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1.
Artigo em Inglês | MEDLINE | ID: mdl-38568311

RESUMO

Layered double hydroxides (LDH) hold great promise as phosphate adsorbents; however, the conventional binary LDH exhibits low adsorption rate and adsorption capacity. In this study, Mg and La were chosen as binary metals in the synthesis of Mg-La LDH to enhance phosphate efficient adsorption. Different molar ratios of Mg to La (2:1, 3:1, and 4:1) were investigated to further enhance P adsorption. The best performing Mg-La LDH, with Mg to La ratio is 4:1 (LDH-4), presented a larger adsorption capacity and faster adsorption rate than other Mg-La LDH. The maximum adsorption capacity (87.23 mg/g) and the rapid adsorption rate in the initial 25 min of LDH-4 (70 mg/(g·h)) were at least 1.6 times and 1.8 times higher than the others. The kinetics, isotherms, the effect of initial pH and co-existing anions, and the adsorption-desorption cycle experiment were studied. The batch experiment results proved that the chemisorption progress occurred on the single-layered LDH surface and the optimized LDH exhibited strong anti-interference capability. Furthermore, the structural characteristics and adsorption mechanism were further investigated by SEM, BET, FTIR, XRD, and XPS. The characterization results showed that the different metal ratios could lead to changes in the metal hydroxide layer and the main ions inside. At lower Mg/La ratios, distortion occurred in the hydroxide layer, resulting in lower crystallinity and lower performance. The characterization results also proved that the main mechanisms of phosphate adsorption are electrostatic adsorption, ion exchange, and inner-sphere complexation. The results emphasized that the Mg-La LDH was efficient in phosphate removal and could be successfully used for this purpose.

2.
Heliyon ; 10(7): e28304, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38571656

RESUMO

Background: The aim of this study was to assess whether intravenous dexamethasone was noninferior to perineural dexamethasone as an adjuvant to ropivacaine for a combination of saphenous and sciatic nerve blocks in patients undergoing foot and ankle surgery. Methods: This was a prospective, blinded, randomized noninferiority study. Seventy-five patients, aged 18-75 years, with an American Society of Anesthesiologists (ASA) physical status I-III who underwent foot and ankle surgery were involved. Patients scheduled for ultrasound-guided popliteal sciatic nerve block and saphenous nerve block were randomized to receive 0.375% ropivacaine with 7.5 mg of dexamethasone perineurally (Dex-PN), 10 mg of dexamethasone intravenously (Dex-IV) or neither (Placebo). The primary outcome was the duration of analgesia. The major secondary outcomes were the composite pain intensity and opioid consumption score at 0-48 h intervals after anesthesia. Results: The mean analgesic duration was 26.2 h in the Dex-IV group and 27.9 h in the Dex-PN group (duration difference, -1.7; 95% CI, -3.8 to 0.43; P = 0.117), and both durations were significantly longer than that in the placebo group (17.6 h, P < 0.001). Conditions for establishing non-inferiority were met. Conclusions: Our findings indicate that a single 10-mg intravenous dose of dexamethasone was noninferior to the combined dose of ropivacaine plus deaxmethasone in terms of duration of analgesia for foot and ankle surgery.

3.
Sci Total Environ ; 928: 172542, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636860

RESUMO

Household-related microbiome is closely related with human health. However, the knowledge about profiles of antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) which are carried by microbes inside homes and their temporal dynamics are rather limited. Here we monitored the seasonal changes of bacterial community (especially pathogenic bacteria), ARGs, and VFGs in household dust samples during two years. Based on metagenomic sequencing, the dust-related bacterial pathogenic community, ARGs, and VFGs all harbored the lowest richness in spring among four seasons. Their structure (except that of VFGs) also exhibited remarkable differences among the seasons. The structural variations of ARGs and VFGs were almost explained by mobile genetic elements (MGEs), bacterial pathogens, and particulate matter-related factors, with MGEs explaining the most. Moreover, the total normalized abundance of ARGs or VFGs showed no significant change across the seasons. Results of metagenomic binning and microbial network both showed that several pathogenic taxa (e.g., Ralstonia pickettii) were strongly linked with numerous ARGs (mainly resistant to multidrug) and VFGs (mainly encoding motility) simultaneously. Overall, these findings underline the significance of MGEs in structuring ARGs and VFGs inside homes along with seasonal variations, suggesting that household dust is a neglected reservoir for ARGs and VFGs.

