Effect of low-purine diet on the serum uric acid of gout patients in different clinical subtypes: a prospective cohort study.

BACKGROUND: The pathogenic causes of primary gout include urate overproduction and/or renal or extra-renal urate underexcretion. The aim of this study was to evaluate the association of gout subtypes with the response to low-purine diet (LPD). METHODS: This is a single-center prospective clinical study. Gout patients visiting from 2019 to 2022, from Shandong Gout Clinic Center at the Affiliated Hospital of Qingdao University, China, assigned to three groups according to clinical subtypes, were enrolled and all treated with 2-week low-purine diet. General characteristics, serum uric acid (sUA) and other clinical biochemical variables before and after the diet were evaluated. RESULTS: A total of 626 gout patients (age 41.20 ± 13.41 years, male 98.0%) were included. Of these, 69 (11.0%) were overproduction type, 428 (68.37%) were underexcretion type, and 129 (20.61%) were combined type. Overall, there was a substantial decrease in sUA after a 2-week LPD (p < 0.001). In addition, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum triglycerides (TG), serum total cholesterol (TC), blood urea nitrogen (BUN) and serum creatinine (Scr) levels were lower than those at baseline (p < 0.05). On the other hand, there were significant differences in the reduction of sUA among different types, the rank order being overproduction type (- 88.81 ± 63.01 µmol/L) > combined type (- 65.22 ± 44.13 µmol/L) > underexcretion type (- 57.32 ± 61.19 µmol/L). After adjusting for age, BMI and baseline sUA and eGFR, there were still significant differences in the decline of serum uric acid among different types. Higher baseline sUA (95%CI - 0.285, - 0.191; p < 0.001) and BUN (95%CI - 6.751, - 0.602; p < 0.001) were correlated with greater decrease of sUA. CONCLUSIONS: Our findings support the protective role of low-purine diet on sUA levels in gout patients, especially overproduction type. Furthermore, LPD could exert a beneficial effect on gout patients' blood pressure, BMI, blood lipid, BUN and Scr levels. Trial registration Registered with ChiCTR, No. ChiCTR1900022981 at 06/05/2019.

Cholinergic nucleus degeneration and its association with gait impairment in Parkinson's disease.

BACKGROUND: The contribution of cholinergic degeneration to gait disturbance in Parkinson's disease (PD) is increasingly recognized, yet its relationship with dopaminergic-resistant gait parameters has been poorly investigated. We investigated the association between comprehensive gait parameters and cholinergic nucleus degeneration in PD. METHODS: This cross-sectional study enrolled 84 PD patients and 69 controls. All subjects underwent brain structural magnetic resonance imaging to assess the gray matter density (GMD) and volume (GMV) of the cholinergic nuclei (Ch123/Ch4). Gait parameters under single-task (ST) and dual-task (DT) walking tests were acquired using sensor wearables in PD group. We compared cholinergic nucleus morphology and gait performance between groups and examined their association. RESULTS: PD patients exhibited significantly decreased GMD and GMV of the left Ch4 compared to controls after reaching HY stage > 2. Significant correlations were observed between multiple gait parameters and bilateral Ch123/Ch4. After multiple testing correction, the Ch123/Ch4 degeneration was significantly associated with shorter stride length, lower gait velocity, longer stance phase, smaller ankle toe-off and heel-strike angles under both ST and DT condition. For PD patients with HY stage 1-2, there were no significant degeneration of Ch123/4, and only right side Ch123/Ch4 were corrected with the gait parameters. However, as the disease progressed to HY stage > 2, bilateral Ch123/Ch4 nuclei showed correlations with gait performance, with more extensive significant correlations were observed in the right side. CONCLUSIONS: Our study demonstrated the progressive association between cholinergic nuclei degeneration and gait impairment across different stages of PD, and highlighting the potential lateralization of the cholinergic nuclei's impact on gait impairment. These findings offer insights for the design and implementation of future clinical trials investigating cholinergic treatments as a promising approach to address gait impairments in PD.

Key links in the physiological regulation of the immune system and disease induction: T cell receptor -CD3 complex.

