Laser-driven noncontact bubble transfer printing via a hydrogel composite stamp.

Transfer printing that enables heterogeneous integration of materials into spatially organized, functional arrangements is essential for developing unconventional electronic systems. Here, we report a laser-driven noncontact bubble transfer printing via a hydrogel composite stamp, which features a circular reservoir filled with hydrogel inside a stamp body and encapsulated by a laser absorption layer and an adhesion layer. This composite structure of stamp provides a reversible thermal controlled adhesion in a rapid manner through the liquid-gas phase transition of water in the hydrogel. The ultrasoft nature of hydrogel minimizes the influence of preload on the pick-up performance, which offers a strong interfacial adhesion under a small preload for a reliable damage-free pick-up. The strong light-matter interaction at the interface induces a liquid-gas phase transition to form a bulge on the stamp surface, which eliminates the interfacial adhesion for a successful noncontact printing. Demonstrations of noncontact transfer printing of microscale Si platelets onto various challenging nonadhesive surfaces (e.g., glass, key, wrench, steel sphere, dry petal, droplet) in two-dimensional or three-dimensional layouts illustrate the unusual capabilities for deterministic assembly to develop unconventional electronic systems such as flexible inorganic electronics, curved electronics, and micro-LED display.

BatchDTA: implicit batch alignment enhances deep learning-based drug-target affinity estimation.

Candidate compounds with high binding affinities toward a target protein are likely to be developed as drugs. Deep neural networks (DNNs) have attracted increasing attention for drug-target affinity (DTA) estimation owning to their efficiency. However, the negative impact of batch effects caused by measure metrics, system technologies and other assay information is seldom discussed when training a DNN model for DTA. Suffering from the data deviation caused by batch effects, the DNN models can only be trained on a small amount of 'clean' data. Thus, it is challenging for them to provide precise and consistent estimations. We design a batch-sensitive training framework, namely BatchDTA, to train the DNN models. BatchDTA implicitly aligns multiple batches toward the same protein through learning the orders of candidate compounds with respect to the batches, alleviating the impact of the batch effects on the DNN models. Extensive experiments demonstrate that BatchDTA facilitates four mainstream DNN models to enhance the ability and robustness on multiple DTA datasets (BindingDB, Davis and KIBA). The average concordance index of the DNN models achieves a relative improvement of 4.0%. The case study reveals that BatchDTA can successfully learn the ranking orders of the compounds from multiple batches. In addition, BatchDTA can also be applied to the fused data collected from multiple sources to achieve further improvement.

Tunable high energy pulse generation in the range of 2.9-3.6†µm enabled by an actively Q switched Er3+/Dy3+ codoped fluoride fiber oscillator.

We demonstrate, for the first time, an actively Q switched red-diode-clad-pumped Er3+/Dy3+ codoped fluoride fiber oscillator. Its wavelength can be continuously tuned over the range of 2.906-3.604 µm (698 nm), representing the widest tuning span of pulsed fluoride fiber oscillators in the mid-infrared. In addition, the achieved pulse energy at each wavelength of >2.95 µm is also higher than that of a previously reported pulsed fluoride fiber oscillator at the corresponding wavelength, to the best of our knowledge. By tuning the wavelength to 3.204 µm, the highest pulse energy of 82 µJ has been gotten with a pulse width of 520 ns at a repetition rate of 500 Hz.

ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia.

ARMC5 is implicated in several pathological conditions, but its function remains unknown. We have previously identified CUL3 and RPB1 (the largest subunit of RNA polymerase II (Pol II) as potential ARMC5-interacting proteins. Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1. ARMC5, CUL3, and RBX1 formed an active E3 specific for RPB1. Armc5 deletion caused a significant reduction in RPB1 ubiquitination and an increase in an accumulation of RPB1, and hence an enlarged Pol II pool in normal tissues and organs. The compromised RPB1 degradation did not cause generalized Pol II stalling nor depressed transcription in the adrenal glands but did result in dysregulation of a subset of genes, with most upregulated. We found RPB1 to be highly expressed in the adrenal nodules from patients with primary bilateral macronodular adrenal hyperplasia (PBMAH) harboring germline ARMC5 mutations. Mutant ARMC5 had altered binding with RPB1. In summary, we discovered that wildtype ARMC5 was part of a novel RPB1-specific E3. ARMC5 mutations resulted in an enlarged Pol II pool, which dysregulated a subset of effector genes. Such an enlarged Pol II pool and gene dysregulation was correlated to adrenal hyperplasia in humans and KO mice.