4.
J Colloid Interface Sci ; 667: 22-31, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38615620

RESUMO

Recently, there has been a significant increase in interest in using photocatalysis for the energy conversion of polluting gases. In this research, sodium and ruthenium bimetallic functional sites co-modified bismuth tungstate (Ru/Na-Bi2WO6) nanoflower photocatalyst was synthesized via the hydrothermal method. The CO2 reduction products on the Bi2WO6 substrate were CO (1.66 µmol/g/h, 68 %) and CH4 (0.78 µmol/g/h, 32 %). After optimization, a significant change in the CO2 products of the Bi2WO6-based composite material was observed, with CO (0.61 µmol/g/h, 3.6 %) and CH4 (16.1 µmol/g/h, 96.4 %). Results showed that the dominance of CH4 as the main product in the Ru/Na-BWO system is attributed to the effective doping of Na, which generates impurity energy levels composed of oxygen vacancies, lowering the conduction band position of Bi2WO6, thereby suppressing CO generation, and enhancing CH4 selectivity by changing the CO2 activation pathway. The remarkable performance is ascribed to the synergized adsorption and activation of CO2 by the tandem Na+ sites and Ru0 sites. Specifically, the doped Na+ sites play a major role in promoting the adsorption CO2 molecules, while the Ru0 sites play a dominant role in facilitating the activation of the intermediates.

5.
Heliyon ; 10(7): e28629, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38590883

RESUMO

Objectives: The present study was conducted to explore the performance of micronutrients in the prediction and prevention of coronavirus disease 2019 (COVID-19). Methods: This is an observational case-control study. 149 normal controls (NCs) and 214 COVID-19 patients were included in this study. Fat-soluble and water-soluble vitamins were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and inorganic elements were detected by inductively coupled plasma-mass spectrometry (ICP-MS) analysis. A logistic regression model based on six micronutrients were constructed using DxAI platform. Results: Many micronutrients were dysregulated in COVID-19 compared to normal control (NC). 25-Hydroxyvitamin D3 [25(OH)D3], magnesium (Mg), copper (Cu), calcium (Ca) and vitamin B6 (pyridoxic acid, PA) were significantly independent risk factors for COVID-19. The logistic regression model consisted of 25(OH)D3, Mg, Cu, Ca, vitamin B5 (VB5) and PA was developed, and displayed a strong discriminative capability to differentiate COVID-19 patients from NC individuals [area under the receiver operating characteristic curve (AUROC) = 0.901]. In addition, the model had great predictive ability in discriminating mild/normal COVID-19 patients from NC individuals (AUROC = 0.883). Conclusions: Our study showed that micronutrients were associated with COVID-19, and our logistic regression model based on six micronutrients has potential in clinical management of COVID-19, and will be useful for prediction of COVID-19 and screening of high-risk population.

6.
Int Wound J ; 21(4): e14867, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38597295

RESUMO

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.


Assuntos
Diabetes Mellitus Experimental , Oxigenoterapia Hiperbárica , Humanos , Animais , Camundongos , Cicatrização/fisiologia , Diabetes Mellitus Experimental/terapia , Células Endoteliais da Veia Umbilical Humana , Tecido Adiposo Branco
7.
Gastroenterol. hepatol. (Ed. impr.) ; 47(4): 352-365, Abr. 2024. tab, graf
Artigo em Inglês | IBECS | ID: ibc-231802

RESUMO

Background: The leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays an important role in stem cell differentiation, organ development and cancer. Whether LGR4 affects the progression of hepatocellular carcinoma (HCC) remains unknown. This study aimed to reveal the role of LGR4 in HCC. Methods: Clinical samples of HCC were collected to assess the expression of LGR4 and its correlation with patients’ clinical characteristics. The expression level of LGR4 in HCC cells was altered by pharmacological and genetic methods, and the role of LGR4 in HCC progression was analyzed by in vivo and in vitro assays. HCC was induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) in wild-type and LGR4 deficient mice, the effect of LGR4 on HCC was examined by histopathological evaluation and biochemical assays. Results: LGR4 expression was up-regulated in HCC samples, and its expression level was positively correlated with tumor size, microvascular invasion (MVI), TNM stage and pathological differentiation grade of HCC patients. In the mouse HCC model induced by DEN+CCl4, knockdown of LGR4 effectively inhibited the progression of HCC. Silencing of LGR4 inhibited the proliferation, migration, invasion, stem cell-like properties and Warburg effect of HCC cells. These phenotypes were promoted by R-spondin2 (Rspo2), an endogenous ligand for LGR4. Rspo2 markedly increased the nuclear translocation of β-catenin, whereas IWR-1, an inhibitor of Wnt/β-catenin signaling, reversed its effect. Deficiency of LGR4 significantly reduced the nuclear translocation of β-catenin and the expression of its downstream target genes cyclinD1 and c-Myc. Conclusions: LGR4 promotes HCC progression via Wnt/β-catenin signaling pathway. (AU)


