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1.
Medicine (Baltimore) ; 103(18): e38003, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701295

ABSTRACT

This study aims to investigate the ability of bone marrow imaging using third-generation dual-energy computed tomography (CT) virtual noncalcium (VNCa) to differentiate between multiple myeloma (MM) with diffuse bone marrow infiltration and red bone marrow (RBM). Bone marrow aspiration or follow-up results were used as reference. We retrospectively reviewed 188 regions of interests (ROIs) from 21 patients with confirmed MM and diffuse bone marrow infiltrations who underwent VNCa bone marrow imaging between May 2019 and September 2022. At the same time, we obtained 98 ROIs from 11 subjects with RBM for comparative study, and 189 ROIs from 20 subjects with normal yellow bone marrow for the control group. The ROIs were delineated by 2 radiologists independently, the interobservers reproducibility was evaluated by interclass correlation coefficients. The correlation with MRI grade results was analyzed by Spearman correlation coefficient. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal threshold for differentiating between these groups and to assess diagnostic performance. There were statistically significant differences in VNCa CT values of bone marrow among the MM, RBM, and control groups (all P < .001), with values decreasing sequentially. A strong positive rank correlation was observed between normal bone marrow, subgroup MM with moderately and severe bone marrow infiltration divided by MRI and their corresponding CT values (ρ = 0.897, 95%CI: 0.822 to 0.942, P < .001). When the CT value of VNCa bone marrow was 7.15 HU, the area under the curve (AUC) value for differentiating RBM and MM was 0.723, with a sensitivity of 50.5% and a specificity of 89.8%. When distinguishing severe bone marrow infiltration of MM from RBM, the AUC value was 0.80 with a sensitivity 70.9% and a specificity 78.9%. The AUC values for MM, RBM, and the combined group compared to the control group were all >0.99, with all diagnostic sensitivity and specificity exceeding 95%. VNCa bone marrow imaging using third-generation dual-energy CT accurately differentiates MM lesions from normal bone marrow or RBM. It demonstrates superior diagnostic performance in distinguishing RBM from MM with diffuse bone marrow infiltration.


Subject(s)
Bone Marrow , Multiple Myeloma , Tomography, X-Ray Computed , Humans , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/pathology , Multiple Myeloma/diagnosis , Male , Female , Middle Aged , Retrospective Studies , Bone Marrow/diagnostic imaging , Bone Marrow/pathology , Aged , Diagnosis, Differential , Tomography, X-Ray Computed/methods , Adult , ROC Curve , Reproducibility of Results , Sensitivity and Specificity
2.
Am J Transl Res ; 16(4): 1165-1176, 2024.
Article in English | MEDLINE | ID: mdl-38715828

ABSTRACT

OBJECTIVES: This study aims to investigate the potential therapeutic role of Elabela (ELA) in mitigating the sepsis-induced inflammatory storm, a phenomenon commonly associated with multiple organ dysfunction syndrome (MODS) and increased mortality. Our findings show the pathogenesis of sepsis, identifying ELA as a promising therapeutic target. METHODS: We conducted a comprehensive analysis of electronic medical records and blood samples from septic patients to assess the incidence of severe organ complication and characterize the inflammatory response. Subsequently, we measured the expression levels of ELA and various inflammatory factors in serum, and performed correlation analysis to explore the relationship between them, aiming to identify the cells and inflammatory pathways targeted by ELA. Furthermore, animal and cellular experiments were conducted to investigate the molecular mechanism underlying the therapeutic effect of ELA. RESULTS: Our findings revealed a higher prevalence of severe organ complications among septic patients, contributing to adverse prognoses and increased mortality. Notably, these patients exhibited significantly elevated levels of inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in their sera, indicating a robust inflammatory response. Correlation analysis revealed a negative correlation between ELA and IL-1ß in septic patients. Through animal and cellular experiments, we demonstrated that ELA inhibits the cleavage of caspase-1 and gasdermin D (GSDMD), thereby attenuating pyroptosis and the inflammatory response. CONCLUSIONS: ELA is a promising therapeutic agent for mitigating the deleterious effects of sepsis. Its ability to inhibit macrophage pyroptosis and suppress the inflammatory response offers a novel approach.

