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Characterizing the transcriptional and translational gene expression patterns at the single-cell level within their three-dimensional (3D) tissue context is essential for revealing how genes shape tissue structure and function in health and disease. However, most existing spatial profiling techniques are limited to 5-20 µm thin tissue sections. Here, we developed Deep-STARmap and Deep-RIBOmap, which enable 3D in situ quantification of thousands of gene transcripts and their corresponding translation activities, respectively, within 200-µm thick tissue blocks. This is achieved through scalable probe synthesis, hydrogel embedding with efficient probe anchoring, and robust cDNA crosslinking. We first utilized Deep-STARmap in combination with multicolor fluorescent protein imaging for simultaneous molecular cell typing and 3D neuron morphology tracing in the mouse brain. We also demonstrate that 3D spatial profiling facilitates comprehensive and quantitative analysis of tumor-immune interactions in human skin cancer.
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High entropy material (HEM) has emerged as an appealing material platform for various applications, and specifically, the electrochemical performances of HEM could be further improved through self-assembled structure design. However, it remains a big challenge to construct such high-entropy self-assemblies primarily due to the compositional complexity. Herein, we propose a bottom-up directional freezing route to self-assemble high-entropy hydrosols into porous nanosheets. Taking Prussian blue analogue (PBA) as an example, the simultaneous coordination-substitution reactions yield stable high-entropy PBA hydrosols. During subsequent directional freezing process, the anisotropic growth of ice crystals could guide the two-dimensional confined assembly of colloidal nanoparticles, resulting in high-entropy PBA nanosheets (HE-PBA NSs). Thanks to the high-entropy and self-assembled structure design, the HE-PBA NSs manifests markedly enhanced sodium storage kinetics and performances in comparison with medium/low entropy nanosheets and high entropy nanoparticles.
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ABSTRACT: Postoperative cognitive dysfunction is a severe complication of the central nervous system that occurs after anesthesia and surgery, and has received attention for its high incidence and effect on the quality of life of patients. To date, there are no viable treatment options for postoperative cognitive dysfunction. The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research. To identify the signaling mechanisms contributing to postoperative cognitive dysfunction, we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset, which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus 3 days after tibial fracture. The dataset was enriched in genes associated with the biological process "regulation of immune cells," of which Chill was identified as a hub gene. Therefore, we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fracture surgery. Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 1 24 hours post-surgery, and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests. In addition, protein expression levels of proinflammatory factors (interleukin-1ß and inducible nitric oxide synthase), M2-type macrophage markers (CD206 and arginase-1), and cognition-related proteins (brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B) were measured in hippocampus by western blotting. Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment, downregulated interleukin-1ß and nducible nitric oxide synthase expression, and upregulated CD206, arginase-1, pNR2B, and brain-derived neurotropic factor expression compared with vehicle treatment. Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1. Collectively, our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus. Therefore, recombinant chitinase-3-like protein 1 may have therapeutic potential for postoperative cognitive dysfunction.
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PURPOSE: While reactive oxygen species (ROS) have been identified as key redox signaling agents contributing to aging process, which and how specific oxidants trigger healthy longevity remain unclear. This paper aimed to explore the precise role and signaling mechanism of superoxide (O2â¢-) in health and longevity. METHODS: A tool for precise regulation of O2â¢- levels in vivo was developed based on the inhibition of superoxide dismutase 1 (SOD1) by tetrathiomolybdate (TM) in Caenorhabditis elegans (C. elegans). Then, we examined the effects of TM on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the signaling mechanism for longevity induced by TM-O2â¢- was screened by transcriptome analysis and tested in sod-1 and argk-1 RNAi strains, sod-2, sod-3, and daf-16 mutants. RESULTS: TM promoted longevity in C. elegans with a concomitant extension of healthy lifespan as indicated by increasing fertility and mobility and reducing lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanically, TM could precisely regulate O2â¢- levels in nematodes via modulating SOD1 activity. An O2â¢- scavenger Mn(III)TBAP abolished TM-induced lifespan extension, while an O2â¢- generator paraquat at low concentration mimicked the life prolongation effects. The longevity in TM-treated worms was abolished by sod-1 RNAi but was not affected in sod-2 or sod-3 mutants. Further transcriptome analysis revealed arginine kinase ARGK-1 and its downstream insulin/insulin-like growth factor 1 signaling (IIS) as potential effectors for TM-O2â¢â¾-induced longevity, and argk-1 RNAi or daf-16 mutant nullified the longevity. CONCLUSIONS: These findings indicate that it is feasible to precisely control specific oxidant in vivo and O2â¢- orchestrates TM-induced health and longevity in C. elegans via ARGK-1-IIS axis.
