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Circadian clocks serve as internal pacemakers that influence many basic homeostatic processes; consequently, the expression and function of their components are tightly regulated by intricate networks of feedback loops that fine-tune circadian processes. Our knowledge of these components and pathways is far from exhaustive. In recent decades, the nuclear envelope has emerged as a global gene regulatory machine, although its role in circadian regulation has not been explored. We report that transcription of the core clock component BMAL1 is positively modulated by the inner nuclear membrane protein MAN1, which directly binds the BMAL1 promoter and enhances its transcription. Our results establish a novel connection between the nuclear periphery and circadian rhythmicity, therefore bridging two global regulatory systems that modulate all aspects of bodily functions.

Treatment response and prognosis estimation in advanced pulmonary adenocarcinoma are challenged by the significant heterogeneity of the disease. The current Response Evaluation Criteria in Solid Tumors (RECIST) criteria, despite providing a basis for solid tumor response evaluation, do not fully encompass this heterogeneity. To better represent these nuances, we introduce the intertumoral heterogeneity response score (THRscore), a measure built upon and expanding the RECIST criteria. This retrospective study included patients with 3–10 measurable advanced lung adenocarcinoma lesions who underwent first‐line chemotherapy or targeted therapy. The THRscore, derived from the coefficient of variation in size for each measurable tumor before and 4–6 weeks posttreatment, unveiled a correlation with patient outcomes. Specifically, a high THRscore was associated with shorter progression‐free survival, lower tumor response rate, and a higher tumor mutation burden. These associations were further validated in an external cohort, confirming THRscore's effectiveness in stratifying patients based on progression risk and treatment response, and enhancing the utility of RECIST in capturing complex tumor behaviors in lung adenocarcinoma. These findings affirm the promise of THRscore as an enhanced tool for tumor response assessment in advanced lung adenocarcinoma, extending the RECIST criteria's utility. [ABSTRACT FROM AUTHOR]

Exploiting China's high-speed rail (HSR) as a quasi-natural experiment, we examine the relationship between the HSR connection and green innovation. The opening of HSR can promote green innovation by facilitating the flow of innovation factors. Using the multiperiod difference-in-differences (DID) model, we find that the regional green innovation performance significantly becomes better following the opening of HSR in the local city. Moreover, in examining the specific mechanisms at work, we find evidence that HSR stimulates green patents through increased labor mobility and research capital mobility. Further analyses show that the facilitating effect of HSR is heterogeneous among cities. Our paper sheds new light on the effects of HSR on social welfare in the case of sustainable economy., Author(s): Zixuan Zhu [1]; Xiaoyan Lin [1]; Hao Yang (corresponding author) [1] 1. Introduction As one of the major technological innovations in the history of railway transportation, high-speed rail (HSR) [...]

[Display omitted] • The LPS-induced tree shrews exhibited severe shortness of breath, resulting in hypoxemia. • The induced group of animals exhibited 72 ∼ 120 h endpoints, and none of them recover. • Diffuse alveolar damage was observed in the lungs of the tree shrew, which is the histological hallmark for the acute phase of ARDS. • 3D reconstruction of the lung CT images was used to accurately measure the extent and distribution of the whole lung injury in LPS-induced tree shrews. Acute respiratory distress syndrome (ARDS) is a leading cause of respiratory failure, with substantial attributable morbidity and mortality. The small animal models that are currently used for ARDS do not fully manifest all of the pathological hallmarks of human patients, which hampers both the studies of disease mechanism and drug development. To examine whether the phenotypic changes of primate-like tree shrews in response to a one-hit lipopolysaccharides (LPS) injury resemble human ARDS features. LPS was administered to tree shrews through intratracheal instillation; then, the animals underwent CT or PET/CT imaging to examine the changes in the structure and function of the whole lung. The lung histology was analyzed by H&E staining and immunohistochemical staining of inflammatory cells. Results demonstrated that tree shrews exhibited an average survival time of 3–5 days after LPS insult, as well as an obvious symptom of dyspnea before death. The ratios of PaO 2 to FiO 2 (P/F ratio) were close to those of moderate ARDS in humans. CT imaging showed that the scope of the lung injury in tree shrews after LPS treatment were extensive. PET/CT imaging with 18F-FDG displayed an obvious inflammatory infiltration. Histological analysis detected the formation of a hyaline membrane, which is usually present in human ARDS. This study established a lung injury model with a primate-like small animal model and confirmed that they have similar features to human ARDS, which might provide a valuable tool for translational research. [ABSTRACT FROM AUTHOR]