3.
JCI Insight ; 9(9)2024 May 08.
Article in English | MEDLINE | ID: mdl-38716725

ABSTRACT

IgA nephropathy (IgAN) represents the main cause of renal failure, while the precise pathogenetic mechanisms have not been fully determined. Herein, we conducted a cross-species single-cell survey on human IgAN and mouse and rat IgAN models to explore the pathogenic programs. Cross-species single-cell RNA sequencing (scRNA-Seq) revealed that the IgAN mesangial cells (MCs) expressed high levels of inflammatory signatures CXCL12, CCL2, CSF1, and IL-34 and specifically interacted with IgAN macrophages via the CXCL12/CXCR4, CSF1/IL-34/CSF1 receptor, and integrin subunit alpha X/integrin subunit alpha M/complement C3 (C3) axes. IgAN macrophages expressed high levels of CXCR4, PDGFB, triggering receptor expressed on myeloid cells 2, TNF, and C3, and the trajectory analysis suggested that these cells derived from the differentiation of infiltrating blood monocytes. Additionally, protein profiling of 21 progression and 28 nonprogression IgAN samples revealed that proteins CXCL12, C3, mannose receptor C-type 1, and CD163 were negatively correlated with estimated glomerular filtration rate (eGFR) value and poor prognosis (30% eGFR as composite end point). Last, a functional experiment revealed that specific blockade of the Cxcl12/Cxcr4 pathway substantially attenuated the glomerulus and tubule inflammatory injury, fibrosis, and renal function decline in the mouse IgAN model. This study provides insights into IgAN progression and may aid in the refinement of IgAN diagnosis and the optimization of treatment strategies.


Subject(s)
Disease Progression , Glomerulonephritis, IGA , Macrophages , Single-Cell Analysis , Adult , Animals , Female , Humans , Male , Mice , Rats , Chemokine CXCL12/metabolism , Disease Models, Animal , Glomerular Filtration Rate , Glomerulonephritis, IGA/immunology , Glomerulonephritis, IGA/pathology , Interleukins , Macrophages/immunology , Macrophages/metabolism , Mesangial Cells/pathology , Mesangial Cells/metabolism , Mesangial Cells/immunology , Receptors, CXCR4/metabolism , Receptors, CXCR4/genetics , Rats, Wistar
4.
Plant Physiol Biochem ; 212: 108741, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38772167

ABSTRACT

Wurfbainia villosa and Wurfbainia longiligularis are the two primary plant sources of Fructus Amomi, a traditional Chinese medicine. Both plants are rich in volatile terpenoids, including monoterpenes and sesquiterpenes, which are the primary medicinal components of Fructus Amomi. The trans-isopentenyl diphosphate synthase (TIDS) gene family plays a key part in determining terpenoid diversity and accumulation. However, the TIDS gene family have not been identified in W. villosa and W. longiligularis. This study identified thirteen TIDS genes in W. villosa and eleven TIDS genes in W. longiligularis, which may have expanded through segmental replication events. Based on phylogenetic analysis and expression levels, eight candidate WvTIDSs and five WlTIDSs were selected for cloning. Functional characterization in vitro demonstrated that four homologous geranyl diphosphate synthases (GPPSs) (WvGPPS1, WvGPPS2, WlGPPS1, WlGPPS2) and two geranylgeranyl diphosphate synthases (GGPPSs) (WvGGPPS and WlGGPPS) were responsible for catalyzing the biosynthesis of geranyl diphosphate (GPP), whereas two farnesyl diphosphate synthases (FPPSs) (WvFPPS and WlFPPS) catalysed the biosynthesis of the farnesyl diphosphate (FPP). A comparison of six proteins with identified GPPS functions showed that WvGGPPS and WlGGPPS exhibited the highest activity levels. These findings indicate that homologous GPPS and GGPPS together promote the biosynthesis of GPP in W. villosa and W. longiligularis, thus providing sufficient precursors for the synthesis of monoterpenes and providing key genetic elements for Fructus Amomi variety improvement and molecular breeding.