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Hemerocallis L. possesses abundant germplasm resources and holds significant value in terms of ornamental, edible, and medicinal aspects. However, the quality characteristics vary significantly depending on different varieties. Selection of a high-quality variety with a characteristic aroma can increase the economic value of Hemerocallis flowers. The analytic hierarchy process (AHP) is an effective decision-making method for comparing and evaluating multiple characteristic dimensions. By applying AHP, the aromatic character of 60 varieties of Hemerocallis flowers were analyzed and evaluated in the present study. Headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) was employed to identify volatile components in Hemerocallis flowers. Thirteen volatile components were found to contribute to the aroma of Hemerocallis flowers, which helps in assessing their potential applications in essential oil, aromatherapy, and medical treatment. These components include 2-phenylethanol, geraniol, linalool, nonanal, decanal, (E)-ß-ocimene, α-farnesene, indole, nerolidol, 3-furanmethanol, 3-carene, benzaldehyde and benzenemethanol. The varieties with better aromatic potential can be selected from a large amount of data using an AHP model. This study provides a comprehensive understanding of the characteristics of the aroma components in Hemerocallis flowers, offers guidance for breeding, and enhances the economic value of Hemerocallis flowers.
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Flores , Cromatografía de Gases y Espectrometría de Masas , Microextracción en Fase Sólida , Compuestos Orgánicos Volátiles , Compuestos Orgánicos Volátiles/análisis , Compuestos Orgánicos Volátiles/química , Microextracción en Fase Sólida/métodos , Flores/química , Odorantes/análisis , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/análisis , Aceites Volátiles/química , Aceites Volátiles/análisis , Sesquiterpenos/análisis , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/análisis , Alcohol Feniletílico/química , Alquenos , IndolesRESUMEN
In this study, the volatile components in 40 samples of Tartary buckwheat and common buckwheat from 6 major producing areas in China were analyzed. A total of 77 volatile substances were identified, among which aldehydes and hydrocarbons were the main volatile components. Odor activity value analysis revealed 26 aromatic compounds, with aldehydes making a significant contribution to the aroma of buckwheat. Seven key compounds that could be used to distinguish Tartary buckwheat from common buckwheat were identified. The orthogonal partial least squares-discriminant analysis was effectively used to classify Tartary buckwheat and common buckwheat from different producing areas. This study provides valuable information for evaluating buckwheat quality, breeding high-quality varieties, and enhancing rational resource development.