The most important factor that distinguishes a youthful appearance from an aged one is the shape of the lower face. This study aimed to examine the outcome of volume reduction of the lower face using laser-assisted liposuction (SmartLipo) at the time of rhytidectomy in Asians. There were 20 patients (Group 1) for whom only extended deep-plane rhytidectomy were performed, while extended deep-plane rhytidectomy with laser-assisted liposuction was performed on 42 patients (Group 2). This study was performed retrospectively. The FACE-Q questionnaire was given to evaluate the subjective result of the patient. Efficacy was evaluated by measuring the fat quantity at the midpoint and anterior border of the masseter muscle on each side by using an ultrasound scan in Group 2. Then, the correlation between the change in the quantity of fat and the FACE-Q was investigated. The overall satisfaction, and satisfaction for the lower face, jawline, and the area under the chin were significantly higher for Group 2 for which the procedure was concurrently performed in comparison to Group 1. In Group 2, change in the fat was reduced by 21.2% (Rt.) and 22.5% (Lt.) at the mid-point and 24.5% (Rt.) and 26.4% (Lt.) at the anterior border of the masseter muscle. Changes in the fat quantity and lower face satisfaction displayed a significant correlation. With a greater reduction in fat quantity, the score of lower face satisfaction was higher. In addition, with a higher level of satisfaction for the lower face and jawline, the overall satisfaction score displayed a higher positive correlation. Laser-assisted liposuction was useful for the additive procedure at the time of rhytidectomy and improved patient's satisfaction after surgery. [ABSTRACT FROM AUTHOR]

Recently, double‐network or multiple‐network hydrogel constructed by physical methods has been considered a green method to improve the comprehensive properties of biomass hydrogel. Herein, a novel physically cross‐linked hydrogel with multiple network of gellan gum/chitosan/calcium ion (GG–CS–Ca) was constructed by self‐assembly to accomplish the synergistic improvement of mechanical strength and uranium adsorption property compared to adsorbents GG–Ca and carboxymethyl konjac glucomannan/GG–Al originated from gellan gum previously prepared. Moreover, the driving mechanism of self‐assembly of GG–CS–Ca was deduced by 13C solid state nuclear magnetic resonance spectroscopy (13C‐SSNMR), rheological analysis, and phase transition analysis. The results indicated electrostatic interaction was dominant during the self‐assembly of GG–CS–Ca. The self‐assembly mechanism was also illustrated by investigating the x‐ray photoelectron spectrometer (XPS) combined with the analysis of the phase transition process. Comprehensively, the self‐assembly constructed GG–CS–Ca hydrogel network contained three kinds of network including the GG–CS network constructed by electrostatic action of protonated CS with negative charged GG, the GG–Ca network constructed by ionic cross‐linking of COO− in GG and Ca2+, and the GG network formed after the phase transformation of GG hot sol by cooling. It explored a new method for constructing biomass‐based physical hydrogels with both favorable mechanical strength and uranium adsorption capacity in uranium removal. Highlights: A novel physically cross‐linked hydrogel (GG–CS–Ca) with multiple network was constructed by self‐assembly.The GG–CS–Ca hydrogel accomplished the synergistic improvement of mechanical strength and uranium adsorption properties.The self‐assembly mechanism of constructing the GG–CS–Ca hydrogel network contained three aspects.The electrostatic interaction was the dominant action during the self‐assembly of GG–CS–Ca. [ABSTRACT FROM AUTHOR]

Pathological cardiac hypertrophy is a key contributor to heart failure, and the molecular mechanisms underlying honokiol (HNK)‐mediated cardioprotection against this condition remain worth further exploring. This study aims to investigate the effect of HNK on angiotensin II (Ang II)‐induced myocardial hypertrophy and elucidate the underlying mechanisms. Sprague–Dawley rats were exposed to Ang II infusion, followed by HNK or vehicle treatment for 4 weeks. Our results showed that HNK treatment protected against Ang II‐induced myocardial hypertrophy, fibrosis and dysfunction in vivo and inhibited Ang II‐induced hypertrophy in neonatal rat ventricular myocytes in vitro. Mechanistically, HNK suppressed the Ang II‐induced Nur77 expression at the transcriptional level and promoted ubiquitination‐mediated degradation of Nur77, leading to dissociation of the Nur77–LKB1 complex. This facilitated the translocation of LKB1 into the cytoplasm and activated the LKB1‐AMPK pathway. Our findings suggest that HNK attenuates pathological remodelling and cardiac dysfunction induced by Ang II by promoting dissociation of the Nur77–LKB1 complex and subsequent activation of AMPK signalling. This study uncovers a novel role of HNK on the LKB1‐AMPK pathway to protect against cardiac hypertrophy. [ABSTRACT FROM AUTHOR]