5.
Tree Physiol ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775221

ABSTRACT

Pinus armandii is an ecologically and economically important evergreen tree species native to western China. Dendroctonus armandi and pathogenic ophiostomatoid fungi pose substantial threats to P. armandii. With the interplay between species, the defense mechanisms of P. armandii have evolved to withstand external biotic stressors. However, the interactions between P. armandii and pathogenic ophiostomatoid fungal species/strains remain poorly understood. We aimed to analyze the pathophysiological and molecular changes in P. armandii following artificial inoculation with four ophiostomatoid species (Graphilbum parakesiyea, Leptographium qinlingense, Ophiostoma shennongense, and Ophiostoma sp. 1). The study revealed that L. qinlingense produced the longest necrotic lesions, and G. parakesiyea produced the shortest. All strains induced monoterpenoid release, and monoterpene levels of P. armandii were positively correlated with fungal virulence (R2 = 0.93, P < 0.01). Co-inoculation of two dominant highly (L. qinlingense) and weakly virulent (O. shennongense) pathogens reduced the pathogenicity of the highly virulent fungi. Transcriptomic analysis of P. armandii (LQ: L. qinlingense treatments, QS: co-inoculation treatments, and OS: O. shennongense treatments) showed that the expression pattern of differentially expressed genes (DEGs) between QS and OS was similar, but different from that of LQ. The DEGs (LQ vs. QS) involved in flavonoid biosynthesis and phenylpropanoid biosynthesis were downregulated. Notably, compared with LQ, QS significantly decreased the expression of host defense-related genes. This study provides a valuable theoretical basis for managing infestations of D. armandi and associated ophiostomatoid fungi.

6.
Reprod Biol Endocrinol ; 22(1): 57, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38769525

ABSTRACT

BACKGROUND: Primary Sjögren syndrome (pSS) is often related to adverse neonatal outcomes. But it's currently controversial whether pSS has an adverse effect on female fertility and clinical pregnancy condition. More importantly, it's unclear regarding the role of pSS in oocyte and embryonic development. There is a lack of comprehensive understanding and evaluation of fertility in pSS patients. OBJECTIVE: This study aimed to investigate oocyte and embryonic development, ovarian reserve, and clinical pregnancy outcomes in Primary Sjögren syndrome (pSS) patients during in vitro fertilization (IVF) treatment from multi-IVF centers. METHODS: We performed a muti-central retrospective cohort study overall evaluating the baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical pregnancy outcomes between the pSS patients and control patients who were matched by Propensity Score Matching. RESULTS: Following PSM matching, baseline characteristics generally coincided between the two groups. Ovarian reserve including anti-müllerian hormone (AMH) and antral follicle counting (AFC) were significantly lower in the pSS group vs comparison (0.8 vs. 2.9 ng/mL, P < 0.001; 6.0 vs. 10.0, P < 0.001, respectively). The pSS group performed significant reductions in numbers of large follicles, oocytes retrieved and MII oocytes. Additionally, pSS patients exhibited obviously deteriorate rates of oocyte maturation, 2PN cleavage, D3 good-quality embryo, and blastocyst formation compared to comparison. As for clinical pregnancy, notable decrease was found in implantation rate (37.9% vs. 54.9%, P = 0.022). The cumulative live birth rate (CLBR) following every embryo-transfer procedure was distinctly lower in the pSS group, and the conservative and optimal CLBRs following every complete cycle procedure were also significantly reduced in the pSS group. Lastly, the gestational weeks of the newborns in pSS group were distinctly early vs comparison. CONCLUSION: Patients with pSS exhibit worse conditions in terms of female fertility and clinical pregnancy, notably accompanied with deteriorate oocyte and embryo development. Individualized fertility evaluation and early fertility guidance are essential for these special patients.


