[Mechanism of traditional Chinese medicine in regulating NLRP3 inflammasomes to alleviate renal interstitial fibrosis in diabetic nephropathy: a review].

Diabetic nephropathy(DN), a progressive chronic kidney disease(CKD) induced by diabetes mellitus, is the main cause of end-stage renal disease. Renal interstitial fibrosis(RIF) is an irreversible factor in the progression and deterioration of the renal function in DN. Chronic inflammation has become a key link in the pathogenesis of DN-RIF. The NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome is an important inflammatory regulator regulated by a variety of signals. It promotes the production of pro-inflammatory cytokines and induces renal inflammatory cell infiltration to participate in the process of renal fibrosis, demonstrating a complex mechanism of action. In view of the important role of NLRP3 inflammasomes in the prevention and treatment of DN-RIF, a large number of experimental studies have demonstrated that traditional Chinese medicine(TCM) can reduce the inflammation by regulating the pathways involving NLRP3 inflammasome, thereby slowing down the progression of DN-RIF and improving the renal function. This paper reviews the relationship between NLRP3 inflammasomes and DN-RIF, and the research progress in the mechanism of TCM intervention in NLRP3 inflammasomes to alleviate DN-RIF, aiming to provide new ideas for the targeted treatment of DN-RIF.

Mechanical guidance to self-organization and pattern formation of stem cells.

The self-organization of stem cells (SCs) constitutes the fundamental basis of the development of biological organs and structures. SC-driven patterns are essential for tissue engineering, yet unguided SCs tend to form chaotic patterns, impeding progress in biomedical engineering. Here, we show that simple geometric constraints can be used as an effective mechanical modulation approach that promotes the development of controlled self-organization and pattern formation of SCs. Using the applied SC guidance with geometric constraints, we experimentally uncover a remarkable deviation in cell aggregate orientation from a random direction to a specific orientation. Subsequently, we propose a dynamic mechanical framework, including cells, the extracellular matrix (ECM), and the culture environment, to characterize the specific orientation deflection of guided cell aggregates relative to initial geometric constraints, which agrees well with experimental observation. Based on this framework, we further devise various theoretical strategies to realize complex biological patterns, such as radial and concentric structures. Our study highlights the key role of mechanical factors and geometric constraints in governing SCs' self-organization. These findings yield critical insights into the regulation of SC-driven pattern formation and hold great promise for advancements in tissue engineering and bioactive material design for regenerative application.

[Clinical Features and Prognostic Analysis of Newly Diagnosed Diffuse Large B-cell Lymphoma Combined with Hemophagocytic Syndrome].

OBJECTIVE: To compare the clinical features and prognosis between newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients with and without hemophagocytic syndrome (HPS). METHODS: The clinical data of 45 DLBCL patients in Gansu Provincial Hospital from January 2012 to December 2021 were retrospectively analyzed. The patients were divided into HPS group (15 cases) and non-HPS group (30 cases). The clinical features and prognosis of the two groups were compared, and survival analysis was performed using Kaplan-Meier method. RESULTS: Patients with HSP were mostly characterized by fever, cytopenia and splenomegaly. The levels of ferritin and soluble CD25 increased in all patients. The level of fibrinogen decreased in 66.67% patients, while triglyceride increased in 53.33% patients, and bone marrow hemophagocytosis occurred in 80.00% patients. Compared with non-HSP group, the proportions of patients with advanced stage (Ann Arbor stage III/IV) and lactate dehydrogenase (LDH) ≥240 U/L were higher in HSP group (both P < 0.05). The median survival time of HSP group was 8.0 months, which was significantly shorter than 45.5 months of non-HSP group (P < 0.001). CONCLUSION: The DLBCL patients with HPS have later Ann Arbor stage, higher LDH and shorter overall survival time compared with patients without HPS.

Punicalagin promotes mincle-mediated phagocytosis of macrophages via the NF-κB and MAPK signaling pathways.

