Tartronic Acid as a Potential Inhibitor of Pathological Calcium Oxalate Crystallization.

Kidney stones are a pervasive disease with notoriously high recurrence rates that require more effective treatment strategies. Herein, tartronic acid is introduced as an efficient inhibitor of calcium oxalate monohydrate (COM) crystallization, which is the most prevalent constituent of human kidney stones. A combination of in situ experimental techniques and simulations are employed to compare the inhibitory effects of tartronic acid with those of its molecular analogs. Tartronic acid exhibits an affinity for binding to rapidly growing apical surfaces of COM crystals, thus setting it apart from other inhibitors such as citric acid, the current preventative treatment for kidney stones. Bulk crystallization and in situ atomic force microscopy (AFM) measurements confirm the mechanism by which tartronic acid interacts with COM crystal surfaces and inhibits growth. These findings are consistent with in vivo studies that reveal the efficacy of tartronic acid is similar to that of citric acid in mouse models of hyperoxaluria regarding their inhibitory effect on stone formation and alleviating stone-related physical harm. In summary, these findings highlight the potential of tartronic acid as a promising alternative to citric acid for the management of calcium oxalate nephropathies, offering a new option for clinical intervention in cases of kidney stones.

Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice.

Inflammatory bowel disease (IBD) is a chronic, lifelong gastrointestinal disease, characterized by periods of activity and remission. The etiology of IBD is closely related to environmental factors. Previous studies have shown that the cyanotoxin microcystin-LR (MC-LR) causes intestinal damage, even IBD. To explore MC-LR's effects and potential mechanisms on IBD occurrence and development, we used dextran-sulfate sodium gavage (DSS) and MC-LR together for the first time in mice. There were four groups of mice: (A) mice given PBS gavage (control, CT); (B) mice given 3% DSS gavage (DSS); (C) mice given 200 µg/kg MC-LR gavage (MC-LR); and (D) mice given 3% DSS + 200 µg/kg MC-LR gavage (DSS + MC-LR). Compared with the CT group, the MC-LR group and the DSS group demonstrated more severe colitis results, which presented as higher weight loss, an increased Disease Activity Index (DAI) score, shorter colon length, a higher degree of tissue structural damage, more apoptotic cells, and greater pro-inflammatory cytokines. Similarly, the DSS + MC-LR group showed more severe colitis compared with the DSS group. Subsequent experiments confirmed that MC-LR or DSS increased the expression of pyroptosis-related proteins mediated by the nucleotide-binding domain-like receptor protein 3 (NLRP3). Likewise, compared with the DSS group, the DSS + MC-LR group expressed these proteins at a higher level. In conclusion, our research is the first to show that MC-LR may induce colitis, and even IBD, through NLRP3 inflammasome-mediated pyroptosis, and it could aggravate DSS-induced colitis in the same way.

Effects of a Nurse-led Survivorship Care Program on the Health and Resilience of Primary Caregivers of Patients With Advanced Head and Neck Cancer: A Randomized Controlled Trial.

OBJECTIVES: The present study aimed to evaluate the effects of a nurse-led survivorship care program (SCP) on emotional distress, social support, physical health, mental health, and resilience in primary caregivers of patients with advanced head and neck cancer. DATA SOURCES: A randomized controlled trial was conducted. One hundred patient-primary caregiver dyads were randomized into the nurse-led SCP group (experimental) or the usual care group (control). Participants completed a self-reported questionnaire, including measures of emotional distress, social support, physical health, mental health, and resilience. After 6 months, the experimental group reported a significant improvement in emotional distress, social support, physical health, mental health, and resilience. Compared with the control group, measures of emotional distress, physical health, overall resilience, and the resilience aspects of equanimity and perseverance improved in the experimental group. CONCLUSION: An SCP may feasibly help alleviate emotional distress, improve social support, increase physical and mental health, and strengthen resilience in the primary caregivers of patients with head and neck cancer. Health care providers should encourage primary caregivers to join an SCP. IMPLICATIONS FOR NURSING PRACTICE: The nurse-led SCP can be applied before patients complete treatment, which may increase the positive effect on physical health and adaptation.