Subject(s)
Fertility , Fertilization in Vitro , Pregnancy Outcome , Propensity Score , Sjogren's Syndrome , Humans , Female , Pregnancy , Adult , Pregnancy Outcome/epidemiology , Fertilization in Vitro/methods , Retrospective Studies , Sjogren's Syndrome/complications , Sjogren's Syndrome/epidemiology , Fertility/physiology , Ovarian Reserve/physiology , Pregnancy Rate , Infertility, Female/therapy , Infertility, Female/epidemiology , Infertility, Female/etiology
7.
Heliyon ; 10(10): e31094, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38778967

ABSTRACT

Climate change is a major global concern. Greenhouse gas emissions that cause global climate change are directly or indirectly affected by human activities. Individual low-carbon behaviors are crucial in reducing CO2 emissions and improving environmental and ecological health. To effectively promote individual low-carbon behavior, this study designed a questionnaire on the factors influencing individual low-carbon intentions and behavior based on theoretical models of environmental behavior. A total of 2430 valid questionnaires were collected in China. This study focuses on analyzing the impact of demographic characteristics, internal and external factors on individual low-carbon behaviors and their interrelationships. The research shows correlations between internal and external factors in determining low-carbon intention or behaviors. Internal factors-related low-carbon behavior is not closely linked with demographic variables, whereas the external factors-related low-carbon behavior vary significantly by age, residence, education, marital status, occupation, and income. The findings have important implications for designing effective policies to promote low-carbon behaviors, such as creating a more favorable external environment and increasing the use of policy tools for reducing CO2 emission.

8.
Front Psychol ; 15: 1348269, 2024.
Article in English | MEDLINE | ID: mdl-38746920

ABSTRACT

Introduction: The caring behavior of hospice nurses toward patients positively impacts their professional careers and significantly improves the quality of hospice services. A positive and supportive work environment may protect nurses against negative emotions that may affect the humanistic care they provide, and their job satisfaction. This study aimed to explore the impact of the nursing work environment on caring behavior. We also investigated the chain mediating effect of psychological capital and empathy on this relationship among Chinese hospice nurses. Methods: The Practice Environment Scale (PES), the Psychological Capital Questionnaire (PCQ), the Empathy Ability Scale for Hospice Nurses, and the Caring Behaviors Inventory (CBI) were used to survey 393 Chinese hospice nurses. SPSS 27.0 and Mplus 8.0 were used for statistical processing to analyze the mediating effects. Results: The nursing work environment positively predicted caring behavior. Furthermore, it was found that psychological capital and empathy jointly mediate the relationship between the nursing work environment and caring behavior. Conclusion: This study reveals how the nursing work environment affects the caring behavior of hospice nurses. Hospital managers need to provide hospice nurses with a favorable working environment from the perspective of positive psychology, continuously monitor their psychological state, improve their caring behavior, and provide references for developing intervention plans to promote the caring behavior of hospice nurses in the future.

9.
Sci Total Environ ; 931: 172938, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38703850

ABSTRACT

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.


Subject(s)
Cadmium , Mitochondria , Pyroptosis , Testis , Animals , Cadmium/toxicity , Male , Mice , Testis/drug effects , Testis/metabolism , Pyroptosis/drug effects , Mitochondria/metabolism , Mitochondria/drug effects , Environmental Pollutants/toxicity , Proteostasis , Mitochondrial Proteins/metabolism , Environmental Exposure/adverse effects , DNA, Mitochondrial , ATP-Dependent Proteases/metabolism , Proteotoxic Stress
10.
MedComm (2020) ; 5(5): e535, 2024 May.
Article in English | MEDLINE | ID: mdl-38741887

ABSTRACT

Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation-specific homologous factor (EHF), a member of the E26 transformation-specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma-associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor-associated macrophages (TAMs) through the C-C motif chemokine 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co-expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF-mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2-TAMs to inhibit EHF-driven CCA development.