T cell receptor (TCR) is a kind of surface marker that are specific to T cells. The TCR regulates T cell function and participates in the body's immunological response to prevent immune dysregulation and inflammatory reactions by identifying and binding exogenous antigens. Due to its brief intracellular segment, TCR requires intracellular molecules to assist with signaling. Among these, the CD3 molecule is one of the most important. The CD3 molecule involves in TCR structural stability as well as T cell activation signaling. A TCR-CD3 complex is created when TCR and CD3 form a non-covalent bond. Antigen recognition and T cell signaling are both facilitated by the TCR-CD3 complex. When a CD3 subunit is absent, a TCR-CD3 complex cannot form, and none of the subunits is transported to the cell surface. Thus, T cells cannot develop. Consequently, research on the physiological functions and potential pathogenicity of CD3 subunits can clarify the pathogenesis of immune system diseases and can offer fresh approaches to the treatment of it. In this review, the structure and function of the TCR-CD3 complex in the immune system was summarized, the pathogenicity of each CD3 subunit and therapeutic approaches to related diseases was explored and research directions for the development of new targeted drugs was provided.

Improvements and challenges in intraperitoneal laparoscopic para-aortic lymphadenectomy: The novel "tent-pitching" antegrade approach and vascular anatomical variations in the para-aortic region.

INTRODUCTION: This study introduces and compares a new intraperitoneal laparoscopic para-aortic lymphadenectomy method to reach the level of the renal vein, the "tent-pitching" antegrade approach with the retrograde approach in gynecological malignancy surgeries in terms of success rate, complication incidence, and the number of lymph nodes removed. It focuses on the feasibility, safety, and effectiveness. Meanwhile, this article reports on the vascular anatomical variations discovered in the para-aortic region to enhance surgical safety. MATERIAL AND METHODS: This was a retrospective cohort study including patients undergone laparoscopic para-aortic lymphadenectomy at a single center from January 2020 to December 2023 for high-risk endometrial and early-stage ovarian cancer. Patient charts were reviewed for mode of operation, perioperative complications, operative details, and histopathology. The patients were divided into anterograde group and retrograde group according to the operation mode. The two groups were further compared based on the success rate of lymph node clearance at the renal vein level, perioperative complications, and the number of removed lymph nodes. Quantitative data were analyzed using the t-test, non-normally distributed data using the rank-sum test, and categorical data using Fisher's exact test and the chi-square test, with statistical significance defined as P < 0.05. RESULTS: Among 173 patients, the antegrade group showed higher surgery success (97.5% vs 68.82%), more lymph nodes removed (median 14 vs 7), and less median blood loss. The operation time was shorter in the antegrade group. Postoperative complications like lymphocele and venous thrombosis were lower in the antegrade group. Vascular abnormalities were found in 28.9% of patients, with accessory lumbar vein routing anomaly and accessory renal arteries being most common. CONCLUSIONS: The antegrade approach is feasible, safe, and effective, improving surgical exposure, reducing difficulty without additional instruments or puncture sites, and minimizing organ damage risk. It is effective in achieving better access to the renal vein and removing more para-aortic lymph nodes than the retrograde method. Recognizing and carefully managing the diverse vascular abnormalities in the para-aortic area, including variations in renal arteries, veins, and the inferior vena cava, is essential to reduce intraoperative bleeding and the likelihood of converting to open surgery.

Production of Coal Fines in Deep Coal Seam via Morphologic, Flow-Channel, Mineral Analyses: Evidence from Coalbed Methane Wells in the Qinshui Basin.

During the development of deep coalbed methane (CBM), the production of coal fines is common and suppresses the yield of CBM. This work takes the deep CBM wells in the Qinshui Basin as a case study, and the output, composition, morphology, and sources of coal fines were investigated through scanning electron microscopy, X-ray diffraction, proximate analysis, and particle size measurement including image analysis, laser diffraction, and dynamic light scattering. The results indicate that, in comparison with shallow CBM wells, deep wells produce a greater quantity of coal fines which are darker in color and have smaller particle sizes, with the majority being less than 10 µm. The coal fines exist predominantly as aggregates that contained the iron-bearing and clay minerals. Based on the Liddinger particle settling model, the water production volume required for the coal fines to return to the surface in the Wuxiang block was calculated to be 8.55 m3/d. This work can provide a scientific basis for the prevention and control of coal fines in deep CBM wells.

Study on the Permeability Enhancement of Propped Fractures under the Action of a Coal Fine Plugging Removal Agent.

