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RATIONALE: Renal artery rupture due to allograft infection, especially by fungi, is a serious clinical complication that can occur after kidney transplantation, and may lead to graft loss and death. PATIENT CONCERNS: Two kidney recipients from China who developed renal artery rupture at our hospital on 5 days (47-year-old female) and 45 days (39-year-old male) after surgery. DIAGNOSES: The male had immunoglobulin A nephropathy as a primary disease, and experienced a postoperative attack of vascular rejection and mixed infection by Mucor and bacteria. The female had chronic glomerulonephritis as a primary disease, and experienced renal artery rupture near the anastomosis site with infection by fungi and other pathogens. INTERVENTIONS: The male received resection of the implanted kidney and antibiotic therapy with intravenous vancomycin (0.5 g, 2 days) and amphotericin B (530 mg in 33 days). The female received replacing the segment of renal arterial and internal iliac artery by saphenous vein, as well as antibiotic therapy with amphotericin B (320 mg in 8 days). OUTCOMES: The male was recovered and received a second transplantation, while the female was discharged on postoperative day 19. LESSONS: In both patients, prompt surgery and aggressive treatment with an antifungal drug (amphotericin B) and antidrugs led to successful rescue.
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Transplante de Rim , Artéria Renal , Humanos , Pessoa de Meia-Idade , Transplante de Rim/efeitos adversos , Feminino , Masculino , Artéria Renal/cirurgia , Adulto , Antifúngicos/uso terapêutico , Antibacterianos/uso terapêutico , Anfotericina B/uso terapêutico , Anfotericina B/administração & dosagem , Vancomicina/uso terapêutico , Vancomicina/administração & dosagem , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/etiologia , Ruptura/cirurgiaRESUMO
Monkeypox virus (MPXV) is a DNA virus belonging to the Orthopoxvirus genus within the Poxviridae family which can cause a zoonotic infection. The unexpected non-endemic outbreak of mpox in 2022 is considered as a new global threat. It is imperative to take proactive measures, including enhancing our understanding of MPXV's biology and pathogenesis, and developing novel antiviral strategies. The host immune responses play critical roles in defensing against MPXV infection while the virus has also evolved multiple strategies for immune escape. This review summarizes the biological features, antiviral immunity, immune evasion mechanisms, pathogenicity, and prevention strategies for MPXV.
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Background: Psoriatic arthritis (PsA) is an immune-mediated form of chronic inflammatory arthritis associated with psoriasis (PsO). It constitutes a significant comorbidity of PsO and is distinguished by the presence of widespread musculoskeletal inflammation. Objective: The aim of this study is to precisely detect asymptomatic PsA using ultrasound (US) examinations and to distinguish between various stages of PsO. Methods: All patients with moderate-to-severe PsO, who consented to undergo musculoskeletal US examinations during their hospitalization between September 2020 and January 2022, were enrolled in the study. We compared patients' demographic characteristics, comorbidities, disease duration, relevant laboratory parameters, and musculoskeletal US findings. Results: A total of 547 patients with PsO were included in the study, and 114 of them received a diagnosis of PsA. Furthermore, 16.45 % of patients with moderate to severe PsO displayed subclinical PsA. We observed a significantly higher frequency of abnormal US findings in patients with PsA compared to those without PsA, with a sensitivity of 95.61 % and a specificity of 79.22 %. Additionally, the incidence of enthesitis and synovitis varied significantly between PsA and non-PsA patients, and they were identified as independent variables predicting the presence of PsA. Furthermore, the interphalangeal joint, knee joint, and calcaneal tendon were the most frequently affected areas in PsA, as indicated by the observed US changes. Conclusion: Ultrasound examination proves to be a valuable tool for detecting subclinical PsA, facilitating early screening of the condition. Particular attention should be directed towards changes in the interphalangeal joint, knee joint, and calcaneal tendon when reviewing ultrasound images of asymptomatic patients.
