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ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu Guizhi Decoction (CGD) has a long history of use in China for the treatment of influenza, which involves the use of a variety of aromatic herbs. Our previous studies have found that the contents of aromatic constituents in CGD affected the efficacy of treatment of influenza-infected mice, suggesting a clue that essential oil from CGD may play a relatively important role in ameliorating influenza induced pneumonia. AIM OF THE STUDY: To evaluate the anti-influenza potential of essential oil derived from Chaihu Guizhi Decoction (CGD-EO), to characterize and predict the key active components in CGD-EO, and to explore the mechanism of action of CGD-EO. MATERIALS AND METHODS: CGD-EO was obtained by steam distillation, and the components of the essential oil were characterized by gas chromatography-mass spectrometry (GC-MS) in conjunction with the retention index. The constituents absorbed into the blood of mice treated with CGD-EO were analyzed by headspace solid phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). The potential anti-influenza active constituents and their possible action pathway were predicted by simulation using a network pharmacology approach. The protective effect of CGD-EO and its major components on H1N1/PR8-infected cells was determined using the CCK8 assay kit. Mice infected with influenza A virus H1N1/PR8 were administered different doses of CGD-EO orally and the body weights and lung weights were recorded. Mice with varying degrees of H1N1/PR8 infection were administered CGD-EO orally, and their daily weight, water consumption, and clinical indicators were recorded. Necropsies were conducted on days 3 and 5, during which lung weights were measured and lung tissues were preserved. Furthermore, the mRNA expression of the H1N1/PR8 virus and inflammatory factors in lung tissue was analyzed using RT-qPCR. RESULTS: (E)-cinnamaldehyde was the most abundant compound in the CGD-EO. The results of serum medicinal chemistry combined with network pharmacological analysis indicated that (E)-cinnamaldehyde and 3-phenyl-2-propenal may be potential active components of the CGD-EO anti-influenza, and may be involved in the NF-κB signalling pathway. In vitro studies have demonstrated that both CGD-EO and cinnamaldehyde exert a protective effect on MDCK cells infected with H1N1/PR8. In a 0.5 TCID50 H1N1/PR8-induced influenza model, mice treated with CGD-EO at a dose of 63.50 µg/kg exhibited a reduction in lung index, pathological lung lesions, and H1N1/PR8 viral gene levels. In addition, CGD-EO treatment was found to regulate the levels of inflammatory cytokines, including IL-6, TNF-α, and IFN-γ. Moreover, following three days of administration, an upregulation of NF-κB mRNA levels in mouse lung tissue was observed in response to CGD-EO treatment. CONCLUSIONS: The findings of our study indicate CGD-EO exerts a protective effect against H1N1-induced cytopathic lesions in vitro and is capable of alleviating H1N1-induced pneumonitis in mice. Moreover, it appears to be more efficacious in the treatment of mild symptoms of H1N1 infection. Studies have demonstrated that CGD-EO has antiviral potential to attenuate influenza-induced lung injury by modulating inflammatory cytokines and NF-κB signalling pathways during the early stages of influenza infection. It is possible that (E)-cinnamaldehyde is a potential active ingredient in the anti-influenza efficacy of CGD-EO.

Assuntos

Antivirais , Medicamentos de Ervas Chinesas , Óleos Voláteis , Infecções por Orthomyxoviridae , Animais , Óleos Voláteis/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Infecções por Orthomyxoviridae/tratamento farmacológico , Antivirais/farmacologia , Camundongos Endogâmicos BALB C , Pneumonia Viral/tratamento farmacológico , Masculino , Células Madin Darby de Rim Canino , Cães , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Pulmão/metabolismo , Humanos , Feminino , Pneumonia/tratamento farmacológico , Pneumonia/virologia , Pneumonia/metabolismo

