and speed measurements is proposed by integrating a GaN optoelectronic chip with a stepped disc. The optoelectronic chip that integrates a light-emitting diode (LED) and a photodiode (PD) is fabricated by wafer-level microfabrication. The disc is designed with a spiral staircase shape, and has increasing thickness distribution along the circumferential direction. The sensing mechanism is that the optoelectronic chip measures angle-dependent intensity change of the light reflected off the stepped disc. Through a series of performance tests, the chip is highly sensitive to a continuous rotation from 0 ∘ to 360 ∘, and produces photocurrent to indicate the rotational angle and speed. A rotational speed up to 5000 rpm is measured with a relative error less than 1.27%. The developed sensing architecture provides an alternative solution for constructing a low-cost, miniaturized, and high-efficiency rotational angle and speed sensing system.

Effect of temperature on GaN-integrated optical transceiver chips.

The gallium nitride (GaN) integrated optical transceiver chip based on multiple quantum wells (MQW) structure exhibits great promise in the fields of communication and sensing. In this Letter, the effect of ambient temperature on the performance of GaN-integrated optical transceiver chips including a blue MQW light-emitting diode (LED) and a MQW photodiode (PD) is comprehensively studied. Temperature-dependent light-emitting and current-voltage characteristics of the blue MQW LEDs are measured with the ambient temperature ranging from -70°C to 120°C. The experimental results reveal a decline in the electroluminescent (EL) intensity and an obvious redshift in the emission peak wavelength of the LED with increasing ambient temperature. The light detection performance of MQW PD under different temperatures is also measured with the illumination of an external blue MQW LED, indicating an enhancement in the PD sensitivity as the temperature rises. Finally, the temperature effect on the MQW PD under the illumination of the MQW LED on the GaN-integrated optical transceiver chip is characterized, and the PD photocurrent increases with higher ambient temperature. Furthermore, the measured temperature characteristics indicate that the GaN-integrated optical transceiver chip offers a promising application potential for optoelectronic temperature sensor.

Large-sized light-emitting diode integrated with a thermopile for on-chip temperature and power monitoring.

A large-sized multiple quantum well (MQW) light-emitting diode (LED) integrated with a thermopile for on-chip temperature and power monitoring is presented in this study. Seven thermopile structures, fully compatible with the fabrication of LEDs, are strategically placed at different locations on the LED to monitor its temperature during the operation. Additionally, the thermopile allows for monitoring the power of the LED, as there exists an approximate linear relationship between the light output power and temperature. Compared to traditional methods of measuring LED temperature, the thermopile offers several advantages, including no moving parts, long lifetime, no maintenance, high reliability, and direct conversion without intermediate processes. The results demonstrate that the integration of the thermopiles onto the LED provides superior temperature and power monitoring capabilities. Furthermore, this integrated solution has the potential to enable real-time management and control of LED temperature.

Collinear optical links based on a GaN-integrated chip for fiber-optic acoustic detection.

This Letter reports a collinear optical interconnect architecture for acoustic sensing via a monolithic integrated GaN optoelectronic chip. The chip is designed with a ring-shaped photodiode (PD) surrounding a light-emitting diode (LED) of a spectral range from 420-530 nm. The axisymmetric structure helps the coaxial propagation of light transmission and reception. By placing this multiple-quantum wells (MQW)-based device and a piece of aluminum-coated polyethylene terephthalate (Al/PET) film on fiber ends, an ultra-compact acoustic sensing system is built. The sound vibrations can be simply detected by direct measurement of the diaphragm deformation-induced power change. An average signal noise ratio (SNR) of 40 dB and a maximum sensitivity of 82 mV/Pa are obtained when the acoustic vibration frequency changes from 400 Hz to 3.2 kHz. This work provides a feasible solution to miniaturize the sensing system footprint and reduce the cost.

Self-regulation of light emission of an AlGaInP quantum well diode.