Antecedentes: El receptor de acoplamiento de proteínas G de secuencia repetida 4 (LGR4), rico en leucina, juega un papel importante en la diferenciación de células madre, el desarrollo de órganos y el cáncer. Se desconoce si LGR4 afecta la progresión del carcinoma hepatocelular (HCC). El objetivo de este estudio es revelar el papel de LGR4 en el HCC. Métodos: Se recolectaron muestras clínicas de HCC para evaluar la expresión de LGR4 y su correlación con los resultados clínicos de HCC. Alterar los niveles de expresión de LGR4 en las células de HCC mediante métodos farmacológicos y genéticos y analizar el papel de LGR4 en la progresión del cáncer de hígado mediante mediciones in vivo e in vitro. El HCC fue inducido en ratones de tipo salvaje y con defectos de LGR4 con Nitrosamina de dietilo (DEN) y cloruro de carbono (CCl4), y los efectos de LGR4 sobre el HCC fueron detectados por evaluación histopatológica y determinación bioquímica. Resultados: La expresión de LGR4 está regulada en HCC, y su nivel de expresión está positivamente relacionado con el tamaño tumoral, la infiltración microvascular (MVI), la etapa de TNM y el grado de diferenciación patológica en pacientes con HCC. En el modelo de HCC de ratón inducido por DEN+CCl4, golpear bajo LGR4 inhibió efectivamente la progresión del HCC. El silencio de LGR4 inhibe la proliferación, migración, invasión, propiedades similares a las células madre y el efecto Warburg de las células HCC. Estos fenotipos son promovidos por el ligando endógeno roof slab-specific sponge 2 (Rspo2)de LGR4. El Rspo2 aumentó significativamente la translocación nuclear de la proteína beta-catenina, mientras que el inhibidor de la señalización Wnt/beta-cateninaIWR-1 revirtió su acción... (AU)


Assuntos
Leucina , Células-Tronco , Neoplasias , Carcinoma Hepatocelular
8.
Chemotherapy ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38508148

RESUMO

Introduction With the increasing use of Blinatumomab in relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), including MRD-positive cases, awareness of its adverse effects has gradually improved. Pneumocystis jiroveci pneumonia (PCP) associated with Blinatumomab therapy is rare. Case Presentation We present a case of PCP in a patient undergoing Blinatumomab therapy. A 70-year-old female diagnosed with Philadelphia-like, CRLF2 overexpression B-cell precursor ALL received Blinatumomab as consolidation therapy after achieving complete remission with prior induction chemotherapy. On the second day of Blinatumomab infusion, she developed intermittent low-grade fever, and chest computed tomography revealed subtle infiltrates and nodules. Despite empiric trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, she progressed to significant shortness of breath and type I respiratory failure, with increased lactate dehydrogenase and ß-D-glucan assays. Chest computed tomography showed diffuse ground-glass opacities with scattered small nodules. The dry cough prompted next-generation sequencing of peripheral blood, which tested positive for pneumocystis jiroveci without evidence of other pathogens. Consequently, the patient was diagnosed with PCP. The first cycle of Blinatumomab had to be discontinued, and therapeutic dosages of TMP-SMX and dexamethasone were administered, resulting in full recovery and stable condition during follow-ups. Conclusion PCP is rare in B-cell precursor ALL patients receiving Blinatumomab therapy but manifests with early onset and rapid disease progression. Despite prophylaxis, PCP infection cannot be ignored during Blinatumomab therapy. Therefore, heightened attention is warranted when using Blinatumomab therapy.