Near-infrared pumped, octave-tunable, on-chip mid-infrared Raman soliton source.

This article proposes and numerically demonstrates a widely tunable on-chip Raman soliton source based on a cascaded As2Se3 waveguide. The cascaded sub-waveguides (input and output) with varying widths act as nonlinear devices, while a tapered waveguide is arranged between them to achieve low-loss transmission. The input waveguide provides anomalous dispersion in the near-infrared band, thereby enabling the 1.96 µm source for Raman soliton self-frequency shift (SSFS) pumping. The output waveguide exhibits large anomalous dispersion and good mode confinement in the mid-infrared band thus supporting further SSFS process. A 2.29∼4.57 µm tunable Raman source is theoretically realized in this on-chip platform. This work presents a simple and easy-to-implement strategy to extend the tuning range of on-chip sources. Notably, to the best of our knowledge, this is the first demonstration of the cascading strategy for SSFS process in an on-chip platform. The proposed tunable source has great potential in integrated spectroscopy, gas sensing, and LiDAR applications.

NIR to MIR ultra-broadband supercontinuum laser source based on all-silica fibers.

We demonstrated an ultra-broadband supercontinuum (SC) laser source with a wavelength range spanning the near-infrared (NIR) to mid-infrared (MIR) region. The SC spectrum was generated in a very short piece of highly nonlinear silica fiber (HNLF) which has a zero-dispersion wavelength (ZDW) of 1.55 µm. The pump source used has a spectral coverage of 1.5∼2.4 µm which covers the ZDW of HNLF, resulting in a dramatic blue and red shift of the spectrum through strong non-linear effects. As the pump laser pulse launched into HNLF, a SC spectrum with broadband range of 0.92∼2.92 µm and maximum average power of 5.09 W was achieved, which sets record coverage of HNLF-based watts magnitude SC laser sources for now, to the best of the authors' knowledge. The setup consists of silica fiber that can be considered easy-to-implement and with a cost-effectiveness scheme for ultra-broadband SC generation that could be easily applied to optical fiber sensing and spectral imaging technology.

Efficient Raman pulse fiber laser pumped by a dissipative soliton resonance pulse near 2 µm.

A high-efficiency Raman conversion from 1.987 µm to 2.177 µm is demonstrated experimentally in 45 m GeO2-doped silica fiber, adopting a dissipative soliton resonance (DSR) rectangular pulse as the pump. Over the entire spectral distribution, the spectral purity of the first-order Raman pulse is up to 96.8%, suggesting a nearly complete pump depletion before the onset of cascaded Raman shifts. The corresponding pump-to-Raman conversion efficiency of 67.4% is the highest up to date in this spectral region. Meanwhile, a large Raman pulse energy of 1.03 µJ was obtained at the repetition rate near MHz level, corresponding to 0.893 W average power. In the total output, the Raman-dominated spike has a Full Width Half Maximum (FWHM) of 1.18 ns far narrower than DSR's pulse duration of 10.25 ns. The results indicate that DSR is a promising candidate for developing efficient Raman nanosecond pulse fiber laser in mid-infrared (MIR) region.

Nano-Ni/Co-PBA as high-performance cathode material for aqueous sodium-ion batteries.

