Regular use of aspirin and statins reduces the risk of cancer in individuals with systemic inflammatory diseases.

Aspirin has shown potential for cancer prevention, but a recent large randomized controlled trial found no evidence for a reduction in cancer risk. Given the anti-inflammatory effects of aspirin, systemic inflammatory diseases (SIDs), such as osteoporosis, cardiovascular diseases, and metabolic diseases, could potentially modify the aspirin-cancer link. To investigate the impact of aspirin in people with SIDs, we conducted an observational study on a prospective cohort of 478,615 UK Biobank participants. Individuals with at least one of the 41 SIDs displayed a higher cancer risk than those without SIDs. Regular aspirin use showed protective effects exclusively in patients with SID, contrasting an elevated risk among their non-SID counterparts. Nonetheless, aspirin use demonstrated preventative potential only for 9 of 21 SID-associated cancer subtypes. Cholesterol emerged as another key mediator linking SIDs to cancer risk. Notably, regular statin use displayed protective properties in patients with SID but not in their non-SID counterparts. Concurrent use of aspirin and statins exhibited a stronger protective association in patients with SID, covering 14 common cancer subtypes. In summary, patients with SIDs may represent a population particularly responsive to regular aspirin and statin use. Promoting either combined or individual use of these medications within the context of SIDs could offer a promising chemoprevention strategy.

NIT24 and NIT29-mediated IAA synthesis of Xanthomonas oryzae pv. oryzicola suppresses immunity and boosts growth in rice.

Auxin plays a pivotal role in the co-evolution of plants and microorganisms. Xanthomonas oryzae pv. oryzicola (Xoc) stands as a significant factor that affects rice yield and quality. However, the current understanding of Xoc's capability for indole 3-acetic acid (IAA) synthesis and its mechanistic implications remains elusive. In this study, we performed a comprehensive genomic analysis of Xoc strain RS105, leading to the identification of two nitrilase enzyme family (NIT) genes, designated as AKO15524.1 and AKO15829.1, subsequently named NIT24 and NIT29, respectively. Our investigation unveiled that the deletion of NIT24 and NIT29 resulted in a notable reduction in IAA synthesis capacity within RS105, thereby impacting extracellular polysaccharide production. This deficiency was partially ameliorated through exogenous IAA supplementation. The study further substantiated that NIT24 and NIT29 have nitrilase activity and the ability to catalyse IAA production in vitro. The lesion length and bacterial population statistics experiments confirmed that NIT24 and NIT29 positively regulated the pathogenicity of RS105, suggesting that NIT24 and NIT29 may regulate Xoc invasion by affecting IAA synthesis. Furthermore, our analysis corroborated mutant strains, RS105_ΔNIT24 and RS105_ΔNIT29, which elicited the outbreak of reactive oxygen species, the deposition of callose and the upregulation of defence-related gene expression in rice. IAA exerted a significant dampening effect on the immune responses incited by these mutant strains in rice. In addition, the absence of NIT24 and NIT29 affected the growth-promoting effect of Xoc on rice. This implies that Xoc may promote rice growth by secreting IAA, thus providing a more suitable microenvironment for its own colonization. In summary, our study provides compelling evidence for the existence of a nitrilase-dependent IAA biosynthesis pathway in Xoc. IAA synthesis-related genes promote Xoc colonization by inhibiting rice immune defence response and affecting rice growth by increasing IAA content in Xoc.

Synaptic Resistor Circuits Based on Al Oxide and Ti Silicide for Concurrent Learning and Signal Processing in Artificial Intelligence Systems.

Neurobiological circuits containing synapses can process signals while learning concurrently in real time. Before an artificial neural network (ANN) can execute a signal-processing program, it must first be programmed by humans or trained with respect to a large and defined data set during learning processes, resulting in significant latency, high power consumption, and poor adaptability to unpredictable changing environments. In this work, a crossbar circuit of synaptic resistors (synstors) is reported, each synstor integrating a Si channel with an Al oxide memory layer and Ti silicide Schottky contacts. Individual synstors are characterized and analyzed to understand their concurrent signal-processing and learning abilities. Without any prior training, synstor circuits concurrently execute signal processing and learning in real time to fly drones toward a target position in an aerodynamically changing environment faster than human controllers, and with learning speed, performance, power consumption, and adaptability to the environment significantly superior to an ANN running on computers. The synstor circuit provides a path to establish power-efficient intelligent systems with real-time learning and adaptability in the capriciously mutable real world.

Interstitial pneumonitis associated with combined regimen of immunotherapy and conventional therapies-pharmacovigilance database analysis with real-world data validation.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized. METHODS: A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation. RESULTS: Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05-8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60-184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78-1.04; P = 0.160) and 1.49 (95% CI, 0.95-2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34-50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89-7.92; P = 0.12) and 0.66 (95% CI, 0.03-4.55; P = 0.71), respectively, using ICI monotherapy as reference. CONCLUSIONS: Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP.