9.
BMC Health Serv Res ; 24(1): 375, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532406

RESUMO

BACKGROUND: The clinical outcomes of diabetes can be influenced by primary care providers' (PCP) treatment approaches. This study explores the association between PCP approaches to management and performance measured by established diabetes metrics and related costs. METHODS: In phase one, Electronic Medical Records were used to extract diabetes related metrics using Healthcare Effectiveness Data and Information Set (HEDIS), for patients with diabetes who had office visits to 44 PCP practices from April 2019 to March 2020. Using those metrics and scoring system, PCP practices were ranked and then categorized into high- and low-performing groups (top and bottom 25%, n = 11 each), with a total of 19,059 clinic visits by patients with a diagnosis of diabetes. Then extensive analysis was performed to evaluate a correlation between treatment approaches and diabetes outcomes across the top and bottom performing practices. In phase 2, patients with diabetes who were attributed to the aforementioned PCP practices were identified in a local health plan claims data base (a total of 3,221 patients), and the allowed amounts from their claims were used to evaluate differences in total and diabetes-related healthcare costs by providers' performance. RESULTS: Comparing 10,834 visits in high-performing practices to 8,235 visits in low-performing practices, referrals to certified diabetes care and education specialists and provider-to-provider electronic consults (e-consults) were higher in high-performing practices (Z = 6.06, p < .0001), while traditional referrals were higher in low-performing practices (Z = -6.94, p < .0001). The patient-to-provider ratio was higher in the low-performing group (M = 235.23) than in the high-performing group (M = 153.26) (Z = -2.82, p = .0048). Claims data analysis included 1,825 and 1,396 patients from high- and low-performing providers, respectively. The patient-to-provider ratio was again higher in the low-performing group (p = .009, V = 0.62). Patients receiving care from lower-performing practices were more likely to have had a diabetes-related hospital observation (5.7% vs. 3.9%, p = .02; V = 0.04) and higher diabetes-related care costs (p = .002; d = - 0.07); these differences by performance status persisted when controlling for differences in patient and physician characteristics. Patients seeing low-performing providers had higher Charlson Comorbidity Index scores (Mdn = 3) than those seeing high-performing providers (Mdn = 2). CONCLUSIONS: Referrals to the CDCES and e-Consult were associated with better measured diabetes outcomes, as were certain aspects of cost and types of hospital utilization. Higher patients to providers ratio and patients with more comorbidities were observed in low performing group.


Assuntos
Diabetes Mellitus , Humanos , Atenção à Saúde , Custos de Cuidados de Saúde , Benchmarking
10.
Heliyon ; 10(5): e27369, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38486774

RESUMO

Background: Heart rate, as the four vital signs of human body, is a basic indicator to measure a person's health status. Traditional electrocardiography (ECG) measurement, which is routinely monitored, requires subjects to wear lead electrodes frequently, which undoubtedly places great restrictions on participants' activities during the normal test. At present, the boom of wearable devices has created hope for non-invasive, simple operation and low-cost daily heart rate monitoring, among them, Ballistocardiogram signal (BCG) is an effective heart rate measurement method, but in the actual acquisition process, the robustness of non-invasive vital sign collection is limited. Therefore, it is necessary to develop a method to improve the robustness of heart rate monitoring. Objective: Therefore, in view of the problem that the accuracy of untethered monitoring heart rate is not high, we propose a method aimed at detecting the heartbeat cycle based on BCG to accurately obtain the beat-to-beat heart rate in the sleep state. Methods: In this study, we implement an innovative J-wave detection algorithm based on BCG signals. By collecting BCG signals recorded by 28 healthy subjects in different sleeping positions, after preprocessing, the data feature set is formed according to the clustering of morphological features in the heartbeat interval. Finally, a J-wave recognition model is constructed based on bi-directional long short-term memory (BiLSTM), and then the number of J-waves in the input sequence is counted to realize real-time detection of heartbeat. The performance of the proposed heartbeat detection scheme is cross-verified, and the proposed method is compared with the previous wearable device algorithm. Results: The accuracy of J wave recognition in BCG signal is 99.67%, and the deviation rate of heart rate detection is only 0.27%, which has higher accuracy than previous wearable device algorithms. To assess consistency between method results and heart rates obtained by the ECG, seven subjects are compared using Bland-Altman plots, which show no significant difference between BCG and ECG results for heartbeat cycles. Conclusions: Compared with other studies, the proposed method is more accurate in J-wave recognition, which improves the accuracy and generalization ability of BCG-based continuous heartbeat cycle extraction, and provides preliminary support for wearable-based untethered daily monitoring.

