The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening.

A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin and transcriptional changes across 22 murine cell types, analyzed alongside previous mouse and human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during maturation and aging, are enriched for cell-type identity TFBSs. Conversely, cCREs gaining accessibility throughout life have a lower abundance of cell identity TFBSs but elevated activator protein 1 (AP-1) levels. We implicate TF redistribution toward these AP-1 TFBS-rich cCREs, in synergy with mild downregulation of cell identity TFs, as driving early-life cCRE accessibility loss and altering developmental and metabolic gene expression. Such remodeling can be triggered by elevating AP-1 or depleting repressive H3K27me3. We propose that AP-1-linked chromatin opening drives organismal maturation by disrupting cell identity TFBS-rich cCREs, thereby reprogramming transcriptome and cell function, a mechanism hijacked in aging through ongoing chromatin opening.

Structural equation model analysis of the effect of visceral fat on osteoporosis.

BACKGROUND: Osteoporosis is a considerable public health challenge in Moyu County, Xinjiang. Here, we evaluated the influencing factors of osteoporosis in this region. METHODS: We recruited 7,761 participants and randomized them into normal and osteoporotic populations based on T-score. The effects of general conditions, body composition, calcium sources and exercise, respiratory exposure, and daily diet on osteoporosis were analyzed. Furthermore, a structural equation model was constructed to uncover the direct and indirect influencing factors of osteoporosis. RESULTS: Among the participants, 1,803 (23.23%) had normal bone mass while 1,496 (19.28%) had osteoporosis. The univariate analysis showed significant differences in the general conditions, body composition, calcium sources and exercise, respiratory exposure, and daily diet. Stratification based on age (45 years) and body mass index (BMI) (18.5 kg/m2) showed variations in the body composition between the two groups; however, the visceral fat differed significantly. Logistic regression analysis affirmed the association of visceral fat index as it was included in all equations, except for age and female menopause. The structural equation exhibited that the general conditions, body composition, and, calcium sources, and exercise were direct factors of osteoporosis, while respiratory exposure and daily diet were indirect factors. The standardized path coefficient was highest in general conditions, followed by body composition, and lastly, calcium sources and exercise. CONCLUSION: Obesity, besides age and female menopause, is also an influencing factor of osteoporosis. The visceral fat index plays a vital role in osteoporosis. Our findings may provide experimental evidence for early prevention and treatment of osteoporosis.

Compact step-added T-type PAC for enhanced hydrogen detection: A photoacoustic frequency shift approach.

In this study, we introduce an innovative photoacoustic frequency shift (PAFS) technique for hydrogen (H2) detection, complemented by both theoretical models and practical experiments. To mitigate cross-sensitivity, we analyzed the sound speeds of six different gases, confirming minimal interference with H2 due to significant velocity disparities. Central to our approach is the design of a miniaturized step-added T-type Photoacoustic Cell (PAC), with parameters meticulously optimized for enhanced performance. Using COMSOL Multiphysics' Thermal Viscous Acoustics module, we conducted simulations to evaluate the quality factor and acoustic pressure, both crucial for the sensor's efficiency. Additionally, we assessed the system's stability, influenced by gas flow, through gas velocity distribution analyses using the Computational Fluid Dynamics module. Experimental investigations focused on the system's sensing performance, revealing a distinct frequency shift of âˆ¼45 Hz for every 1 % change in H2 concentration, with a high linear correlation (R2 = 0.99825). The system's response and recovery times were measured at 1.09 s and 1.25 s, respectively. Long-term stability, evaluated over 3000 s using Allan deviation, indicated a minimum detection limit (MDL) of 102.47 ppm at an integration time of 375 s. These findings validate the efficacy of the step-added T-type PAC in H2 detection.

Lysosome-Targeted and pH-Activatable Phototheranostics for NIR-II Fluorescence Imaging-Guided Nasopharyngeal Carcinoma Phototherapy.

