Chip-based label-free incoherent super-resolution optical microscopy.

The photo-kinetics of fluorescent molecules have enabled the circumvention of the far-field optical diffraction limit. Despite its enormous potential, the necessity to label the sample may adversely influence the delicate biology under investigation. Thus, continued development efforts are needed to surpass the far-field label-free diffraction barrier.

Machine learning combining external validation to explore the immunopathogenesis of diabetic foot ulcer and predict therapeutic drugs.

Diabetic foot ulcer (DFU) is a severe complication of diabetes, often leading to amputation due to poor wound healing and infection. The immune-related pathogenesis of DFU remains unclear, and therapeutic drugs are limited. This study aimed to explore the immune mechanisms of DFU and identify potential therapeutic drugs using machine learning and single-cell approaches.

Rapid Onset of Pain Relief with Crisugabalin in Patients with Diabetic Peripheral Neuropathic Pain: Findings from a Multicenter, Randomized, Double-Blind, Controlled Study.

Introduction: This study aims to evaluate the efficacy and safety of Crisugabalin in patients with diabetic peripheral neuropathic pain (DPNP), with a focus on its rapid onset of action.

Methods: All the analyses in this study were based on data from a phase 2/3 adaptive randomized clinical trial that enrolled 596 patients. Participants were categorized into four treatment groups according to the intervention received: Crisugabalin 40 mg/day, Crisugabalin 80 mg/day, placebo, and Pregabalin 300 mg/day.

Non-Isothermal Crystallization Behavior of a Zr-Based Amorphous Alloy Composite Prepared by Selective Laser Melting.

ZrCuAlCo bulk amorphous alloy composites were prepared by selective laser melting (SLM) technology under different processing conditions and their non-isothermal crystallization behaviors were systematically investigated. The results show that the crystallization phases are CuZr and CuZr for both gas-atomized powder and SLMed samples. The dependence of volume fraction of CuZr and CuZr on laser energy density can be fitted by an exponential function.

Causal association between varicose veins and atrial fibrillation: A 2-sample bidirectional Mendelian randomization study.

This study selected genome-wide association study data from the FinnGen database and utilized a bidirectional 2-sample Mendelian randomization (MR) method to explore the causal association between varicose veins (VV) and atrial fibrillation (AF). Inverse variance weighted (IVW) was used as the primary analytical method to assess the causal relationship between VV and AF, supplemented by Weighted median, MR-Egger and Simple 1mode. Cochran's Q test, MR-Egger regression intercept and Mendelian randomization pleiotropy residual sum and outlier were used as sensitivity analyses to detect heterogeneity and multilevel pleiotropy.

Residue Y362 is crucial for FLIP to impart catalytic activity to pro-caspase-8 to suppress necroptosis.

The pro-form of caspase-8 prevents necroptosis by functioning in a proteolytically active complex with its catalytic-dead homolog, FLICE (FADD [Fas-associated death domain]-like interleukin 1β-converting enzyme)-like inhibitory protein long-form (FLIP). However, how FLIP imparts caspase-8 the catalytic activity to suppress necroptosis remains elusive. Here, we show that the protease-like domain of FLIP is essential for the activity of the caspase-8-FLIP heterodimer in blocking necroptosis.

Analysis of the Improvement Sequence in Insomnia Symptoms and Factors Influencing the Treatment Outcomes of Smartphone-Delivered CBT in Patients with Insomnia Disorder.

Background: The effectiveness of medication combined with smartphone-delivered cognitive behavioral therapy for insomnia (CBT-I) has been well verified, but there are few studies on the sequence of remission of insomnia symptoms. This study aims to understand the sequence of symptom improvement and the factors influencing the treatment effectiveness in patients with insomnia.

Methods: Smartphone-delivered CBT, as a form of Online CBT, allows for training through mobile devices at any time and place.

Association of glycogen synthase kinase-3β with cognitive impairment in type 2 diabetes patients: a six-year follow-up study.

Background: Our previous multicenter case-control study showed that aging, up-regulation of platelet glycogen synthase kinase-3β (GSK-3β), impaired olfactory function, and ApoE ϵ4 genotype were associated with cognitive decline in type 2 diabetes mellitus (T2DM) patients. However, the causal relationship between these biomarkers and the development of cognitive decline in T2DM patients remains unclear.