Punicalagin (PUN) is a polyphenol derived from the pomegranate peel. It has been reported to have many beneficial effects, including anti-inflammatory, anti-oxidant, and anti-proliferation. However, the role of PUN in macrophage phagocytosis is currently unknown. In this study, we found that pre-treatment with PUN significantly enhanced phagocytosis by macrophages in a time- and dose-dependent manner in vitro. Moreover, KEGG enrichment analysis by RNA-sequencing showed that differentially expressed genes following PUN treatment were significantly enriched in phagocyte-related receptors, such as the C-type lectin receptor signaling pathway. Among the C-type lectin receptor family, Mincle (Clec4e) significantly increased at the mRNA and protein level after PUN treatment, as shown by qRT-PCR and western blotting. Small interfering RNA (siRNA) mediated knockdown of Mincle in macrophages resulted in down regulation of phagocytosis. Furthermore, western blotting showed that PUN treatment enhanced the phosphorylation of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) in macrophages at the early stage. Mincle-mediated phagocytosis by PUN was inhibited by PDTC (a NF-κB inhibitor) and SB203580 (a p38 MAPK inhibitor). In addition, PUN pre-treatment enhanced phagocytosis by peritoneal and alveolar macrophages in vivo. After intraperitoneal injection of Escherichia coli (E.coli), the bacterial load of peritoneal lavage fluid and peripheral blood in PUN pre-treated mice decreased significantly. Similarly, the number of bacteria in the lung tissue significantly reduced after intranasal administration of Pseudomonas aeruginosa (PAO1). Taken together, our results reveal that PUN enhances bacterial clearance in mice by activating the NF-κB and MAPK pathways and upregulating C-type lectin receptor expression to enhance phagocytosis by macrophages.

PHE-SICH-CT-IDS: A benchmark CT image dataset for evaluation semantic segmentation, object detection and radiomic feature extraction of perihematomal edema in spontaneous intracerebral hemorrhage.

BACKGROUND AND OBJECTIVE: Intracerebral hemorrhage is one of the diseases with the highest mortality and poorest prognosis worldwide. Spontaneous intracerebral hemorrhage (SICH) typically presents acutely, prompt and expedited radiological examination is crucial for diagnosis, localization, and quantification of the hemorrhage. Early detection and accurate segmentation of perihematomal edema (PHE) play a critical role in guiding appropriate clinical intervention and enhancing patient prognosis. However, the progress and assessment of computer-aided diagnostic methods for PHE segmentation and detection face challenges due to the scarcity of publicly accessible brain CT image datasets. METHODS: This study establishes a publicly available CT dataset named PHE-SICH-CT-IDS for perihematomal edema in spontaneous intracerebral hemorrhage. The dataset comprises 120 brain CT scans and 7,022 CT images, along with corresponding medical information of the patients. To demonstrate its effectiveness, classical algorithms for semantic segmentation, object detection, and radiomic feature extraction are evaluated. The experimental results confirm the suitability of PHE-SICH-CT-IDS for assessing the performance of segmentation, detection and radiomic feature extraction methods. RESULTS: This study conducts numerous experiments using classical machine learning and deep learning methods, demonstrating the differences in various segmentation and detection methods on the PHE-SICH-CT-IDS. The highest precision achieved in semantic segmentation is 76.31%, while object detection attains a maximum precision of 97.62%. The experimental results on radiomic feature extraction and analysis prove the suitability of PHE-SICH-CT-IDS for evaluating image features and highlight the predictive value of these features for the prognosis of SICH patients. CONCLUSION: To the best of our knowledge, this is the first publicly available dataset for PHE in SICH, comprising various data formats suitable for applications across diverse medical scenarios. We believe that PHE-SICH-CT-IDS will allure researchers to explore novel algorithms, providing valuable support for clinicians and patients in the clinical setting. PHE-SICH-CT-IDS is freely published for non-commercial purpose at https://figshare.com/articles/dataset/PHE-SICH-CT-IDS/23957937.

High-Temperature Phase Transition with Switchable Dielectric Behavior and Significant Photoluminescence Changes in a Zero-Dimensional Hybrid SbBr6 Perovskite.

In the past decade, metal halide materials have been favored by many researchers because of their excellent physical and chemical properties under thermal, electrical, and light stimuli, such as ferroelectricity, dielectric, nonlinearity, fluorescence, and semiconductors, greatly promoting their application in optoelectronic devices. In this study, we successfully constructed an unleaded organic-inorganic hybrid perovskite crystal: [Cl-C6H4-(CH2)2NH3]3SbBr6 (1), which underwent a high-temperature reversible phase transition near Tp = 368 K. The phase transition behavior of 1 was characterized by differential scanning calorimetry, accompanied by a thermal hysteresis of 6 K. In addition, variable-temperature Raman spectroscopy analysis and PXRD further verified the sensitivity of 1 to temperature and the phase transition from low symmetry to high symmetry. Temperature-dependent dielectric testing shows that 1 can be a sensitive switching dielectric constant switching material. Remarkably, 1 exhibits strong photoluminescence emission with a wavelength of 478 nm and a narrow band gap of 2.7 eV in semiconductors. As the temperature increases and decreases, fluorescence undergoes significant changes, especially near Tc, which further confirms the reversible phase transition of 1. All of these findings provide new avenues for designing and assembling new phase change materials with high Tp and photoluminescence properties.