The retention of coal fines in propped fractures impedes the efficient flow of gas and water, leading to a substantial decrease in coal seam permeability and gas production efficiency. In this article, a coal fine plugging removal agent with good dispersion stability and powerful powder-carrying capacity was developed to study the coal fine plugging removal and permeability enhancement in the propped fracture. The results show that 0.8% SDS + 0.4% NaCl + 0.8% BS-12 was the most effective coal fine plugging removal agent compounding system. Increasing the injection rate of the plugging removal agent and performing recycles of intermittent unblocking when it was used as a plugging agent will effectively enhance the gas-liquid two-phase effective permeability of propped fractures and improve the release of retained coal fines. After three recycles of intermittent unblocking, the coal fine discharging rate can be increased to more than 90%, resulting in a 3.88 times increase of the gas-liquid two-phase permeability compared to that with the single unblocking cycle. This method has important practical significance and theoretical value for solving the problem of coal fine plugging in fractures and ensuring the stable and efficient discharge of coalbed gas-water-coal fines.

The Difference between Stress Deformation and Adsorption Deformation of Coal Reservoirs and Its Role in Permeability Prediction.

The key to the variation in permeability within coal reservoirs lies in the stress-induced deformation and desorption-induced deformation during the coalbed methane (CBM) production. The differences in sample scale and measurement methods between stress-induced deformation and desorption-induced deformation significantly affect the accuracy of permeability measurements. Therefore, in order to elucidate the relationship between stress-induced deformation and adsorption-induced deformation, as well as the influencing factors, and to assess the accuracy of permeability evolution prediction, this study conducted a series of parallel experiments, including compression deformation experiments under stress loading (stress-induced deformation), methane adsorption-induced deformation experiments (adsorption-induced deformation), µCT scanning, and overburden permeability measurements.The results of the study indicate that stress-induced deformation and adsorption-induced deformation are negatively correlated but exhibit a relatively weak correlation. Stress-induced deformation encompasses deformation of coal matrix, minerals, and fractures, whereas adsorption-induced deformation primarily reflects coal matrix deformation. While there is some overlap between the two, they are not entirely identical. The main influencing factor of stress-induced deformation is the mechanical strength of coal, with minerals in coal increasing the Young's modulus of coal reservoirs. Among them, minerals that are more dispersed and have smaller particles have a more significant impact on stress-induced deformation. The primary influencing factor of adsorption-induced deformation is the deformation capability of the coal matrix, with minerals and fractures having less significant effects. Permeability changes are controlled by fracture deformation, but stress-induced deformation measurements weakly reflect this aspect, leading to an inability to accurately predict the scale of the impact of effective stress changes on permeability during CBM production and CO2-ECBM processes. In contrast, adsorption-induced deformation relatively accurately reflects the deformation capability of the coal matrix and provides a more accurate prediction of permeability rebound under the condition of almost unchanged effective stress in the late stages of mining. Therefore, deformation parameters under stress loading are challenging to directly apply to the prediction of permeability evolution, while adsorption-induced deformation parameters can be effectively utilized.

The impact of anxiety on gait impairments in Parkinson's disease: insights from sensor-based gait analysis.

BACKGROUND: Sensor-based gait analysis provides a robust quantitative tool for assessing gait impairments and their associated factors in Parkinson's disease (PD). Anxiety is observed to interfere with gait clinically, but this has been poorly investigated. Our purpose is to utilize gait analysis to uncover the effect of anxiety on gait in patients with PD. METHODS: We enrolled 38 and 106 PD patients with and without anxiety, respectively. Gait parameters were quantitively examined and compared between two groups both in single-task (ST) and dual-task (DT) walking tests. Multiple linear regression was applied to evaluate whether anxiety independently contributed to gait impairments. RESULTS: During ST, PD patients with anxiety presented significantly shorter stride length, lower gait velocity, longer stride time and stance time, longer stance phase, smaller toe-off (TO) and heel-strike (HS) angles than those without anxiety. While under DT status, the differences were diminished. Multiple linear regression analysis demonstrated that anxiety was an independent factor to a serials of gait parameters, particularly ST-TO (B = -2.599, (-4.82, -0.38)), ST-HS (B = -2.532, (-4.71, -0.35)), ST-TO-CV (B = 4.627, (1.71, 7.64)), ST-HS-CV(B = 4.597, (1.66, 7.53)), ST stance phase (B = 1.4, (0.22, 2.58)), and DT stance phase (B = 1.749, (0.56, 2.94)). CONCLUSION: Our study discovered that anxiety has a significant impact on gait impairments in PD patients, especially exacerbating shuffling steps and prolonging stance phase. These findings highlight the importance of addressing anxiety in PD precision therapy to achieve better treatment outcomes.