11.
Heliyon ; 10(9): e30636, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38765161

ABSTRACT

Numerous research works have investigated the potential impact of endocrine hormones on the severity of COVID-19-related pneumonia in individuals. However, there are few studies on the effect of pre-onset neuroendocrine hormones on the prognosis of COVID-19 patients. This study looked into the prognostic value of pre-onset hair hormone levels in COVID-19 infected individuals. This study included 27 patients with COVID-19 and collected patient information and laboratory indicators. The hormone levels in hair were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Within 28 days, 63 % of the patients in this study passed away. With 28-day mortality as the outcome index, urea nitrogen, CURB-65 score and pneumonia severity score (PSI) of 2 groups were statistically significant (P < 0.05). Among all hormone levels detected in hair, only progesterone level was substantially correlated negatively with COVID-19 patients' 28-day mortality(P < 0.05). The level of progesterone in hair was substantially adversely connected with the death rate at 28 days of COVID-19 patients, according to correlation and logistic regression analysis(P < 0.05). Among patients with COVID-19 pneumonia, hair progesterone levels were strongly associated with 28-day mortality, which emphasizes hair progesterone's importance as a prognostic factor.

12.
J Pharm Anal ; 14(3): 295-307, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38618252

ABSTRACT

Triterpenoids widely exist in nature, displaying a variety of pharmacological activities. Determining triterpenoids in different matrices, especially in biological samples holds great significance. High-performance liquid chromatography (HPLC) has become the predominant method for triterpenoids analysis due to its exceptional analytical performance. However, due to the structural similarities among botanical samples, achieving effective separation of each triterpenoid proves challenging, necessitating significant improvements in analytical methods. Additionally, triterpenoids are characterized by a lack of ultraviolet (UV) absorption groups and chromophores, along with low ionization efficiency in mass spectrometry. Consequently, routine HPLC analysis suffers from poor sensitivity. Chemical derivatization emerges as an indispensable technique in HPLC analysis to enhance its performance. Considering the structural characteristics of triterpenoids, various derivatization reagents such as acid chlorides, rhodamines, isocyanates, sulfonic esters, and amines have been employed for the derivatization analysis of triterpenoids. This review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of triterpenoids. Moreover, the limitations and challenges encountered in previous studies are discussed, and future research directions are proposed to develop more effective derivatization methods.

13.
Nurs Open ; 11(4): e2150, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38629398

ABSTRACT

AIM: To explore factors promoting and hindering resilience in youth with inflammatory bowel disease (IBD) based on Kumpfer's resilience framework. DESIGN: A descriptive qualitative study design with an interpretative approach was used. METHODS: Participants consisted of 10 youths with IBD from a tertiary hospital in Beijing (China) recruited using the purposive sampling method. Data were collected by semi-structured interviews from December 2020 to March 2021. The directed content analysis was performed for data analysis. RESULTS: Both promoting factors and hindering factors could be divided into personal factors and environmental factors. Thirteen themes were identified. The promoting factors included acceptance of illness, strict self-management, previous treatment experience, life goals, family support, medical support and peer encouragement. Stigma, lack of communication, negative cognition, societal incomprehension, economic pressure and academic and employment pressure were hindering factors. CONCLUSION: Health care professionals need to develop greater awareness of factors, stemming from both the individual and the outside world, that hinder or promote resilience in order to aid young patients with IBD. Building targeted nursing measures to excavate the internal positive quality of patients, provide external support and promote the development of resilience.


Subject(s)
Inflammatory Bowel Diseases , Resilience, Psychological , Humans , Adolescent , Qualitative Research , Health Personnel , Inflammatory Bowel Diseases/therapy , China
14.
Chemosphere ; 357: 142030, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38626814

ABSTRACT

Male fertility has been declining in recent decades, and a growing body of research points to environmental and lifestyle factors as the cause. The widespread use of radiation technology may result in more people affected by male infertility, as it is well established that radiation can cause reproductive impairment in men. This article provides a review of radiation-induced damage to male reproduction, and the effects of damage mechanisms and pharmacotherapy. It is hoped that this review will contribute to the understanding of the effects of radiation on male reproduction, and provide information for research into drugs that can protect the reproductive health of males.