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Background: Psoriasis is a chronic autoimmune inflammatory skin condition characterized by erythema, papules, and scales. It imposes a heavy psychological and social strain on both patients and their families. Surprisingly, there's limited research delving into the disease burden and coping strategies of spouses contending with psoriasis. Objective: The objective is to explore the disease burden faced and coping strategies utilized by spouses of individuals living with psoriasis. This exploration aims to offer insights crucial for devising mental health support and intervention strategies. Methods: The research methodology employed in this study was phenomenological, a qualitative approach. A total of fifteen spouses of patients with psoriasis were selected using an objective sampling method for in-depth, semi-structured interviews. Thematic analysis was then applied to the recorded interview data to derive meaningful themes. Results: This study has identified and analyzed three core themes concerning the disease burden and coping strategies of spouses of patients with psoriasis: Overwhelming disease burden; Lack of support system; Coping strategies (Problem - centered coping strategies: Proactive acquisition of disease knowledge; Active confrontation of illness - related issues; Behavioral habit alteration; and Emotional - centered coping strategies: Active acceptance and normalization; Passive acceptance and internalized stigma; Avoidance of disease - related problems). Conclusion: This study adds valuable insights into comprehending the disease burden encountered by spouses of patients with psoriasis and sheds light on the coping strategies they employ. Healthcare providers should proactively recognize and address the burden experienced by spouses early on. Establishing a robust support network is crucial, and promoting adaptive coping strategies can significantly aid spouses in effectively navigating and managing the complexities associated with psoriasis.
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Electrochemically active bacteria (EAB) exhibit promising prospects for space exploration and life support systems. However, the effects of the space environment on EAB are unclear. In this study, the effects of simulated microgravity on the current generation of mixed-culture EAB were illustrated, and the underlying mechanism was elucidated. The results demonstrated that the electrochemical activity of mixed-culture EAB was enhanced, which was mainly due to the enrichment of Geobacter and the increase in EAB biomass. Additionally, the genes and proteins of the biofilm changed obviously under simulated microgravity conditions, including: I) genes related to signal transfer, II) genes related to cell wall synthesis, and III) genes related to riboflavin synthesis. This study first revealed the enrichment in EAB abundance, the increase in EAB biomass, and the promotion of current generation under simulated microgravity.
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Ausência de Peso , Estudos de Casos e Controles , Bactérias/genética , Bactérias/metabolismo , Biofilmes , Transporte de ElétronsRESUMO
Ustekinumab is a biological therapy that has been approved for treating moderate-to-severe psoriasis. Although injection site reactions, nasopharyngitis, headaches, and infections are the common adverse events associated with ustekinumab, the development of bullous pemphigoid (BP) is also thought to be related to ustekinumab. Given that psoriasis itself can be complicated by BP, it is worthwhile to investigate the relationship between ustekinumab, psoriasis, and BP. Here we report a case of a male patient who developed BP twice after psoriasis treatment with ustekinumab. The patient's psoriasis and BP were brought under control by discontinuing ustekinumab and administering methotrexate, minocycline, and topical corticosteroids. Because of the increasing use of biologics in patients with psoriasis, BP should be considered a potential adverse event associated with ustekinumab.
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Intricate associations between rhizosphere microbial communities and plants play a critical role in developing and maintaining of soil ecological functioning. Therefore, understanding the assembly patterns of rhizosphere microbes in different plants and their responses to environmental changes is of great ecological implications for dynamic habitats. In this study, a developing mid-channel bar was employed in the Yangtze River to explore the assembly processes of rhizosphere fungal communities among various plant species using high-throughput sequencing-based null model analysis. The results showed a rare significant variation in the composition and alpha diversity of the rhizosphere fungal community among various plant species. Additionally, the soil properties were found to be the primary drivers instead of plant species types. The null model analysis revealed that the rhizosphere fungal communities were primarily driven by stochastic processes (i.e., undominated processes of ecological drift), and the predominance varied with various plant species. Moreover, the assembly processes of rhizosphere fungal communities were significantly related to the changes in soil properties (i.e., soil total carbon, total nitrogen, organic matter, and pH). The co-occurrence network analysis revealed that many keystone species belonged to unclassified fungi. Notably, five network hubs were almost unaffected by the measured soil properties and aboveground plant traits, indicating the effect of stochastic processes on the rhizosphere fungal community assembly. Overall, these results will provide insights into the underlying mechanisms of fungal community assembly in the rhizosphere soils, which are significant for maintaining the functional stability of a developing ecosystem.