Currently, clinical therapeutic strategies for nasopharyngeal carcinoma (NPC) confront insurmountable dilemmas in which surgical resection is incomplete and chemotherapy/radiotherapy has significant side effects. Phototherapy offers a maneuverable, effective, and noninvasive pattern for NPC therapy. Herein, we developed a lysosome-targeted and pH-responsive nanophototheranostic for near-infrared II (NIR-II) fluorescence imaging-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of NPC. A lysosome-targeted S-D-A-D-S-type NIR-II phototheranostic molecule (IRFEM) is encapsulated within the acid-sensitive amphiphilic DSPE-Hyd-PEG2k to form IRFEM@DHP nanoparticles (NPs). The prepared IRFEM@DHP exhibits a good accumulation in the acidic lysosomes for facilitating the release of IRFEM, which could disrupt lysosomal function by generating an amount of heat and ROS under laser irradiation. Moreover, the guidelines of NIR-II fluorescence enhance the accuracy of PTT/PDT for NPC and avoid damage to normal tissues. Remarkably, IRFEM@DHP enable efficient antitumor effects both in vitro and in vivo, opening up a new avenue for precise NPC theranostics.

For a Colorful Life: Recent Advances in Anthocyanin Biosynthesis during Leaf Senescence.

Leaf senescence is the last stage of leaf development, and it is accompanied by a leaf color change. In some species, anthocyanins are accumulated during leaf senescence, which are vital indicators for both ornamental and commercial value. Therefore, it is essential to understand the molecular mechanism of anthocyanin accumulation during leaf senescence, which would provide new insight into autumn coloration and molecular breeding for more colorful plants. Anthocyanin accumulation is a surprisingly complex process, and significant advances have been made in the past decades. In this review, we focused on leaf coloration during senescence. We emphatically discussed several networks linked to genetic, hormonal, environmental, and nutritional factors in regulating anthocyanin accumulation during leaf senescence. This paper aims to provide a regulatory model for leaf coloration and to put forward some prospects for future development.

Genome-Wide Identification of GAST Family Members and Their Potential Roles in Epicotyl Dormancy in Chinese Cork Oak (Quercus variabilis).

Chinese cork oak (Quercus variabilis Blume) is a widespread tree species with high economic and ecological values. Chinese cork oak exhibits epicotyl dormancy, causing emergence heterogeneity and affecting the quality of seedling cultivation. Gibberellic acid-stimulated transcript (GAST) is a plant-specific protein family that plays a crucial regulatory role in plant growth, development, and seed germination. However, their evolution in Chinese cork oak and roles in epicotyl dormancy are still unclear. Here, a genome-wide identification of the GAST gene family was conducted in Chinese cork oak. Ten QvGAST genes were identified, and nine of them were expressed in seed. The physicochemical properties and promoter cis-acting elements of the selected Chinese cork oak GAST family genes indicated that the cis-acting elements in the GAST promoter are involved in plant development, hormone response, and stress response. Germinated seeds were subjected to gibberellins (GAs), abscisic acid (ABA), and fluridone treatments to show their response during epicotyl dormancy release. Significant changes in the expression of certain QvGAST genes were observed under different hormone treatments. QvGAST1, QvGAST2, QvGAST3, and QvGAST6 exhibited upregulation in response to gibberellin. QvGAST2 was markedly upregulated during the release of epicotyl dormancy in response to GA. These findings suggested that QvGAST2 might play an important role in epicotyl dormancy release. This study provides a basis for further analysis of the mechanisms underlying the alleviation of epicotyl dormancy in Chinese cork oak by QvGASTs genes.

Statistical Models for High-Risk Intestinal Metaplasia with DNA Methylation Profiling.