KIF2C: An important factor involved in signaling pathways, immune infiltration, and DNA damage repair in tumorigenesis.

BACKGROUNDS: Poorly regulated mitosis and chromosomal instability are common characteristics in malignant tumor cells. Kinesin family member 2 C (KIF2C), also known as mitotic centromere-associated kinesin (MCAK) is an essential component during mitotic regulation. In recent years, KIF2C was shown to be dysregulated in several tumors and was involved in many aspects of tumor self-regulation. Research on KIF2C may be a new direction and target for anti-tumor therapy. OBJECT: The article aims at reviewing current literatures and summarizing the research status of KIF2C in malignant tumors as well as the oncogenic signaling pathways associated with KIF2C and its role in immune infiltration. RESULT: In this review, we summarize the KIF2C mechanisms and signaling pathways in different malignant tumors, and briefly describe its involvement in pathways related to classical chemotherapeutic drug resistance, such as MEK/ERK, mTOR, Wnt/ß-catenin, P53 and TGF-ß1/Smad pathways. KIF2C upregulation was shown to promote tumor cell migration, invasion, chemotherapy resistance and inhibit DNA damage repair. It was also highly correlated with microRNAs, and CD4 +T cell and CD8 +T cell tumor immune infiltration. CONCLUSION: This review shows that KIF2C may function as a new anticancer drug target with great potential for malignant tumor treatment and the mitigation of chemotherapy resistance.

Burnout among radiology residents: a systematic review and meta-analysis.

OBJECTIVE: To analyze the prevalence of burnout among radiology residents. METHOD: Five databases (PubMed, Web of Science, Embase, PsycINFO, and Scopus) were searched for studies reporting burnout in radiology residents for the period up to November 7, 2022. RESULTS: A total of 423 studies were identified, and eventually, 16 studies were selected for the qualitative analysis, of which 11 studies were used in the meta-analysis. There was a total of 2164 radiology residents. Six studies reported the prevalence of burnout but the data could not be pooled due to their inconsistent definitions of burnout. The mean scores of three burnout subscales indicated a moderate to high degree of severity: emotional exhaustion = 25.2 (95% CI, 22.1-28.3; I2 = 94.4%), depersonalization = 10.2 (95% CI, 8.5-11.9; I2 = 93.0%), and low perception of personal accomplishment = 32.9 (95% CI, 30.5-35.4; I2 = 94.4%). The pooled prevalence of high-degree emotional exhaustion was 49.9% (95% CI, 43.6-56.1%; I2 = 55.7%), high-degree depersonalization was 45.1% (95% CI, 38.3-52.0%; I2 = 63.2%), and high-degree diminished personal accomplishment was 58.2% (95% CI, 36.0-77.6%; I2 = 84.9%). The impact of the COVID-19 pandemic on radiology residents was not investigated. In addition, there are inconsistent findings on the effects of female sex, seniority, and social support on burnout. CONCLUSIONS: About half of the radiology residents showed at least one of the three burnout manifestations (emotional exhaustion, depersonalization, and personal accomplishment), with a moderate to high degree of severity. CLINICAL RELEVANCE STATEMENT: Such a high prevalence and severity of burnout among radiology residents warrant the attention of residency program directors. KEY POINTS: • Burnout, not uncommon among radiology residents, has not been effectively analyzed. • Nearly half of the radiology residents experience at least one of the three manifestations of burnout to a moderate to high degree. • The high prevalence and severe degree of burnout among radiology residents warrant the attention of residency program directors.

TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 may participate in the process of the coexistence of asthma and OSA.

