Effect of metformin on outcomes of patients treated with immune checkpoint inhibitors: a retrospective cohort study.

BACKGROUND: Immune checkpoint inhibitors have transformed the treatment landscape of cancer treatment, but only a fraction of patients responds to treatment, leading to an increasing effort to repurpose clinically approved medications to augment ICI therapy. Metformin has been associated with improved survival outcomes in patients undergoing conventional chemotherapy. However, whether metformin provides survival benefits in patients receiving immune checkpoint inhibitors (ICIs) is unknown. METHODS: We performed a retrospective cohort study at two tertiary referral centers in Taiwan. All adult diabetes mellitus patients who were treated with ICIs between January 2015 and December 2021 were included. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), respectively. RESULTS: In total, 878 patients were enrolled in our study, of which 86 patients used metformin and 78 patients used non-metformin diabetes medications. Compared with non-users, metformin users had a longer median OS (15.4 [IQR 5.6-not reached] vs. 6.1 [IQR, 0.8-21.0] months, P = 0.003) and PFS (5.1 [IQR 2.0-14.3] vs. 1.9 [IQR 0.7-8.6] months, P = 0.041). In a univariate Cox proportional hazard analysis, the use of metformin was associated with a reduction in the risk of mortality (HR: 0.53 [95% confidence interval: 0.35-0.81], P = 0.004) and disease progression (HR: 0.69 [95% CI 0.49-0.99], P = 0.042). The use of metformin remained associated with a lower risk of mortality after adjusting for baseline variables such as age, cancer stage, and underlying comorbidities (OS, HR: 0.55 [95% CI 0.34-0.87], P = 0.011). Similarly, the use of metformin was associated with a lower risk of disease progression. Importantly, the use of metformin before ICI initiation was not associated with a reduction in mortality (HR: 0.61 [95% CI 0.27-1.42], P = 0.25) or disease progression (HR: 0.69 [95% CI 0.33-1.43], P = 0.32). CONCLUSION: The use of metformin is associated with survival benefits in patients undergoing immunotherapy. Prospective clinical trials are warranted to define the role of metformin in augmenting immunotherapy.

Editorial for focus on manipulations of atomic and molecular layers and its applications in energy, environment sciences and optoelectronic devices.

This Focus aims at showcasing the significance of manipulating atomic and molecular layers for various applications. To this end, this Focus collects 15 original research papers featuring the applications of atomic layer deposition, chemical vapor deposition, wet chemistry, and some other methods for manipulations of atomic and molecular layers in lithium-ion batteries, supercapacitors, catalysis, field-effect transistors, optoelectronics, and others.

Enhanced photoluminescence of InGaAs/AlGaAs quantum well with tungsten disulfide quantum dots.

The pristine and diethylenetriamine (DETA)-doped tungsten disulfide quantum dots (WS2 QDs) with an average lateral size of about 5 nm have been synthesized using pulsed laser ablation (PLA). Introduction of the synthesized WS2 QDs on the InGaAs/AlGaAs quantum wells (QWs) can improve the photoluminescence (PL) of the InGaAs/AlGaAs QW as high as 6 fold. On the basis of the time-resolved PL and Kelvin probe measurements, the PL enhancement is attributed to the carrier transfer from the pristine or DETA-doped WS2 QDs to the InGaAs/AlGaAs QW. A heterostructure band diagram is proposed for explaining the carrier transfer, which increases the hole densities in the QW and enhances its PL intensity. This study is expected to be beneficial for the development of the InGaAs-based optoelectronic devices.

Impact of sodium-glucose cotransporter-2 inhibitors on heart failure and mortality in patients with cancer.

OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce heart failure (HF) in at-risk patients and may possess antitumour effects. We examined the effect of SGLT2i on HF and mortality among patients with cancer and diabetes. METHODS: This was a retrospective propensity score-matched cohort study involving adult patients with type 2 diabetes mellitus diagnosed with cancer between January 2010 and December 2021. The primary outcomes were hospitalisation for incident HF and all-cause mortality. The secondary outcomes were serious adverse events associated with SGLT2i. RESULTS: From a total of 8640 patients, 878 SGLT2i recipients were matched to non-recipients. During a median follow-up of 18.8 months, SGLT2i recipients had a threefold lower rate of hospitalisation for incident HF compared with non-SGLT2i recipients (2.92 vs 8.95 per 1000 patient-years, p=0.018). In Cox regression and competing regression models, SGLT2i were associated with a 72% reduction in the risk of hospitalisation for HF (HR 0.28 (95% CI: 0.11 to 0.77), p=0.013; subdistribution HR 0.32 (95% CI: 0.12 to 0.84), p=0.021). The use of SGLT2i was also associated with a higher overall survival (85.3% vs 63.0% at 2 years, p<0.001). The risk of serious adverse events such as hypoglycaemia and sepsis was similar between the two groups. CONCLUSIONS: The use of SGLT2i was associated with a lower rate of incident HF and prolonged overall survival in patients with cancer with diabetes mellitus.