Corrigendum: Progress and perspectives of perioperative immunotherapy in non-small cell lung cancer.

[This corrects the article DOI: 10.3389/fonc.2023.1011810.].

Progress and perspectives of perioperative immunotherapy in non-small cell lung cancer.

Lung cancer is one of the leading causes of cancer-related death. Lung cancer mortality has decreased over the past decade, which is partly attributed to improved treatments. Curative surgery for patients with early-stage lung cancer is the standard of care, but not all surgical treatments have a good prognosis. Adjuvant and neoadjuvant chemotherapy are used to improve the prognosis of patients with resectable lung cancer. Immunotherapy, an epoch-defining treatment, has improved curative effects, prognosis, and tolerability compared with traditional and ordinary cytotoxic chemotherapy, providing new hope for patients with non-small cell lung cancer (NSCLC). Immunotherapy-related clinical trials have reported encouraging clinical outcomes in their exploration of different types of perioperative immunotherapy, from neoadjuvant immune checkpoint inhibitor (ICI) monotherapy, neoadjuvant immune-combination therapy (chemoimmunotherapy, immunotherapy plus antiangiogenic therapy, immunotherapy plus radiotherapy, or concurrent chemoradiotherapy), adjuvant immunotherapy, and neoadjuvant combined adjuvant immunotherapy. Phase 3 studies such as IMpower 010 and CheckMate 816 reported survival benefits of perioperative immunotherapy for operable patients. This review summarizes up-to-date clinical studies and analyzes the efficiency and feasibility of different neoadjuvant therapies and biomarkers to identify optimal types of perioperative immunotherapy for NSCLC.

Impact of high-intensity football on the comprehensive quality of physical functions / Impacto do futebol americano de alta intensidade na qualidade integral de funções físicas / Impacto del fútbol americano de alta intensidad en la calidad integral de las funciones físicas

ABSTRACT Introduction: Football is a high-intensity, high-speed, high-strength physical exercise. It can effectively improve the overall qualities of endurance, strength, and speed. Objective: To determine whether football training impacts the physical function and quality of students. Methods: We use the physiological and biochemical indicators of football players to monitor their physical functions. Results: Football training can significantly improve the physical fitness of college students in terms of cardiopulmonary function, endurance, explosive power, flexibility, body balance, and coordination sensitivity. Conclusion: Football training can significantly reduce the basic heart rate of college students. It also significantly improves the flexibility and coordination sensitivity of these students. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: O futebol americano é uma atividade física de alta intensidade, velocidade e força. Ele pode efetivamente aprimorar as qualidades de resistência, força e velocidade. Objetivo: Determinar se o treino de futebol americano tem impacto sobre a função e a qualidade físicas dos estudantes. Métodos: Os indicadores fisiológicos e bioquímicos dos jogadores foram utilizados para monitorar suas funções físicas. Resultados: O treino em futebol americano pode melhorar significativamente a aptidão física dos estudantes universitários no que diz respeito a sua função cardiopulmonar, resistência, poder de explosão, flexibilidade, equilíbrio, e sensibilidade motora. Conclusão: O treino de futebol americano é capaz de reduzir significativamente a frequência cardíaca em repouso dos estudantes. Também trouxe melhoras significativas em sua flexibilidade e sensibilidade motora. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: El fútbol americano es una actividad física de alta intensidad, velocidad y fuerza. Este puede efectivamente mejorar las calidades de resistencia, fuerza y velocidad. Objetivo: Determinar si el entrenamiento de fútbol americano tiene impacto sobre la función y la calidad físicas de los estudiantes. Métodos: Los indicadores fisiológicos y bioquímicos de los jugadores fueron utilizados para monitorear sus funciones físicas. Resultados: El entrenamiento en fútbol americano puede mejorar significativamente la aptitud física de los estudiantes universitarios en lo que respecta a su función cardiopulmonar, resistencia, poder de explosión, flexibilidad, equilibrio y sensibilidad motora. Conclusión: El entrenamiento de fútbol americano es capaz de reducir significativamente la frecuencia cardíaca en reposo de los estudiantes. También les aportó mejoras significativas en su flexibilidad y sensibilidad motora. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Biomimetic Mechanoswitchable Interfaces for High-Performance Spatial Gas Bubble Maneuvering.

