High-Entropy Photothermal Materials.

High-entropy (HE) materials, celebrated for their extraordinary chemical and physical properties, have garnered increasing attention for their broad applications across diverse disciplines. The expansive compositional range of these materials allows for nuanced tuning of their properties and innovative structural designs. Recent advances have been centered on their versatile photothermal conversion capabilities, effective across the full solar spectrum (300-2500 nm). The HE effect, coupled with hysteresis diffusion, imparts these materials with desirable thermal and chemical stability. These attributes position HE materials as a revolutionary alternative to traditional photothermal materials, signifying a transformative shift in photothermal technology. This review delivers a comprehensive summary of the current state of knowledge regarding HE photothermal materials, emphasizing the intricate relationship between their compositions, structures, light-absorbing mechanisms, and optical properties. Furthermore, the review outlines the notable advances in HE photothermal materials, emphasizing their contributions to areas, such as solar water evaporation, personal thermal management, solar thermoelectric generation, catalysis, and biomedical applications. The review culminates in presenting a roadmap that outlines prospective directions for future research in this burgeoning field, and also outlines fruitful ways to develop advanced HE photothermal materials and to expand their promising applications.

Structure of GPR101-Gs enables identification of ligands with rejuvenating potential.

GPR101 is an orphan G protein-coupled receptor actively participating in energy homeostasis. Here we report the cryo-electron microscopy structure of GPR101 constitutively coupled to Gs heterotrimer, which reveals unique features of GPR101, including the interaction of extracellular loop 2 within the 7TM bundle, a hydrophobic chain packing-mediated activation mechanism and the structural basis of disease-related mutants. Importantly, a side pocket is identified in GPR101 that facilitates in silico screening to identify four small-molecule agonists, including AA-14. The structure of AA-14-GPR101-Gs provides direct evidence of the AA-14 binding at the side pocket. Functionally, AA-14 partially restores the functions of GH/IGF-1 axis and exhibits several rejuvenating effects in wild-type mice, which are abrogated in Gpr101-deficient mice. In summary, we provide a structural basis for the constitutive activity of GPR101. The structure-facilitated identification of GPR101 agonists and functional analysis suggest that targeting this orphan receptor has rejuvenating potential.

Targeting PRSS23 with tipranavir induces gastric cancer stem cell apoptosis and inhibits growth of gastric cancer via the MKK3/p38 MAPK-IL24 pathway.

Gastric cancer stem cells (GCSCs) contribute to the refractory features of gastric cancer (GC) and are responsible for metastasis, relapse, and drug resistance. The key factors drive GCSC function and affect the clinical outcome of GC patients remain poorly understood. PRSS23 is a novel serine protease that is significantly up-regulated in several types of cancers and cancer stem cells, and related to tumor progression and drug resistance. In this study, we investigated the role of PRSS23 in GCSCs as well as the mechanism by which PRSS23 regulated the GCSC functions. We demonstrated that PRSS23 was critical for sustaining GCSC survival. By screening a collection of human immunodeficiency virus (HIV) protease inhibitors (PIs), we identified tipranavir as a PRSS23-targeting drug, which effectively killed both GCSC and GC cell lines (its IC50 values were 4.7 and 6.4 µM in GCSC1 cells and GCSC2 cells, respectively). Administration of tipranavir (25 mg·kg-1·d-1, i.p., for 8 days) in GCSC-derived xenograft mice markedly inhibited the growth of subcutaneous GCSC tumors without apparent toxicity. In contrast, combined treatment with 5-FU plus cisplatin did not affect the tumor growth but causing significant weight loss. Furthermore, we revealed that tipranavir induced GCSC cell apoptosis by suppressing PRSS23 expression, releasing MKK3 from the PRSS23/MKK3 complex to activate p38 MAPK, and thereby activating the IL24-mediated Bax/Bak mitochondrial apoptotic pathway. In addition, tipranavir was found to kill other types of cancer cell lines and drug-resistant cell lines. Collectively, this study demonstrates that by targeting both GCSCs and GC cells, tipranavir is a promising anti-cancer drug, and the clinical development of tipranavir or other drugs specifically targeting the PRSS23/MKK3/p38MAPK-IL24 mitochondrial apoptotic pathway may offer an effective approach to combat gastric and other cancers.