Giant optical anisotropy of oblique-aligned ZnO nanowire arrays.

A combined method of modified oblique-angle deposition and hydrothermal growth was adopted to grow an optically anisotropic nanomaterial based on single crystalline ZnO nanowire arrays (NWAs) with highly oblique angles (75°-85°), exhibiting giant in-plane birefringence and optical polarization degree in emission. The in-plane birefringence of oblique-aligned ZnO NWAs is almost one order of magnitude higher than that of natural quartz. The strong optical anisotropy in emission due to the optical confinement was observed. The oblique-aligned NWAs not only allow important technological applications in passive photonic components but also benefit the development of the optoelectronic devices in polarized light sensing and emission.

Electronic structures of well-aligned Er-doped ZnO nanorod arrays.

Electronic structures of well-aligned Er-doped ZnO (ZnO:Er) nanorod arrays (NRAs) synthesized by a solution-based hydrothermal process were characterized by high-resolution transmission electron microscopy (HRTEM) and X-ray absorption fine structure (XAFS). HRTEM and angular dependent X-ray absorption near-edge structure analysis at O K and Zn L3 edges indicates that the spontaneous polarization is along the [0001] direction. The analysis of Er L3-edge XAFS demonstrates that the local structure around Er in the ZnO:Er NRAs was transformed from O(h) to C(4v), after annealing.

Visible-Light-Assisted Photoelectrochemical Biosensing of Uric Acid Using Metal-Free Graphene Oxide Nanoribbons.

In this study, we demonstrate the visible-light-assisted photoelectrochemical (PEC) biosensing of uric acid (UA) by using graphene oxide nanoribbons (GONRs) as PEC electrode materials. Specifically, GONRs with controlled properties were synthesized by the microwave-assisted exfoliation of multi-walled carbon nanotubes. For the detection of UA, GONRs were adopted to modify either a screen-printed carbon electrode (SPCE) or a glassy carbon electrode (GCE). Cyclic voltammetry analyses indicated that all Faradaic currents of UA oxidation on GONRs with different unzipping/exfoliating levels on SPCE increased by more than 20.0% under AM 1.5 irradiation. Among these, the GONRs synthesized under a microwave power of 200 W, namely GONR(200 W), exhibited the highest increase in Faradaic current. Notably, the GONR(200 W)/GCE electrodes revealed a remarkable elevation (~40.0%) of the Faradaic current when irradiated by light-emitting diode (LED) light sources under an intensity of illumination of 80 mW/cm2. Therefore, it is believed that our GONRs hold great potential for developing a novel platform for PEC biosensing.

Photoconductive enhancement of single ZnO nanowire through localized Schottky effects.

We demonstrated the Au nanoparticle (NP) decoration as an effective way to enhance both photocurrent and photoconductive gain of single ZnO nanowire (NW) photodetectors (PDs) through localized Schottky effects. The enhancement is caused by the enhanced space charge effect due to the existence of the localized Schottky junctions under open-circuit conditions at the NW surfaces, leading to a more pronounced electron-hole separation effect. Since the band-bending under illumination varies relatively small for an Au NP-decorated ZnO NW, the decay of gain is less prominent with increased excitation power, demonstrating the feasibility for a PD to maintain a high gain under high-power illumination.

UV light emission from GZO/ZnO/GaN heterojunction diodes with carrier confinement layers.

In this work, GZO/ZnO/GaN diodes with the light emitting ZnO layer sandwiched between two SiO(2) thin films was fabricated and characterized. We observed a strong excitonic emission at the wavelength 377nm with the Mg(2+) deep level transition and oxygen vacancy induced recombination significantly suppressed. In comparison, light emission from the GZO/GaN device (without SiO(2) barriers) is mainly dominant by defect radiation. Furthermore, the device with confinement layers demonstrated a much higher UV intensity than the blue-green emission of the GZO/GaN p-n device.

Cell tracking and detection of molecular expression in live cells using lipid-enclosed CdSe quantum dots as contrast agents for epi-third harmonic generation microscopy.