11.
Int J Mol Sci ; 25(6)2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38542373

RESUMO

The glycoside hydrolase 13 (GH13) family is crucial for catalyzing α-glucoside linkages, and plays a key role in plant growth, development, and stress responses. Despite its significance, its role in plants remains understudied. This study targeted four GH13 subgroups in wheat, identifying 66 GH13 members from the latest wheat database (IWGSC RefSeq v2.1), including 36 α-amylase (AMY) members, 18 1,4-α-glucan-branching enzyme (SBE) members, 9 isoamylase (ISA) members, and 3 pullulanase (PU) members. Chromosomal distribution reveals a concentration of wheat group 7 chromosomes. Phylogenetic analysis underscores significant evolutionary distance variations among the subgroups, with distinct molecular structures. Replication events shaped subgroup evolution, particularly in regard to AMY members. Subcellular localization indicates AMY member predominance in extracellular and chloroplast regions, while others localize solely in chloroplasts, confirmed by the heterologous expression of TaSEB16 and TaAMY1 in tobacco. Moreover, 3D structural analysis shows the consistency of GH13 across species. Promoter cis-acting elements are suggested to be involved in growth, stress tolerance, and starch metabolism signaling. The RNA-seq data revealed TaGH13 expression changes under drought and submergence stress, and significant expression variation was observed between strong and weak gluten varieties during seed germination using quantitative real-time PCR (qRT-PCR), correlating with seed starch content. These findings demonstrate the pivotal role of GH13 family gene expression in wheat germination, concerning variety preference and environmental stress. Overall, this study advances the understanding of wheat GH13 subgroups, laying the groundwork for further functional studies.


Assuntos
Genoma de Planta , Triticum , Triticum/metabolismo , Filogenia , Glicosídeo Hidrolases/metabolismo , Amido/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Família Multigênica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
12.
BMC Psychol ; 12(1): 178, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549177

RESUMO

As the implementers of government policies, junior civil servants bear the responsibility of providing services to the public. Whether they can put themselves in the people's shoes and show more active service consciousness directly reflects the government's management ability and the realization of service-oriented government goals. Although proactive service behavior has been studied, it has not been brought into the field of government administration. Hence, from the perspective of servant leadership, this study attempts to introduce proactive service behavior (PSB) into the field of government administration, and discusses the promotion strategies of junior civil servants' PSB in China. Through the statistical analysis of 416 junior civil servants collected in the two stages, this study verifies that servant leadership has a significant positive impact on public service motivation and PSB of junior civil servants. Public service motivation (PSM) can partially mediate the promotion effect of servant leadership on junior civil servants' PSB. Role identity can positively moderate the relationship between servant leadership and junior civil servants' PSM, and then affect their PSB. Therefore, this study suggests that leading cadres should integrate servant leadership into daily life, take the lead in providing quality services to their subordinates, and then inspire more proactive service to the masses.


Assuntos
Liderança , Comportamento Social , Humanos , China
13.
Plant Physiol ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431527

RESUMO

Black goji berry (Lycium ruthenicum Murray) contains a rich source of health-promoting anthocyanins which are used in herbal medicine and nutraceutical foods in China. A natural variant producing white berries allowed us to identify two key genes involved in the regulation of anthocyanin biosynthesis in goji berries: one encoding a MYB transcription factor (LrAN2-like) and one encoding a basic helix-loop-helix (bHLH) transcription factor (LrAN1b). We previously found that LrAN1b expression was lost in the white berry variant, but the molecular basis for this phenotype was unknown. Here, we identified the molecular mechanism for loss of anthocyanins in white goji berries. In white goji, the LrAN1b promoter region has a 229-bp deletion that removes 3 MYB-binding elements and 1 bHLH-binding element, which are key to its expression. Complementation of the white goji berry LrAN1b allele with the LrAN1b promoter restored pigmentation. Virus-induced gene silencing of LrAN1b in black goji berry reduced fruit anthocyanin biosynthesis. Molecular analyses showed that LrAN2-like and another bHLH transcription factor LrJAF13 can activate LrAN1b by binding directly to the MYB-recognizing element (MRE) and bHLH-recognizing element (BRE) of its promoter-deletion region. LrAN1b expression is enhanced by the interaction of LrAN2-like with LrJAF13 and the WD40 protein LrAN11. LrAN2-like and LrAN11 interact with either LrJAF13 or LrAN1b to form two MYB-bHLH-WD40 (MBW) complexes, which hierarchically regulate anthocyanin biosynthesis in black goji berry. This study on a natural variant builds a comprehensive anthocyanin regulatory network that may be manipulated to tailor goji berry traits.

14.
Am J Physiol Gastrointest Liver Physiol ; 326(4): G460-G472, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38440827