A direction-selective cortico-brainstem pathway adaptively modulates innate behaviors.

Sensory cortices modulate innate behaviors through corticofugal projections targeting phylogenetically-old brainstem nuclei. However, the principles behind the functional connectivity of these projections remain poorly understood. Here, we show that in mice visual cortical neurons projecting to the optic-tract and dorsal-terminal nuclei (NOT-DTN) possess distinct response properties and anatomical connectivity, supporting the adaption of an essential innate eye movement, the optokinetic reflex (OKR). We find that these corticofugal neurons are enriched in specific visual areas, and they prefer temporo-nasal visual motion, matching the direction bias of downstream NOT-DTN neurons. Remarkably, continuous OKR stimulation selectively enhances the activity of these temporo-nasally biased cortical neurons, which can efficiently promote OKR plasticity. Lastly, we demonstrate that silencing downstream NOT-DTN neurons, which project specifically to the inferior olive-a key structure in oculomotor plasticity, impairs the cortical modulation of OKR and OKR plasticity. Our results unveil a direction-selective cortico-brainstem pathway that adaptively modulates innate behaviors.

[Advances in live-imaging aging reporter mice].

Aging is an independent risk factor for chronic diseases in the elderly, and understanding aging mechanisms is one of the keys to achieve early prevention and effective intervention for the diseases. Aging process is dynamic and systemic, making it difficult for mechanistic study. With recent advances in aging biomarkers and development of live-imaging technologies, more and more reporter mouse models have been generated, which can live monitor the aging process, and help investigate aging mechanisms at systemic level and develop intervention strategies. This review summarizes recent advances in live-imaging aging reporter mouse models based on widely used aging biomarkers (p16Ink4a, p21Waf1/Cip1, p53 and Glb1), and discusses their applications in aging research.

Quantification of Visual Feature Selectivity of the Optokinetic Reflex in Mice.

The optokinetic reflex (OKR) is an essential innate eye movement that is triggered by the global motion of the visual environment and serves to stabilize retinal images. Due to its importance and robustness, the OKR has been used to study visual-motor learning and to evaluate the visual functions of mice with different genetic backgrounds, ages, and drug treatments. Here, we introduce a procedure for evaluating OKR responses of head-fixed mice with high accuracy. Head fixation can rule out the contribution of vestibular stimulation on eye movements, making it possible to measure eye movements triggered only by visual motion. The OKR is elicited by a virtual drum system, in which a vertical grating presented on three computer monitors drifts horizontally in an oscillatory manner or unidirectionally at a constant velocity. With this virtual reality system, we can systematically change visual parameters like spatial frequency, temporal/oscillation frequency, contrast, luminance, and the direction of gratings, and quantify tuning curves of visual feature selectivity. High-speed infrared video-oculography ensures accurate measurement of the trajectory of eye movements. The eyes of individual mice are calibrated to provide opportunities to compare the OKRs between animals of different ages, genders, and genetic backgrounds. The quantitative power of this technique allows it to detect changes in the OKR when this behavior plastically adapts due to aging, sensory experience, or motor learning; thus, it makes this technique a valuable addition to the repertoire of tools used to investigate the plasticity of ocular behaviors.

Efficient Warming Textile Enhanced by a High-Entropy Spectrally Selective Nanofilm with High Solar Absorption.