Prussian blue analogues (PBAs) are reliable and promising cathode materials for aqueous sodium-ion batteries (ASIBs) owing to their open three-dimensional frameworks, outstanding stability, and low production costs. However, PBAs containing only a single type of transition-metal ion often have limited charge-storage capacities in aqueous systems. This study reports the first example of K0.11Ni0.39Co0.79[Fe(CN)6]·2.04H2O nanoparticles (Ni/Co-PBA) being used as a high-capacity cathode material for ASIBs. Owing to multi-electron redox reactions involving Co and Fe ions, Ni/Co-PBA has an initial capacity of 65 mAh g-1and a capacity retention rate of 80% after 1000 cycles at 1.0 A g-1, indicating its outstanding cycle performance and capacity retention. Ex-situ x-ray diffraction spectroscopy, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and the galvanostatic intermittent titration technique were used to analyze the redox mechanisms and kinetics of Ni/Co-PBA. Ni/Co-PBA-based ASIBs are among the most promising energy-storage technologies for large-scale fixed energy-storage systems because of their outstanding electrochemical performance, low costs, and high efficiency.

Association between the NEP rs701109 polymorphism and the clinical efficacy and safety of sacubitril/valsartan in Chinese patients with heart failure.

OBJECTIVE: Sacubitril/valsartan is a commonly used medicine for treating heart failure (HF) patients, but the treatment effects significantly vary. Neprilysin (NEP) and carboxylesterase 1 (CES1) play an important role in the efficacy of sacubitril/valsartan. The purpose of this study was to explore the relationship between NEP and CES1 gene polymorphisms and the efficacy and safety of sacubitril/valsartan treatment in HF patients. METHODS: Genotyping of 10 single nucleotide polymorphisms (SNPs) of the NEP and CES1 genes in 116 HF patients was performed by the Sequenom MassARRAY method, and logistic regression and haplotype analysis were used to evaluate the associations between SNPs and the clinical efficacy and safety of sacubitril/valsartan in HF patients. RESULTS: A total of 116 Chinese patients with HF completed the whole trial, and T variations in rs701109 in NEP gene were an independent risk factor (P = 0.013, OR = 3.292, 95% CI:1.287-8.422) for the clinical efficacy of sacubitril/valsartan. Furthermore, haplotype analysis of 6 NEP SNPs (including rs701109) was performed and showed that the CGTACC and TGTACC haplotypes were significantly associated with clinical efficacy (OR = 0.095, 95%CI: 0.012-0.723, P = 0.003; OR = 5.586, 95% CI: 1.621-19.248, P = 0.005). Moreover, no association was found between SNPs of other selected genes in terms of efficacy in HF patients, and no association was observed between SNPs and symptomatic hypotension. CONCLUSION: Our results suggest an association between rs701109 and sacubitril/valsartan response in HF patients. Symptomatic hypotension is not associated with the presence of NEP polymorphisms.

Pharmacokinetics, safety, and bioequivalence of apixaban tablets in healthy Chinese subjects under fasting and fed conditions.

OBJECTIVE: To evaluate the pharmacokinetics (PK), safety, and bioequivalence of two formulations of apixaban in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: A single-center, randomized, open, single-dose, two-period crossover PK study was carried out under fasting and fed conditions in 64 healthy subjects enrolled in either the fasting (36 subjects) or the fed (28 subjects) arms of the study. Subjects received a single oral dose of 2.5 mg apixaban tablets as test (T) or reference (R) formulation. The primary PK parameters determined were the area under the plasma concentration-time curve from zero to t and ∞ (AUC0-t and AUC0-∞) and the maximal plasma concentration (Cmax). Safety was assessed mainly from the occurrence of adverse events (AEs). RESULTS: A single drop-out in the fed arm of the trial was excluded from the statistical evaluation. The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) for T/R using AUC0-t were 95.4 - 100.9% and 97.8 - 103.8%, and for AUC0-∞ were 95.3 - 100.6% and 98.3 - 104.3% under fasting (36 subjects) and fed (27 subjects) conditions, respectively. Similarly, the 90% CIs for Cmax were 94.6 - 103.1% and 88.8 - 102.0% under fasting (36 subjects) and the fed (27 subjects) conditions, respectively. Therefore, the 90% CIs for the T/R AUC and Cmax ratios were within the standard range for bioequivalence (80.0 - 125.0%). There were no serious adverse events (SAEs). CONCLUSION: The test and reference 2.5 mg apixaban tablets were bioequivalent and both showed good tolerability and safety.