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Background: Randomized controlled trials indicated guselkumab, the first anti-interleukin-23 monoclonal antibody, is efficacious in plaque psoriasis. However, guselkumab's performance in real life is scarcely examined, especially in China. Objectives: This work aimed to assess the long-term effectiveness of guselkumab in actual clinical practice in China. Methods: A retrospective study was performed for plaque psoriasis cases administered guselkumab in Shanghai Skin Disease Hospital between January 2020 and September 2022. Results: A total of 37 patients were included (29 men, 78.4%), with a mean follow-up period of 72.3 ± 26.7 weeks (range of 12-108 weeks). At baseline, clinical examination revealed a mean PASI of 12.3 ± 7.1, a mean BSA of 17.1 ± 18.1, and a mean DLQI of 7.7 ± 4.3. Twenty-two (62.9%) and 17 (48.6%) cases achieved PASI 90 and PASI 100 responses at week 28. From weeks 60 to 92, >80% of cases achieved PASI 90 and PASI 100 responses. Regarding safety, no cases of serious AEs were recorded. A total of nine cases (24.3%) had different abnormal results in HBV markers, and two were T-SPOT positive. There was no hepatitis B virus or tuberculosis outbreak in these patients. Conclusion: This real-life study confirmed the long-term efficacy and safety of guselkumab in daily clinical practice.
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Background: Little is known about different Ixekizumab (IXE) dosing regimens during routine clinical practice. Objectives: To evaluate the real-world effectiveness and safety of different IXE dosing regimens in patients with psoriasis. Materials & Methods: This study retrospectively compared patients who were dosed with IXE every two or four weeks (80 mg/week following a starting dose of 160 mg at Week 0). At Weeks 0, 4, and 12, the Psoriasis Area and Severity Index (PASI) and the Dermatology Life Quality Index (DLQI) were recorded, with adverse events also documented. Results: In total, 66 patients were analysed, of whom 30 (45.5%) and 36 (54.5%) were included in the two-week and four-week IXE dosing groups, respectively. In the overall patient cohort, 86.3%, 60.6%, and 31.8% exhibited PASI 75, PASI, 90, and PASI 100 responses at Week 12, respectively. The mean baseline PASI score was 12.4±7.6 and the mean baseline DLQI score was 11.3±6.9, with these values declining rapidly following IXE administration to 1.6±2.4, and 2.6±4.0 at Week 12, respectively. Response rates were elevated in the two-week group as compared to the four-week group at Weeks 4 and 12 of treatment, but these differences were not significant. Adverse events were reported in 25 patients (37.9%), with injection site reactions being most common, followed by infections. Conclusion: IXE is effective and safe in a real-world setting for the treatment of plaque psoriasis. Moreover, patients can reduce their medical expenses by choosing a four-week dosing regimen while still attaining therapeutic benefits.
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Psoríase , Humanos , Estudos Retrospectivos , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversosRESUMO
Background: Data pertaining to biologic agents used for treating psoriasis in real-world settings are lacking at present. To compare drug survival at 52 weeks for a range of biologics used to treat psoriasis under real-world conditions. Methods: This was a retrospective, single-center, observational study of a cohort of patients diagnosed with plaque psoriasis treated using ixekizumab, secukinumab, guselkumab, or adalimumab between January 2020 and December 2021. Baseline demographic characteristics, duration of psoriasis, and prior biological treatments for all patients were recorded. Drug survival rates were analyzed in different patient groups using Kaplan-Meier curves and Log rank tests. Results: In total, this study included 386 plaque psoriasis patients, of whom 70, 175, 36, and 105 were, respectively, treated using ixekizumab, secukinumab, guselkumab, and adalimumab. Over a 52-week period, the overall cumulative drug survival rates for ixekizumab, secukinumab, guselkumab, and adalimumab were 67.1%, 63.0%, 72.2%, and 37.1%, respectively. Lack of efficacy was the primary cause of discontinuation for these biologic therapies, followed by economic burden and adverse event incidence. Conclusion: These results suggest that guselkumab exhibited superior drug survival, drug survival outcomes for ixekizumab and secukinumab were comparable, and significantly better than those of adalimumab in China. Preventing a loss of drug efficacy represents a primary approach to improving biologic drug survival in psoriasis patients.