Solar and radiative warming are smart approaches to maintaining the human body at a metabolically comfortable temperature in both indoor and outdoor scenarios. Nevertheless, existing warming textiles are ineffective in frigid climates because the solar absorption of selective absorbing coating is significantly reduced when coated on rough textile surface. Herein, for the first time, high-entropy nitrides based spectrally selective film (SSF) is introduced on common cotton through a one-step magnetron sputtering method. The well-designed refractive index gradient enables destructive interference effects, offering a roughness-insensitive high solar absorptance (92.8%) and low thermal emittance (39.2%). Impressively, the solar absorptance is 9.1% higher than the reported best-performing selective nanofilm-based textile. As a result, such a textile achieves a record-high photothermal conversion efficiency (82.2% under 0.6 suns, at 0 °C). This textile yields a 3.5 °C drop in the set-point of indoor air-conditioner temperature. Besides, in a winter morning with an air temperature of 7.5 °C, it warms up the human skin by as large as 12 °C under weak sunlight (350 W m-2 ). More importantly, such a superior radiative warming performance is achieved by engineering the widely used cotton without compromising its breathability and durability, showing great potential for practical applications.

Enabling Highly Enhanced Solar Thermoelectric Generator Efficiency by a CuCrMnCoAlN-Based Spectrally Selective Absorber.

Harvesting solar energy to enhance thermoelectric generator efficiency is a highly effective strategy. However, it is a grand challenge but essential to increase solar-thermal conversion efficiency. A spectrally selective absorber, which is capable of boosting solar absorptance (α) while suppressing thermal emittance (ε), shows great potential to elevate the solar-thermal conversion efficiency. Herein, we fabricate a multilayer spectrally selective absorber with the assistance of high-entropy nitrides, which shows outstanding spectral selectivity (α/ε = 95.2/10.9%). Benefitting from the high-entropy nitrides, it is experimentally demonstrated that the as-deposited absorber exhibits superior thermal stability, which is crucial to ensure service life. Under 1000 W·m-2 simulated solar illumination, it achieves a very high surface temperature of 109.6 °C, making it suitable to enhance the efficiency of solar thermoelectric generators. Impressively, the integration of the proposed absorber with a commercial thermoelectric generator efficiently reinforces thermoelectric performance, offering a high output power of 1.99 mW. More importantly, by taking advantage of a thermal concentration strategy, it enables a further increase of the output power by 2.98 mW. This work provides a promising solar-thermal material to boost high thermoelectric performance and extends the application category of high-entropy nitrides.

[Umbelliferone improves chronic hypoxia-induced pulmonary hypertension by inhibiting the RhoA/ROCK signaling pathway and autophagy].

This study aimed to investigate the effects of hypoxia on RhoA/Rho-kinase (ROCK) signaling pathway and autophagy in pulmonary artery smooth muscle cells (PASMCs), and to explore the underlying mechanism of Umbelliferone (Umb) in ameliorating chronic hypoxic pulmonary hypertension. PASMCs were cultured from Sprague-Dawley (SD) rats and randomly divided into control group, hypoxia group, hypoxia + Umb intervention group and normoxia + Umb intervention group. Alpha smooth muscle actin (α-SMA) and LC3 were assessed by immunofluorescence staining. Protein expression of RhoA, ROCK2, p-MYPT1, LC3-II, Beclin-1, p62, C-Caspase 3, Bax and Bcl-2 was analyzed by Western blotting. In in vivo study, SD rats were divided into control group, hypoxia group and hypoxia + Umb intervention group. Weight ratio of the right ventricle (RV)/left ventricle plus septum (LV+S) was detected, and pulmonary arterial morphological features were examined by HE staining. The results indicated that compared with the control group, the LC3-II/LC3-I ratio and expression of Beclin-1 were significantly increased, while p62 expression was significantly decreased, and the expressions of RhoA, ROCK2 and p-MYPT1 were significantly increased in PASMCs of hypoxia group (P < 0.05). The changes of LC3-II/LC3-I ratio, the expressions of Beclin-1, p62, RhoA, ROCK2 and p-MYPT1 in PASMCs were reversed by Umb treatment (P < 0.05). Consistently, the pulmonary arterial wall was thickened and the RV/(LV+S) ratio was increased in hypoxic rats, which were significantly improved by Umb treatment (P < 0.05). These results suggest that Umb can improve hypoxia-induced pulmonary hypertension by inhibiting the RhoA/ROCK signaling pathway and autophagy in PASMCs.