We demonstrated that lipid-enclosed CdSe quantum dots (LEQDs) can function as versatile contrast agents in epi-detection third harmonic generation (THG) microscopy for biological applications in vivo. With epi-THG intensities 20 times stronger than corresponding fluorescence intensities from the same LEQDs under the same conditions of energy absorption, such high brightness LEQDs were proved for the abilities of cell tracking and detection of specific molecular expression in live cancer cells. Using nude mice as an animal model, the distribution of LEQD-loaded tumor cells deep in subcutaneous tissues were imaged with high THG contrast. This is the first demonstration that THG contrast can be manipulated in vivo with nanoparticles. By linking LEQDs with anti-Her2 antibodies, the expression of Her2/neu receptors in live breast cancer cells could also be easily detected through THG. Compared with fluorescence modalities, the THG modality also provides the advantage of no photobleaching and photoblinkin g effects. Combined with a high penetration 1230 nm laser, these novel features make LEQDs excellent THG contrast agents for in vivo deep-tissue imaging in the future.

Biocompatible bacteria@Au composites for application in the photothermal destruction of cancer cells.

We have successfully transformed the infectious E. coli bacteria into biocompatible bacteria@Au composites for photothermal therapy.

Raman selection rule for surface optical phonons in ZnS nanobelts.

We report Raman scattering results for high-quality wurtzite ZnS nanobelts (NBs) grown by chemical vapor deposition. In the Raman spectrum, the ensembles of ZnS NBs exhibit first order phonon modes at 274 cm(-1) and 350 cm(-1), corresponding to A1/E1 transverse optical and A1/E1 longitudinal optical phonons, in addition to a strong surface optical (SO) phonon mode at 329 cm(-1). The existence of the SO band is confirmed by its shift with different surrounding dielectric media. Polarization dependent Raman spectra were recorded on a single ZnS NB and for the first time a SO phonon band has been detected on a single nanobelt. Different selection rules for the SO phonon mode are shown from their corresponding E1/A1 phonon modes, and were attributed to the breaking of anisotropic translational symmetry on the NB surface.

Light extraction enhancement with radiation pattern shaping of LEDs by waveguiding nanorods with impedance-matching tips.

Syringe-like ZnO nanorods (NRs) were fabricated on InGaN/GaN light emitting diodes (LEDs) by a hydrothermal method. Without sacrificing the electrical performances of LEDs, syringe-like NRs can enhance light extraction capability by 10.5% at 20 mA and shape the radiation profile with a view angle collimated from 136° to 121°. By performing optical experiments and simulation, it is found that the superior light extraction efficiency with a more collimated radiation pattern is attributed to the waveguiding effect of NRs and the mitigation of abrupt index change by the tapered ends of syringe-like ZnO NRs. This work demonstrates the importance of the nanostructure morphology in LED performances and provides the architecture design guidelines of nanostructures to a variety of optical devices.

19.2% Efficient InP Heterojunction Solar Cell with Electron-Selective TiO2 Contact.

We demonstrate an InP heterojunction solar cell employing an ultrathin layer (∼10 nm) of amorphous TiO2 deposited at 120 °C by atomic layer deposition as the transparent electron-selective contact. The TiO2 film selectively extracts minority electrons from the conduction band of p-type InP while blocking the majority holes due to the large valence band offset, enabling a high maximum open-circuit voltage of 785 mV. A hydrogen plasma treatment of the InP surface drastically improves the long-wavelength response of the device, resulting in a high short-circuit current density of 30.5 mA/cm2 and a high power conversion efficiency of 19.2%.

Ultrahigh sensitive piezotronic strain sensors based on a ZnSnO3 nanowire/microwire.

We demonstrated a flexible strain sensor based on ZnSnO(3) nanowires/microwires for the first time. High-resolution transmission electron microscopy indicates that the ZnSnO(3) belongs to a rhombohedral structure with an R3c space group and is grown along the [001] axis. On the basis of our experimental observation and theoretical calculation, the characteristic I-V curves of ZnSnO(3) revealed that our strain sensors had ultrahigh sensitivity, which is attributed to the piezopotential-modulated change in Schottky barrier height (SBH), that is, the piezotronic effect. The on/off ratio of our device is ∼587, and a gauge factor of 3740 has been demonstrated, which is 19 times higher than that of Si and three times higher than those of carbon nanotubes and ZnO nanowires.

Strain-gated piezotronic transistors based on vertical zinc oxide nanowires.

Strain-gated piezotronic transistors have been fabricated using vertically aligned ZnO nanowires (NWs), which were grown on GaN/sapphire substrates using a vapor-liquid-solid process. The gate electrode of the transistor is replaced by the internal crystal potential generated by strain, and the control over the transported current is at the interface between the nanowire and the top or bottom electrode. The current-voltage characteristics of the devices were studied using conductive atomic force microscopy, and the results show that the current flowing through the ZnO NWs can be tuned/gated by the mechanical force applied to the NWs. This phenomenon was attributed to the piezoelectric tuning of the Schottky barrier at the Au-ZnO junction, known as the piezotronic effect. Our study demonstrates the possibility of using Au droplet capped ZnO NWs as a transistor array for mapping local strain. More importantly, our design gives the possibility of fabricating an array of transistors using individual vertical nanowires that can be controlled independently by applying mechanical force/pressure over the top. Such a structure is likely to have important applications in high-resolution mapping of strain/force/pressure.