When an AlGaInP quantum well (QW) diode is biased with a forward voltage and illuminated with an external shorter-wavelength light beam, the diode is in a superposition state of both light emission and detection. The two different states take place simultaneously, and both the injected current and the generated photocurrent begin to mix. Here, we make use of this intriguing effect and integrate an AlGaInP QW diode with a programmed circuit. The AlGaInP QW diode with the dominant emission peak wavelength centered around 629.5 nm is excited by a 620-nm red-light source. The photocurrent is then extracted as a feedback signal to regulate the light emission of the QW diode in real time without an external or monolithically integrated photodetector, paving a feasible way to autonomously adjust the brightness of the QW diode for intelligent illumination in response to changes in the environmental light condition.

Multiplexing of bias-controlled modulation modes on a monolithic III-nitride optoelectronic chip.

III-nitride optoelectronic chips have tremendous potential for developing integrated computing and communication systems with low power consumption. The monolithic, top-down approaches are advantageous for simplifying the fabrication process and reducing the corresponding manufacturing cost. Herein, an ultraviolet optical interconnection system is investigated to discover the way of multiplexing between emission and absorption modulations on a monolithic optoelectronic chip. All on-chip components, the transmitter, monitor, waveguide, modulator, and receiver, share the same quantum well structure. As an example, two bias-controlled modulation modes are used to modulate video and audio signals in the experiment presented in this Letter. The results show that our on-chip optoelectronic system works efficiently in the near ultraviolet band, revealing the potential breadth of GaN optoelectronic integration.

Miniature GaN optoelectronic temperature sensor.

The combination of plastic optical fiber (POF) with monolithically integrated transmitter and receiver is becoming increasingly attractive for the development of miniature optoelectronic sensing systems. Here, we propose a temperature sensing system by integrating a GaN optoelectronic chip with a POF and aluminum (Al) reflector. Owing to the overlap between electroluminescence and responsivity spectra of multiple quantum well (MQW) diodes, both the transmitter and the receiver having identical MQW structures are monolithically integrated on a tiny GaN chip by using the same fabrication process flow. Environmental temperature change leads to thermal deformation in the Al reflector, which reflects the transmitted light back with a light pulse. The reflected light is coupled into the guided POF again and sensed by the on-chip receiver. Finally, the temperature information is read out as electrical signals. When the ambient temperature changes from 20.1°C to 100°C, the optically induced electrical signal decreases from -3.04 µA to -3.13 µA. The results suggest that the monolithically integrated GaN device offers a promising option for optoelectronic temperature sensing systems.

Vertically stacked quantum well diodes for multifunctional applications.

Dual-functioning multiple quantum well (MQW) diodes can simultaneously transmit and receive information through visible light. Here, we report vertically stacked red, green, and blue (RGB) MQW diodes for light detection and display applications. Both blue and green MQW diodes are monolithically integrated with distributed Bragg reflector (DBR) filters to realize the separation of light. The versatile RGB MQW transmitter/receiver system not only creates full-color display but also effectively separates RGB light into various colors. These results open feasible routes to generate multifunctional device for the development of full-color display and light receiver.

Full-duplex visible light communication system using a single channel.

Multiple quantum well (MQW) III-nitride diodes can emit light and detect light at the same time. In particular, given the overlapping region between the emission spectrum and the detection spectrum, the III-nitride diode can absorb photons of shorter wavelengths generated from another III-nitride diode with the same MQW structure. In this study, a wireless visible light communication system was established using two pairs of identical III-nitride diodes with different wavelengths. In this system, two green light diode chips were used to transmit and receive green light signals on both sides. We have integrated two blue light chips with optical filtering in the middle of the optical link to carry out blue light communication, with one end transmitting and one end receiving. Simultaneously, green light was allowed to pass through two blue light chips for optical communication. Combined with a distributed Bragg reflection (DBR) coating, we proposed using four chips in one optical path to carry out optical communication between chips with the same wavelength and used the coating principle to gate the optical wavelength to filter the clutter of green light chips on both sides to make the channel purer and the symbols easier to demodulate. Based on this multifunctional equipment, advanced single-optical path, III-nitride, full-duplex optical communication links can be developed for the deployment of the Internet of Things.

Injectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment.

Although combination chemoimmunotherapy shows promising clinical results for cancer treatment, this approach is largely restricted by variable objective response rate and severe systemic adverse effects of immunotherapeutic antibody and chemotherapeutic drugs. Therefore, an in situ-formed therapeutic silk-chitosan composite scaffold is fabricated in this study to allow local release of the chemotherapeutic drug doxorubicin (DOX) and JQ1 (small molecular inhibitor used for the extraterminal protein BRD4 and bromodomain) with control release kinetics. DOX-JQ1@Gel contains a pH-degradable group that releases therapeutics in a weak acidic tumor microenvironment. The released DOX could directly kill tumor cells or lead to immunogenic cell death, thereby triggering the response of antitumor immunity. Meanwhile, chemotherapy-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to trigger the response of antitumor immunity. Finally, the DOX-JQ1@Gel is locally injected to evaluate its synergistic cancer therapeutic effect, which is expected to improve objective response rate of immunotherapy and minimize systemic side effects.

Monolithically integrated voltage-controlled MOSFET-LED device based on a GaN-on-silicon LED epitaxial wafer.

We report a novel monolithically integrated voltage-controlled metal-oxide-semiconductor field effect transistor (MOSFET)-LED device based on a GaN-on-silicon LED epitaxial wafer. An N-channel enhancement mode MOSFET and an InGaN/GaN multiple-quantum-well (MQW) thin-film LED featured with a suspended membrane are in series connection to constitute the monolithically integrated device without external metal interconnection. A recessed gate structure and AlGaN channel are innovatively adopted to realize an enhancement mode transistor. The fabrication of the MOSFET-LED includes no additional ion implantation or epitaxial growth compared with that of a common MQW LED, which greatly simplifies the device structure and production processes. The measured turn-on voltage of the LED is approximately 4 V, and the threshold voltage of the MOSFET is extrapolated as 5.2 V. The results demonstrate relatively good dimming and switching capacities of the integrated MOSFET-LED. This integration scheme also has potential to achieve a large-scale optoelectronic integrated circuit.

Epigenetic alteration by DNA-demethylating treatment restores apoptotic response to glucocorticoids in dexamethasone-resistant human malignant lymphoid cells.

BACKGROUND: Glucocorticoids (GCs) are often included in the therapy of lymphoid malignancies because they kill several types of malignant lymphoid cells. GCs activate the glucocorticoid receptor (GR), to regulate a complex genetic network, culminating in apoptosis. Normal lymphoblasts and many lymphoid malignancies are sensitive to GC-driven apoptosis. Resistance to GCs can be a significant clinical problem, however, and correlates with resistance to several other major chemotherapeutic agents. METHODS: We analyzed the effect of treatment with the cytosine analogue 5 aza-2' deoxycytidine (AZA) on GC resistance in two acute lymphoblastic leukemia (T or pre-T ALL) cell lines- CEM and Molt-4- and a (B-cell) myeloma cell line, RPMI 8226. Methods employed included tissue culture, flow cytometry, and assays for clonogenicity, cytosine extension, immunochemical identification of proteins, and gene transactivation. High throughput DNA sequencing was used to confirm DNA methylation status. CONCLUSIONS: Treatment of these cells with AZA resulted in altered DNA methylation and restored GC-evoked apoptosis in all 3 cell lines. In CEM cells the altered epigenetic state resulted in site-specific phosphorylation of the GR, increased GR potency, and GC-driven induction of the GR from promoters that lie in CpG islands. In RPMI 8226 cells, expression of relevant coregulators of GR function was altered. Activation of p38 mitogen-activated protein kinase (MAPK), which is central to a feed-forward mechanism of site-specific GR phosphorylation and ultimately, apoptosis, occurred in all 3 cell lines. These data show that in certain malignant hematologic B- and T-cell types, epigenetically controlled GC resistance can be reversed by cell exposure to a compound that causes DNA demethylation. The results encourage studies of application to in vivo systems, looking towards eventual clinical applications.