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Aims: Redox signaling plays a key role in skeletal muscle remodeling induced by exercise and prolonged inactivity, but it is unclear which oxidant triggers myofiber hypertrophy due to the lack of strategies to precisely regulate individual oxidants in vivo. In this study, we used tetrathiomolybdate (TM) to dissociate the link between superoxide (O2â¢-) and hydrogen peroxide and thereby to specifically explore the role of O2â¢- in muscle hypertrophy in C2C12 cells and mice. Results: TM can linearly regulate intracellular O2â¢- levels by inhibition of superoxide dismutase 1 (SOD1). A 70% increase in O2â¢- levels in C2C12 myoblast cells and mice is necessary and sufficient for triggering hypertrophy of differentiated myotubes and can enhance exercise performance by more than 50% in mice. SOD1 knockout blocks TM-induced O2â¢- increments and thereby prevents hypertrophy, whereas SOD1 restoration rescues all these effects. Scavenging O2â¢- with antioxidants abolishes TM-induced hypertrophy and the enhancement of exercise performance, whereas the restoration of O2â¢- levels with a O2â¢- generator promotes muscle hypertrophy independent of SOD1 activity. Innovation and Conclusion: These findings suggest that O2â¢- is an endogenous initiator of myofiber hypertrophy and that TM may be used to treat muscle wasting diseases. Our work not only suggests a novel druggable mechanism to increase muscle mass but also provides a tool for precisely regulating O2â¢- levels in vivo.
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Sodium-ion batteries (SIBs) represent a promising energy storage technology with great safety. Because of their high operating potential, superior structural stability, and prominent thermal stability, polyanion-type phosphates have garnered significant interest in superior prospective cathode materials for SIBs. Nevertheless, the disadvantages of poor intrinsic electronic conductivity, sluggish kinetics, and volume variation during sodiation/desodiation remain great challenges for satisfactory rate performance and cycle stability, which severely hinder their further practical applications. In this work, by adjusting the amounts of pretreated multiwalled carbon nanotubes (CNT) added intentionally at the beginning of the preparation, biphasic polyanion-type phosphate materials (marked as NFC) are synthesized through a one-pot solid state reaction methodology, which are composed of CNT-interwoven Na3V2(PO4)2F3 (NVPF) and a small amount of Na3V2(PO4)3 (NVP). Benefiting from the improved electronic conductivity and unique composition and structure, the optimized sample (labeled as NFC-2) illustrates exceptional cycle stability and remarkable rate performance. The discharge capacities of the NFC-2 electrode are 114.8 and 78.6 mAh g-1 tested at 20 and 5000 mA g-1, respectively. Notably, such an electrode still gives out 75.7% capacity retention upon 10â¯000 cycles at 5000 mA g-1. In situ X-ray diffraction analysis demonstrates that the NFC-2 cathode has outstanding structural reversibility during charge/discharge cycles. More importantly, such a biphasic material has achieved impressive electrochemical performance within a wide operating temperature range of -20-50 °C. When temperature is decreased to -20 °C, the NFC-2 electrode still delivers an initial discharge capacity of 102.4 mAh g-1 and exhibits a remarkable capacity retention of 97.8% even after 500 cycles at 50 mA g-1. In addition, the sodium-ion full cell assembled by integrating NFC-2 cathode and hard carbon anode shows a satisfying energy density of 431.3 Wh kg-1 at 20 mA g-1 with a better long-term cycle performance. The synergistic effect among high energy NVPF, conductive CNT, and stable NVP may lead to the great improvement in the electrochemical sodium storage performance of the NFC-2 sample. Such biphasic polyanion-type phosphate materials will inject new ideas into the material design for SIBs with excellent electrochemical performance and further promote practical applications of this advanced energy storage technology.
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Benefiting from anionic and cationic redox reactions, Li-rich materials have been regarded as next-generation cathodes to overcome the bottleneck of energy density. However, they always suffer from cracking of polycrystalline (PC) secondary particles and lattice oxygen release, resulting in severe structural deterioration and capacity decay upon cycling. Single-crystal (SC) design has been proven as an effective strategy to relieve these issues in traditional Li-rich cathodes with PC morphology. Herein, we first reviewed the main synthesis routes of SC Li-rich materials including solid-state reaction, molten salt-assisted, and hydrothermal/solvothermal methods, in which the differences in grain morphology, electrochemical behaviors, and other properties induced by various routes were analyzed and discussed. Furthermore, the distinct characteristics were compared between SC and PC cathodes from the aspects of irreversible capacity, structural stability, capacity/voltage degradation, and gas release. Besides, recent advances in layered SC Li-rich oxide cathodes were summarized in detail, where the unique structural designs and modification strategies could greatly promote their structural/electrochemical stability. At last, challenges and perspectives for the emerging SC Li-rich cathodes were proposed, which provided an exceptional opportunity to achieve high-energy-density and high-stability Li-ion/metal batteries.