High-efficiency ultrafast optical-to-electrical converters based on InAs nanowire-plasmonic arrays.

There has been a growing interest in developing high-efficiency ultrafast optical-to-electrical converters for advanced imaging and sensing applications. Here, we propose a three-dimensional (3D) plasmonic platform based on InAs nanowire arrays with self-assembled gold gratings, which converts a telecom-wavelength (1550 nm) optical beam to sub-picosecond current pulses with quantum efficiency up to 18.3%, while operating in photovoltaic mode, i.e., at zero bias. Using a comprehensive 3D photoresponse model, we reveal that the incident photons form tightly confined fields near the gratings at nanowire tips, and thus a majority of the photogenerated carriers are efficiently routed to the metal within a few tens of nanometers distance, resulting in ultrafast current pulses. In addition, we show that the amplitude of current pulses is robust to the nanowire surface quality and can be effectively tuned by varying the doping levels in nanowires. This work paves a way to realizing a low-power, highly compact, and low-cost device scheme for ultrafast pulse generation.

Room-Temperature Midwavelength Infrared InAsSb Nanowire Photodetector Arrays with Al2O3 Passivation.

Developing uncooled photodetectors at midwavelength infrared (MWIR) is critical for various applications including remote sensing, heat seeking, spectroscopy, and more. In this study, we demonstrate room-temperature operation of nanowire-based photodetectors at MWIR composed of vertical selective-area InAsSb nanowire photoabsorber arrays on large bandgap InP substrate with nanoscale plasmonic gratings. We accomplish this by significantly suppressing the nonradiative recombination at the InAsSb nanowire surfaces by introducing ex situ conformal Al2O3 passivation shells. Transient simulations estimate an extremely low surface recombination velocity on the order of 103 cm/s. We further achieve room-temperature photoluminescence emission from InAsSb nanowires, spanning the entire MWIR regime from 3 to 5 µm. A dry-etching process is developed to expose only the top nanowire facets for metal contacts, with the sidewalls conformally covered by Al2O3 shells, allowing for a higher internal quantum efficiency. Based on these techniques, we fabricate nanowire photodetectors with an optimized pitch and diameter and demonstrate room-temperature spectral response with MWIR detection signatures up to 3.4 µm. The results of this work indicate that uncooled focal plane arrays at MWIR on low-cost InP substrates can be designed with nanostructured absorbers for highly compact and fully integrated detection platforms.

Feasibility of achieving high detectivity at short- and mid-wavelength infrared using nanowire-plasmonic photodetectors with p-n heterojunctions.

Photodetection at short- and mid-wavelength infrared (SWIR and MWIR) enables various sensing systems used in heat seeking, night vision, and spectroscopy. As a result, uncooled photodetection at these wavelengths is in high demand. However, these SWIR and MWIR photodetectors often suffer from high dark current, causing them to require bulky cooling accessories for operation. In this study, we argue for the feasibility of improving the room-temperature detectivity by significantly suppressing dark current. To realize this, we propose using (1) a nanowire-based platform to reduce the photoabsorber volume, which in turn reduces trap state population and hence generation-recombination current, and (2) p-n heterojunctions to prevent minority carrier diffusion from the large bandgap substrate into the nanowire absorber. We prove these concepts by demonstrating a comprehensive three-dimensional photoresponse model to explore the level of detectivity offered by vertical InAs(Sb) nanowire photodetector arrays with self-assembled plasmonic gratings. The resultant electrical simulations show that the dark current can be reduced by three to four orders at room temperature, leading to a peak detectivity greater than 3.5 × 1010 cm Hz1/2 W-1 within the wavelength regime of 2.0-3.4 µm, making it comparable to the best commercial and research InAs p-i-n homojunction photodiodes. In addition, we show that the plasmonic resonance peaks can be easily tuned by simply varying the exposed nanowire height. Finally, we investigate the impact of nanowire material properties, such as carrier mobility and carrier lifetime, on the nanowire photodetector detectivity. This work provides a roadmap for the electrical design of nanowire optoelectronic devices and stimulates further experimental validation for uncooled photodetectors at SWIR and MWIR.

InGaAs-GaAs Nanowire Avalanche Photodiodes Toward Single-Photon Detection in Free-Running Mode.