Repair and Mechanism of Oligopeptide SEP-3 on Oxidative Stress Liver Injury Induced by Sleep Deprivation in Mice.

To investigate the effects of bonito oligopeptide SEP-3 on the repair of liver damage and regulation of liver biorhythm in sleep-deprived mice (SDM), C57BL/6 male mice were subjected to sleep deprivation by modified multi-platform water environment method, and were given different doses of bonito oligopeptide SEP-3 in groups. To determine the liver organ index, liver tissue-related apoptotic protein levels, Wnt/ß-Catenin pathway-related protein expression levels, serum alanine transaminase (ALT), glutamicum transaminase (AST), glucocorticoid (GC), and adrenocorticotropin (ACTH) content in each group of mice, four time points were selected to examine the mRNA expression levels of circadian clock-related genes in mouse liver tissue. The results showed that low, medium, and high doses of SEP-3 significantly increased SDM, ALT, and AST (p < 0.05), and medium and high doses of SEP-3 significantly reduced SDM liver index and GC and ACTH. As SEP-3 increased the apoptotic protein and Wnt/ß-Catenin pathway, mRNA expression gradually tended to normal (p < 0.05). This suggests that sleep deprivation can cause excessive oxidative stress in mice, which can lead to liver damage. Additionally, oligopeptide SEP-3 achieves the repair of liver damage by inhibiting SDM hepatocyte apoptosis, activating liver Wnt/ß-Catenin pathway, and promoting hepatocyte proliferation and migration, and suggests that oligopeptide SEP-3 is closely related to repair of liver damage by regulating the biological rhythm of SDM disorder.

Water-Lubricated Aluminum Vanadate for Enhanced Rechargeable Magnesium Ion Storage.

Magnesium ion batteries (MIBs) have attracted much attention due to their low cost and high safety properties. However, the intense charge repulsion effect and sluggish diffusion dynamics of Mg2+ ions result in unsatisfactory electrochemical performance of conventional cathode materials in MIBs. This work reports water-lubricated aluminum vanadate (HAlVO) as high-performance cathode material for Mg2+ ions storage and investigates the capacity fade mechanism of water-free aluminum vanadate (AlVO). The charge density difference based on density functional theory calculation is performed to analyze the charge transfer process of water-lubricated/free aluminum vanadates (HAlVO/AlVO). The different charge transfer phenomena of two materials and the charge shielding effect of water molecule in HAlVO are revealed. Moreover, the single-phase structural evolution process and the Mg2+ ions storage mechanism of HAlVO are further investigated deeply by different in situ and ex situ characterization methods. This work proves that HAlVO is a potential candidate cathode material to satisfy the high-performance reversible Mg2+ ions storage, and the water-lubricated method is an effective strategy to improve the electrochemical performance of vanadium oxides cathode.

The key roles of organelles and ferroptosis in Alzheimer's disease.

Alzheimer's disease (AD), an age-related neurodegenerative disease, is a striking global health problem. Ferroptosis is a newly discovered form of cell death characterized by iron-dependent lipid peroxidation products and the accumulation of lethal reactive oxygen species. Strict regulation of iron metabolism is essential to ensure neuronal homeostasis. Excess and deficiency of iron are both associated with neurodegeneration. Studies have shown that oxidative stress caused by cerebral iron metabolism disorders in the body is involved in the process of AD, ferroptosis may play an important role in the pathogenesis of AD, and regulating ferroptosis is expected to be a new direction for the treatment of AD. Various organelles are closely related to ferroptosis: mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosome are involved in the regulation of ferroptosis from the aspects of iron metabolism and redox imbalance. In this review, the relationship between AD and the dysfunction of organelles (including mitochondria, endoplasmic reticulum, lysosome, and Golgi apparatus) and the role of organelles in ferroptosis of AD were reviewed to provide insights for understanding the relationship between organelles and ferroptosis in AD and the treatment of AD.