OBJECTIVE: To investigate the role of TWIK-related acid-sensitive potassium channels TASK-1 and TASK-3 in the mechanism of asthma combined with obstructive sleep apnea (OSA) in mice. METHOD: C57BL/6 mice were randomly divided into four groups: control group (NS-RA), asthma group (OVA-RA), OSA group (NS-IH), and asthma combined with OSA group (OVA-IH). After monitoring lung function in each group, the expression levels of TASK-1 and TASK-3 mRNA and protein in lung tissues were measured, and the correlation between the changes of both and lung function was analyzed. RESULTS: A total of 64 male mice were studied. Penh, serum IgE concentrations, and the percentage of eosinophils in bronchoalveolar lavage fluid (BALF) were higher in OVA-RA and OVA-IH mice compared with NS-RA (P < 0.05),while the above indexes were slightly elevated in NS-IH mice compared with NS-RA (P > 0.05), where the Penh and the percentage of eosinophils in BALF was higher in OVA-IH mice than NS-IH (P < 0.05).Increased TASK-3 mRNA expression (P < 0.05) as well as TASK-1 and TASK-3 protein expression (P > 0.05) in lung tissues of OVA-RA and NS-IH mice compared with NS-RA, and TASK-3 mRNA expression was slightly more in the OVA-IH group compared with NS-RA (P > 0.05), but less compared with OVA-RA (P < 0.05) or NS-IH (P > 0.05), while TASK-1 and TASK-3 protein expression was increased in the OVA-IH group compared with the remaining three groups, and TASK-3 protein expression was associated with lung function impairment was positively correlated with the degree of lung function impairment (P < 0.05). CONCLUSION: Task-1 and Task-3 may be involved in the pathogenesis of asthma with OSA by affecting lung function.

Non-apoptotic programmed cell deaths in diabetic pulmonary dysfunction: the new side of advanced glycation end products.

Diabetes mellitus (DM) is a chronic metabolic disorder that affects multiple organs and systems, including the pulmonary system. Pulmonary dysfunction in DM patients has been observed and studied for years, but the underlying mechanisms have not been fully understood. In addition to traditional mechanisms such as the production and accumulation of advanced glycation end products (AGEs), angiopathy, tissue glycation, oxidative stress, and systemic inflammation, recent studies have focused on programmed cell deaths (PCDs), especially the non-apoptotic ones, in diabetic pulmonary dysfunction. Non-apoptotic PCDs (NAPCDs) including autophagic cell death, necroptosis, pyroptosis, ferroptosis, and copper-induced cell death have been found to have certain correlations with diabetes and relevant complications. The AGE-AGE receptor (RAGE) axis not only plays an important role in the traditional pathogenesis of diabetes lung disease but also plays an important role in non-apoptotic cell death. In this review, we summarize novel studies about the roles of non-apoptotic PCDs in diabetic pulmonary dysfunction and focus on their interactions with the AGE-RAGE axis.

B cell repopulation trajectory after rituximab treatment in autoimmune diseases: a longitudinal observational study.

To investigate B-cell repopulation trajectory and the associated factors in patients with autoimmune diseases (AIDs) who underwent rituximab (RTX) treatment. This is a retrospective study in a large tertiary medical center. Kaplan-Meier analysis and Cox regression were used to investigate factors associated with B-cell repopulation. Latent class trajectory modeling (LCTM) was employed to identify distinct B-cell repopulation trajectory longitudinally. A total of 224 patients were included, with a cumulative follow-up time of 193.6 person-years. Patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV), connective tissue disease, and IgG4-related disease exhibited significant differences in B-cell repopulation time (p = 0.0055 by log-rank test). Multivariate Cox regression identified that higher levels of IgA (HR 1.21, 95%CI 1.01-1.45, p = 0.040) and concurrent glucocorticoid use (HR = 0.37,95%CI 0.20-0.67, p = 0.001) were associated with B-cell repopulation. The cluster showing prolonged B-cell depletion, identified by LCTM, had lower proportions of male (27% vs. 48.5%, p = 0.033), smoke history (17.6% vs. 38.7%, p = 0.025), higher proportions of AAV (44.3% vs. 15.2%, p = 0.004), RTX dose (p = 0.042), history of cyclophosphamide use (70.4% vs. 48.5%, p = 0.003), meanwhile glucocorticoid use (94.8% vs. 72.7%, p = 0.001). The trajectory of B-cell repopulation after RTX infusion in AIDs was heterogeneous. Certain factors were associated with B-cell repopulation, and a specific cluster of patients demonstrated prolonged B-cell depletion after RTX treatment.