RESUMO

Monolithic catalysts with excellent O3 catalytic decomposition performance were prepared by in situ loading of Co-doped KMn8O16 on the surface of nickel foam. The triple-layer structure with Co-doped KMn8O16/Ni6MnO8/Ni foam was grown spontaneously on the surface of nickel foam by tuning the molar ratio of KMnO4 to Co(NO3)2·6H2O precursors. Importantly, the formed Ni6MnO8 structure between KMn8O16 and nickel foam during in situ synthesis process effectively protected nickel foam from further etching, which significantly enhanced the reaction stability of catalyst. The optimum amount of Co doping in KMn8O16 was available when the molar ratio of Mn to Co species in the precursor solution was 2:1. And the Mn2Co1 catalyst had abundant oxygen vacancies and excellent hydrophobicity, thus creating outstanding O3 decomposition activity. The O3 conversion under dry conditions and relative humidity of 65%, 90% over a period of 5 hr was 100%, 94% and 80% with the space velocity of 28,000 hr-1, respectively. The in situ constructed Co-doped KMn8O16/Ni foam catalyst showed the advantages of low price and gradual applicability of the preparation process, which provided an opportunity for the design of monolithic catalyst for O3 catalytic decomposition.

Assuntos

Compostos de Manganês , Níquel , Óxidos , Ozônio , Óxidos/química , Níquel/química , Compostos de Manganês/química , Ozônio/química , Catálise , Umidade , Cobalto/química , Modelos Químicos , Poluentes Atmosféricos/química

RESUMO

OBJECTIVE: Total cavo-pulmonary connection (TCPC) is a palliative treatment for single ventricular malformations. For high-risk patients (preoperative mean pulmonary arterial pressure, mPAP > 15 mmHg), between the inhaled and oral targeted medications, the application of intravenous treprostinil as a bridge therapy to achieve "seamless" management is core postoperative treatment. This study intends to explore the effect of different administration regimens on early postoperative recovery. METHODS: This was a retrospective cohort study. High-risk pediatric patients (age ≤ 14 years) who underwent TCPC procedure in Fu Wai Hospital from 2015 to 2022 were included. Since the regimen of treprostinil was standardized in our center in 2021, the patients in 2020 and before were included in group 1, patients in 2021 and 2022 were included in group 2. The hemodynamic parameters were compared before and after the maintenance dose of treprostinil. The differences of demographic characteristics, surgical data and postoperative recovery were compared between the two groups. RESULTS: A total of 51 pediatric patients were included. Group 1 included 35 patients who received treprostinil at 1-3 postoperative days and an average dose of 12 ± 4 ng/(kg·min). Group 2 included 16 patients who received treprostinil within postoperative 1 day and an average dose of 22 ± 7 ng/(kg·min). There were no significant differences between the two groups in terms of age, weight, preoperative percutaneous oxygen saturation and mPAP,  heterotaxy syndrome, TCPC procedure type, other concurrent procedure, cardiopulmonary bypass time and aortic cross-clamp proportion (p > 0.05). After 24 h of treprostinil treatment, the mPAP in group 1 reduced from 17 ± 3 mmHg to 15 ± 2 mmHg (p < 0.001), and in group 2 from 17 ± 2 mmHg to 14 ± 2 mmHg (p < 0.001), with no difference between groups. In the postoperative recovery, patients in Group 2 exhibited a reduced duration of mechanical ventilation, 19 (11, 25) hours vs 69 (23, 189) hours, p = 0.001; a shorter stay in the ICU, 8 (6, 12) days vs 16 (9,26) days, p = 0.006; and a shorter postoperative length of stay, 27 (17,55) days vs 39 (29,58) days, p = 0.032. Patients in Group 2 also exhibited a lower incidence of thromboembolic events, 0 (0/26) vs 26% (9/35), p = 0.043; and the need for renal replacement therapy, 0 (0/26) vs 31% (11/35), p = 0.011. CONCLUSION: Treprostinil reduces pulmonary artery pressure after TCPC procedure. The standardized application of treprostinil may improve the postoperative recovery which should be proven by randomized controlled trials or matched cohort studies in the future.