The on-demand manipulation of gas bubbles in aqueous ambient environments is fundamental to many fields such as microfluidics and biochemical microanalysis. However, most bubble manipulation strategies are limited to restricted locomotion on the confined surfaces without spatial convenience of transport. Herein, we report a kind of biomimetic bubble manipulator with mechanoswitchable interfaces (MSIs), featuring the advantages of parallel bubble control and spatial maneuvering flexibility. By the synergic action between Janus aluminum membrane and superaerophilic microfiber array, the gas-MSI interfacial adhesion can be reversibly switched to achieve capturing/releasing underwater bubbles. Moreover, the adhesion force of MSI can be readily tuned by diverse experimental parameters including surface roughness, fiber number, diameter, and spacing of the neighboring microfibers, which are further systematically investigated. Relying on this mobile platform, we demonstrate a series of powerful applications including bubble parallel control, bubble array regrouping, arbitrary bubble transport and even manipulating underwater solids through bubbles, which are otherwise challenging for conventional approaches. We envision that this versatile platform will bring new insights into potential applications, such as cross-species sample control and handheld gas microsyringe.

Magnetism-Actuated Superhydrophobic Flexible Microclaw: From Spatial Microdroplet Maneuvering to Cross-Species Control.

The flexible maneuvering of microliter liquid droplets is significant in both fundamental science and practical applications. However, most current strategies are limited to the rigid locomotion on confined geographies platforms, which greatly hinder their practical uses. Here, we propose a magnetism-actuated superhydrophobic flexible microclaw (MSFM) with hierarchical structures for water droplet manipulation. By virtue of precise femtosecond laser patterning on magnetism-responsive poly(dimethylsiloxane) (PDMS) films doped with carbonyl iron powder, this MSFM without chemical contamination exhibits powerful spatial droplet maneuvering advantages with fast response (<100 ms) and lossless water transport (∼50 cycles) in air. We further performed quantitative analysis of diverse experimental parameters including petal number, length, width, and iron element proportion in MSFM impacting the applicable maneuvering volumes. By coupling the advantages of spatial maneuverability and fast response into this versatile platform, typical unique applications are demonstrated such as programmable coalescence of droplets, collecting debris via droplets, tiny solid manipulation in aqueous severe environments, and harmless living creature control. We envision that this versatile MSFM should provide great potential for applications in microfluidics and cross-species robotics.

A Gibbs sampler for the multidimensional four-parameter logistic item response model via a data augmentation scheme.

The four-parameter logistic (4PL) item response model, which includes an upper asymptote for the correct response probability, has drawn increasing interest due to its suitability for many practical scenarios. This paper proposes a new Gibbs sampling algorithm for estimation of the multidimensional 4PL model based on an efficient data augmentation scheme (DAGS). With the introduction of three continuous latent variables, the full conditional distributions are tractable, allowing easy implementation of a Gibbs sampler. Simulation studies are conducted to evaluate the proposed method and several popular alternatives. An empirical data set was analysed using the 4PL model to show its improved performance over the three-parameter and two-parameter logistic models. The proposed estimation scheme is easily accessible to practitioners through the open-source IRTlogit package.

Hierarchical Hydrophilic/Hydrophobic/Bumpy Janus Membrane Fabricated by Femtosecond Laser Ablation for Highly Efficient Fog Harvesting.