[Potential Ecological Risk Assessment and Source Analysis of Heavy Metals in Soil-crop System in Xiong'an New District].

In order to evaluate the distribution characteristics of fluorine geochemistry in the surface soil and human health risk in Xiong'an New District, GIS spatial analysis and correlation analysis were used to analyze the depleted and enriched features and influencing factors of soil fluoride and to carry out the soil fluoride health risk assessment. The uncertainty of the health risk assessment results was studied based on the Monte Carlo stochastic simulation. The results showed that the average content of fluorine was 641 mg·kg-1, which was 1.34 times the background value of the national A-layer soil. The excess fluorine and high-grade samples accounted for more than 85%, and the overall soil fluorine content was relatively high. The average content of fluoride of the irrigation water samples was 0.85 mg·L-1, the spatial distribution characteristics of which were affected by the hydrochemical type and flow direction of shallow groundwater. The vertical spatial variation of soil fluoride, mainly affected by the vertical distribution of soil physicochemical properties such as soil organic carbon and texture, was not obvious. The depletion and enrichment of topsoil fluorine was mainly controlled by the geological background, and its spatial distribution was affected by external inputs, such as human factors (agricultural irrigation water, fertilization, and atmospheric dry and wet deposition). The soil fluoride content was significantly correlated with the iconic indicators of the geomorphological environment, including the content of Al2O3, Fe2O3, MgO, K2O, soil organic carbon (Corg.), cation exchange capacity (CEC), clay, and silt (P<0.01). The results of human health risk assessment showed that oral intake was the main exposure risk route of soil fluoride. The non-carcinogenic health risk index HQ of adults was less than 1, and the harm could be ignored. The probability of non-carcinogenic health risk exceeding the threshold for adults and children was 34.3% and 27.6%, respectively, and daily soil intake was the most sensitive parameter.

Non-target and target analysis to identify and characterize thiophenes in soil from an abandoned coking plant.

There is concern about the large amounts of aromatic compounds emitted during coking. Previous studies of coking emissions have been focused on polycyclic aromatic hydrocarbons, dioxin-like compounds, phenols, and volatile organic compounds, but previously unidentified compounds produced during coking may also harm human health. Here, the main pollutants in 69 soil samples from an abandoned coking plant were identified by non-target screening using two-dimensional gas chromatography time-of-flight mass spectrometry. Polycyclic aromatic hydrocarbons, long-chain alkanes, and thiophenes were dominant. High concentrations of thiophenes (benzothiophenes, dibenzothiophenes, and benzonaphtholthiophenes) were found. Quantitative analysis of 12 thiophenes (selected because of their concentrations and detection frequencies) was performed, and the concentrations were 0.03-647 µg/g dry weight, which were extremely high compared with concentrations in soil from uncontaminated sites and other industrial sites. Dibenzothiophene and benzo[b]naphtho[2,1-d]thiophene were dominant, accounting for 69% of the total thiophene concentration. Thiophene profiles in very contaminated areas were different from the profile in coal but similar to the profile in tar. Thiophenes in soil at the coking plant may have been supplied in tar leaks, wastewater, coke oven gases, and exhaust gases. A toxicity assessment indicated a strong likelihood of oxidative stress being induced by exposure to multiple thiophenes at the coking plant. The results suggest that thiophene emissions from coking plants should attract more attention than currently.

Halogen-regulating induced reversible high-temperature dielectric and thermal transitions in novel layered organic-inorganic hybrid semiconducting crystals.

Organic-inorganic hybrid metal halides for high-temperature phase transition have become increasingly popular owing to their wide operating temperature range in practical applications, e.g., energy storage, permittivity switches and opto-electronic devices. This paper describes the subtle assembly of two new hybrid perovskite crystals, [Cl-C6H4-(CH2)2NH3]2CdX4 (X = Br 1; Cl 2), undergoing high-T reversible phase transformations around 335 K/356 K. Differential scanning calorimetry (DSC), differential thermal analysis (DTA) and VT PXRD tests uncover their reversible first-order phase transition behaviors. Furthermore, the compounds exhibit switchable dielectricity near T, making them potential dielectric switching materials. Hirshfeld surface analysis well discloses a distinct difference in hydrogen-bonding interaction between 1 and 2. UV spectra and computational analysis demonstrate that the compounds are a type of direct-band-gap semiconductor. This research will contribute an effective approach to the structure and development of multifunctional molecular hybrid crystals.