Assuntos

Anti-Hipertensivos , Epoprostenol , Hipertensão Arterial Pulmonar , Humanos , Epoprostenol/análogos & derivados , Epoprostenol/administração & dosagem , Epoprostenol/uso terapêutico , Feminino , Masculino , Estudos Retrospectivos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Criança , Pré-Escolar , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/cirurgia , Adolescente , Lactente , Administração Intravenosa , Cardiopatias Congênitas/cirurgia , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Técnica de Fontan/métodos , Técnica de Fontan/efeitos adversos

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, but the molecular mechanisms underlying IBD are incompletely understood. In this study, we explored the role and regulating mechanism of otubain 2 (OTUB2), a deubiquitinating enzyme, in IBD. METHODS: To study the function of OTUB2 in IBD, we generated Otub2-/- mice and treated them with dextran sulfate sodium (DSS) to induce experimental colitis. Bone marrow transplantation was performed to identify the cell populations that were affected by OTUB2 in colitis. The molecular mechanism of OTUB2 in signal transduction was studied by various biochemical methods. RESULTS: OTUB2 was highly expressed in colon-infiltrating macrophages in both humans with IBD and mice with DSS-induced experimental colitis. Colitis was significantly aggravated in Otub2-/- mice and bone marrow chimeric mice receiving Otub2-/- bone marrow. OTUB2-deficiency impaired the production of cytokines and chemokines in macrophages in response to the NOD2 agonist muramyl dipeptide (MDP). Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2. Mechanistically, OTUB2 inhibited the proteasomal degradation of RIPK2 by removing K48-linked polyubiquitination on RIPK2, which was mediated by the active C51 residue in OTUB2. In mice, OTUB2 ablation abolished the protective effects of MDP administration in colitis. CONCLUSION: This study identified OTUB2 as a novel regulator of intestinal inflammation.

Assuntos

Proteína Adaptadora de Sinalização NOD2 , Proteína Serina-Treonina Quinase 2 de Interação com Receptor , Transdução de Sinais , Animais , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Camundongos , Proteína Adaptadora de Sinalização NOD2/metabolismo , Humanos , Colite/metabolismo , Colite/induzido quimicamente , Modelos Animais de Doenças , Camundongos Knockout , Camundongos Endogâmicos C57BL , Inflamação/metabolismo , Ubiquitinação

RESUMO

BACKGROUND: Studies have shown that abnormal temperature at night is a risk factor for respiratory health. However, there is limited evidence on the impact of hot and cold nights on cause-specific diseases such as pneumonia, which is a leading cause of morbidity and mortality in children. METHODS: We collected daily data on pneumonia hospitalisations in children under five years from 2011 to 2017 in three low-, middle- and high-income countries (Bangladesh, China, and Australia). The intensity of hot and cold nights was measured by excess temperature. A space-time-stratified case-crossover analysis was used to estimate the association between hot and cold nights and childhood pneumonia hospitalisations. We further estimated the fraction of childhood pneumonia hospitalisations attributable to hot and cold nights. RESULTS: Both hot and cold nights were associated with an increased risk of hospitalisations for childhood pneumonia in low-, middle-, and high-income countries, with a greater disease burden from hot nights. Specifically, the fraction of childhood pneumonia attributable to hot nights was the largest in Australia [21.2%, 95% confidence interval (CI): 11.8%-28.1%], followed by Bangladesh (15.2%, 95% CI: 4.1%-23.8%) and China (2.7%, 95% CI: 0.4%-4.7%). Additionally, the fraction of childhood pneumonia attributable to cold nights was 1.3% (95% CI: 0.4%-2.0%) in Bangladesh and 0.4% (95% CI: 0.1%-0.7%) in China. CONCLUSION: This multi-country study suggests that hot and cold nights are not only associated with a higher risk of pneumonia hospitalisations in children but also responsible for substantial fraction of hospitalisations, with a greater impact from hot nights.

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PURPOSE OF REVIEW: Ischemic stroke is the second deadly disease worldwide, but current treatment is very limited. The brain, rich in lipids and high in oxygen consumption, is susceptible to damage from oxidative stress after ischemic stroke. Thus, antioxidants are promising neuroprotective agents for treatment and prevention of ischemic stroke. Coenzyme Q10 is the only lipophilic antioxidant that can be synthesized de novo by cells and plays a key role as an electron carrier in the oxidative phosphorylation of the mitochondrial electron transport chain. However, the reduced form of coenzyme Q10 (Ubiquinol) levels are significantly deficient in the brain. The aim of this article is to review the therapeutic effects and mechanisms of coenzyme Q10 in ischemic stroke. RECENT FINDINGS: Current studies have found that coenzyme Q10 protects and treats ischemic stroke through multiple mechanisms based on the evidence from in vitro experiments, in vivo experiments, and clinical observations. For the first time, we reviewed the neuroprotective effects of coenzyme Q10 in ischemic stroke. Coenzyme Q10 exerts neuroprotective effects after ischemic stroke through anti-oxidative stress, anti-nitrosative stress, anti-inflammation, and anti-cell death. Here, we provided the evidence on the therapeutic and preventive effects of coenzyme Q10 in ischemic stroke and suggested the potential value of coenzyme Q10 as a medication candidate.