Red-diode-clad-pumped Er3+/Dy3+ codoped ZrF4 fiber: A promising mid-infrared laser platform.

We report, for the first time, to the best of our knowledge, mid-infrared (mid-IR) laser generation, from a red-diode-clad-pumped Er3+/Dy3+ codoped ZrF4 fiber laser. A free-running laser at ∼3.4 µm, mainly from the 4F9/2→4I9/2 transition of Er3+, directly excited by a 659-nm laser diodehas been achieved at room temperature with a maximum power of 0.8 W and 8.8% slope efficiency. In this system, the long-lived 4I11/2 and 4I13/2 states are rapidly depopulated by energy transfer to the codoped Dy3+ ions and energy transfer upconversion between the Er3+ ions, resulting in the accelerated recycling of ions. Additionally, the free-running dual-wavelength operation state at ∼3.3 and ∼3.5 µm is also observed, producing a total maximum power of 0.95 W with 10.7% slope efficiency, representing the first watt-class output from a diode-pumped rare-earth-doped fiber laser far beyond 3 µm. By employing a diffraction grating, continuous spectral tuning across the 642-nm range from 3053.9 to 3695.9 nm has been demonstrated. The proposed scheme provides, to the best of our knowledge, a promising new platform for laser generation in the mid-IR region of 3-4 µm.

The receptor tyrosine kinase EPHB6 regulates catecholamine exocytosis in adrenal gland chromaffin cells.

The erythropoietin-producing human hepatocellular receptor EPH receptor B6 (EPHB6) is a receptor tyrosine kinase that has been shown previously to control catecholamine synthesis in the adrenal gland chromaffin cells (AGCCs) in a testosterone-dependent fashion. EPHB6 also has a role in regulating blood pressure, but several facets of this regulation remain unclear. Using amperometry recordings, we now found that catecholamine secretion by AGCCs is compromised in the absence of EPHB6. AGCCs from male knockout (KO) mice displayed reduced cortical F-actin disassembly, accompanied by decreased catecholamine secretion through exocytosis. This phenotype was not observed in AGCCs from female KO mice, suggesting that testosterone, but not estrogen, contributes to this phenotype. Of note, reverse signaling from EPHB6 to ephrin B1 (EFNB1) and a 7-amino acid-long segment in the EFNB1 intracellular tail were essential for the regulation of catecholamine secretion. Further downstream, the Ras homolog family member A (RHOA) and FYN proto-oncogene Src family tyrosine kinase (FYN)-proto-oncogene c-ABL-microtubule-associated monooxygenase calponin and LIM domain containing 1 (MICAL-1) pathways mediated the signaling from EFNB1 to the defective F-actin disassembly. We discuss the implications of EPHB6's effect on catecholamine exocytosis and secretion for blood pressure regulation.

Study on soliton self-frequency shift in a Tm-doped fiber amplifier seeded by a Kelly-sideband-suppressed conventional soliton.

We experimentally present mid-infrared Raman soliton self-frequency shift (SSFS) process in a Tm-doped fiber amplifier using sideband-suppressed conventional solitons as seed pulses. The strong Kelly sidebands of the soliton oscillator were efficiently suppressed (more than 21 dB) using a home-made all-fiber Lyot filter (AFLF). As a result, the Raman solitons with a continuously tunable wavelength of 1.95-2.34 µm were achieved, with a high soliton energy conversion of >93% over the range of 1.95-2.24 µm. The conversion efficiency and tunable range of Raman solitons were both significantly improved, comparing to the same amplifier seeded with sideband-unsuppressed pulses.

High-stability, linearly polarized mode-locking generation from a polarization-maintaining fiber oscillator around 2.8 µm.