The shortage of freshwater is threatening sustainable economic development and ecological security worldwide. Janus membrane, as a highly efficient method to collect the invisible fog water in the wet environment, is still hindered by some inherent limitations: (1) poor condensation of fog droplets on the superhydrophobic side due to the ultralow adhesive force of droplets with substrate and (2) insufficient detachment of droplets from the superhydrophilic side in time, which hampers the continuous water transport in the micropores. Herein, inspired by the desert beetle's back with alternating hydrophobic/hydrophilic bumps and the cactus thorn with an asymmetric geometry, we design and fabricate a kind of hierarchical hydrophilic/hydrophobic/bumpy Janus (HHHBJ) membrane by femtosecond laser ablation on an aluminum membrane to achieve the self-driven fog collection, which achieves over 250% enhancement in the water collection efficiency over the conventional Janus membrane. Even when the mist flow is applied to the surface at an incident angle of 45°, the collection efficiency increases by 600%. The mechanism of the HHHBJ film with excellent fog collection efficiency is mainly related to the continuous efficient fog condensation on the top surface and droplet removal on the bottom surface in time. We believe the proposed multi-bioinspired HHHBJ film with droplet self-driven collection ability provides insights to conceive and construct a highly efficient fog collection system in broad fields.

In Situ Tuning Underwater Bubble Movement on Slippery Lubricant-Infused Anisotropic Microgrooved Surface by Unidirectional Mechanical Strain.

Numerous studies have focused on designing and fabricating functional interfaces that control movement behavior of underwater gas bubbles, which are ubiquitous in a variety of natural and industrial settings. Nevertheless, developing surfaces with in situ tunable bubble movement remain elusive because of current complicated tuning strategies on the specific materials. Inspired by natural pitcher plant and rice leaves, here we report a kind of slippery lubricant-infused anisotropic microgrooved surface (SLI-AMGS) fabricated by femtosecond laser direct writing technology and realize the in situ reversible switching between underwater bubble sliding and pinning by unidirectional mechanical tensile strain. Different experimental parameters including lubricant oil film thickness, bubble volumes and laser power have been researched to manifest the relationship with bubble sliding behaviors. The underlying mechanism of in situ reversible switching mainly lies on the decrease of the lubricant oil film thickness during the process of mechanical stretching in which the uniform and stable oil film layer becomes uneven. This uneven lubricant oil film results in an extraordinary increase of contact angle hysteresis and resistance. At last, we demonstrate a real-time dynamic modulation of the underwater bubble on the SLI-AMGS with a changing mechanical tensile strain for several repeatable times in different acid-based environments. Our work manifests great potential applications in widespread fields including underwater bubble microfluidics and microbubble robots.

Unidirectional Transport and Effective Collection of Underwater CO2 Bubbles Utilizing Ultrafast-Laser-Ablated Janus Foam.

Manipulating gas bubbles in aqueous ambient is of great importance for applications in water treatment, gas collection, and matter transport. Here, a kind of Janus foam is designed and fabricated by one-step ultrafast laser ablation of one side of the copper film, which is treated to be superhydrophobic. Janus foam exhibits not only the capability of unidirectional transport of underwater bubbles but also gas collection with favorable efficiency up to ∼15 mL cm-2 min-1. The underlying physical mechanism is attributed to the cooperation of the buoyancy, adhesion, and wetting gradient forces imposed on the bubbles. As a paradigm, the underwater chemical reaction between the unidirectional CO2 gas flow and the alkaline phenolphthalein solution is demonstrated via Janus foam. This facile and low-cost fabrication approach for Janus foam will find broad potential applications in effective bubble transport, carbon capture, and controllable chemical reactions under aqueous conditions.

Femtosecond Mathieu Beams for Rapid Controllable Fabrication of Complex Microcages and Application in Trapping Microobjects.