Probing surface band bending of surface-engineered metal oxide nanowires.

We in situ probed the surface band bending (SBB) by ultraviolet photoelectron spectroscopy (UPS) in conjunction with field-effect transistor measurements on the incompletely depleted ZnO nanowires (NWs). The diameter range of the NWs is ca. 150-350 nm. Several surface treatments (i.e., heat treatments and Au nanoparticle (NP) decoration) were conducted to assess the impact of the oxygen adsorbates on the SBB. A 100 °C heat treatment leads to the decrease of the SBB to 0.74 ± 0.15 eV with 29.9 ± 3.0 nm width, which is attributed to the removal of most adsorbed oxygen molecules from the ZnO NW surfaces. The SBB of the oxygen-adsorbed ZnO NWs is measured to be 1.53 ± 0.15 eV with 43.2 ± 2.0 nm width. The attachment of Au NPs to the NW surface causes unusually high SBB (2.34 ± 0.15 eV with the wide width of 53.3 ± 1.6 nm) by creating open-circuit nano-Schottky junctions and catalytically enhancing the formation of the charge O(2) adsorbates. These surface-related phenomena should be generic to all metal oxide nanostructures. Our study is greatly beneficial for the NW-based device design of sensor and optoelectronic applications via surface engineering.

Supersensitive, ultrafast, and broad-band light-harvesting scheme employing carbon nanotube/TiO2 core-shell nanowire geometry.

We demonstrate a novel, feasible strategy for practical application of one-dimensional photodetectors by integrating a carbon nanotube and TiO(2) in a core-shell fashion for breaking the compromise between the photogain and the response/recovery speed. Radial Schottky barriers between carbon nanotube cores and TiO(2) shells and surface states at TiO(2) shell surface regulate electron transport and also facilitate the separation of photogenerated electrons and holes, leading to ultrahigh photogain (G = 1.4 × 10(4)) and the ultrashort response/recovery times (4.3/10.2 ms). Additionally, radial Schottky junction and defect band absorption broaden the detection range (UV-visible). The concept using metallic core oxide-shell geometry with radial Schottky barriers holds potential to pave a new way to realize nanostructured photodetectors for practical use.

Taper PbZr(0.2)Ti(0.8)O3 nanowire arrays: from controlled growth by pulsed laser deposition to piezopotential measurements.

Single crystalline PbZr(0.2)Ti(0.8) (PZT) nanowires arrays (NWAs) with taper morphology were epitaxially grown on SrTiO(3) (STO) substrate using pulse laser deposition. The taper morphology was attributed to the overcoating of PZT layer via a lateral growth of PZT clusters/adatoms during PZT NW growth. The growth window for PZT film or nanowire was systematically studied at varied temperatures and pressures. The proposed growth mechanism of the taper PZT NWAs was investigated from a layer by layer growth via Frank-Van Der Merwe growth, followed by a formation of three-dimensional islands via Stranski-Krastanow growth, and then axial growth on the lowest energy (001) plane with growth direction of [001] via vapor-solid growth mechanism. However, under certain conditions such as at higher or lower pressure (>400 or <200 mTorr) or substrate temperatures (>850 °C and <725 °C), formation of the PZT NWs is suppressed while the epitaxial PZT thin film via the layer-by-layer growth remains. The controllable growth directions of the PZT NWAs on (001), (110), and (111) STO substrates were demonstrated. The piezopotential of the taper PZT NWAs using a conducting atomic force microscope with the average voltage output of ~18 mV was measured. The theoretical piezopotential of a PZT NW was calculated to compare with the measured outputs, providing a comprehensively experimental and theoretical understanding of the piezoelectricity for the PZT NW.

Significant enhancement of yellow-green light emission of ZnO nanorod arrays using Ag island films.

Surface plasmon (SP) mediated emission from ZnO nanorod arrays (NRAs)/Ag/Si structures has been investigated. The ratio of visible emission to UV emission can be increased by over 30 times via coupling with SP without deterioration of the crystal quality. The fact that the effect of SP crucially depends on the size of Ag island films provides the feasibility to significantly enhance the yellow-green emission of the ZnO nanostructures without sacrificing the crystallinity of ZnO.