Subject(s)
Reproduction , Male , Humans , Reproduction/radiation effects , Reproduction/drug effects , Infertility, Male/prevention & control , Infertility, Male/etiology , Genitalia, Male/radiation effects , Animals
15.
Int J Biol Macromol ; 267(Pt 1): 131323, 2024 May.
Article in English | MEDLINE | ID: mdl-38574912

ABSTRACT

Sphingolipids serve as essential components of biomembrane and possess significant bioactive properties. Sphingosine-1-phophate (S1P) plays a key role in plant resistance to stress, but its specific impact on plant growth and development remains to be fully elucidated. Cotton fiber cells are an ideal material for investigating the growth and maturation of plant cells. In this study, we examined the content and composition of sphingosine (Sph) and S1P throughout the progression of fiber cell development. The content of S1P elevated gradually during fiber elongation but declined during the transition stage. Exogenous application of S1P promoted fiber elongation while using of FTY720 (an antagonist of S1P), and DMS (an inhibitor of LCBK) hindered fiber elongation. Cotton Long Chain Base Kinase 1 (GhLCBK1) was notably expressed during the fiber elongation stage, containing all conserved domains of LCBK protein and localized in the endoplasmic reticulum. Overexpression GhLCBK1 increased the S1P content and promoted fiber elongation while retarded secondary cell wall (SCW) deposition. Conversely, downregulation of GhLCBK1 reduced the S1P levels, and suppressed fiber elongation, and accelerated SCW deposition. Transcriptome analysis revealed that upregulating GhLCBK1 or applying S1P induced the expression of GhEXPANSIN and auxin related genes. Furthermore, the levels of IAA were elevated and reduced in the fibers when up-regulating or down-regulating GhLCBK1, respectively. Our investigation demonstrated that GhLCBK1 and its product S1P facilitated the elongation of fiber cells by affecting auxin biosynthesis. This study contributes novel insights into the intricate regulatory pathways involved in fiber cell elongation, identifying GhLCBK1 as a potential target gene and laying the groundwork for enhancing fiber quality via genetic manipulation.


Subject(s)
Gene Expression Regulation, Plant , Gossypium , Indoleacetic Acids , Lysophospholipids , Phosphotransferases (Alcohol Group Acceptor) , Sphingosine , Sphingosine/analogs & derivatives , Sphingosine/metabolism , Gossypium/genetics , Gossypium/metabolism , Phosphotransferases (Alcohol Group Acceptor)/metabolism , Phosphotransferases (Alcohol Group Acceptor)/genetics , Indoleacetic Acids/metabolism , Indoleacetic Acids/pharmacology , Gene Expression Regulation, Plant/drug effects , Lysophospholipids/metabolism , Cotton Fiber , Plant Proteins/metabolism , Plant Proteins/genetics , Cell Wall/metabolism , Cell Wall/drug effects
16.
Cell Rep ; 43(4): 114094, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38613784

ABSTRACT

The importance of trained immunity in antitumor immunity has been increasingly recognized, but the underlying metabolic regulation mechanisms remain incompletely understood. In this study, we find that squalene epoxidase (SQLE), a key enzyme in cholesterol synthesis, is required for ß-glucan-induced trained immunity in macrophages and ensuing antitumor activity. Unexpectedly, the shunt pathway, but not the classical cholesterol synthesis pathway, catalyzed by SQLE, is required for trained immunity induction. Specifically, 24(S),25-epoxycholesterol (24(S),25-EC), the shunt pathway metabolite, activates liver X receptor and increases chromatin accessibility to evoke innate immune memory. Meanwhile, SQLE-induced reactive oxygen species accumulation stabilizes hypoxia-inducible factor 1α protein for metabolic switching into glycolysis. Hence, our findings identify 24(S),25-EC as a key metabolite for trained immunity and provide important insights into how SQLE regulates trained-immunity-mediated antitumor activity.