Machine learning and genetic algorithm-guided directed evolution for the development of antimicrobial peptides.

INTRODUCTION: Antimicrobial peptides (AMPs) are valuable alternatives to traditional antibiotics, possess a variety of potent biological activities and exhibit immunomodulatory effects that alleviate difficult-to-treat infections. Clarifying the structure-activity relationships of AMPs can direct the synthesis of desirable peptide therapeutics. OBJECTIVES: In this study, the lipopolysaccharide-binding domain (LBD) was identified through machine learning-guided directed evolution, which acts as a functional domain of the anti-lipopolysaccharide factor family of AMPs identified from Marsupenaeus japonicus. METHODS: LBDA-D was identified as an output of this algorithm, in which the original LBDMj sequence was the input, and the three-dimensional solution structure of LBDB was determined using nuclear magnetic resonance. Furthermore, our study involved a comprehensive series of experiments, including morphological studies and in vitro and in vivo antibacterial tests. RESULTS: The NMR solution structure showed that LBDB possesses a circular extended structure with a disulfide crosslink at the terminus and two 310-helices and exhibits a broad antimicrobial spectrum. In addition, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that LBDB induced the formation of a cluster of bacteria wrapped in a flexible coating that ruptured and consequently killed the bacteria. Finally, coinjection of LBDB, Vibrio alginolyticus and Staphylococcus aureus in vivo improved the survival of M. japonicus, demonstrating the promising therapeutic role of LBDB for treating infectious disease. CONCLUSIONS: The findings of this study pave the way for the rational drug design of activity-enhanced peptide antibiotics.

Experimental research on compressive strength deterioration of coal seam floor sandstone under the action of acidic mine drainage.

In sulphur-coal symbiotic coal seams, after the mining of sulphide iron ore, when the coal resources are mined, the mine water accumulated in the roadway mining area will have a certain impact on the stability of the surrounding rock of the coal seam roadway. Taking the floor sandstone of sulfur coal symbiotic coal seam as the research object, the roof fissure water with pH values of 7.48, 4.81 and 2.62 was used as the experimental solution. 10 experimental schemes were designed to measure the compressive strength of the samples under the action of AMD, and the hydrochemical analysis of AMD was conducted. The pore structures of the samples before and after the action of AMD were analyzed. Based on the hydrochemistry and pore structure, the deterioration mechanism of compressive strength of the coal seam floor sandstone under the action of AMD was explained. The results indicated that the compressive strength of the samples decreased with the increasing action time of AMD. The compressive strength decreased with the increment of the porosity. The concentration of H+ ion in AMD was relatively small. Na2O in albite dissolved and reacted with water, leading to an increase in the concentration of Na+ ion. Soluble substances such as MgCl2 and CaSO4 in the pore structure dissolved, leading to an increase in the concentration of Ca2+ and Mg2+ ions. The dissolution of soluble substances and the physical-chemical reactions between solutions and minerals were the essential causes of the continuous deterioration of the compressive strength of the coal seam floor sandstone. The results of this study can provide a theoretical basis for the deterioration of the mechanical properties of the peripheral rock in the roadway of the sulphur coal seam, and can also provide a certain engineering reference for the sulphur coal seam roadway.

Mother-child dyadic responses to children facing challenges: An examination across ethnicities.

The current study (a) examined ethnic differences in mothers' and children's responses to children's performance in a challenging task, (b) tested the associations among children's desire for assistance, maternal control, and children's emotional responses to the challenge, and (c) explored whether these associations held across three ethnicities-Asian Americans (AA), Latinx Americans (LA), and European Americans (EA). Results showed that children's emotional arousal significantly increased and emotional valence became significantly less positive over the course of children experiencing repeated challenges in front of their mothers. In terms of ethnic differences, LA mothers exhibited more control than EA mothers, but LA children responded less negatively to the challenging task than EA children. AA dyads did not significantly differ from LA or EA dyads on any maternal or child responses. However, regardless of ethnicity, stronger child desire for assistance was associated with greater maternal control and greater maternal control was associated with less emotional arousal and more positive child emotional valence. These findings suggest that, in a challenging context, maternal control is likely experienced by children as guidance that mitigates decreases in positive emotion. Our work has implications for interventions to encourage more emotionally responsive parental involvement with children in late childhood and early adolescence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Prevalence and predictors of help-seeking behavior among post-partum women with urinary incontinence in China and Indonesia: A cross-sectional survey based on Andersen Help-Seeking Model.