[Efficacy and Safety of Bendamustine in the Conditioning Regiment for Autologous Hematopoietic Stem Cell Transplantation in Patients with Lymphoma].

OBJECTIVE: To investigate the clinical efficacy and safety of bendamustine in the conditioning regimen for autologous stem cell transplantation in patients with lymphoma. METHODS: The clinical data of 35 patients with lymphoma, including 5 patients of Hodgkin lymphoma and 30 patients of non-Hodgkin lymphoma, who underwent autologous stem cell transplantation after pretreatment with BeEAM regimen from January 2020 to June 2022 in Gansu Provincial Hospital were retrospectively analyzed. Hematopoietic reconstitution, disease outcome after transplantation and the side effects were analyzed. RESULTS: All 35 patients achieved hematopoietic reconstitution after AHSCT，the median time to neutrophil engraftment was 11 (8-15) days, and the median time to platelet engraftment was 12 (9-17) days. Among the 35 patients, 4 patients died at the end of follow-up, including 3 patients died of lymphoma recurrence or progression and 1 patient died of cerebral hemorrhage. Among 34 patients, 30 had no disease progression at the end of follow-up. The OS rates of patients at 12 and 24 months after transplantation were 90.97% and 90.97%, respectively. The 12 and 24 months PFS rates were 89.64% and 84.92%, respectively. Thiry-five patients underwent grade 3-4 bone marrow suppression. The non-hematological toxicity of BeEAM pretreatment regimen mainly included nausea, vomiting, diarrhea, and oral mucositis, 35 patients experienced nausea and vomiting, but only 4 patients had grade 3-4 nausea and vomiting. Eight patients experienced Grade 1-2 diarrhea. Oral mucositis occurred in 12 patients, including 1 patient of grade 3 oral mucositis. One patient with grade 3 oral mucositis also had grade 3-4 hypokalemia and hypon atremia. 8.6% of patients experienced Grade 1-2 abnormal liver and kidney function. An addition, infectious fever occurred in 18 patients during neutropenia. All patients improved after symptomatic treatment, and there were no transplant-related death. CONCLUSION: Bendamustine as a pretreatment regimen for autologous stem cell transplantation in lymphoma is effective, and the side effects are tolerable.

The Functional Prognosis of Rescue Conscious Sedation During Mechanical Thrombectomy on Patients with Acute Anterior Circulation Ischemic Stroke: A Single-Center Retrospective Study.

INTRODUCTION: Based on real-world case data, this study intends to explore and analyze the impact of rescue conscious sedation (CS) on the clinical outcomes of patients with anterior circulation acute ischemic stroke (AIS) receiving mechanical thrombectomy (MT). METHODS: This retrospective study enrolled patients with anterior circulation AIS who received MT and were treated with either single local anesthesia (LA) or rescue CS during MT between January 2018 and October 2021. We used univariate and multivariate logistic regression methods to compare the impact of LA and CS on the clinical outcomes of patients with AIS who received MT, including the mRS at 90 days, the incidence of poststroke pneumonia (PSP), the incidence of symptomatic intracranial cerebral hemorrhage (sICH), and the mortality rate. RESULTS: We reviewed 314 patient cases with AIS who received MT. Of all patients, 164 met our search criteria. Eighty-nine patients received LA, and 75 patients received rescue CS. There was no significant difference between the two groups in the 90-day good prognosis (45.3% vs. 51.7%, p = 0.418) and mortality (17.3% vs. 22.5%, p = 0.414). Compared with the LA group, the incidence of postoperative pneumonia in the rescue CS group (44% vs. 25.8%, p = 0.015) was more significant. Multivariate stepwise logistic regression analysis revealed that intraoperative remedial CS was independently associated with PSP following MT. In a subgroup analysis, rescue CS was found to significantly increase the incidence of PSP in patients with dysphagia (OR = 7.307, 95% CI 2.144-24.906, p = 0.001). As the severity of the National Institutes of Health Stroke Scale (NIHSS) increased, intraoperative rescue CS was found to increase the risk of PSP (OR = 1.155, 95% CI 1.034-1.290, p = 0.011) by 5.1% compared to that of LA (OR = 1.104, 95% CI 1.013-1.204, p = 0.024). CONCLUSION: Compared to LA, rescue CS during MT does not significantly improve the 90 days of good prognosis and reduce the incidence of sICH and mortality in patients with anterior circulation AIS. However, it has a significantly increased risk of poststroke pneumonia (PSP), particularly in patients with dysphagia.