Structured laser beam based microfabrication technology provides a rapid and flexible way to create some special microstructures. As an important member in the propagation of invariant structured optical fields, Mathieu beams (MBs) exhibit regular intensity distribution and diverse controllable parameters, which makes it extremely suitable for flexible fabrication of functional microstructures. In this study, MBs are generated by a phase-only spatial light modulator (SLM) and used for femtosecond laser two-photon polymerization (TPP) fabrication. Based on structured beams, a dynamic holographic processing method for controllable three-dimensional (3D) microcage fabrication has been presented. MBs with diverse intensity distributions are generated by controlling the phase factors imprinted on MBs with a SLM, including feature parity, ellipticity parameter q, and integer m. The focusing properties of MBs in a high numerical aperture laser microfabrication system are theoretically and experimentally investigated. On this basis, complex two-dimensional microstructures and functional 3D microcages are rapidly and flexibly fabricated by the controllable patterned focus, which enhances the fabrication speed by 2 orders of magnitude compared with conventional single-point TPP. The fabricated microcages act as a nontrivial tool for trapping and sorting microparticles with different sizes. Finally, culturing of budding yeasts is investigated with these microcages, which demonstrates its application as 3D cell culture scaffolds.

A note on monotonicity of item response functions for ordered polytomous item response theory models.

A monotone relationship between a true score (τ) and a latent trait level (θ) has been a key assumption for many psychometric applications. The monotonicity property in dichotomous response models is evident as a result of a transformation via a test characteristic curve. Monotonicity in polytomous models, in contrast, is not immediately obvious because item response functions are determined by a set of response category curves, which are conceivably non-monotonic in θ. The purpose of the present note is to demonstrate strict monotonicity in ordered polytomous item response models. Five models that are widely used in operational assessments are considered for proof: the generalized partial credit model (Muraki, 1992, Applied Psychological Measurement, 16, 159), the nominal model (Bock, 1972, Psychometrika, 37, 29), the partial credit model (Masters, 1982, Psychometrika, 47, 147), the rating scale model (Andrich, 1978, Psychometrika, 43, 561), and the graded response model (Samejima, 1972, A general model for free-response data (Psychometric Monograph no. 18). Psychometric Society, Richmond). The study asserts that the item response functions in these models strictly increase in θ and thus there exists strict monotonicity between τ and θ under certain specified conditions. This conclusion validates the practice of customarily using τ in place of θ in applied settings and provides theoretical grounds for one-to-one transformations between the two scales.

A Comparison of Constrained Item Selection Methods in Multidimensional Computerized Adaptive Testing.

The construction of assessments in computerized adaptive testing (CAT) usually involves fulfilling a large number of statistical and non-statistical constraints to meet test specifications. To improve measurement precision and test validity, the multidimensional priority index (MPI) and the modified MPI (MMPI) can be used to monitor many constraints simultaneously under a between-item and a within-item multidimensional framework, respectively. As both item selection methods can be implemented easily and computed efficiently, they are important and useful for operational CATs; however, no thorough simulation study has compared the performance of these two item selection methods under two different item bank structures. The purpose of this study was to investigate the efficiency of the MMPI and the MPI item selection methods under the between-item and within-item multidimensional CAT through simulations. The MMPI and the MPI item selection methods yielded similar performance in measurement precision for both multidimensional pools and yielded similar performance in exposure control and constraint management for the between-item multidimensional pool. For the within-item multidimensional pool, the MPI method yielded slightly better performance in exposure control but yielded slightly worse performance in constraint management than the MMPI method.

Fibrinogen-derived fibrinostatin inhibits tumor growth through anti-angiogenesis.

Angiogenesis is a prerequisite of tumor growth and metastasis and, thus, anti-angiogenesis treatment has become an important part of cancer therapy. A 15-amino acid peptide of the fibrinogen α chain, fibrinostatin, was previously found in serum samples of gastric cancer patients. Herein we demonstrated that fibrinostatin has anti-angiogenesis activity in several angiogenesis models and it reduces tumor growth in mouse xenografts and allografts. Increased tumor necrosis and reduced microvessel density in tumors were observed in mouse xenograft models. Fibrinostatin inhibited proliferation and induced apoptosis in HUVEC, but not in cancer cells. In addition, fibrinostatin specifically entered HUVEC. Fibrinostatin also prevented migration, adhesion and tubule formation of HUVEC in vitro. A single-dose acute toxicity testing and a repeated-dose chronic toxicity study in the mouse, rat and monkey indicated that fibrinostatin had a wide margin of safety. Taken together, fibrinostatin shows promise as a potential anti-angiogenesis therapeutic agent.