INTRODUCTION: Urinary incontinence (UI) is a prevalent condition among post-partum women, and it can significantly affect their physical and psychosocial well-being. Therefore, it's crucial for post-partum women to discuss any UI symptoms they may be experiencing with their healthcare provider and seek appropriate treatment. PURPOSE: To investigate what leads post-partum women with UI to seek help in China and Indonesia based on the Andersen Help-Seeking Model. METHODS: A cross-sectional digital survey among post-partum women (6 weeks to 1 year) was conducted from May to November 2021 in China and Indonesia. The survey contents included: (1) demographic characteristics, (2) social support, (3) health care needs, (4) capacity and resources. For analysis, descriptive statistics, independent sample t-tests and chi-square tests were used to determine the differences between help-seeking and non-help-seeking women with UI, and logistic regression analysis and the receiver operating characteristic curve (ROC) was used to determine the predictors of heal-seeking behavior in post-partum women with UI. RESULTS: The prevalence of UI was 25 % (215/868) and 31 % (187/605) among post-partum women in China and Indonesia. Among post-partum women with UI, the help-seeking rate was 46 % (98/215) and 52 % (98/187) in China and Indonesia. Incontinence quality of Life, support from women of the family (Yes), knowing the available department for UI (Yes), current knowledge of UI and the current status of UI were independent risk factors for China (P<0.05). Support from husband (Yes), being asked about UI by a doctor (Yes) and the current status of UI were independent risk factors for Indonesia. The obtained area under ROC curve (AUC) for the model were 0.884 and 0.935 in China and Indonesia. CONCLUSIONS: The prevalence of UI and the rate of seeking help for UI in Indonesia were higher than those in China. Social support, needs and the availability of resources and organizational support to assist patients in their help-seeking efforts, were the main predictors affecting help-seeking behavior among post-partum women with UI.

Corrigendum: Single- and dual-task gait performance and their diagnostic value in early-stage Parkinson's disease.

[This corrects the article DOI: 10.3389/fneur.2022.974985.].

Prevalence and Influencing Factors of Help-Seeking Behavior Among Women with Urinary Incontinence: A Systematic Review and Meta-Analysis.

Purpose: This systematic review and meta-analysis aimed to investigate the mean (weighted) prevalence of help-seeking behavior among women with urinary incontinence (UI) in relevant subgroups and the related influencing factors. Materials and Methods: Six English and four Chinese databases were systematically searched between 1996 and July 10, 2022. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included studies. All statistical analyses were conducted using RevMan 5.4. Results: The mean (weighted) prevalence of help-seeking behavior based on the 41 included studies, including a total of 32,640 women with UI, was 28% (95% confidence interval [CI]: 22%-34%). We performed a subgroup analysis based on UI type, population, region, publication time, case definition of help-seeking, and use of validated tools to determine UI. The results of the subgroup analysis showed that the pooled prevalence of help-seeking behavior was 23% (95% CI: 14%-32%) among pregnant and maternity women, 27% (95% CI: 19%-35%) among menopausal women, 24% (95% CI: 14%-35%) among 20- to 50-year-old women, 31% (95% CI: 25%-36%) among those older than 50 years, 24% (95% CI: 17%-30%) in Asia, and 33% (95% CI: 22%-44%) in Europe. Meanwhile, the pooled odds ratio showed that education level, UI type, UI severity, and quality of life significantly influenced help-seeking behavior among women with UI. Conclusions: This systematic review revealed that the pooled prevalence of help-seeking behaviors among women with UI is 28%. These influencing factors have important implications for adapting to health care and social care systems.

Determination of the preferred epitaxy for III-nitride semiconductors on wet-transferred graphene.

Transferred graphene provides a promising III-nitride semiconductor epitaxial platform for fabricating multifunctional devices beyond the limitation of conventional substrates. Despite its tremendous fundamental and technological importance, it remains an open question on which kind of epitaxy is preferred for single-crystal III-nitrides. Popular answers to this include the remote epitaxy where the III-nitride/graphene interface is coupled by nonchemical bonds, and the quasi-van der Waals epitaxy (quasi-vdWe) where the interface is mainly coupled by covalent bonds. Here, we show the preferred one on wet-transferred graphene is quasi-vdWe. Using aluminum nitride (AlN), a strong polar III-nitride, as an example, we demonstrate that the remote interaction from the graphene/AlN template can inhibit out-of-plane lattice inversion other than in-plane lattice twist of the nuclei, resulting in a polycrystalline AlN film. In contrast, quasi-vdWe always leads to single-crystal film. By answering this long-standing controversy, this work could facilitate the development of III-nitride semiconductor devices on two-dimensional materials such as graphene.