Synthetic integrin antibodies discovered by yeast display reveal αV subunit pairing preferences with ß subunits.

Integrins are cell surface receptors that mediate the interactions of cells with their surroundings and play essential roles in cell adhesion, migration, and homeostasis. Eight of the 24 integrins bind to the tripeptide Arg-Gly-Asp (RGD) motif in their extracellular ligands, comprising the RGD-binding integrin subfamily. Despite similarity in recognizing the RGD motif and some redundancy, these integrins can selectively recognize RGD-containing ligands to fulfill specific functions in cellular processes. Antibodies against individual RGD-binding integrins are desirable for investigating their specific functions, and were selected here from a synthetic yeast-displayed Fab library. We discovered 11 antibodies that exhibit high specificity and affinity toward their target integrins, i.e. αVß3, αVß5, αVß6, αVß8, and α5ß1. Of these, six are function-blocking antibodies and contain a ligand-mimetic R(G/L/T)D motif in their CDR3 sequences. We report antibody-binding specificity, kinetics, and binding affinity for purified integrin ectodomains, as well as intact integrins on the cell surface. We further used these antibodies to reveal binding preferences of the αV subunit for its 5 ß-subunit partners: ß6 = ß8 > ß3 > ß1 = ß5.

Synthetic integrin antibodies discovered by yeast display reveal αV subunit pairing preferences with ß subunits.

Eight of the 24 integrin heterodimers bind to the tripeptide Arg-Gly-Asp (RGD) motif in their extracellular ligands, and play essential roles in cell adhesion, migration, and homeostasis. Despite similarity in recognizing the RGD motif and some redundancy, these integrins can selectively recognize RGD-containing ligands including fibronectin, vitronectin, fibrinogen, nephronectin and the prodomain of the transforming growth factors to fulfill specific functions in cellular processes. Subtype-specific antibodies against RGD-binding integrins are desirable for investigating their specific functions. In this study, we discovered 11 antibodies that exhibit high specificity and affinity towards integrins αVß3, αVß5, αVß6, αVß8, and α5ß1 from a synthetic yeast-displayed Fab library. Of these, 6 are function-blocking antibodies containing an R(G/L/T) D motif in their CDR3 sequences. We report antibody binding specificity, kinetics, and binding affinity for purified integrin ectodomains as well as intact integrins on the cell surface. We further employed these antibodies to reveal binding preferences of the αV subunit for its 5 ß-subunit partners: ß6=ß8>ß3>ß1=ß5.

Touchless Input/Output Interface for Device-to-Device Communication.

Multiple quantum well (MQW) III-nitride diodes show selectable functionalities of light-emitting and light-detecting behaviors, enabling direct touchless device-to-device communication. Here, we propose and demonstrate a touchless input/output (I/O) interface using a single MQW III-nitride diode. By integrating an MQW III-nitride diode with a memory via a control circuit, optical signals are converted into electrical ones to be written into a memory, and consequently, electrical information is read out from the memory to be translated into optical signals for visible light communication (VLC). The MQW III-nitride diode can not only lead to a touchless ″writing″ action but also offer a ″reading″ process through light. Such touchless I/O interface would provide new forms of interactivity for device-to-device communication technologies.

Complex resistivity spectrum of pollutant soils with low-concentration heavy metals.