We consider the newly developed multinomial mixed-link models for a high-risk intestinal metaplasia (IM) study with DNA methylation data. Different from the traditional multinomial logistic models commonly used for categorical responses, the mixed-link models allow us to select the most appropriate link function for each category. We show that the selected multinomial mixed-link model (Model 1) using the total number of stem cell divisions (TNSC) based on DNA methylation data outperforms the traditional logistic models in terms of cross-entropy loss from ten-fold cross-validations with significant p-values 8.12×10-4 and 6.94×10-5. Based on our selected model, the significance of TNSC's effect in predicting the risk of IM is justified with a p-value less than 10-6. We also select the most appropriate mixed-link models (Models 2 and 3) when an additional covariate, the status of gastric atrophy, is available. When the status is negative, mild, or moderate, we recommend Model 2; otherwise, we prefer Model 3. Both Models 2 and 3 can predict the risk of IM significantly better than Model 1, which justifies that the status of gastric atrophy is informative in predicting the risk of IM.

Adaptor protein 14-3-3zeta promotes corneal wound healing via regulating cell homeostasis, a potential novel therapy for corneal injury.

Severe corneal injury can lead to blindness even after prompt treatment. 14-3-3zeta, a member of an adaptor protein family, contributes to tissue repair by enhancing cellular viability and inhibiting fibrosis and inflammation in renal disease or arthritis. However, its role in corneal regeneration is less studied. In this study, filter disc of 2-mm diameter soaked in sodium hydroxide with a concentration of 0.5 N was placed at the center of the cornea for 30 s to establish a mouse model of corneal alkali injury. We found that 14-3-3zeta, which is mainly expressed in the epithelial layer, was upregulated following injury. Overexpression of 14-3-3zeta in ocular tissues via adeno-associated virus-mediated subconjunctival delivery promoted corneal wound healing, showing improved corneal structure and transparency. In vitro studies on human corneal epithelial cells showed that 14-3-3zeta was critical for cell proliferation and migration. mRNA-sequencing in conjunction with KEGG analysis and validation experiments revealed that 14-3-3zeta regulated the mRNA levels of ITGB1, PIK3R1, FGF5, PRKAA1 and the phosphorylation level of Akt, suggesting the involvement of the PI3K-Akt pathway in 14-3-3zeta-mediated tissue repair. 14-3-3zeta is a potential novel therapeutic candidate for treating severe corneal injury.

Causes of Corneal Melt After the Boston Keratoprosthesis Type I: The Chinese People's Liberation Army General Hospital Experience.

PURPOSE: The purpose of this study was to evaluate the long-term incidence, risk factors, and the management of corneal melt following Boston type I keratoprosthesis (B-KPro I) implantation. METHODS: This is a retrospective observational case series. Data were collected regarding demographics, preoperative characteristics, incidence, and outcomes of corneal melt in 102 patients who underwent B-KPro I in the Chinese PLA General Hospital between 2011 and 2018, with a follow-up period ranging from 4 to 11 years. RESULTS: Chemical burn was the most common indication for B-KPro I (n = 56; 53.8%), followed by ocular trauma (n = 26; 25.0%). During the follow-up period (107 ± 25.7 months), corneal melt occurred in 60 cases among 37 eyes (35.6%), with an incidence of 20.2% at 1 year after surgery. Fourteen cases presented with recurrent corneal melt. Patients with multiple corneal allograft failures had a higher risk of corneal melt. Thermal burns, compared with alkali burns, significantly elevated the odds ratio (OR) of corneal melt (OR, 5.11; 95% confidence interval, 1.05-24.86; P = 0.043). CONCLUSIONS: Corneal melt significantly reduced the retention time of KPro ( P < 0.01), and its coexistence with other complications further shortened the retention time. A specific pattern of corneal melt occurrence was identified, with a peak incidence at 1 year postoperatively. Our findings suggest variations in the risk of corneal melt among different indications, with thermal burns carrying the highest OR. Moreover, each previous failed keratoplasty doubled the risk of corneal melt after B-KPro I.