UBR4/POE facilitates secretory trafficking to maintain circadian clock synchrony.

Ubiquitin ligases control the degradation of core clock proteins to govern the speed and resetting properties of the circadian pacemaker. However, few studies have addressed their potential to regulate other cellular events within clock neurons beyond clock protein turnover. Here, we report that the ubiquitin ligase, UBR4/POE, strengthens the central pacemaker by facilitating neuropeptide trafficking in clock neurons and promoting network synchrony. Ubr4-deficient mice are resistant to jetlag, whereas poe knockdown flies are prone to arrhythmicity, behaviors reflective of the reduced axonal trafficking of circadian neuropeptides. At the cellular level, Ubr4 ablation impairs the export of secreted proteins from the Golgi apparatus by reducing the expression of Coronin 7, which is required for budding of Golgi-derived transport vesicles. In summary, UBR4/POE fulfills a conserved and unexpected role in the vesicular trafficking of neuropeptides, a function that has important implications for circadian clock synchrony and circuit-level signal processing.

Entropy-Assisted High-Entropy Oxide with a Spinel Structure toward High-Temperature Infrared Radiation Materials.

Developing advanced materials with a high-entropy concept is one of the hot trends in materials science. The configurational entropy of high-entropy materials can be tuned by introducing different atomic species, which can also impart a result in excellent physical and chemical properties. In this work, we synthesized a solid-solution oxide (Cu, Mn, Fe, Cr)3O4 by a simple and scalable solid-phase synthesis method. We extensively investigated the microstructure and chemical composition, indicating that (Cu, Mn, Fe, Cr)3O4 has a single-phase spinel structure. Simultaneously, we reasonably evaluated the position occupied by the elements of (Cu, Mn, Fe, Cr)3O4 in a spinel structure as (Cu0.75Fe0.25)(Fe0.25Cr0.375Mn0.375)2O4. Here, we first evaluated the infrared radiation performance of (Cu, Mn, Fe, Cr)3O4. The new, high-entropy oxide (HEO) (Cu, Mn, Fe, Cr)3O4 powder exhibits high infrared emissivity values of 0.879 and 0.848 in the wavelengths of 0.78-2.5 and 2.5-16 µm, respectively, and has excellent thermal stability. More importantly, the infrared emissivity values of as-prepared HEO coating reach 0.955 (0.78-2.5 µm) at room temperature and 0.936 (3-16 µm) at 800 °C. This work provides a viable strategy toward the laboratory mass production of this HEO for infrared radiation materials, which shows great potential in the energy-related applications.

Homeostatic control of nuclear-encoded mitochondrial gene expression by the histone variant H2A.Z is essential for neuronal survival.

Histone variants are crucial regulators of chromatin structure and gene transcription, yet their functions within the brain remain largely unexplored. Here, we show that the H2A histone variant H2A.Z is essential for neuronal survival. Mice lacking H2A.Z in GABAergic neurons or Purkinje cells (PCs) present with a progressive cerebellar ataxia accompanied by widespread degeneration of PCs. Ablation of H2A.Z in other neuronal subtypes also triggers cell death. H2A.Z binds to the promoters of key nuclear-encoded mitochondrial genes to regulate their expression and promote organelle function. Bolstering mitochondrial activity genetically or by organelle transplant enhances the survival of H2A.Z-ablated neurons. Changes in bioenergetic status alter H2A.Z occupancy at the promoters of nuclear-encoded mitochondrial genes, an adaptive response essential for cell survival. Our results highlight that H2A.Z fulfills a key, conserved role in neuronal survival by acting as a transcriptional rheostat to regulate the expression of genes critical to mitochondrial function.

Author Correction: GPR120: A bi-potential mediator to modulate the osteogenic and adipogenic differentiation of BMMSCs.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Defecation function and quality of life in patients with slow-transit constipation after colectomy.