Soil contamination by heavy metals occurs globally, with varying degrees of severity, especially in agricultural fields. Investigating the frequency response characteristics of different types of heavy metal pollutants through induced polarization can provide valuable evidence for surveys based on this method. Soil specimens with varying low concentrations of copper (Cu), chromium (Cr), cadmium (Cd), and lead (Pb) heavy metals were prepared for this study, and parameters including complex resistivity, amplitude-frequency, and resistivity phase were measured. Our findings reveal the following trends: Complex resistivity decreases as heavy metal concentrations increase, demonstrating significant shifts within lower concentration ranges but presenting limitations for assessing pollution in high-concentration areas. Conversely, amplitude-frequency increases with higher heavy metal concentrations, displaying excellent performance in high-concentration scenarios. The differences in complex resistivity and amplitude-frequency among different types of heavy metal pollutants are distinct. In contrast, the absolute phase decreases with rising heavy metal concentrations. The resistivity phase spectra for various heavy metal pollutants exhibit unique patterns. For example, copper-contaminated soil exhibits phase peaks in the frequency range of 8-32 Hz, whereas chromium-contaminated soil shows phase peaks at 16-64 Hz. Cadmium-contaminated soil displays phase peaks ranging from 0.25 Hz to 2 Hz, while lead-contaminated soil exhibits phase peaks within the 0.5 Hz-4 Hz range. Leveraging the frequency range corresponding to phase peaks as an identification method for heavy metal pollution types proves effective. The frequency response characteristics of induced polarization vary significantly among different types and concentrations of heavy metal pollutants, providing important foundations for the application of induced polarization method in the field of heavy metal pollution detection.

Compact Fluorescence Detection System Based on a Monolithic DBR-Integrated III-Nitride LED Chip.

Portable applications of fluorescence detection systems have gained much attention in various fields and require system components to be small and compact. In this work, we report on a compact fluorescence detection system and demonstrate its application for fluorescence sensing and imaging. The light source and filter are integrated on a single chip for the proposed system, which not only realizes the separation between excitation and fluorescent lights but also improves the light-emitting diode (LED) light extraction efficiency. Furthermore, the detection system allows for a removable sample unit. The results indicate that the performance of the distributed Bragg reflector (DBR) filter based on an amorphous dielectric film is excellent with selection ratios larger than 4600:1. The peak emission wavelength of the LED is 528 nm. The influence of green light leakage can be neglected, and the fluorescent red light is dominant when the fluorescence detection system is used for sensing and imaging. The low-cost and monolithic DBR-integrated III-nitride LED chip makes the proposed architecture a competitive candidate for portable fluorescence detection applications.

Parenchymal expression of CD40 exacerbates adenovirus-induced hepatitis in mice.

UNLABELLED: The healthy adult human liver expresses low levels of major histocompatibility complex class II (MHC II) and undetectable levels of immune costimulatory molecules. However, high levels of MHC II, CD40, and B7 family molecules are expressed in the activated Kupffer cells and hepatocytes of patients with viral hepatitis. The precise role of these molecules in viral clearance and immune-mediated liver injury is not well understood. We hypothesized that parenchymal CD40 expression enhances T cell recruitment and effector functions, which may facilitate viral clearance and alleviate liver injury. To test this hypothesis, we generated novel liver-specific, conditional CD40 transgenic mice, and we challenged them intravenously with a recombinant replication-deficient adenovirus carrying Cre recombinase (AdCre). Wild-type mice infected with AdCre developed a relatively mild course of viral hepatitis and recovered spontaneously. CD40 expression in the livers of transgenic animals, however, resulted in CD80 and CD86 expression. The dysregulation of population dynamics and effector functions of intrahepatic lymphocytes (IHLs) resulted in severe lymphocytic infiltration, apoptosis, necroinflammation, and serum alanine aminotransferase elevations in a dose-dependent fashion. To our surprise, an early expansion and subsequent contraction of IHLs (especially CD8(+) and natural killer cells), accompanied by increased granzyme B and interferon-γ production, did not lead to faster viral clearance in CD40 transgenic mice. CONCLUSION: Our results demonstrate that hepatic CD40 expression does not accelerate adenoviral clearance but rather exacerbates liver injury. This study unveils a previously unknown deleterious effect of hepatic CD40 on adenovirus-induced liver inflammation.