RESUMO

Current therapy for hepatic injury induced by the accumulation of bile acids is limited. Leucine-rich repeat G protein-coupled receptor 4 (LGR4), also known as GPR48, is critical for cytoprotection and cell proliferation. Here, we reported a novel function for the LGR4 in cholestatic liver injury. In the bile duct ligation (BDL)-induced liver injury model, hepatic LGR4 expression was significantly downregulated. Deficiency of LGR4 in hepatocytes (Lgr4LKO) notably decreased BDL-induced liver injury measured by hepatic necrosis, fibrosis, and circulating liver enzymes and total bilirubin. Levels of total bile acids in plasma and liver were markedly reduced in these mice. However, deficiency of LGR4 in macrophages (Lyz2-Lgr4MKO) demonstrated no significant effect on liver injury induced by BDL. Deficiency of LGR4 in hepatocytes significantly attenuated S1PR2 and the phosphorylation of protein kinase B (AKT) induced by BDL. Recombinant Rspo1 and Rspo3 potentiated the taurocholic acid (TCA)-induced upregulation in S1PR2 and phosphorylation of AKT in hepatocytes. Inhibition of S1PR2-AKT signaling by specific AKT or S1PR2 inhibitors blocked the increase of bile acid secretion induced by Rspo1/3 in hepatocytes. Our studies indicate that the R-spondins (Rspos)-LGR4 signaling in hepatocytes aggravates the cholestatic liver injury by potentiating the production of bile acids in a S1PR2-AKT-dependent manner.NEW & NOTEWORTHY Deficiency of LGR4 in hepatocytes alleviates BDL-induced liver injury. LGR4 in macrophages demonstrates no effect on BDL-induced liver injury. Rspos-LGR4 increases bile acid synthesis and transport via potentiating S1PR2-AKT signaling in hepatocytes.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Colestase , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fígado/metabolismo , Colestase/complicações , Colestase/metabolismo , Hepatócitos/metabolismo , Ácidos e Sais Biliares/metabolismo , Ductos Biliares/metabolismo , Ligadura , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
15.
Sci Total Environ ; 923: 171427, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38432362

RESUMO

Earthworms play vital functions affecting plant growth and metal accumulation from downground to aboveground. Soil metal mobilization may be combined with use of earthworm and hyperaccumulator-Solanum nigrum to improve its remediation efficiency. Understanding the effects of specific-species earthworm belonging to different ecological categories on mechanisms underlying of S. nigrum is critical for metal-polluted remediation. However, seldom studies concerned earthworm-assisted phytoremediation of metal contaminated soil in Northern China. This study investigated the effects of earthworm (Eisenia fetida, Amynthas hupeiensis and Drawida gisti) on S. nigrum with exposure to uncontaminated and [Cd-As-Cu-Pb]-contaminated soil (referred to as S0 and S1) for 60 days, respectively. In S1 soil, A. hupeiensis (anecic) had stronger effects on growth and metal accumulation in the organs (root, stem, and leaf) of S. nigrum than D. gisti (endogeic) and E. fetida (epigeic), attributing to their ecological category. The BAF values of S. nigrum were generally ranking in Cd (0.66-5.13) > As (0.03-1.85) > Cu (0.03-0.06) > Pb (0.01-0.05); the BAFCd values were ranking in leaf (2.34-5.13) > root (1.96-4.14) > stem (0.66-1.33); BAFAs, BAFCu, and BAFPb were root (0.04-1.63) > stem (0.01-0.09) ≈ leaf (0.01-0.06). A. hupeiensis decreased the TF values of S. nigrum from the roots to the shoots. Co-effects of metal stress and earthworm activity on metal uptake by shoots suggested that A. hupeiensis increased the uptake of As, Cu, and Pb (by 56.3 %, 51.5 %, and 16.2 %, p < 0.05), but not Cd, which appeared to remain steady for prolonged durations. Alterations in the integrated biomarker response index version 2 (IBRv2) values demonstrated that A. hupeiensis (12.65) improved the resistance capacity (stimulated GSH, SnGS1, and SnCu-SOD) of S. nigrum under metal-containing conditions, compared with E. fetida and D. gisti (IBRv2 were 9.61 and 9.11). This study may provide insights into the patterns of 'soil-earthworm-plant system' on improving remediation efficiency of S. nigrum, from the perspective of earthworm ecological niche partitioning.


Assuntos
Oligoquetos , Poluentes do Solo , Solanum nigrum , Animais , Cádmio/análise , Oligoquetos/fisiologia , Solanum nigrum/metabolismo , Chumbo/metabolismo , Poluentes do Solo/análise , China , Solo , Biodegradação Ambiental
16.
Am J Transl Res ; 16(2): 466-476, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463575