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Laser powder bed fusion (LPBF) of complex-structure 316L stainless steel (316L ss) parts has a wide application prospects in aerospace, biomedical, and defense industry fields. However, the surface roughness (Ra) of the LPBF sample is unsatisfactory due to the process characteristics of layer-by-layer selective melting and cumulative forming, which limits its applications in the engineering field. Herein, a gradient voltage electrochemical polishing strategy is proposed based on the characteristics of electrochemical polishing technology, which can polish complex structures. The mechanisms of polishing process parameters and polishing strategy on the surface finish of LPBF parts are investigated. The gradient voltage polishing strategy is extended to complex structures, and the Ra of the inner surfaces of square and round tubes are successfully reduced to about 1 µm. The gradient electrochemical polishing process for surface finish post-treatment of LPBF parts can broaden the engineering applications of complex-structure metal parts.
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Pathogenic variants in HFE and non-HFE genes have been identified in hemochromatosis in different patient populations, but there are still a certain number of patients with unexplained primary iron overload. We recently identified in Chinese patients a recurrent p.(Arg639Gln) variant in SURP and G-patch domain containing 2 (SUGP2), a potential mRNA splicing-related factor. However, the target gene of SUGP2 and affected iron-regulating pathway remains unknown. We aimed to investigate the pathogenicity and underlying mechanism of this variant in hemochromatosis. RNA-seq analysis revealed that SUGP2 knockdown caused abnormal alternative splicing of CIRBP pre-mRNA, resulting in an increased normal splicing form of CIRBP V1, which in turn increased the expression of BMPER by enhancing its mRNA stability and translation. Furthermore, RNA-protein pull-down and RNA immunoprecipitation assays revealed that SUGP2 inhibited splicing of CIRBP pre-mRNA by a splice site variant at CIRBP c.492 and was more susceptible to CIRBP c.492 C/C genotype. Cells transfected with SUGP2 p.(Arg639Gln) vector showed up-regulation of CIRBP V1 and BMPER expression and down-regulation of pSMAD1/5 and HAMP expression. CRISPR-Cas9 mediated SUGP2 p.(Arg622Gln) knock-in mice showed increased iron accumulation in the liver, higher total serum iron, and decreased serum hepcidin level. A total of 10 of 54 patients with hemochromatosis (18.5%) harbored the SUGP2 p.(Arg639Gln) variant and carried CIRBP c.492 C/C genotype, and had increased BMPER expression in the liver. Altogether, the SUGP2 p.(Arg639Gln) variant down-regulates hepcidin expression through the SUGP2/CIRBP/BMPER axis, which may represent a novel pathogenic factor for hemochromatosis.