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"Brain fog," a persistent cognitive impairment syndrome, stands out as a significant neurological aftermath of coronavirus disease 2019 (COVID-19). Yet, the underlying mechanisms by which COVID-19 induces cognitive deficits remain elusive. In our study, we observed an upregulation in the expression of genes linked to the inflammatory response and oxidative stress, whereas genes associated with cognitive function were downregulated in the brains of patients infected with COVID-19. Through single-nucleus RNA sequencing (snRNA-seq) analysis, we found that COVID-19 infection triggers the immune responses in microglia and astrocytes and exacerbates oxidative stress in oligodendrocytes, oligodendrocyte progenitors (OPCs), and neurons. Further investigations revealed that COVID-19 infection elevates LUC7L2 expression, which inhibits mitochondrial oxidative phosphorylation (OXPHOS) and suppresses the expression of mitochondrial complex genes such as MT-ND1, MT-ND2, MT-ND3, MT-ND4L, MT-CYB, MT-CO3, and MT-ATP6. A holistic approach to protect mitochondrial complex function, rather than targeting a single molecular, should be an effective therapeutic strategy to prevent and treat the long-term consequences of "long COVID."

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As a novel type of macrocycles with attractive planar chirality, pillar[5]arenes have gained increasing research interest over the past decades, enabling their widespread applications in diverse fields such as porous materials, molecular machines, and chiral luminescence materials. However, the catalytic methodology towards the enantioselective synthesis of planar chiral pillar[5]arenes remains elusive. Here we report a novel method for the enantioselective synthesis of planar chiral pillar[5]arenes via asymmetric Sonogashira coupling, giving access to a wide range of highly functionalized planar chiral pillar[5]arenes, including both homo- and hetero-rimmed ones, with excellent enantioselectivities. Attractively, the resultant planar chiral pillar[5]arenes show great potential for widespread use in many areas such as chiral luminescent materials. This work not only enables the successful synthesis of planar chiral pillar[5]arenes with abundant structural and functional diversity as key building blocks for practical applications but also enriches the asymmetric cross-coupling methodologies in organic synthetic chemistry.

RESUMO

BACKGROUND: Oncocytic thyroid carcinoma (OTC) is a rare subtype of thyroid cancer known for its distinctive morphology and high likelihood of recurrence, setting it apart from follicular thyroid carcinoma (FTC). Despite this, there is limited research comparing the clinicopathological characteristics and outcomes of OTC and FTC. METHODS: We retrospectively searched through the Surveillance, Epidemiology, and End-Results (SEER) database (2004-2015) for histologically diagnosed OTC and FTC patients. Kaplan-Meier analysis, propensity score matching (PSM), univariate Cox proportional risk regression model, and subgroup analysis were employed to investigate the prognostic effect of clinicopathological features and treatment regimens on survival outcomes of OTC and FTC patients. RESULTS: 2329 OTC patients and 5679 FTC patients were included in the study. OTC patients were prone to older age, white race, lymph node metastasis, distal metastasis, extension and multiple primary tumors compared with FTC patients. After using a 1:1 PSM matching ratio, there were no significant differences in demographic and clinicopathological characteristics between the matched groups. Further Cox regression analysis showed that OTC patients had lower overall survival (OS) and cancer-specific survival (CSS) in contrast with FTC patients. Subgroup survival analysis suggested that the OTC patients were related to lower OS in subgroups including those over 55 years old, male sex, white ethnicity, extrathyroidal extension, single primary tumor, surgery and without chemotherapy compared with the FTC patients in these subgroups. In addition, the OTC patients were connected with lower CSS in subgroups including male sex, white ethnicity, married status, tumor size is less than 20 mm or more than 40 mm, N0 stage, localized stage, single primary tumor, surgery, radiotherapy, and without chemotherapy compared with the FTC patients in these subgroups. Meanwhile, the OTC patients had lower CSS compared to FTC patients regardless of age and extrathyroidal extension. CONCLUSIONS: The results suggested that OTC patients have unique clinical features and poorer prognoses compared to FTC patients. Surgical resection and radioactive iodine therapy are recommended for OTC patients and FTC patients. It is worth noting that the prognosis of OTC relies largely on the selection of treatment strategies. Therefore, our results highlighted the clinical significance of the early distinguishment and the correct choice of treatment in OTC patients.