Phenotypic comparison and the potential antitumor function of immortalized bone marrow-derived macrophages (iBMDMs).

Introduction: Macrophages are an important component of innate immunity and involved in the immune regulation of multiple diseases. The functional diversity and plasticity make macrophages to exhibit different polarization phenotypes after different stimuli. During tumor progression, the M2-like polarized tumor-associated macrophages (TAMs) promote tumor progression by assisting immune escape, facilitating tumor cell metastasis, and switching tumor angiogenesis. Our previous studies demonstrated that functional remodeling of TAMs through engineered-modifying or gene-editing provides the potential immunotherapy for tumor. However, lack of proliferation capacity and maintained immune memory of infused macrophages restricts the application of macrophage-based therapeutic strategies in the repressive tumor immune microenvironment (TIME). Although J2 retrovirus infection enabled immortalization of bone marrow-derived macrophages (iBMDMs) and facilitated the mechanisms exploration and application, little is known about the phenotypic and functional differences among multi kinds of macrophages. Methods: HE staining was used to detect the biosafety of iBMDMs, and real-time quantitative PCR, immunofluorescence staining, and ELISA were used to detect the polarization response and expression of chemokines in iBMDMs. Flow cytometry, scratch assay, real-time quantitative PCR, and crystal violet staining were used to analyze its phagocytic function, as well as its impact on tumor cell migration, proliferation, and apoptosis. Not only that, the inhibitory effect of iBMDMs on tumor growth was detected through subcutaneous tumor loading, while the tumor tissue was paraffin sectioned and flow cytometry was used to detect its impact on the tumor microenvironment. Results: In this study, we demonstrated iBMDMs exhibited the features of rapid proliferation and long-term survival. We also compared iBMDMs with RAW264.7 cell line and mouse primary BMDMs with in vitro and in vivo experiments, indicating that the iBMDMs could undergo the same polarization response as normal macrophages with no obvious cellular morphology changes after polarization. What's more, iBMDMs owned stronger phagocytosis and pro-apoptosis functions on tumor cells. In addition, M1-polarized iBMDMs could maintain the anti-tumor phenotypes and domesticated the recruited macrophages of receptor mice, which further improved the TIME and repressed tumor growth. Discussion: iBMDMs can serve as a good object for the function and mechanism study of macrophages and the optional source of macrophage immunotherapy.

Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.

An evidence-based guideline on treating lumbar disc herniation with traditional Chinese medicine.

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.

Neuroticism and openness exhibit an anti-correlation pattern to dissociable default mode network: using resting connectivity and structural equation modeling analysis.

The default mode network (DMN) can be subdivided into ventral and dorsal subsystems, which serve affective cognition and mental sense construction, respectively. An internally dissociated pattern of anti-correlations was observed between these two subsystems. Although numerous studies on neuroticism and openness have demonstrated the neurological functions of the DMN, little is known about whether different subsystems and hubs regions within the network are engaged in different functions in response to the two traits. We recruited 223 healthy volunteers in this study and collected their resting-state functional magnetic resonance imaging (fMRI) and NEO Five-Factor Inventory scores. We used independent component analysis (ICA) to obtain the DMN, before further decomposing it into the ventral and dorsal subsystems. Then, the network coherence of hubs regions within subsystems was extracted to construct two structural equation models (SEM) to explore the relationship between neuroticism and openness traits and DMN. We observed that the ventral DMN could significantly predict positive openness and negative neuroticism. The dorsal DMN was diametrically opposed. Additionally, the medial prefrontal cortex (mPFC) and middle temporal gyrus (MTG), both of which are core hubs of the subnetworks within the DMN, are significantly positively correlated with neuroticism and openness. These findings may point to a biological basis that neuroticism and openness are engaged in opposite mechanisms and support the hypothesis about the functional dissociation of the DMN.

Superconductivity in a Layered Cobalt Oxychalcogenide Na2CoSe2O with a Triangular Lattice.