Subject(s)
Mice, Inbred C57BL , Squalene Monooxygenase , Animals , Squalene Monooxygenase/metabolism , Mice , Cholesterol/metabolism , Cholesterol/biosynthesis , Cholesterol/analogs & derivatives , Liver X Receptors/metabolism , Macrophages/metabolism , Macrophages/immunology , Macrophages/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Reactive Oxygen Species/metabolism , Immunity, Innate/drug effects , Humans , Cell Line, Tumor
17.
Sci Total Environ ; 928: 172345, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38621537

ABSTRACT

Fine particulate matter (PM2.5) causes millions of premature deaths each year worldwide. Oxidative potential (OP) has been proposed as a better metric for aerosol health effects than PM2.5 mass concentration alone. In this study, we report for the first time online measurements of PM2.5 OP in wintertime Beijing and surroundings based on a dithiothreitol (DTT) assay. These measurements were combined with co-located PM chemical composition measurements to identify the main source categories of aerosol OP. In addition, we highlight the influence of two distinct pollution events on aerosol OP (spring festival celebrations including fireworks and a severe regional dust storm). Source apportionment coupled with multilinear regression revealed that primary PM and oxygenated organic aerosol (OOA) were both important sources of OP, accounting for 41 ± 12 % and 39 ± 10 % of the OPvDTT (OP normalized by the sampled air volume), respectively. The small remainder was attributed to fireworks and dust, mainly resulting from the two distinct pollution events. During the 3.5-day spring festival period, OPvDTT spiked to 4.9 nmol min-1 m-3 with slightly more contribution from OOA (42 ± 11 %) and less from primary PM (31 ± 15 %). During the dust storm, hourly-averaged PM2.5 peaked at a very high value of 548 µg m-3 due to the dominant presence of dust-laden particles (88 % of total PM2.5). In contrast, only mildly elevated OPvDTT values (up to 1.5 nmol min-1 m-3) were observed during this dust event. This observation indicates that variations in OPvDTT cannot be fully explained using PM2.5 alone; one must also consider the chemical composition of PM2.5 when studying aerosol health effects. Our study highlights the need for continued pollution control strategies to reduce primary PM emissions, and more in-depth investigations into the source origins of OOA, to minimize the health risks associated with PM exposure in Beijing.

18.
Comput Biol Med ; 174: 108446, 2024 May.
Article in English | MEDLINE | ID: mdl-38631118

ABSTRACT

OBJECTIVE: Depression and anxiety, prevalent coexisting mood disorders, pose a clinical challenge in accurate differentiation, hindering effective healthcare interventions. This research addressed this gap by employing a streamlined Symptom Checklist 90 (SCL-90) designed to minimize patient response burden. Utilizing machine learning algorithms, the study sought to construct classification models capable of distinguishing between depression and anxiety. METHODS: The study included 4262 individuals currently experiencing depression alone (n = 2998), anxiety alone (n = 716), or both depression and anxiety (n = 548). Counterfactual diagnosis was used to construct a causal network on the dataset. Employing a causal network, the SCL-90 was simplified. Items that have causality with only depression, only anxiety and both depression and anxiety were selected, and these streamlined items served as input features for four distinct machine learning algorithms, facilitating the creation of classification models for distinguishing depression and anxiety. RESULTS: Cross-validation demonstrated the performance of the classification models with the following metrics: (1) K-nearest neighbors (AUC = 0.924, Acc = 92.81 %); (2) support vector machine (AUC = 0.937, Acc = 94.38 %); (3) random forest (AUC = 0.918, Acc = 94.38 %); and (4) adaptive boosting (AUC = 0.882, Acc = 94.38 %). Notably, the support vector machine excelled, with the highest AUC and superior accuracy. CONCLUSION: Incorporating the simplified SCL-90 and machine learning presents a promising, efficient, and cost-effective tool for the precise identification of depression and anxiety.