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PURPOSE: To assess the value of glutamate chemical exchange saturation transfer (GluCEST) after whole-brain radiotherapy (WBRT) as an imaging marker of radiation-induced brain injury (RBI) and to preliminarily show the feasibility of multiparametric MRI-guided organ at risk (OAR) avoidance. METHODS: Rats were divided into two groups: the control (CTRL) group (n = 9) and the RBI group (n = 9). The rats in the RBI group were irradiated with an X­ray radiator and then subjected to a water maze experiment 4 weeks later. In combination with high-performance liquid chromatography (HPLC), we evaluated the value of GluCEST applied to glutamate changes for RBI and investigated the effect of such changes on glutamatergic neuronal function. RESULTS: The average GluCEST values were markedly lower in the hippocampus and cerebral cortex. Positive correlations were observed between GluCEST values and regional homogeneity (ReHo) values in both the hippocampus and the cerebral cortex. HPLC showed a positive correlation with GluCEST values in the hippocampus. GluCEST values were positively correlated with spatial memory. CONCLUSION: GluCEST MRI provides a visual assessment of glutamate changes in RBI rats for monitoring OAR cognitive toxicity reactions and may be used as a biomarker of OAR avoidance as well as metabolism to facilitate monitoring and intervention in radiation damage that occurs after radiotherapy.

RESUMO

Objectives: In-depth understanding of osteonecrosis of femoral head (ONFH) has revealed that degeneration of the hip cartilage plays a crucial role in ONFH progression. However, the underlying molecular mechanisms and susceptibility to environmental factors in hip cartilage that contribute to ONFH progression remain elusive. Methods: We conducted a multiomics study and chemical-gene interaction analysis of hip cartilage in ONFH. The differentially expressed genes (DEGs) involved in ONFH progression were identified in paired hip cartilage samples from 36 patients by combining genome-wide DNA methylation profiling, gene expression profiling, and quantitative proteomics. Gene functional enrichment and pathway analyses were performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Functional links between proteins were discovered through protein-protein interaction (PPI) networks. The ONFH-associated chemicals were identified by integrating the DEGs with the chemical-gene interaction sets in the Comparative Toxicogenomics Database (CTD). Finally, the DEGs, including MMP13 and CHI3L1, were validated via quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Results: Twenty-two DEGs were identified across all three omics levels in ONFH cartilage, 16 of which were upregulated and six of which were downregulated. The collagen-containing extracellular matrix (ECM), ECM structural constituents, response to amino acids, the relaxin signaling pathway, and protein digestion and absorption were found to be primarily involved in cartilage degeneration in ONFH. Moreover, ten major ONFH-associated chemicals were identified, including, benzo(a)pyrene, valproic acid, and bisphenol A. Conclusion: Overall, our study identified several candidate genes, pathways, and chemicals associated with cartilage degeneration in ONFH, providing novel clues into the etiology and biological processes of ONFH progression.