Unconventional superconductivity in bulk materials under ambient pressure is extremely rare among the 3d transition metal compounds outside the layered cuprates and iron-based family. It is predominantly linked to highly anisotropic electronic properties and quasi-two-dimensional (2D) Fermi surfaces. To date, the only known example of a Co-based exotic superconductor is the hydrated layered cobaltate, NaxCoO2·yH2O, and its superconductivity is realized in the vicinity of a spin-1/2 Mott state. However, the nature of the superconductivity in these materials is still a subject of intense debate, and therefore, finding a new class of superconductors will help unravel the mysteries of their unconventional superconductivity. Here, we report the discovery of superconductivity at ∼6.3 K in our newly synthesized layered compound Na2CoSe2O, in which the edge-shared CoSe6 octahedra form [CoSe2] layers with a perfect triangular lattice of Co ions. It is the first 3d transition metal oxychalcogenide superconductor with distinct structural and chemical characteristics. Despite its relatively low TC, this material exhibits very high superconducting upper critical fields, µ0HC2(0), which far exceeds the Pauli paramagnetic limit by a factor of 3-4. First-principles calculations show that Na2CoSe2O is a rare example of a negative charge transfer superconductor. This cobalt oxychalcogenide with a geometrical frustration among Co spins shows great potential as a highly appealing candidate for the realization of unconventional and/or high-TC superconductivity beyond the well-established Cu- and Fe-based superconductor families and opens a new field in the physics and chemistry of low-dimensional superconductors.

Artificial intelligence in liver imaging: methods and applications.

Liver disease is regarded as one of the major health threats to humans. Radiographic assessments hold promise in terms of addressing the current demands for precisely diagnosing and treating liver diseases, and artificial intelligence (AI), which excels at automatically making quantitative assessments of complex medical image characteristics, has made great strides regarding the qualitative interpretation of medical imaging by clinicians. Here, we review the current state of medical-imaging-based AI methodologies and their applications concerning the management of liver diseases. We summarize the representative AI methodologies in liver imaging with focusing on deep learning, and illustrate their promising clinical applications across the spectrum of precise liver disease detection, diagnosis and treatment. We also address the current challenges and future perspectives of AI in liver imaging, with an emphasis on feature interpretability, multimodal data integration and multicenter study. Taken together, it is revealed that AI methodologies, together with the large volume of available medical image data, might impact the future of liver disease care.

Exploring the biological behavior and underlying mechanism of KITLG in triple-negative breast cancer.

The tyrosine-kinase receptor that is specified by the KIT locus is demarcated by KITLG. This multifaceted factor is instrumental during in-utero germ and neural cell maturation and hematopoiesis, ostensibly reflecting its role in facilitating cell migration. Concurrently, KITLG is prone to a mutation in germ cell tumors, entailing a presumed connection to tumorigenesis. Despite this, the intricacies of its function in breast cancer and the relevant mechanisms remain elusive. Multiple independent databases depict a consistently low expression of KITLG within tissues affected by triple-negative breast cancers (TNBC), a trend strongly coupled with reduced survival rates. Interestingly, non-triple-negative breast cancers exhibit a markedly high expression of KITLG compared to the norm. An initial analysis of the GEO database speculates that KITLG may serve as an oncogene suppressor in TNBC, hinting at varied roles for KITLG isoforms within this disease context. In conclusion, our preliminary analysis offers valuable insights into the role and expression pattern of KITLG in TNBC. We provide evidence supporting its consideration as a promising new prognostic marker, thereby potentially enriching therapeutic strategies for TNBC. Indeed, given the limited advances in molecularly targeted therapy for TNBC, a significant need exists for a more precise therapeutic approach and a comprehensive understanding of its inherent mechanisms of action.

Clinical efficacy of ceftazidime/avibactam combination therapy for severe hospital-acquired pulmonary infections caused by carbapenem-resistant and difficult-to-treat Pseudomonas aeruginosa.