Single-photon detection at near-infrared (NIR) wavelengths is critical for light detection and ranging (LiDAR) systems used in imaging technologies such as autonomous vehicle trackers and atmospheric remote sensing. Portable, high-performance LiDAR relies on silicon-based single-photon avalanche diodes (SPADs) because of their extremely low dark count rate (DCR) and afterpulsing probability, but their operation wavelengths are typically limited up to 905 nm. Although InGaAs-InP SPADs offer an alternative platform to extend the operation wavelengths to eye-safe ranges, their high DCR and afterpulsing severely limit their commercial applications. Here we propose a new separate absorption and multiplication avalanche photodiode (SAM-APD) platform composed of vertical InGaAs-GaAs nanowire arrays for single-photon detection. Among a total of 4400 nanowires constituting one photodiode, each avalanche event is confined in a single nanowire, which means that the avalanche volume and the number of filled traps can be drastically reduced in our approach. This leads to an extremely small afterpulsing probability compared with conventional InGaAs-based SPADs and enables operation in free-running mode. We show a DCR below 10 Hz, due to reduced fill factor, with photon count rates of 7.8 MHz and timing jitter less than 113 ps, which suggest that nanowire-based NIR focal plane arrays for single-photon detection can be designed without active quenching circuitry that severely restricts pixel density and portability in NIR commercial SPADs. Therefore, the proposed work based on vertical nanowires provides a new degree of freedom in designing avalanche photodetectors and could be a stepping stone for high-performance InGaAs SPADs.

Uncooled Photodetector at Short-Wavelength Infrared Using InAs Nanowire Photoabsorbers on InP with p- n Heterojunctions.

In this work, we demonstrate an InAs nanowire photodetector at short-wavelength infrared (SWIR) composed of vertically oriented selective-area InAs nanowire photoabsorber arrays on InP substrates, forming InAs-InP heterojunctions. We measure a rectification ratio greater than 300 at room temperature, which indicates a desirable diode performance. The dark current density, normalized to the area of nanowire heterojunctions, is 130 mA/cm2 at a temperature of 300 K and a reverse bias of 0.5 V, making it comparable to the state-of-the-art bulk InAs p- i- n photodiodes. An analysis of the Arrhenius plot of the dark current at reverse bias yields an activation energy of 175 meV from 190 to 300 K, suggesting that the Shockley-Read-Hall (SRH) nonradiative current is the primary contributor to the dark current. By using three-dimensional electrical simulations, we determine that the SRH nonradiative current originates from the acceptor-like surface traps at the nanowire-passivation heterointerfaces. The spectral response at room temperature is also measured, with a clear photodetection signature observed at wavelengths up to 2.5 µm. This study provides an understanding of dark current for small band gap selective-area nanowires and paves the way to integrate these improved nanostructured photoabsorbers on large band gap substrates for high-performance photodetectors at SWIR.

A three-dimensional insight into correlation between carrier lifetime and surface recombination velocity for nanowires.

The performance of nanowire-based devices is predominantly affected by nonradiative recombination on their surfaces, or sidewalls, due to large surface-to-volume ratios. A common approach to quantitatively characterize surface recombination is to implement time-resolved photoluminescence to correlate surface recombination velocity with measured minority carrier lifetime by a conventional analytical equation. However, after using numerical simulations based on a three-dimensional (3D) transient model, we assert that the correlation between minority carrier lifetime and surface recombination velocity is dependent on a more complex combination of factors, including nanowire geometry, energy-band alignment, and spatial carrier diffusion in 3D. To demonstrate this assertion, we use three cases-GaAs nanowires, InGaAs nanowires, and InGaAs inserts embedded in GaAs nanowires-and numerically calculate the carrier lifetimes by varying the surface recombination velocities. Using this information, we then investigate the intrinsic carrier dynamics within those 3D structures. We argue that the conventional analytical approach to determining surface recombination in nanowires is of limited applicability, and that a comprehensive computation in 3D can provide more accurate analysis. Our study provides a solid theoretical foundation to further understand surface characteristics and carrier dynamics for 3D nanostructured materials.

Exploring time-resolved photoluminescence for nanowires using a three-dimensional computational transient model.

Time-resolved photoluminescence (TRPL) has been implemented experimentally to measure the carrier lifetime of semiconductors for decades. For the characterization of nanowires, the rich information embedded in TRPL curves has not been fully interpreted and meaningfully mapped to the respective material properties. This is because their three-dimensional (3-D) geometries result in more complicated mechanisms of carrier recombination than those in thin films and analytical solutions cannot be found for those nanostructures. In this work, we extend the intrinsic power of TRPL by developing a full 3-D transient model, which accounts for different material properties and drift-diffusion, to simulate TRPL curves for nanowires. To show the capability of the model, we perform TRPL measurements on a set of GaAs nanowire arrays grown on silicon substrates and then fit the measured data by tuning various material properties, including carrier mobility, Shockley-Read-Hall recombination lifetime, and surface recombination velocity at the GaAs-Si heterointerface. From the resultant TRPL simulations, we numerically identify the lifetime characteristics of those material properties. In addition, we computationally map the spatial and temporal electron distributions in nanowire segments and reveal the underlying carrier dynamics. We believe this study provides a theoretical foundation for interpretation of TRPL measurements to unveil the complex carrier recombination mechanisms in 3-D nanostructured materials.