Assuntos

Necrose da Cabeça do Fêmur , Perfilação da Expressão Gênica , Mapas de Interação de Proteínas , Humanos , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/genética , Necrose da Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Proteômica/métodos , Metilação de DNA/efeitos dos fármacos , Redes Reguladoras de Genes , Multiômica

RESUMO

Changes in plant morphology due to mechanical stimulation are known as thigmo responses. As climbing organs in plants, tendrils can sense mechanical stimulation after attaching to a support and then change their morphology within a short time. Here, the thigmo responses of cucumber tendril were investigated. Our results showed that mechanical stimulation stopped tendril elongation and that tendril length was determined by the distance from the support in cucumber. The mimicry touch treatment indicated that mechanical stimulation stopped tendril elongation by inhibiting cell expansion. RNA-seq data showed that three gibberellin (GA) metabolic genes (CsGA2ox3, CsCYP714A2, and CsCYP714A3) were upregulated in mechanically stimulated tendrils, and a major endogenous bio-active GA (GA4) was reduced in mechanically stimulated tendrils. The roles of CsGA2ox3, CsCYP714A2, and CsCYP714A3 in GA deactivation were confirmed by their overexpression in transgenic Arabidopsis. Moreover, exogenous GA treatment recovered tendril elongation under mechanical stimulation, whereas exogenous uniconazole treatment inhibited tendril elongation without mechanical stimulation, suggesting that mechanical stimulation stopped tendril elongation, depending on GA deactivation. In summary, our results suggest that GA deactivation plays an important role in tendril thigmo response, ensuring that tendrils obtain a suitable final length according to their distance from the support in cucumber.

RESUMO

The study aimed to investigating the mechanisms of relieved intestinal barrier damage by dynamic high-pressure microfluidization assisted with galactooligosaccharide- glycated whey protein isolate. The modifications changed the multi-structure, and the modified whey protein isolate could promote the proliferation of IEC-6 cells and contributed to the restoration of LPS-induced occludin damage in IEC-6 cells. Also, it could repair cyclophosphamide-induced ileal villus rupture and crypt destruction in BALB/c mice, significantly altered the abundance of dominant bacteria, which were associated with propionic acid, butyric acid, isovaleric acid, and valeric acid. Ileum transcriptomics revealed that the modified whey protein isolate significantly regulate of the levels of Cstad, Cyp11a1, and Hs6st2 genes, relating to the increase of propionic acid, isovaleric acid, and valeric acid. In conclusion, galactooligosaccharide- modified whey protein isolate could regulate the level of Cstad, Cyp11a1 and Hs6st2 genes by altering the gut microbial structure and the level of SCFAs, thereby repairing the intestinal barrier.

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BACKGROUND: Everolimus is an effective treatment for renal angiomyolipoma associated with TSC (TSC-RAML). However, its impact on hematologic parameters in TSC-RAML patients remains unclear. METHODS: Hematologic data were collected from TSC-RAML patients undergoing everolimus treatment in two registered clinical trials. Dynamic changes in hematologic parameters during treatment were analyzed. Additionally, we also explored variations in hematologic impact based on gender and age within the patient population. RESULT: A total of 55 patients from the two clinical trials are included in this analysis. Hemoglobin, white blood cells (WBC), lymphocytes, neutrophils, and platelet showed significant decreases during everolimus treatment (P < 0.05). However, the decline in hemoglobin, WBC, and neutrophils attenuated by the 12th month (P ≥ 0.05). Aspartate transaminase (AST), Alanine transferase (ALT), total cholesterol (TC), and triglyceride (TG) increased significantly during everolimus treatment (P < 0.05), and these increases persisted throughout the year-long treatment. Hemoglobin decreased significantly more in male patients (- 15 vs - 6, P = 0.010), and AST showed a more significant increase in males (7.0 vs 3.0, P = 0.041). Platelet counts decreased significantly more in younger patients (≤ 30 years old) compared to older patients (- 50 vs - 14, P = 0.020). CONCLUSION: Everolimus administration in TSC-RAML patients may increase hematologic risks, with male and younger patients potentially exhibiting greater susceptibility to these effects.