Concentrations, Profiles, and Health Risks of Organic Ultraviolet Filters in Eight Food Categories Determined through the Sixth Chinese Total Diet Study.

Ultraviolet (UV) filters are emerging contaminants that have been found in high concentrations in human tissues. Food intake is generally considered to be the primary route of human exposure to contaminants. In this study, 184 composite food samples, prepared from 4268 individual samples in eight categories collected from 23 Chinese provinces for the sixth Chinese total diet study, were analyzed. The total and median UV filter concentrations in food samples were 1.5-68.3 and 7.9 ng/g wet weight, respectively. The highest median concentrations were found in decreasing order in meat, cereals, and legumes. In total, 15 UV filters were analyzed. 2-Ethylhexyl salicylate, homosalate, and 2-ethylhexyl-4-methoxycinnamate were dominant and made median contributions of 34.1%, 22.6%, and 14.5%, respectively, and 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol contributed the median of 0.03%, of the total UV filter concentrations. The estimated total daily UV filter intake in animal-origin foods and total UV filter concentration in human milk from the same province were significantly correlated (r = 0.44, p < 0.05). Predicted absorption, distribution, metabolism, and elimination properties led to 10 UV filters being prioritized as most likely to be retained in human tissues. The prioritization results and toxicity assessments indicated that octocrylene and 2-ethylhexyl-4-methoxycinnamate have stronger effects in vivo and therefore require more attention than others.

Iguratimod suppresses Tfh cell differentiation in primary Sjögren's syndrome patients through inhibiting Akt/mTOR/STAT3 signaling.

BACKGROUND: Iguratimod (IGU) reduces hypergammaglobulinemia and disease activity in pSS (primary Sjögren's syndrome) patients. However, the therapeutical mechanism of IGU for pSS remains largely unknown. This study aimed to investigate the regulation of Tfh cell differentiation by IGU in pSS patients. METHODS: We prospectively enrolled 13 pSS patients treated with IGU for 3 months and examined circulating T cell and B cell subsets by flow cytometry. We measured Tfh cell differentiation treated by IGU in pSS patients and healthy controls. Transcriptome analysis combined with molecular docking were employed to identify potential therapeutical targets of IGU, which were verified by Western blot and Tfh cell differentiation. RESULTS: Tfh, plasmablast, and plasma cells were suppressed by IGU treatment at 1 and 3 months. Tfh cell differentiation and function were significant inhibited by IGU in pSS patients and healthy controls in vitro. Pyruvate dehydrogenase kinase 1 (PDK1) was identified as a target of IGU during Tfh cell differentiation, and the downstream Akt phosphorylation was attenuated by IGU. Moreover, the activity of mTORC1 and phosphorylation of STAT3 were suppressed by IGU, with downregulation of BCL6 and upregulation of PRDM1. Finally, Akt activator restored IGU-suppressed Tfh cell differentiation. CONCLUSIONS: IGU suppresses Tfh cell differentiation in pSS patients through interacting with PDK1 and suppressing Akt-mTOR-STAT3 signaling.

Enhanced Cell Wall and Cell Membrane Activity Promotes Heat Adaptation of Enterococcus faecium.

Enterococcus faecium (E. faecium) is widely used in foods and is known as a probiotic to treat or prevent diarrhea in pets and livestock. However, the poor resistance of E. faecium to high temperature processing procedures limits its use. Strain domestication is a low-cost and effective method to obtain high-temperature-resistant strains. In this study, heat treatment was performed from 45 °C to 70 °C and the temperature was gradually increased by 5 °C every 3 days. After domestication, the survival rates of the high temperature adaptation strain RS047-wl under 65 °C water bath for 40 min was 11.5 times higher than WT RS047. Moreover, the saturated fatty acid (SFA) contents in cell membrane and the cell volume significantly increased in the RS047-wl. The combined transcriptomic, metabolomic, and proteomics analysis results showed a significant enhancement of cell wall and membrane synthesis ability in the RS047-wl. In conclusion, one of the main factors contributing to the improved high temperature resistance of RS047-wl was its enhanced ability to synthesize cell wall and membrane, which helped maintain normal cell morphology. Developing a high-temperature-resistant strain and understanding its mechanism enables it to adapt to high temperatures. This lays the groundwork for its future development and application.