BACKGROUND: Although total or subtotal colectomy for slow-transit constipation (STC) has been proven to be a definite treatment, the associated defecation function and quality of life (QOL) are rarely studied. AIM: To evaluate the effectiveness of surgery for STC regarding defecation function and QOL. METHODS: From March 2013 to September 2017, 30 patients undergoing surgery for STC in our department were analyzed. Preoperative, intra-operative, and postoperative 3-mo, 6-mo, 1-year, and 2-year follow-up details were recorded. Defecation function was assessed by bowel movements, abdominal pain, bloating, straining, laxative, enema use, diarrhea, and the Wexner constipation and incontinence scales. QOL was evaluated using the gastrointestinal QOL index and the 36-item short form survey. RESULTS: The majority of patients (93.1%, 27/29) stated that they benefited from the operation at the 2-year follow-up. At each time point of the follow-up, the number of bowel movements per week significantly increased compared with that of the preoperative conditions (P < 0.05). Similarly, compared with the preoperative values, a marked decline was observed in bloating, straining, laxative, and enema use at each time point of the follow-up (P < 0.05). Postoperative diarrhea could be controlled effectively and notably improved at the 2-year follow-up. The Wexner incontinence scores at 6-mo, 1-year, and 2-year were notably lower than those at the 3-mo follow-up (P < 0.05). Compared with those of the preoperative findings, the Wexner constipation scores significantly decreased following surgery (P < 0.05). Thus, it was reasonable to find that the gastrointestinal QOL index scores clearly increase (P < 0.05) and that the 36-item short form survey results displayed considerable improvements in six spheres (role physical, role emotional, physical pain, vitality, mental health, and general health) following surgery. CONCLUSION: Total or subtotal colectomy for STC is not only effective in alleviating constipation-related symptoms but also in enhancing patients' QOL.

Successful rescue using tracheal intubation cannula for severe central airway stenosis after tracheotomy: A CARE compliant case report.

INTRODUCTION: Central airway stenosis is a life-threating requiring immediate medical intervention. There are several options for treating central airway stenosis, including rigid bronchoscopy, bronchoscopic high-power laser therapy, high-frequency electric needle knife, and balloon-expanding stents. However, interventional techniques may be unavailable in an emergent situation or at smaller local hospitals. In this case report, we publicly demonstrate for the first time that a tracheal intubation catheter may be applied as a temporary alternative to interventional bronchoscopic treatment. PATIENT CONCERNS: A 72-year old male patient was admitted with a 1-year history of intermittent dyspnea, which was exacerbated for one day. One day prior to admission to our hospital, the patient presented with cyanosis due to an exacerbation of dyspnea.A tracheotomy was performed and the patient had been carrying a tracheotomy cannula for 6 months. DIAGNOSIS: The ventilator alarm indicated high airway resistance and the nurses were unable to insert the suction pipes into the airway. Immediate fiberoptic bronchoscopy showed diffuse edema and stenosis of the inferior tracheal airways. INTERVENTIONS: Tracheal intubation was used to temporarily replace the tracheotomy cannula, which successfully expanded the narrowed airways. OUTCOMES: The blood oxygen saturation returned to normal, and dyspnea was quickly relieved. CONCLUSION: In emergent situations, tracheal intubation catheters may be used in patients with post-tracheotomy central airway stenosis, not only for surviving the most dangerous phase but for also prolonging the survival time for further treatments.

Light Up the Brain: The Application of Optogenetics in Cell-Type Specific Dissection of Mouse Brain Circuits.

The exquisite intricacies of neural circuits are fundamental to an animal's diverse and complex repertoire of sensory and motor functions. The ability to precisely map neural circuits and to selectively manipulate neural activity is critical to understanding brain function and has, therefore been a long-standing goal for neuroscientists. The recent development of optogenetic tools, combined with transgenic mouse lines, has endowed us with unprecedented spatiotemporal precision in circuit analysis. These advances greatly expand the scope of tractable experimental investigations. Here, in the first half of the review, we will present applications of optogenetics in identifying connectivity between different local neuronal cell types and of long-range projections with both in vitro and in vivo methods. We will then discuss how these tools can be used to reveal the functional roles of these cell-type specific connections in governing sensory information processing, and learning and memory in the visual cortex, somatosensory cortex, and motor cortex. Finally, we will discuss the prospect of new optogenetic tools and how their application can further advance modern neuroscience. In summary, this review serves as a primer to exemplify how optogenetics can be used in sophisticated modern circuit analyses at the levels of synapses, cells, network connectivity and behaviors.