Methods: To further investigate this potential relationship, we designed a 6-year follow-up study in 273 T2DM patients with normal cognitive in our previous study.

A Yield Stress and Work Hardening Model of Al-Mg-Si Alloy Considering the Strengthening Effect of β" and β' Precipitates.

Precipitates are the primary source of strength for the Al-Mg-Si alloy. Aluminum alloy in the peak-aged state mainly contains β" and β' precipitates. Most of the literature has only considered the strengthening effect of β".

The Effect of Lattice Misfits on the Precipitation at Dislocations: Phase-Field Crystal Simulation.

An atomic-scale approach was employed to simulate the formation of precipitates with different lattice misfits in the early stages of the aging of supersaturated aluminum alloys. The simulation results revealed that the increase in lattice misfits could significantly promote the nucleation rate of precipitates, which results in a larger number and smaller size of the precipitates. The morphologies of the precipitates also vary with the degree of a lattice misfit.

Effect of caffeine and other xanthines on liver sinusoidal endothelial cell ultrastructure.

Xanthines such as caffeine and theobromine are among the most consumed psychoactive stimulants in the world, either as natural components of coffee, tea and chocolate, or as added ingredients. The present study assessed if xanthines affect liver sinusoidal endothelial cells (LSEC). Cultured primary rat LSEC were challenged with xanthines at concentrations typically obtained from normal consumption of xanthine-containing beverages, food or medicines; and at higher concentrations below the in vitro toxic limit.

Atomic-Scale Insights into the Self-Assembly of Alternating AlN/TiN Lamellar Nanostructures via Spinodal Decomposition in AlTiN Coating.

The self-assembly mechanism of alternating AlN/TiN nano-lamellar structures in AlTiN coating is still a mystery, though this coating has been widely used in industry. Here, by using the phase-field crystal method, we studied the atomic-scale mechanisms of the formation of nano-lamellar structures during spinodal decomposition transformation of an AlTiN coating. The results show that the formation of a lamella is characterized by four distinct stages including the generation of dislocations (stage I), formation of islands (stage II), merging of islands (stage III), and flattening of lamellae (stage IV).

Atomic-Scale Insights into the Deformation Mechanism of the Microstructures in Precipitation-Strengthening Alloys.

Clarifying the deformation behaviors of microstructures could greatly help us understand the precipitation-strengthening mechanism in alloys. However, it is still a formidable challenge to study the slow plastic deformation of alloys at the atomic scale. In this work, the phase-field crystal method was used to investigate the interactions between precipitates, grain boundary, and dislocation during the deformation processes at different degrees of lattice misfits and strain rates.

The contribution of inner electron excitation to the electronic stopping power of palladium for protons.

The electronic stopping power of palladium (Pd) for protons is investigated based on time-dependent density functional theory combined with Ehrenfest molecular dynamics simulations. The electronic stopping power of Pd with explicitly considering inner electrons for protons is calculated and the excitation mechanism for the inner electrons of Pd is revealed. The velocity proportionality of the low-energy stopping power of Pd is reproduced.

Label-free superior contrast with c-band ultra-violet extinction microscopy.

In 1934, Frits Zernike demonstrated that it is possible to exploit the sample's refractive index to obtain superior contrast images of biological cells. The refractive index contrast of a cell surrounded by media yields a change in the phase and intensity of the transmitted light wave. This change can be due to either scattering or absorption caused by the sample.

pneumonia after total hip arthroplasty in a dermatomyositis patient: A case report.

Background: pneumonia (PJP) is a serious opportunistic infection that occurs mostly in patients with immunodeficiency and long-term immunosuppressive therapy. In non-human immunodeficiency virus-infected patients, the most important risk factor for PJP is the use of glucocorticoids in combination with other immunosuppressive treatments. The management of glucocorticoids during the perioperative period in patients with dermatomyositis requires special care.

Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone.

Improving the clinical ability and quality of endocrinology department with diagnosis-related groups tool.

Background: To evaluate the use of the diagnosis-related groups (DRGs) tool to promote the diagnosis/treatment ability and quality of the endocrinology department under the new policy of grouping payment-related to disease diagnosis.