Subject(s)
Anxiety , Depression , Machine Learning , Humans , Female , Male , Adult , Depression/diagnosis , Anxiety/diagnosis , Middle Aged , Anxiety Disorders/diagnosis
19.
Sci Total Environ ; 930: 172735, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38663624

ABSTRACT

Existing studies on ventilation in closed spaces mainly considered the average inlet velocity and ignored the influence of inlet turbulent fluctuation. However, the variation in inlet turbulence intensity (TI) is considerable and significantly affects the dispersion of contaminants. This study conducts numerical simulations verified by experiments to investigate the effect of the inlet TI on train contaminants dispersion and analyze infection probability variation. Firstly, the unsteady Reynolds-averaged Navier-Stokes (URANS) method and improved delayed detached eddy simulation (IDDES) method are compared in simulating the internal airflow characteristics based on the on-site measurement. The results indicate that the latter dominates in capturing airflow pulsations more than the former, although the mean airflow results obtained from both methods agree well with experimental results. Furthermore, the IDDES method is employed to investigate the effect of the inlet TI on contaminant dispersion, and the infection risks are also assessed using the improved probability model. The results show that, with the increase of TI from 5 % to 30 %, the contaminant removal grows considerably, with the removal index rising from 0.23 to 1.86. The increased TI leads to the overall and local infection risks of occupants descending significantly, wherein the former decreases from 1.53 % to 0.88 % with a reduction rate of 42 %, and the latter drops from 3.30 % to 2.16 % with a mitigation rate of 35 %. The findings can serve as solid guidelines for numerical method selection in accurately capturing the indoor dynamic airflow distribution and for the ventilation parameters design regarding TI inside trains to mitigate the airborne infection risk.

20.
J Agric Food Chem ; 72(18): 10376-10390, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38661058

ABSTRACT

20(S)-Protopanaxadiol (PPD) is one of the bioactive ingredients in ginseng and possesses neuroprotective properties. Brain-type creatine kinase (CK-BB) is an enzyme involved in brain energy homeostasis via the phosphocreatine-creatine kinase system. We previously identified PPD as directly bound to CK-BB and activated its activity in vitro. In this study, we explored the antidepressive effects of PPD that target CK-BB. First, we conducted time course studies on brain CK-BB, behaviors, and hippocampal structural plasticity responses to corticosterone (CORT) administration. Five weeks of CORT injection reduced CK-BB activity and protein levels and induced depression-like behaviors and hippocampal structural plasticity impairment. Next, a CK inhibitor and an adeno-associated virus-targeting CKB were used to diminish CK-BB activity or its expression in the brain. The loss of CK-BB in the brain led to depressive behaviors and morphological damage to spines in the hippocampus. Then, a polyclonal antibody against PPD was used to determine the distribution of PPD in the brain tissues. PPD was detected in the hippocampus and cortex and observed in astrocytes, neurons, and vascular endotheliocytes. Finally, different PPD doses were used in the chronic CORT-induced depression model. Treatment with a high dose of PPD significantly increased the activity and expression of CK-BB after long-term CORT injection. In addition, PPD alleviated the damage to depressive-like behaviors and structural plasticity induced by repeated CORT injection. Overall, our study revealed the critical role of CK-BB in mediating structural plasticity in CORT-induced depression and identified CK-BB as a therapeutic target for PPD, allowing us to treat stress-related mood disorders.


Subject(s)
Antidepressive Agents , Corticosterone , Creatine Kinase, BB Form , Depression , Disease Models, Animal , Hippocampus , Sapogenins , Animals , Sapogenins/pharmacology , Corticosterone/adverse effects , Male , Antidepressive Agents/pharmacology , Antidepressive Agents/administration & dosage , Depression/chemically induced , Depression/drug therapy , Depression/metabolism , Mice , Humans , Hippocampus/drug effects , Hippocampus/metabolism , Creatine Kinase, BB Form/metabolism , Creatine Kinase, BB Form/genetics , Panax/chemistry , Rats , Mice, Inbred C57BL , Rats, Sprague-Dawley , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Brain/metabolism , Brain/drug effects
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