The impact of sedation on quality metrics of colonoscopy: a single-center experience of 48,838 procedures.

PURPOSE: Investigation of the role of sedation during colonoscopy is meaningful as the advantages of colonoscopy performing with sedation are still controversial. METHODS: Medical records of patients who underwent colonoscopy in our institution were retrospectively analyzed. The sedation rate, adenoma detection rate (ADR), polyp detection rate (PDR), cecal intubation rate (CIR), iatrogenic colonic perforation rate (ICP) were calculated. RESULTS: A total of 48,838 colonoscopies (24,498 in males) dated from July 2007 to February 2017 were analyzed. The median age was 50 years (range 16-85 years). An overall sedation rate was 80.38%. The PDR was 26.77%, and was not statistically different between colonoscopy with or without sedation (26.67% vs 27.22, p = 0.474). ADR was 12.9% regardless of applying sedation or not (13.0% vs 12.44%, p = 0.337). The CIR was 87.42% in all examinations with an adjusted CIR of 90.34%, and was higher when performed with sedation than without sedation (88.92% vs 80.64%, p < 0.0001). Five cases (0.01%) of ICP were reported, all of which occurred in patients under sedation. CONCLUSIONS: The use of sedation is associated with increased CIR, but ADR and PDR remain unchanged with or without sedation. However, perforation rate, albeit very low, is significantly higher in sedated patients.

Canine Adenovirus 2: A Natural Choice for Brain Circuit Dissection.

Canine adenovirus-2 (CAV) is a canine pathogen that has been used in a variety of applications, from vaccines against more infectious strains of CAV to treatments for neurological disorders. With recent engineering, CAV has become a natural choice for neuroscientists dissecting the connectivity and function of brain circuits. Specifically, as a reliable genetic vector with minimal immunogenic and cytotoxic reactivity, CAV has been used for the retrograde transduction of various types of projection neurons. Consequently, CAV is particularly useful when studying the anatomy and functions of long-range projections. Moreover, combining CAV with conditional expression and transsynaptic tracing results in the ability to study circuits with cell- and/or projection-type specificity. Lastly, with the well-documented knowledge of viral transduction, new innovations have been developed to increase the transduction efficiency of CAV and circumvent its tropism, expanding the potential of CAV for circuit analysis.

Characterizing the Role of TaWRKY13 in Salt Tolerance.

The WRKY transcription factor superfamily is known to participate in plant growth and stress response. However, the role of this family in wheat (Triticum aestivum L.) is largely unknown. Here, a salt-induced gene TaWRKY13 was identified in an RNA-Seq data set from salt-treated wheat. The results of RT-qPCR analysis showed that TaWRKY13 was significantly induced in NaCl-treated wheat and reached an expression level of about 22-fold of the untreated wheat. Then, a further functional identification was performed in both Arabidopsis thaliana and Oryza sativa L. Subcellular localization analysis indicated that TaWRKY13 is a nuclear-localized protein. Moreover, various stress-related regulatory elements were predicted in the promoter. Expression pattern analysis revealed that TaWRKY13 can also be induced by polyethylene glycol (PEG), exogenous abscisic acid (ABA), and cold stress. After NaCl treatment, overexpressed Arabidopsis lines of TaWRKY13 have a longer root and a larger root surface area than the control (Columbia-0). Furthermore, TaWRKY13 overexpression rice lines exhibited salt tolerance compared with the control, as evidenced by increased proline (Pro) and decreased malondialdehyde (MDA) contents under salt treatment. The roots of overexpression lines were also more developed. These results demonstrate that TaWRKY13 plays a positive role in salt stress.