Methods: We compared the income structure of the endocrinology department in a 3a general hospital between the first half of 2019 and the same period in 2021. We also observed the changes in cost efficiency indexes (CEIs), time efficiency indexes (TEIs), case-mix index (CMI), number of DRGs, risk weight (RW) proportion, and surgery number in the inpatient department.

Multimodal on-chip nanoscopy and quantitative phase imaging reveals the nanoscale morphology of liver sinusoidal endothelial cells.

Visualization of three-dimensional (3D) morphological changes in the subcellular structures of a biological specimen is a major challenge in life science. Here, we present an integrated chip-based optical nanoscopy combined with quantitative phase microscopy (QPM) to obtain 3D morphology of liver sinusoidal endothelial cells (LSEC). LSEC have unique morphology with small nanopores (50-300 nm in diameter) in the plasma membrane, called fenestrations.

NLRC4 inflammasome-dependent cell death occurs by a complementary series of three death pathways and determines lethality in mice.

Inflammasome is an innate immune defense mechanism, but its overactivation can lead to host death. Here, we show that cell death dictates mouse death caused by NLRC4 inflammasome overactivation. To execute NLRC4-dependent cell death, three death pathways complement each other in a specific order: Pyroptosis pathway requiring caspase-1 and GSDMD is the default path; impairment of it initiates ASC-mediated caspase-8–dependent apoptosis; when these two pathways are blocked, caspase-1 triggers intrinsic apoptotic pathway.

Synthesis of Poly-Substituted Pyridines via Noble-Metal-Free Cycloaddition of Ketones and Imines.

An eco-friendly and noble-metal-free formal [4+2] cycloaddition reaction was developed for the efficient synthesis of biologically interesting poly-substituted pyridines from easily available ketones and imines, whereby two sequential C-C bonds are formed. The given approach features a unique synthetic strategy of imines and ketones with wide substrate scope, good functional group tolerance, mild conditions and operational simplicity, which represents a more direct pathway to synthesize poly-substituted pyridines than traditional methods.

Treatment of Chinese Patients with Hypertriglyceridemia with a Pharmaceutical-Grade Preparation of Highly Purified Omega-3 Polyunsaturated Fatty Acid Ethyl Esters: Main Results of a Randomized, Double-Blind, Controlled Trial.

Introduction: The lipid-modifying potential of omega-3 polyunsaturated fatty acids in Chinese patients is under-researched. We conducted a multicenter, randomized, placebo-controlled, double-blind, parallel-group study of twice-daily treatment with OMACOR (OM3EE), a prescription-only formulation of highly purified ethyl esters of omega-3 polyunsaturated fatty acids in Chinese adult patients (≥18 years) who had elevated baseline fasting serum triglycerides (TG).

Methods: Patients were stratified according to the severity of their hypertriglyceridemia (severe HTG, with baseline TG ≥500 and <1000 mg/dL or moderate HTG, with baseline TG >200 and <500 mg/dL) or use of statins.

Efficacy and Safety of Intra-Articular Platelet-Rich Plasma in Osteoarthritis Knee: A Systematic Review and Meta-Analysis.

Background: Knee osteoarthritis (KOA) is a common disease in aged adults. Intra-articular (IA) injection of platelet-rich plasma (PRP) therapy is an effective minimally invasive treatment for KOA. We aimed to compare the efficacy and safety of platelet-rich plasma (PRP) with placebo or other conservative treatments.

Nonequilibrium Kondo regime current noise spectrum of quantum dot systems with the single impurity Anderson model.

We investigate the nonequilibrium current noise spectrum of single impurity Anderson model quantum dot systems on the basis of the accurate dissipation equation of motion evaluations. By comparing between the equilibrium and nonequilibrium cases and between the non-Kondo and Kondo regimes, we identify the current noise spectrum of the nonequilibrium Kondo features that actually appear in the entire region of ω ∈ [-eV, eV]. It is well known that the primary Kondo characteristics at ω = ±eV = ±(μ - μ) display asymmetrical upturns and remarkable peaks in S(ω) and dS(ω)/dω, respectively.