OBJECTIVES: This retrospective study aimed to identify the effectiveness of ceftazidime/avibactam (CAZ/AVI) and its optimisation programs for severe hospital-acquired pulmonary infections (sHAPi) caused by carbapenem-resistant and difficult-to-treat Pseudomonas aeruginosa (CRPA and DTR-P. aeruginosa). METHODS: We retrospectively analysed observational data on treatment and outcomes of CAZ/AVI for sHAPi caused by CRPA or DTR-P. aeruginosa. The primary study outcomes were to evaluate the clinical and microbiology efficacy of CAZ/AVI. RESULTS: The cohort consisted of 84 in-patients with sHAPi caused by CRPA (n = 39) and DTR-P. aeruginosa (n = 45) who received at least 72 h of CAZ/AVI therapy. The clinical cure rate was 63.1% in total. There was no significant difference in study outcomes between patients treated with CAZ/AVI monotherapy and those managed with combination regimens. CAZ/AVI as first-line therapy possessed prominent clinical benefits regarding infections caused by DTR-P. aeruginosa. The clinical cure rate was positively relevant with loading dose for CAZ/AVI (odds ratio [OR] 0.03; 95% confidence interval [CI] 0.004-0.19; P < 0.001) and with CAZ/AVI administration by prolonged infusion (odds ratio 0.15; 95% confidence interval 0.03-0.77; P = 0.002). APACHE II score>15 (P = 0.013), septic shock at infection onset (P = 0.001), and CAZ/AVI dose adjustment for renal dysfunction (P = 0.003) were negative predictors of clinical cure. CONCLUSION: CAZ/AVI is a valid alternative for sHAPi caused by CPRA and DTR-P. aeruginosa, even when used alone. Optimisations of the treatment with CAZ/AVI in critically ill patients, including loading dose, adequate maintenance dose and prolonged infusion, were positively associated with potential clinical benefits.

Inhibition of SOCS3 signaling in the nucleus tractus solitarii and retrotrapezoid nucleus alleviates hypoventilation in diet-induced obese male mice.

The central leptin signaling system has been found to facilitate breathing and is linked to obesity-related hypoventilation. Activation of leptin signaling in the nucleus tractus solitarii (NTS) and retrotrapezoid nucleus (RTN) enhances respiratory drive. In this study, we investigated how medullary leptin signaling contributes to hypoventilation and whether respective deletion of SOCS3 in the NTS and RTN could mitigate hypoventilation in diet-induced obesity (DIO) male mice. Our findings revealed a decrease in the number of CO2-activated NTS neurons and downregulation of acid-sensing ion channels in DIO mice compared to lean control mice. Moreover, NTS leptin signaling was disrupted, as evidenced by the downregulation of phosphorylated STAT3 and the upregulation of SOCS3 in DIO mice. Importantly, deleting SOCS3 in the NTS and RTN significantly improved the diminished hypercapnic ventilatory response in DIO mice. In conclusion, our study suggests that disrupted medullary leptin signaling contributes to obesity-related hypoventilation, and inhibiting the upregulated SOCS3 in the NTS and RTN can alleviate this condition.

Controllable evolution of NiOOH/Au3+ active species for the oxidation of 5-hydroxymethylfurfural.

To induce the generation of active species at the metal-carrier interface, a new synthetic strategy was successfully developed to reconstruct the Ni MOF-Au via electrochemical activation. This unique configuration not only obtained high-valence NiOOH-Au3+ species, but also stably anchored the Au nanoparticles on the surface of the catalyst. As a result, nearly 99.8% FDCA yield and 100% Faraday efficiency of FDCA were achieved at the optimal potential of 1.57 V vs. RHE. Therefore, this electrochemical reconstruction provides new insights for the development of efficient catalysts in other heterogeneous catalytic reactions.