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BACKGROUND: Depression and anxiety are prevalent after stroke and associated with poor outcomes. We previously co-developed a stroke-specific self-management intervention, HEADS: UP (Helping Ease Anxiety and Depression after Stroke). The two studies reported here aimed to test the feasibility and acceptability of the HEADS: UP course and supporting materials, and research processes ahead of a definitive trial. METHODS: We recruited community-dwelling stroke survivors (SS) ≥ 3 months post-stroke, with symptoms of mood disorder (Hospital Anxiety and Depression Scale ≥ 8). Participants could 'enrol' a family member/ 'other' to take part with them, if desired. Study 1 tested HEADS: UP delivered in-person, and informed optimisation of research processes and intervention delivery and materials. In a pragmatic response to Covid-related socialising restrictions, HEADS: UP was then adapted for online delivery, tested in Study 2. The primary outcome (both studies) was the feasibility (acceptability, fidelity) of the intervention and of research processes. Quantitative data (including patient-reported outcome measures (PROMs) assessing mood and quality of life) and qualitative data were collected pre-/post-intervention. Descriptive statistics were used to analyse quantitative data; a thematic framework approach was used to analyse qualitative data. Both studies received ethical approval prior to commencement. RESULTS: Study 1 Feasibility: 13 (59.1%) of 22 potentially eligible stroke survivors consented; aged 66 (median, interquartile range (IQR) 14); male (n = 9; 69%); 28 (IQR 34) months post-stroke. Of these, n = 10 (76.9%) completed PROMS pre-intervention; n = 6 (46.2%) post-intervention. Acceptability: Nine (69.2%) of the 13 participants attended ≥ 4 core intervention sessions. Aspects of screening and data collection were found to be burdensome. Study 2 Feasibility: SS n = 9 (41%) of 22 potentially eligible stroke survivors consented; aged 58 years (median; IQR 12); male (n = 4; 44.4%); 23 (IQR 34) months post-stroke. Of these, n = 5 (55.6%) completed PROMS pre-intervention; n = 5 (55.6%) post-intervention. Acceptability: Five (55.6%) of the 9 participants attended ≥ 4 core sessions. They found online screening and data collection processes straightforward.

RESUMO

Recent research in spatial transcriptomics allows researchers to analyze gene expression without losing spatial information. Spatial information can assist in cell communication, identification of new cell subtypes, which provides important research methods for multiple fields such as microenvironment interactions and pathological processes of diseases. Identifying spatial domains is an important step in spatial transcriptomics analysis, and improving spatial clustering methods can benefit for identifying spatial domains. In addition to eliminating noise in original gene expression, how to use spatial information to assist clustering has also become a new problem. A variety of calculating methods have been applied to spatial clustering, including contrastive learning methods. However, existing spatial clustering methods based on contrastive learning use data augmentation to generate positive and negative pairs, which will inevitably destroy the biological meaning of the data. We propose a new self-supervised spatial clustering method based on contrastive learning, Augmentation-Free Spatial Clustering (AFSC), which integrates spatial information and gene expression to learn latent representations. We construct a contrastive learning module without negative pairs or data augmentation by designing Teacher and Student Encoder. We also design an unsupervised clustering module to make clustering and contrastive learning be trained together. Experiments on multiple spatial transcriptomics datasets at different resolutions demonstrate that our method performs well in self-supervised spatial clustering tasks. Furthermore, the learned representations can be used for various downstream tasks including visualization and trajectory inference.

RESUMO

Among plants' transcription factor families, the bHLHs family has a significant influence on plant development processes and stress tolerance. However, there have been no relevant studies performed on the bHLHs family in kenaf (Hibiscus cannabinus L). Here, the bHLH transcription factors in kenaf were found using bioinformatics, and a total of 141 kenaf HcbHLH transcription factors were identified. Phylogenetic analysis revealed that these transcription factors were irregularly distributed on 18 chromosomes and separated into 20 subfamilies. Additionally, utilizing the transcriptome data under diverse abiotic pressures, the expression of HcbHLH members was analyzed under different stress conditions. A typical HcbHLH abiotic stress transcription factor, HcbHLH88, was exposed to salt, drought, heavy metals, and ABA. The findings revealed that HcbHLH88 might be activated under salt, drought, cadmium stress, and ABA conditions. Furthermore, HcbHLH88's function under salt stress conditions was studied after it was silenced using the virus-induced gene silencing (VIGS) technique. Reduced antioxidant enzyme activity and stunted plant development were seen in VIGS-silenced seedlings. Stress-related genes were shown to be considerably downregulated in the HcbHLH88-silenced kenaf plants, according to the qRT-PCR study. In conclusion, this study provides the first systematic gene family analysis of the kenaf bHLH gene family and provides a preliminary validation of the salt tolerance function of the HcbHLH88 gene. This study lays the foundation for future research on the regulatory mechanisms of bHLH genes in response to abiotic stresses. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01504-y.