Spatial and temporal dynamic response of abundant and rare aerobic denitrifying bacteria to dissolved organic matter in natural water: A case study of Lake Baiyangdian, China.

Revealing the responses of abundant and rare aerobic denitrifying bacteria to dissolved organic matter (DOM) composition is essential for understanding the aquatic N cycle ecosystems. In this study, fluorescence region integration and high-throughput sequencing techniques were used to investigate the spatiotemporal characteristics and dynamic response of DOM and aerobic denitrifying bacteria. The DOM compositions were significantly different among the four seasons (P < 0.001) without spatial differences. Tryptophan-like substances (P2, 27.89-42.67%) and microbial metabolites (P4, 14.62-42.03%) were the dominant components, and DOM exhibited strong autogenous characteristics. Abundant (AT), moderate (MT), and rare taxa (RT) of aerobic denitrifying bacteria showed significant and spatiotemporal differences (P < 0.05). The responses of α-diversity and niche breadth of AT and RT to DOM differed. The DOM explanation proportion for aerobic denitrifying bacteria exhibited spatiotemporal differences based on redundancy analysis. Foliate-like substances (P3) had the highest interpretation rate of AT in spring and summer, while humic-like substances (P5) had the highest interpretation rate of RT in spring and winter. Network analysis showed that RT networks were more complex than AT networks. Pseudomonas was the main genus associated with DOM in AT on a temporal scale, and was more strongly correlated with tyrosine-like substances (P1), P2, and P5. Aeromonas was the main genus associated with DOM in AT on a spatial scale and was more strongly correlated with P1 and P5. Magnetospirillum was the main genus associated with DOM in RT on a spatiotemporal scale, which was more sensitive to P3 and P4. Special operational taxonomic units were transformed between AT and RT with seasonal changes, but not between the two regions. To summarize, our results revealed that bacteria with different abundances utilized DOM components differently, and provides new insight on the spatiotemporal response of DOM and aerobic denitrifying bacteria in aquatic ecosystems of biogeochemical significance.

The pathogenesis and development of targeted drugs in acute T lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) is mainly classified into acute T- and B-lymphoblastic leukaemia according to the source of its lymphocytes, thymus and bone. Among them, the incidence of adult T-cell accounts for about 25% of adult acute lymphoblastic leukaemia, but the degree of malignancy is high and the treatment rate and prognosis are poor. At this stage, there are few targeted drugs and the commonly used broad-spectrum chemotherapeutic drugs have poor efficacy and many adverse drug reactions. Understanding and investigating the pathogenesis of T-acute lymphoblastic leukaemia is very important for further developing new targeting drugs and improving existing drugs. Dysregulated signalling pathways are the main aetiological factors of T-acute lymphoblastic leukaemia. They play crucial roles in promoting tumour initiation, progression, drug design and therapy responses. This is primarily because signalling pathways are indispensable for many cellular biological processes, including tumour growth, migration, invasion, metastasis and others. As a result, small molecule inhibitors targeting the major kinase components of the signalling pathway have received a lot of attention and have been developed and evaluated in preclinical models and clinical trials. Already marketed drugs are also being repurposed in combination therapies to further improve efficacy and overcome tumour cell resistance. In this review, we have aimed to examine the latest and most classical signalling pathways in the aetiology of T-acute lymphoblastic leukaemia and shed light on potential targets for novel therapeutic agents to act on.

Response of dissolved organic matter to thermal stratification and environmental indication: The case of Gangnan Reservoir.