RESUMO

OBJECTIVE: To analyze the clinical features, diagnosis and treatment and prognosis of the rare hairy cell leukemia (HCL), in order to provide new references for the clinical and basic research of HCL. METHODS: The clinical data of 17 patients with HCL admitted to Fujian Medical University Union Hospital, the Affiliated Hospital of Putian University and the First Affiliated Hospital of Gannan Medical University from January 1, 2016 to July 1, 2023 were collected and retrospectively studied, and the clinical features, diagnosis and treatment effects and prognosis of patients with HCL were analyzed. The Kaplan-Meier method was used for survival analysis. Meanwhile, the latest literature from PubMed was retrieved to systematically discuss the research progress in the diagnosis and treatment of HCL. RESULTS: In this study, there were 11 males and 6 females, the median age at diagnosis was 59.5 (30-81) years old, and the median time from the onset of clinical symptoms or signs to diagnosis was 4.5 (0.5-28.5) months. There were 9 cases (52.94%) with lymphoma B symptoms (fever, night sweating, and weight loss), 15 cases (88.24%) were accompanied by splenomegaly (3 cases of mild splenomegaly, 4 cases of moderate splenomegaly, and 8 cases of megasplenomegaly), the positive rate of BRAFV600E mutation is 76.47% (13/17). All patients in this study were treated, of which 11 were treated with Cladribine, 3 with Interferon, 2 with FC regimen, and 1 with R-CVP regimen + Cladribine. The median follow-up time was 39 (range, 2-83) months, 3 patients died, all due to failure of chemotherapy due to disease progression. The prognosis of HCL-v patients was significantly worse than that of cHCL patients (P=0.01), and there was no significant difference in the impact of different treatment regiments on the OS of HCL patients (P=0.328). CONCLUSION: HCL is a rare clinically indolent hematological tumor, which is sensitive to Cladribine, with the emergence of precision treatments such as the novel molecular-targeted drugs and immunotherapy also plays an indispensable role in clinical practice of HCL.

17.
Elife ; 122024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536726

RESUMO

Mechanism underlying the metabolic benefit of intermittent fasting remains largely unknown. Here, we reported that intermittent fasting promoted interleukin-22 (IL-22) production by type 3 innate lymphoid cells (ILC3s) and subsequent beigeing of subcutaneous white adipose tissue. Adoptive transfer of intestinal ILC3s increased beigeing of white adipose tissue in diet-induced-obese mice. Exogenous IL-22 significantly increased the beigeing of subcutaneous white adipose tissue. Deficiency of IL-22 receptor (IL-22R) attenuated the beigeing induced by intermittent fasting. Single-cell sequencing of sorted intestinal immune cells revealed that intermittent fasting increased aryl hydrocarbon receptor signaling in ILC3s. Analysis of cell-cell ligand receptor interactions indicated that intermittent fasting may stimulate the interaction of ILC3s with dendritic cells and macrophages. These results establish the role of intestinal ILC3s in beigeing of white adipose tissue, suggesting that ILC3/IL-22/IL-22R axis contributes to the metabolic benefit of intermittent fasting.


Obesity refers to a condition where a person has excessive fat accumulation, which can have negative impacts on their health. Managing obesity has typically relied on reducing energy intake and increasing energy use through diets and exercise. For example, intermittent fasting is a diet strategy involving periods of time in a day or week where a person does not eat any food. Research has shown that intermittent fasting may improve the metabolism and increase energy use by enhancing a process known as "beigeing" of white fat tissue. In this process, white fat cells or their precursor cells differentiate into beige fat cells, which can consume excess energy by burning fat. Consequently, understanding how beigeing of white fat cells is activated in intermittent fasting may reveal a promising strategy for tackling obesity and metabolic diseases. Immune cells found in the gut known as innate lymphoid cells (ILCs) may play a role in the metabolic benefits from intermittent fasting. However, the roles of ILCs are complex: some types of ILCs can promote obesity, while others show metabolic benefits through their release of proteins like IL-17 and IL-22, which can help the body to metabolise glucose. To find out if these immune cells play a role in intermittent fasting, Chen, Sun et al. used diet-induced obese mice that had to fast every other day. Intermittent fasting was found to cause a form of ILCs (ILC3s) to release IL-22, which resulted in beigeing of white fat cells in obese mice. Single-cell sequencing techniques of gut immune cells further revealed that intermittent fasting increased forms of signalling in ILC3s and caused ILC3s to interact with other immune cells, such as dendritic cells and macrophages. The findings demonstrate how intermittent fasting causes beigeing of white adipose tissue through ILC3s, revealing mechanisms underpinning the metabolic benefits found from intermittent fasting. More research into this process may help identify new targets for treating obesity.