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Catalysts with high catalytic activity and low production cost are important for industrial application of heterogeneous catalytic ozonation (HCO). In this study, we designed a carbon-coated aluminum oxide carrier (C-Al2O3) and reinforced it with Mn-Fe bimetal assemblages to prepare a high-performance catalyst Mn-Fe/C-Al2O3. The results showed that the carbon embedding significantly improved the abundance of surface oxygen functional groups, conductivity, and adsorption capacity of γ-Al2O3, while preserving its exceptional mechanical strength as a carrier. The prepared Mn-Fe/C-Al2O3 catalyst exhibited satisfactory catalytic ozonation activity and stability in the degradation of p-nitrophenol (PNP). Electron paramagnetic resonance (EPR) and quenching experiments reveal that radical (•OH and •O2-) and nonradical oxidation (1O2) dominated the PNP degradation process. Theoretical calculations corroborated that the anchored atomic Fe and Mn sites regulated the local electronic structure of the catalyst. This modulation effectively promoted the activation of O3 molecules, resulting in the generation of atomic oxygen species (AOS) and reactive oxygen species (ROS). The economic analysis on Mn-Fe/C-Al2O3 revealed that it was a cost-competitive catalyst for HCO. This study not only deepens the understanding on the reaction mechanism of HCO with transition metal/carbon composite catalysts, also provides a high-performance and cost-competitive ozone catalyst for prospective application.

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INTRODUCTION: In primary biliary cholangitis (PBC), approximately 40% of patients respond incompletely to first-line treatment with ursodeoxycholic acid (UDCA), resulting in a poorer prognosis. Although obeticholic acid (OCA) is approved as a second-line therapy, it is not well-tolerated by patients with significant itching or advanced cirrhosis. Peroxisome proliferator-activated receptor (PPAR) agonists, including fibrates traditionally known as antihyperlipidemic agents, have emerged as potent alternatives for treating PBC patients with an incomplete response to UDCA. AREAS COVERED: This article provides a detailed overview of the mechanisms of PPAR agonists and evaluates their efficacy and adverse events, focusing on findings from recent phase III clinical trials. EXPERT OPINION: PPAR agonists are significant alternatives in the treatment of PBC, showing potential to enhance biochemical responses, reduce mortality, and alleviate pruritus. Long-term outcomes for PBC patients, particularly those with advanced disease, and longitudinal data on the antipruritic effects of PPAR agonists require further investigation. Combining PPAR agonists with other treatments and advancing personalized approaches may enhance therapeutic efficacy and patient outcomes. This study provides future perspectives on the roles of PPAR agonists in PBC management.

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BACKGROUND AND OBJECTIVES: The common tendinous ring (CTR), also known as the common annular tendon or annulus of Zinn, is a critical anatomic structure located at the convergence of the orbital apex, superior orbital fissure (SOF), optic canal, and the anterior aspect of the lateral sellar compartment. It plays a vital role in both neurosurgical and neuro-ophthalmological interventions. The aim of this study was to delineate the complex 3-dimensional (3D) topography of the CTR and explore its implications for surgical procedures. METHODS: Ten formalin-fixed skull base specimens from adult Chinese cadavers were meticulously dissected to investigate the morphology of the CTR, focusing particularly on its relationship with the 4 extraocular rectus tendons, the optic strut, the SOF, and the optic canal. Additional skull base specimens were subjected to 3D surface scanning, computed tomography, and histopathological examinations to deepen our understanding of the CTR's structural complexities. RESULTS: The CTR establishes a spatial, 3D tendinous assembly, encompassing 4 rectus tendons, 2 tendinous connections, and a singular common tendinous root. These components interlink to form a distinctive dual-ring configuration, featuring the optic foramen and the oculomotor foramen. The posterior part of the superior rectus tendon demarcates the common boundary between these 2 foramina. The oculomotor foramen itself serves as the central sector of the SOF. Precise incisions of the medial and lateral tendinous connections and fusions are essential for safely opening the CTR. CONCLUSION: The structural composition, interconnections, and dual-ring configuration of the CTR are crucial for precise and safe surgery of orbital apex and adjacent regions.