In this Letter, a high-stability, linearly polarized mode-locked polarization-maintaining (PM) Er3+-doped fluoride fiber oscillator at ∼2.8µm is presented for the first time, to the best of our knowledge, where an InAs-based semiconductor saturable absorber mirror is used as the mode locker, and a film polarizer is employed for maintaining the linearly polarized oscillation. In the free-running state, stable linearly polarized mode-locked pulses (τ=44ps and P=446mW) at 2.795 µm, with a high polarization extinction ratio of >23dB and a low integrated relative intensity noise of 0.087% [1 Hz-10 MHz], have been achieved, which can be strongly immune to external mechanical perturbations. By introducing a ruled reflective diffraction grating into the cavity in a Littman configuration, the continuous wavelength tuning of the linearly polarized mode-locked pulses in the range of 2717-2827 nm is obtained as well. To the best of our knowledge, this marks the first demonstration of a linearly polarized PM fiber oscillator in the >2.5µm mid-infrared region.

Tunable sub-300 fs soliton and switchable dual-wavelength pulse generation from a mode-locked fiber oscillator around 2.8 µm.

In this Letter, we demonstrate, for the first time, to the best of our knowledge, tunable soliton and switchable dual-wavelength pulse generation from a nonlinear polarization rotation mode-locked Er3+-doped fluoride fiber oscillator around 2.8 µm, employing a LiNbO3 birefringent plate (BFP)-based Lyot filter. In the single soliton state, the wavelength can be continuously tuned in the region of 2752.4∼2807.2nm (∼55nm) with a pulse width between 199 and 270 fs, by rotating the BFP with the aid of its spectral filtering effect. At higher pump levels, two kinds of dual-wavelength synchronous mode-locking states (i.e., 2746.4/2782.0 and 2787.2/2825.2 nm) are observed, and can be flexibly switched by adjusting the rotation angle of the BFP. This approach opens up new opportunities for the development of versatile mid-infrared ultrashort laser sources.

Unlocking the ultrafast potential of gold nanowires for mode-locking in the mid-infrared region.

In this Letter, we present the mode-locking operation of a 2.87 µm Ho3+/Pr3+ codoped fluoride fiber laser, helped by the ultrafast nonlinear optical absorption behavior of gold nanowires (GNWs). The mode locker is fabricated by depositing the GNW solution onto a silver mirror. It has a modulation depth of 14.2%, a saturation intensity of 26.2MW/cm2, and a non-saturation loss of 29.9% at 2.87 µm. With an increased pump power, the laser operates in Q-switched mode-locking, fundamental mode-locking, and harmonic mode-locking (HML) states. This represents the first, to our knowledge, mid-infrared mode-locked laser using gold nanomaterials. Additionally, the HML is also the first observation in a laser in this band using material saturable absorbers, implying the capability of GNWs for high repetition rate generation.

Brain-derived neurotrophic factor Val66Met polymorphism is associated with mild cognitive impairment in elderly patients with type 2 diabetes: a case-controlled study.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is reported to be associated with cognitive dysfunction, an important comorbidity factor in patients with type 2 diabetes mellitus (T2DM), especially in elderly populations, however, the underlying pathophysiological mechanisms are unclear. AIM: This study was performed to investigate the association between BDNF Val66Met polymorphism and mild cognitive impairment (MCI) in elderly patients with T2DM. METHODS: In total, 105 MCI and 105 normal cognition controls of T2DM patients were enrolled; all of the patients underwent neuropsychological assessments. BDNF Val66Met polymorphism was genotyped via TaqMan SNP genotyping assay. Data from clinical and laboratory-based examinations were collected. RESULTS: The frequency of the BDNF Met allele was significantly higher in the MCI group than in the controls. Multiple regression analysis indicated an association of the Met allele with MCI in patients with T2DM (OR = 2.54; 95% CI 1.33-4.84; p = 0.005). Stratified by educational level, the BDNF Met allele was significantly associated with MCI in elderly T2DM patients (OR = 3.29; 95% CI 1.26-8.57; p = 0.015) among the group of low educational levels (< 12 years); however, the association was insignificant among those with higher educational levels. DISCUSSION: BDNF Met allele carriers showed a higher frequency of MCI than Val/Val homozygotes in elderly T2DM patients. However, this association was only significant in patients with low education levels. CONCLUSION: BDNF Val66Met polymorphism may have a potential role in MCI in elderly T2DM patients, especially those with low educational levels.