Dissolved Organic Matter (DOM), an important part of the carbon cycle in reservoir ecosystems, has a great impact on aquatic environment to recognize the conversion process of different media DOM. The distribution, spectral characteristics, and sources of DOM in Gangnan Reservoir during thermal stratification were analyzed using ultraviolet-visible absorption spectroscopy and excitation-emission matrix spectroscopy. Three humic-like components (C2, C3, and C4) and two protein-like components (C1 and C5) were identified. The proportions of the humic-like components increased with the progression of thermal stratification (C2 and C3 were dominant), whereas the protein-like components decreased in proportion, and the trend in the interstitial water was constant (C3 and C4 were dominant). The proportion of the humic-like components in the sediments was highest during the stationary period of thermal stratification (C2 and C3 were dominant). C2 and C3 were significantly correlated in the water body and interstitial water (P < 0.001), while C1 and C5 were correlated in the sediment (P < 0.05). In the water body, C2 and C3 were negatively correlated during the formative period of thermal stratification (slope = -1.85; R2 = 0.52), strongly positively correlated during the stationary period (slope = 0.76; R2 = 0.94), and positively correlated during the weakening period of thermal stratification (slope = 0.46; R2 = 0.30). With the progression of thermal stratification, the relative contribution of endogenous substances decreased gradually, whereas the humification degree increased in the water body and interstitial water. The protein-like components and key physicochemical factors (Fe, Mn, TN, TP, and CODMn) were significantly correlated during the formative period (P < 0.05), and humic-like components and key physicochemical factors (NO2--N and TN) were significantly correlated during the stationary and weakening periods (P < 0.05). C1, C4, and C5 indicated NO3--N during the formative period; C2 and C3 indicated NO3--N during the stationary period; and C2 and C4 indicated NO3--N during the weakening period in the water body. These findings enhance the understanding the mutual transformation processes of DOM in reservoir ecosystems and could guide water quality management.

IgD enhances the release of neutrophil extracellular traps (NETs) via FcδR in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder affecting primarily the joints. Neutrophils and the release of neutrophil extracellular traps (NETs) contribute to the pathogenesis of RA. However, IgD, which was abnormally higher in RA, has not been studied for its pathological role in neutrophil activation and NETs formation. To investigate the effects of IgD on neutrophil activation and NETs formation via IgD receptor (FcδR), we collect peripheral blood of RA patients and established adjuvant-induced arthritis (AA) rat model. We found that the expression of FcδR on neutrophils was significantly higher in RA patients compared with healthy controls. As a specific marker of NETs, the level of citrullinated histone H3 was positively correlated with sIgD and FcδR in RA patients. IgD enhances the release of NETs and promotes the proliferation of fibroblast-like synoviocytes (FLS) from RA patients by activating neutrophils. As a competitive FcδR blocker, IgD-Fc-Ig fusion protein could significantly reduce NETs formation and FcδR expression on neutrophils in vitro. In vivo, IgD-Fc-Ig could restrain IgD-induced neutrophil activation and NETs formation, thus inhibited FLS proliferation in AA rats. Data presented here demonstrate that neutrophils could be triggered by IgD to release NETs and take part in FLS proliferation in RA patients with excessive IgD. Blocking IgD-FcδR could inhibit neutrophil activation and NETs formation, and represent an additional attractive novel therapeutic strategy for the treatment of RA.

Exosomes from the Uterine Cavity Mediate Immune Dysregulation via Inhibiting the JNK Signal Pathway in Endometriosis.

Endometriosis is a chronic inflammatory disease with an uncertain pathogenesis. Peritoneal immune dysregulation plays an important role in the pathogenesis of endometriosis. Exosomes are messengers of intercellular communication. This study mainly investigated the role of exosomes from the uterine cavity in endometriosis. Exosomes of the uterine aspirate fluid were isolated and cocultured with macrophages for 48 h. Flow cytometry was used to detect macrophage polarization. A Human MAPK Phosphorylation Antibody Array and Western blot were used to detect the phosphorylation of the MAPK pathway. A microRNA sequencing analysis was used to detect differentially expressed miRNAs. Our research found that exosomes of the uterine aspirate fluid from endometriosis could reduce the proportion of CD80+ macrophages. Additionally, it could inhibit the expression of P-JNK in macrophages. However, the JNK activator anisomycin could increase the proportion of CD80+ macrophages. In addition, exosomes of the uterine aspirate fluid from endometriosis could promote the migration and invasion of endometrial stromal cells by acting on macrophages. The expression of miR-210-3p was increased in both exosomes and the eutopic endometrium in patients with endometriosis through miRNA sequencing, which could also reduce the proportion of CD80+ macrophages. In summary, we propose that exosomes from the uterine cavity in patients with endometriosis may affect the phenotype of macrophages by inhibiting the JNK signaling pathway, thus mediating the formation of an immunological microenvironment conducive to the development of endometriosis.