Daucosterol inhibits cancer cell proliferation by inducing autophagy through reactive oxygen species-dependent manner.

AIMS: This study aims to evaluate the anti-cancer effect of daucosterol and explore its possible mechanism. MAIN METHODS: MTT and colony formation assay were performed to determine the effect of daucosterol on cancer cell proliferation in vitro. H22 allograft model was used for the assessment of its anti-cancer activity in vivo. Intracellular generation of reactive oxygen species (ROS) was measured using DCFH-DA probe with flow cytometry system and a laser scanning confocal microscope. LC3 (microtubule-associated protein 1 light chain 3)-II conversion was monitored with immunofluorescence and immunoblotting to demonstrate daucosterol-induced autophagy. KEY FINDINGS: We found that daucosterol inhibits the proliferation of human breast cancer cell line MCF-7 and gastric cancer cell lines MGC803, BGC823 and AGS in a dose-dependent manner. Furthermore, daucosterol inhibits murine hepatoma H22 cell growth in ICR mice. Daucosterol treatment induces intracellular ROS generation and autophagy, but not apoptotic cell death. Treatment with ROS scavenger GSH (reduced glutathione), NAC (N-acetyl-l-cysteine) or autophagy inhibitor 3-Methyladenine (3-MA) counteracted daucosterol-induced autophagy and growth inhibition in BGC823 and MCF-7 cancer cells. SIGNIFICANCE: Daucosterol inhibits cancer cell proliferation by inducing autophagy through ROS-dependent manner and could be potentially developed as an anti-cancer agent.

Low energy-density recording with a high-repetition-rate laser beam in gold-nanorod-embedded discs.

In this paper, we report on the low energy-density recording with a high-repetition-rate femtosecond pulsed beam in homogenous gold-nanorod-dispersed discs by using low numerical aperture (NA) micro-optics. By focusing a femtosecond pulsed beam at a repetition rate of 82 MHz using a low NA DVD optical head, the spatially-stretched energy density introduces a temperature rising of the polymer matrix. This temperature rising facilitates the surface melting of gold nanorods, which leads to over one-order-of-magnitude reduction in the energy-density threshold for recording, compared with that by focusing single pulses through a high NA objective. Applying this finding, we demonstrate the dual-layer recording in gold-nanorod-dispersed discs with an equivalent capacity of 69 GB. Our results demonstrate the potential of ultra-high density three-dimensional optical memory with a low-cost and DVD-compatible apparatus.

Transcriptional regulation of PES1 expression by c-Jun in colon cancer.

Pescadillo is a nucleolar protein that has been suggested to be involved in embryonic development and ribosome biogenesis. Deregulated expression of human pescadillo (PES1) was described in some tumors, but its precise roles in tumorigenesis remains unclear. In this study, we generated three monoclonal antibodies recognizing PES1 with high specificity and sensitivity, with which PES1 expression in human colon cancer was analyzed immunohistochemically. Out of 265 colon cancer tissues, 89 (33.6%) showed positive PES1 expression, which was significantly higher than in non-cancerous tissues (P<0.001). Silencing of PES1 in colon cancer cells resulted in decreased proliferation, reduced growth of xenografts, and cell cycle arrest in G1 phase, indicating PES1 functions as an oncogene. We then explored the mechanism by which PES1 expression is controlled in human colon cancers and demonstrated that c-Jun, but not JunB, JunD, c-Fos, or mutant c-Jun, positively regulated PES1 promoter transcription activity. In addition, we mapped -274/-264 region of PES1 promoter as the c-Jun binding sequence, which was validated by chromatin immunoprecipitation and electrophoretic mobility shift assays. Moreover, we demonstrated a positive correlation between c-Jun and PES1 expression in colon cancer cells and colon cancer tissues. Upstream of c-Jun, it was revealed that c-Jun NH2-terminal kinases (JNK) is essential for controlling PES1 expression. Our study, in the first place, uncovers the oncogenic role of PES1 in colon cancer and elucidates the molecular mechanism directing PES1 expression.