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Hemocromatosis , Transducción de Señal , Hemocromatosis/genética , Humanos , Ratones , Animales , Masculino , Proteínas de Unión al ARN/genética , Hepcidinas/genética , Hepcidinas/metabolismo , FemeninoRESUMEN
Persistently elevated glycolysis in kidney has been demonstrated to promote chronic kidney disease (CKD). However, the underlying mechanism remains largely unclear. Here, we observed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme, was remarkably induced in kidney proximal tubular cells (PTCs) following ischemia-reperfusion injury (IRI) in mice, as well as in multiple etiologies of patients with CKD. PFKFB3 expression was positively correlated with the severity of kidney fibrosis. Moreover, patients with CKD and mice exhibited increased urinary lactate/creatine levels and kidney lactate, respectively. PTC-specific deletion of PFKFB3 significantly reduced kidney lactate levels, mitigated inflammation and fibrosis, and preserved kidney function in the IRI mouse model. Similar protective effects were observed in mice with heterozygous deficiency of PFKFB3 or those treated with a PFKFB3 inhibitor. Mechanistically, lactate derived from PFKFB3-mediated tubular glycolytic reprogramming markedly enhanced histone lactylation, particularly H4K12la, which was enriched at the promoter of NF-κB signaling genes like Ikbkb, Rela, and Relb, activating their transcription and facilitating the inflammatory response. Further, PTC-specific deletion of PFKFB3 inhibited the activation of IKKß, I κ B α, and p65 in the IRI kidneys. Moreover, increased H4K12la levels were positively correlated with kidney inflammation and fibrosis in patients with CKD. These findings suggest that tubular PFKFB3 may play a dual role in enhancing NF-κB signaling by promoting both H4K12la-mediated gene transcription and its activation. Thus, targeting the PFKFB3-mediated NF-κB signaling pathway in kidney tubular cells could be a novel strategy for CKD therapy.
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Modelos Animales de Enfermedad , Fibrosis , Glucólisis , Histonas , FN-kappa B , Fosfofructoquinasa-2 , Insuficiencia Renal Crónica , Daño por Reperfusión , Animales , Fosfofructoquinasa-2/genética , Fosfofructoquinasa-2/metabolismo , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/metabolismo , Humanos , Ratones , Masculino , Daño por Reperfusión/patología , Daño por Reperfusión/metabolismo , FN-kappa B/metabolismo , Histonas/metabolismo , Ratones Noqueados , Ratones Endogámicos C57BL , Transducción de Señal , Túbulos Renales Proximales/patología , Túbulos Renales Proximales/metabolismo , Ácido Láctico/metabolismo , Riñón/patología , Riñón/metabolismoRESUMEN
Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression-high-fat diet (HFD)-fed mice aged to 90-100 weeks and BTBR ob/ob mice (a genetic model)-and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2high macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2high macrophages may provide therapeutic benefits for DKD.
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Nefropatías Diabéticas , Dieta Alta en Grasa , Riñón , Macrófagos , Glicoproteínas de Membrana , Ratones Noqueados , Obesidad , Receptores Inmunológicos , Animales , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Macrófagos/metabolismo , Obesidad/metabolismo , Obesidad/patología , Obesidad/complicaciones , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Ratones , Riñón/patología , Riñón/metabolismo , Humanos , Masculino , Ratones Endogámicos C57BL , FemeninoRESUMEN
BACKGROUND: Acute Kidney Injury (AKI) is defined as a sudden loss of kidney function, which is often caused by drugs, toxins, and infections. The large spectrum of AKI implies diverse pathophysiological mechanisms. In many cases, AKI can be lethal, and kidney replacement therapy is frequently needed. However, current treatments are not satisfying. Developing novel therapies for AKI is essential. Adult stem cells possess regenerative ability and play an important role in medical research and disease treatment. METHODS: In this study, we isolated and characterized a distinct human urine-derived stem cell, which expressed both proximal tubular cell and mesenchymal stem cell genes as well as certain unique genes. RESULTS: It was found that these cells exhibited robust protective effects on tubular cells and anti- inflammatory effects on macrophages in vitro. In an ischemia-reperfusion-induced acute kidney injury NOD-SCID mouse model, transplantation of USCs significantly protected the kidney morphology and functions in vivo. CONCLUSION: In summary, our results highlighted the effectiveness of USCs in protecting from PTC injury and impeding macrophage polarization, as well as the secretion of pro-inflammatory interleukins, suggesting the potential of USCs as a novel cell therapy in AKI.