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Succession of microbial and plant communities is crucial for the development and the stability of soil ecological functions. The relative role of plant communities and environmental disturbance in shaping the microbial community in a newly established habitat remains unclear. In this study, a mid-channel bar (MCB) exposed to an environmental disturbance gradient in the Yangtze River was studied to explore the effects of such disturbance and plant community traits on the succession of the soil microbial community. Bulk and rhizospheric soils were collected from the MCB and classified according to their level of exposure to environmental disturbance: head, central and tail. These subsequently underwent high-throughput sequencing and interdomain ecological network (IDEN) analysis to identify and characterize the predominant microbial groups present in the soils at each disturbance level. Furthermore, at each site, the presence and distribution of the plant community was also noted. The present study demonstrated that both bulk soil nutrients and plant community exhibited significant spatial distribution dependent on the level of disturbance and this influenced the composition of the microbial community. In less eroded parts of the MCB, i.e., the central, nutrients accumulated, promoting growths of plants. This in turn encouraged a more diverse microbial community, dominated by the bacterial genus Pseudarthrobacter. Plant showed a stronger association with bulk soil microbial communities compared to rhizosphere soil microbial communities. Particularly, Triarrhena sacchariflora and Hemarthria altissima, present in sites of low disturbance, exhibiting a more extensive plant-microbe association. They thus played a key role in shaping the soil microbial community. In general, however, plant species did not directly determine the composition of the bacterial community, but instead altered the nutritive state of the soil to promote microbial growth. Such findings are of significant value for conservation practices of newly formed ecosystems, which requires an integrated understanding of the role of environmental disturbance and plants on soil microbial community assemblage.
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Background: The burden of hepatitis B virus (HBV) infection in China is high. The safety and efficacy of secukinumab in psoriasis patients with HBV infection have not been fully elucidated. Objectives: To investigate the safety and efficacy of secukinumab in psoriasis patients with HBV infection in China. Materials & Methods: In this retrospective study, 20 psoriasis patients with HBV infection were identified, all of whom had been treated with secukinumab for ≥24 weeks Results: Four patients had chronic inactive HBV infection, two patients had occult HBV infection, and the other 14 patients had resolved HBV infection. The HBV-DNA load and HBV markers measured at baseline and Week 24 showed no viral reactivation. Nineteen patients showed normal levels of liver enzymes after 24 weeks of therapy. However, one patient with resolved HBV infection and fatty liver with elevated baseline liver enzymes experienced hepatitis, with negative HBV load at baseline and Week 24. All patients showed a significant improvement in the Psoriasis Area and Severity Index (−13.35 ± 7.41: p < 0.0001), per cent of body surface area (−17.11 ± 17: p = 0.0002), Investigator Global Assessment (−2.55 ± 0.94: p < 0.0001), and Dermatology Life Quality Index (−12.3 ± 7.39; p < 0.0001) Conclusion: Secukinumab showed good efficacy in psoriasis patients with HBV infection. Chronic, inactive, occult and resolved HBV infection may not increase the risk of hepatitis during secukinumab treatment. Patients with poor baseline liver function, without any intervention during secukinumab treatment, may experience hepatitis. Periodic monitoring with HBV markers, HBV-DNA load, and serological liver function tests is necessary during secukinumab treatment.
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Hepatite A , Hepatite B Crônica , Psoríase , Anticorpos Monoclonais Humanizados , DNA Viral , Vírus da Hepatite B , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Psoríase/complicações , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Understanding community assembly is a key issue in recognizing community succession and guiding the restoration of degraded ecosystems. Based on the stress-dominance hypothesis (SDH), along a gradient of increasing environmental stress, the relative importance of environmental filtering is supposed to be dominant but species interaction could be a minor process in assembling communities. However, this hypothesized model of the assembly-rule shift was equivocally supported by various studies. In this study, by examining riparian plant communities with the zonation distribution of species composition along a markedly contrast flooding-stress gradient, a general aim was to clarify whether assembly rules of the communities would be also sorted into the zonation pattern as expected by the SDH. Another aim was to identify how edaphic factors associate with the assembly processes. Firstly, we found that even under the distinct stress gradient, community assembly was not stratified into different rules as the SDH expected, but environmental filtering appeared as a dominant assembly process across the stress gradient. Secondly, although filtering holds as a dominant assembly rule, environmental filters were found different along the gradient. By disentangling the filters of edaphic attributes, we found that the filters significantly shifted from soil physical properties to chemical nutrients governing the filtering process along the gradient. This result revealed that, across the contrast gradient, the environmental deterministic process on assembly is so strong that the other assembly processes became weaker. By synthesizing our results, the SDH may not be applied even under the context of a contrast stress gradient, which suggests that environmental context may be a key in testing and applying the SDH. Finally, in guiding riparian restoration under strong stress, we suggest that soil physical structure rather than chemical nutrients shall be given a priority for consideration in rebuilding the degraded riparian communities.