Assuntos
60552 , Linfócitos , Camundongos , Animais , Linfócitos/metabolismo , Imunidade Inata , Jejum Intermitente , Tecido Adiposo Branco/metabolismo
18.
Front Plant Sci ; 15: 1310346, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444537

RESUMO

Wolfberry, also known as goji berry or Lycium barbarum, is a highly valued fruit with significant health benefits and nutritional value. For more efficient and comprehensive usage of published L. barbarum genomic data, we established the Wolfberry database. The utility of the Wolfberry Genome Database (WGDB) is highlighted through the Genome browser, which enables the user to explore the L. barbarum genome, browse specific chromosomes, and access gene sequences. Gene annotation features provide comprehensive information about gene functions, locations, expression profiles, pathway involvement, protein domains, and regulatory transcription factors. The transcriptome feature allows the user to explore gene expression patterns using transcripts per kilobase million (TPM) and fragments per kilobase per million mapped reads (FPKM) metrics. The Metabolism pathway page provides insights into metabolic pathways and the involvement of the selected genes. In addition to the database content, we also introduce six analysis tools developed for the WGDB. These tools offer functionalities for gene function prediction, nucleotide and amino acid BLAST analysis, protein domain analysis, GO annotation, and gene expression pattern analysis. The WGDB is freely accessible at https://cosbi7.ee.ncku.edu.tw/Wolfberry/. Overall, WGDB serves as a valuable resource for researchers interested in the genomics and transcriptomics of L. barbarum. Its user-friendly web interface and comprehensive data facilitate the exploration of gene functions, regulatory mechanisms, and metabolic pathways, ultimately contributing to a deeper understanding of wolfberry and its potential applications in agronomy and nutrition.

19.
Huan Jing Ke Xue ; 45(3): 1457-1467, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471861

RESUMO

Urban rivers are the main receptors and transporters of microplastic pollution. Understanding the occurrence and environmental risk of microplastics in urban rivers can provide theoretical basis for further control of microplastic pollution. The Sishui River, a tributary of the Yellow River, was selected as the research object. A total of nine water samples were collected from sewage outlets of the Sishui River (Xingyang section). The microplastics in the collected samples were characterized by their sizes, shapes, and colors using a microscope. It was found that microplastics were mostly in the form of transparent fibers and fragments in the water body of sewage outlets, of which the size below 500 µm was relatively high. In addition, PET and PE polymers were identified as the main types using a laser infrared imager. The correlation analysis showed that there was a significant correlation between the PET and PE, indicating that they were similar in origin. The results of the environmental risk assessment showed that the type of microplastics was the main factor affecting the assessment results, whereas the risk values of six sewage samples containing PVC were high. However, the value of pollution load index revealed a low risk level of pollutants in the study area.

20.
Gastroenterology ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38417530

RESUMO

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is characterized by an immune-suppressive microenvironment, which contributes to tumor progression, metastasis, and immunotherapy resistance. Identification of HCC-intrinsic factors regulating the immunosuppressive microenvironment is urgently needed. Here, we aimed to elucidate the role of SYR-Related High-Mobility Group Box 18 (SOX18) in inducing immunosuppression and to validate novel combination strategies for SOX18-mediated HCC progression and metastasis. METHODS: The role of SOX18 in HCC was investigated in orthotopic allografts and diethylinitrosamine/carbon tetrachloride-induced spontaneous models by using murine cell lines, adeno-associated virus 8, and hepatocyte-specific knockin and knockout mice. The immune cellular composition in the HCC microenvironment was evaluated by flow cytometry and immunofluorescence. RESULTS: SOX18 overexpression promoted the infiltration of tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) while diminishing cytotoxic T cells to facilitate HCC progression and metastasis in cell-derived allografts and chemically induced HCC models. Mechanistically, transforming growth factor-beta 1 (TGF-ß1) upregulated SOX18 expression by activating the Smad2/3 complex. SOX18 transactivated chemokine (C-X-C motif) ligand 12 (CXCL12) and programmed death ligand 1 (PD-L1) to induce the immunosuppressive microenvironment. CXCL12 knockdown significantly attenuated SOX18-induced TAMs and Tregs accumulation and HCC dissemination. Antagonism of chemokine receptor 4 (CXCR4), the cognate receptor of CXCL12, or selective knockout of CXCR4 in TAMs or Tregs likewise abolished SOX18-mediated effects. TGFßR1 inhibitor Vactosertib or CXCR4 inhibitor AMD3100 in combination with anti-PD-L1 dramatically inhibited SOX18-mediated HCC progression and metastasis. CONCLUSIONS: SOX18 promoted the accumulation of immunosuppressive TAMs and Tregs in the microenvironment by transactivating CXCL12 and PD-L1. CXCR4 inhibitor or TGFßR1 inhibitor in synergy with anti-PD-L1 represented a promising combination strategy to suppress HCC progression and metastasis.

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