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Intermittent fasting remains a safe and effective strategy to ameliorate various age-related diseases, but its specific mechanisms are not fully understood. Considering that transcription factors (TFs) determine the response to environmental signals, here, we profiled the diurnal expression of 600 samples across four metabolic tissues sampled every 4 over 24 h from mice placed on five different feeding regimens to provide an atlas of TFs in biological space, time, and feeding regimen. Results showed that 1218 TFs exhibited tissue-specific and temporal expression profiles in ad libitum mice, of which 974 displayed significant oscillations at least in one tissue. Intermittent fasting triggered more than 90% (1161 in 1234) of TFs to oscillate somewhere in the body and repartitioned their tissue-specific expression. A single round of fasting generally promoted TF expression, especially in skeletal muscle and adipose tissues, while intermittent fasting mainly suppressed TF expression. Intermittent fasting down-regulated aging pathway and upregulated the pathway responsible for the inhibition of mammalian target of rapamycin (mTOR). Intermittent fasting shifts the diurnal transcriptome atlas of TFs, and mTOR inhibition may orchestrate intermittent fasting-induced health improvements. This atlas offers a reference and resource to understand how TFs and intermittent fasting may contribute to diurnal rhythm oscillation and bring about specific health benefits.
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Although messenger RNA (mRNA) has proved effective as a vaccine, its potential as a general therapeutic modality is limited by its instability and low translation capacity. To increase the duration and level of protein expression from mRNA, we designed and synthesized topologically and chemically modified mRNAs with multiple synthetic poly(A) tails. Here we demonstrate that the optimized multitailed mRNA yielded ~4.7-19.5-fold higher luminescence signals than the control mRNA from 24 to 72 h post transfection in cellulo and 14 days detectable signal versus <7 days signal from the control in vivo. We further achieve efficient multiplexed genome editing of the clinically relevant genes Pcsk9 and Angptl3 in mouse liver at a minimal mRNA dosage. Taken together, these results provide a generalizable approach to synthesize capped branched mRNA with markedly enhanced translation capacity.
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The cytoplasmic pattern recognition receptor, absent in melanoma 2 (AIM2), detects cytosolic DNA, activating the inflammasome and resulting in pro-inflammatory cytokine production and pyroptotic cell death. Recent research has illuminated AIM2's contributions to PANoptosis and host defense. However, the role of AIM2 in acetaminophen (APAP)-induced hepatoxicity remains enigmatic. In this study, we unveil AIM2's novel function as a negative regulator in the pathogenesis of APAP-induced liver damage in aged mice, independently of inflammasome activation. AIM2-deficient aged mice exhibited heightened lipid accumulation and hepatic triglycerides in comparison to their wild-type counterparts. Strikingly, AIM2 knockout mice subjected to APAP overdose demonstrated intensified liver injury, compromised mitochondrial stability, exacerbated glutathione depletion, diminished autophagy, and elevated levels of phosphorylated c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). Furthermore, our investigation revealed AIM2's mitochondrial localization; its overexpression in mouse hepatocytes amplified autophagy while dampening JNK phosphorylation. Notably, induction of autophagy through rapamycin administration mitigated serum alanine aminotransferase levels and reduced the necrotic liver area in AIM2-deficient aged mice following APAP overdose. Mechanistically, AIM2 deficiency exacerbated APAP-induced acute liver damage and inflammation in aged mice by intensifying oxidative stress and augmenting the phosphorylation of JNK and ERK. Given its regulatory role in autophagy and lipid peroxidation, AIM2 emerges as a promising therapeutic target for age-related acute liver damage treatment.