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Ecossistema , Solo , Inundações , Plantas , Estresse FisiológicoRESUMO
Invasive process of alien species is affected by not only the invaded habitats, but also the surrounding landscape matrix. Understanding the effects of landscape matrix on alien species is of great significance for controlling invasive alien species. We surveyed plant communities along the water-level fluctuating zone (WLFZ) of the Three Gorges Reservoir. Invasive status of alien plant species was evaluated. Totally 10 spatial scales of the surrounding landscape matrix in the scope of 2000 m (including WLFZ) were classified, and 14 landscape indices were applied to analyze the landscape matrix composition and configuration. Using the principal component analysis and correlation analysis, the effects of landscape matrix on the alien invasive plant species and associated scale effect were tested. Results showed that a total of 42 alien invasive plant species were found in the WLFZ, belonging to 17 families and 36 genera. Fuling was a dividing place to differentiate invasive species distribution. The number of the alien invasive species between Fuling and the Three Gorges Dam was found more than that between Fuling and Jiangjin. For the all scales (within 2000 m). The higher the landscape matrix fragmentation was, the more difficult the alien species invading. The higher landscape connectivity was, the easier the alien species invading. The effects of landscape matrix composition and configuration on the invasive plant diversity at large scales (1200-2000 m) was more significant than those at small scales (200-1000 m), in which landscape matrix composition and configuration at 1200-1400 m showed the strongest effect, demonstrating a significant spatial scale effect. Different invasive plant species showed the scale effects of landscape matrix composition and configuration. At all scales, Xanthium strumarium and Bidens frondosa showed weak correlations with landscape indices, but Bidens tripartita and Erigeron canadensis showed strong correlations. Landscape matrix was closely related to invasive plant species, and demonstrated a significant scale effect. The alien invasive plant species could be traced to the landscape matrix at large scales. Grassland and forest patches at the small scales could be used as the 'stepping stone' for the alien species transiting before they arrived at the WLFZ. In order to control alien plants in the WLFZ, land-use management and optimization should be strengthened at different scales of landscape matrix on the basis of enhancement of habitat management. A diversified comprehensive control for alien species should thus be taken into account.
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Espécies Introduzidas , Água , China , Ecossistema , Humanos , PlantasRESUMO
The warning cytokine interleukin-33 receptor (IL-33R) mediates local inflammatory responses and plays crucial roles in the pathogenesis of immune diseases such as pulmonary fibrosis and rheumatoid arthritis. Whether and how IL-33R is regulated remain enigmatic. Here, we identified ubiquitin-specific protease 38 (USP38) as a negative regulator of IL-33Rmediated signaling. USP38 deficiency promotes interleukin-33 (IL-33)induced downstream proinflammatory responses in vitro and in vivo. Usp38−/− mice are more susceptible to inflammatory damage and death and developed more serious pulmonary fibrosis after bleomycin treatment. USP38 is constitutively associated with IL-33R and deconjugates its K27-linked polyubiquitination at K511, resulting in its autophagic degradation. We further show that the E3 ubiquitin ligase tumor necrosis factor receptorassociated factor 6 (TRAF6) catalyzes K27-linked polyubiquitination of IL-33R at K511, and that deficiency of TRAF6 inhibits IL-33mediated signaling. Our findings suggest that K27-linked polyubiquitination and deubiquitination of IL-33R by TRAF6 and USP38 reciprocally regulate IL-33R level and signaling, which represents a critical mechanism in the regulation of IL-33triggered lung inflammatory response and pulmonary fibrosis.
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Inflamação/fisiopatologia , Interleucina-33/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fibrose Pulmonar/fisiopatologia , Proteases Específicas de Ubiquitina/metabolismo , Autofagia , Regulação para Baixo , Humanos , Inflamação/metabolismo , Interleucina-33/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Transdução de Sinais , Proteases Específicas de Ubiquitina/genética , UbiquitinaçãoRESUMO
Little real-work data regarding the efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) is available at present. To assess the efficacy and safety of dupilumab at 12 weeks in the treatment of AD in clinical routine clinical practice. A retrospective, single-centre study of adult patients with moderate to severe AD treated with dupilumab for 12 weeks in China. In total, 60 patients (48 male, 12 female; mean age: 53.2 ± 15.6) were enrolled in this retrospective study. These patients exhibited a mean AD disease course of 10.6 years (6.0), 30% exhibited a family history of allergies, and 31 (51.7%) had one or more allergic comorbidities. Following dupilumab treatment for 12 weeks, 83.3% and 42% of patients had achieved EASI-50 and EASI-75, respectively. Overall, adverse events (AEs) were reported by 15% of patients, with the most common being conjunctivitis, injection site reactions, and herpes simplex virus infections. Laboratory testing after 12 weeks revealed pronounced decreases in both circulating eosinophil counts (from 0.6 (0.1-2.8) to 0.3 (0.1-9.7) 109 /L) and total IgE concentrations (from 327 (2.46-2500) to 230 (47.6-2200) U/ml) in these patients. These real-world data reaffirm the safety and efficacy of dupilumab as a treatment for moderate-to-severe AD among Chinese patients in clinical practice.
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Dermatite Atópica , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Riparian ecosystem is structurally unstable due to the frequent disturbances from water fluctuation. Moreover, dams on large rivers tend to trigger fundamental changes of the composition and structure of riparian plant communities, which provides high odds for invasive species to colonize. Yet, how the invasive species distribute along a dam-induced riparian habitat, and how the native species resist to plant invasion are still puzzles. In this study, we investigated spatial distribution of invasive floral species and its correlation with the distance from dam and the dam-triggered flooding stresses, as well as the resistance of native species to plant invasion in the water level fluctuation zone (WLFZ) of the Three Gorges Reservoir (TGR) along the Yangtze River. By our investigation, a total of 43 alien plant species belonging to 14 families and 34 genera were found, including 20 existed and 23 newly discovered alien species recorded. Most of the new invasive species are annual herbs of the Asteraceae family. At the current successional stage, the new invasive species had not yet fully occupied the habitats of the existed invasive species. Longitudinally, number and coverages of the new invasive species showed an opposite distribution pattern to the existed invasive species, but vertically they demonstrated similar pattern. Currently, the new dominant invasive species are mainly concentrated at the intermediate elevation of WLFZ in the middle section of the reservoir, whereas the existed dominant invasive species have proliferated across the whole WLFZ. Additionally, native species showed a weak resistance to plant invasion, and water fluctuation along the elevation exerted the most significant influence on plant invasion. The results indicated that, after a decade of riparian community succession, the invasiveness of alien species remain persisted. The potential penetration site of the invasion may locate at the intermediate section along the vertical and longitudinal dimension.
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Ecossistema , Espécies Introduzidas , Inundações , Plantas , RiosRESUMO
Interleukin-33 (IL-33) which belongs to the interleukin-1 (IL-1) family is an alarmin cytokine with critical roles in tissue homeostasis, pathogenic infection, inflammation, allergy and type 2 immunity. IL-33 transmits signals through its receptor IL-33R (also called ST2) which is expressed on the surface of T helper 2 (Th2) cells and group 2 innate lymphoid cells (ILC2s), thus inducing transcription of Th2-associated cytokine genes and host defense against pathogens. Moreover, the IL-33/IL-33R axis is also involved in development of multiple types of immune-related diseases. In this review, we focus on current progress on IL-33-trigggered signaling events, the important functions of IL-33/IL-33R axis in health and diseases as well as the promising therapeutic implications of these findings.
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Abnormal lipid metabolism is regarded as a crucial cause of psoriasis. The specific mechanism of how phospholipase PLA2G4B mediates local immune dysfunction and skin lesions remains unclear. The aim of this study was to explore the mechanisms of anti-psoriasis and immune suppression effect by inhibiting PLA2G4B in psoriasis progression. We successfully transfected si-PLA2G4B in a murine keratinocyte cell-line PAM212 to verify the effect of progression by PLA2G4B. The Imiquimod psoriasis mouse model was then successfully constructed, followed by emulsion wrapped PLA2G4B-siRNA applied to the skin lesions. The phenotype, pathology, immunofluorescence staining of PLA2G4B, IL17, CD3, and CD1b, and bulk transcriptome analysis were performed to decipher the effect and mechanism of si-PLA2G4B. Interfering with PLA2G4B significantly inhibited the proliferation and migration of PAM212. The interference of PLA2G4B in vivo showed a therapeutic effect on psoriasis, comparable to that of betamethasone. The phenotype and pathology revealed reduced keratinocytes in the si-PLA2G4B group compared to the model mice. Immunofluorescence showed that CD1b, CD3+ T cells, and IL17 were suppressed in the skin lesions. RNA-seq and deconvolution revealed that immune cells such as myeloid dendritic cell and T cell CD8+ naive were inactivated. Th17 reduce the release of inflammatory factors such as IL17 and IL36. Pathway analysis revealed the potential therapeutic mechanism involved in the inhibition of sphingolipid or ceramide secretion. This study verified the anti-psoriatic effect of using si-PLA2G4B. The immune response was alleviated after administration. This phospholipase inhibition-based therapy sheds light on the pharmaceutical potential against psoriasis.