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BACKGROUND: The functional benefit of segmentectomy compared with lobectomy remains controversial. This ambispective study characterizes the changes in pulmonary function as correlated to displacement patterns of residual lung after segmentectomies vs lobectomies. METHODS: Patients with normal preoperative pulmonary function and undergoing segmentectomy or lobectomy between 2017 and 2021 were considered. Pulmonary function testing was scheduled preoperatively and at least 3 months postoperatively. Differences in the proportions of the median forced expiratory volume in 1 second (FEV1) reduction between segmentectomy and lobectomy were calculated. Covariance analysis was used to estimate the adjusted postoperative FEV1 (apoFEV1) and compare the difference value (DV) in apoFEV1 between segmentectomy and lobectomy. RESULTS: The study enrolled 634 patients (334 lobectomies and 300 segmentectomies). Median difference in the proportions of the FEV1 reduction between segmentectomy and lobectomy was 4.58%, with maximal difference observed in right S6 (9.08%) and minimal difference in left S1+2+3 (2.80%). For resections involving the upper lobe, apoFEV1 was significantly higher after segmentectomy than after lobectomy (DV, 0.15-0.22 L), except for left S3 and S1+2+3 segmentectomies (DV, 0.08 L and 0.06 L, respectively). Compared with a lower lobe lobectomy, S6 segmentectomy conferred a higher apoFEV1, whereas S7+8 and S9+10 had a similar apoFEV1 (DV, 0.16-0.18 L, 0.07 L, and 0.00-0.06 L, respectively). Functional recovery after segmentectomy was associated with the number of intersegment planes (P < .01) and the presence of an adjacent nonoperated on lobe (P = .03). CONCLUSIONS: Basilar and left S3 segmentectomies did not preserve more pulmonary function compared with their corresponding lobectomies, possibly due to the presence of multiple intersegmental resection planes.
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Neoplasias Pulmonares , Neumonectomía , Recuperación de la Función , Humanos , Neumonectomía/métodos , Masculino , Femenino , Neoplasias Pulmonares/cirugía , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Volumen Espiratorio Forzado/fisiología , Pruebas de Función Respiratoria , Pulmón/cirugía , Pulmón/fisiopatologíaRESUMEN
INTRODUCTION: While several antidepressants have been identified as potential geroprotectors, the effect and mechanism of sertraline on healthspan remain to be elucidated. Here, we explored the role of sertraline in the lifespan and healthspan of Caenorhabditis elegans. METHODS: The optimal effect concentration of sertraline was first screened in wild-type N2 worms under heat stress conditions. Then, we examined the effects of sertraline on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the expression of serotonin signaling and aging-related genes was investigated to explore the underlying mechanism, and the lifespan assays were performed in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. RESULTS: Sertraline extended the lifespan in C. elegans with concomitant extension of healthspan as indicated by increasing mobility and reducing fertility and lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanistically, ser-7 orchestrated sertraline-induced longevity via the regulation of insulin and AMPK pathways, and sertraline-induced lifespan extension in nematodes was abolished in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. CONCLUSION: Sertraline promotes health and longevity in C. elegans through ser-7-insulin/AMPK pathways.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Caenorhabditis elegans/genética , Longevidad/fisiología , Sertralina/farmacología , Sertralina/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Lipofuscina/metabolismo , Lipofuscina/farmacología , Insulina , Factores de Transcripción Forkhead/genéticaRESUMEN
Although several antidepressants have been identified as potential geroprotectors, the effect and mechanism of fluoxetine, a representative selective serotonin reuptake inhibitor, on longevity have not been fully elucidated. Here, we found that fluoxetine promoted longevity in Caenorhabditis elegans with a concomitant extension of a healthy life span as indicated by increasing mobility, reducing fertility and lipofuscin accumulation, and enhanced resistance to different abiotic stresses. Fluoxetine increased the level of reactive oxygen species (ROS), and antioxidant N-acetylcysteine abolished ROS elevation and the pro-longevity effect of fluoxetine. Additionally, fluoxetine extended life span through the daf-2-sod-3 pathway in daf-16-dependent and -independent manners, and fluoxetine-induced life-span extension was abolished in C. elegans sod-3, daf-2, and daf-16 mutants. In conclusion, these findings suggest that fluoxetine can promote health and longevity in C. elegans via the interaction of ROS and insulin signaling.