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Coal fired power plants are significant contributors to CO 2 emissions and produce solid waste in the form of coal fly ash, posing severe environmental challenges. This study explores the application of dry-impregnated coal fly ash for CO 2 capture from gas stream. The modification of coal fly ash was achieved using alkaline earth metal oxides, specifically CaO and MgO, to alter its physical and chemical properties. Characterization techniques like X-ray fluorescence (XRF), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and BET (Brunauer-Emmett-Teller) analysis were employed for physio-chemical changes in the adsorbent. Breakthrough experiments were conducted using a laboratory-scale fixed packed-bed reactor to assess the influence of temperature and gas flow rate on CO 2 adsorption. Among the synthesized sorbents, calcium oxide-impregnated ash showed the highest CO 2 uptake capacity, achieving 9.41 mg/g at 30 °C and a flow rate of 20 L/hr under atmospheric pressure. Isotherm modeling indicated a heterogeneous adsorbent surface, with the data best fitting the Sips isotherm model. Furthermore, the adsorption data conformed well to the Yoon-Nelson and Thomas kinetic models, affirming their relevance in characterizing the adsorption process under varying conditions. This research emphasizes the potential of coal fly ash-an abundant, cost-free material-as an effective CO 2 adsorbent, contributing to both CO 2 mitigation and landfill waste reduction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: CXCR6+CD8+T cells have been implicated in the pathogenesis of various liver and autoimmune diseases. However, their involvement in primary biliary cholangitis (PBC) has not been elucidated., Methods: We used immunohistochemistry and flow cytometry to quantify CXCR6+CD8+T cells in hepatic tissue and peripheral blood samples obtained from CXCR6+CD8+T cells obtained from PBC patients. Then, we performed comprehensive statistical analyses to access the correlation between the abundance of these cells and clinical as well as pathological data across different stages of PBC., Results: Our research revealed that CXCR6+ cell frequencies in CD3+CD8+T cells from PBC patients significantly exceeded that of healthy controls (HCs) (2.24 vs. 0.61%, p < 0.01). A similar pattern emerged for hepatic CXCR6+CD8+T cell counts, which were notably higher in the PBC cohort compared to HCs. Our cohort consisted of 118 PBC patients, categorized into 62 early-stage (E-PBC) and 56 late-stage (L-PBC) cases. Notably, significant disparities existed between these groups in terms of liver enzyme and lipid profile levels (p < 0.05), with no notable differences observed in gender, age, blood counts, cholesterol levels, or autoantibodies (p > 0.05). Intriguingly, the quantity of hepatic CXCR6+CD8+T cells per high power field (HPF) was significantly elevated in both E-PBC and L-PBC patients as opposed to normal liver samples, indicating a substantial increase in these cells across all stages of PBC (p = 0.000). Spearman's rank correlation analysis showed a positive correlation between CXCR6+CD8+T cell counts and serum levels of Alkaline Phosphatase (AKP) and Gamma-Glutamyl Transferase (GGT), ANA, IgG and IgM, while revealing a negligible correlation with Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST). Subsequent findings indicated significant variances in CXCR6+ cell numbers not only among different PBC stages but also across various degrees of inflammation and fibrosis (p ≤ 0.007). In a follow-up study post-Ursodeoxycholic Acid (UDCA) treatment, stark differences were identified in biochemical and immunohistochemical profiles between responder (31 patients) and non-responder (33 patients) groups (p < 0.05). A Wilcoxon rank-sum test further demonstrated a significant difference in the level of hepatic CXCR6+CD8+T cells between these two response groups (p = 0.002)., Conclusion: CXCR6+CD8+T cells play a vital role in the pathogenesis of PBC, exhibiting correlations with the extent of inflammation, staging of liver fibrosis, and response to pharmacological interventions in PBC patients., (© 2024. Asian Pacific Association for the Study of the Liver.)

Herein, a novel graphite/sulfur iron tailing composite was applied as a peroxydisulfate (PDS) activator for rhodamine B (RhB) degradation in the water. The superior catalytic efficiency of graphite/sulfur iron tailing was achieved through radical (SO 4 •- and •OH) and non-radical ( 1 O 2 ) processes according to the radical quenching experiments and electron paramagnetic resonance analysis. The carbonyl group and Fe species were the main active sites on the surface of graphite/sulfur iron tailing, which was demonstrated by combining Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and reaction kinetic experiments, and a possible degradation mechanism was also proposed. Overall, activated with 0.30 g/L of C-1, PDS achieved a 94.8% removal rate for RhB and maintained a removal rate of over 85% even after five consecutive operation cycles, and this study will benefit the application of iron/carbon composite materials in practical water treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The use of sublobar resection has increased with advances in imaging technologies. However, it is difficult for thoracic surgeons to identify small lung tumours intraoperatively. Radiofrequency identification (RFID) lung-marking systems are useful for overcoming this difficulty; however, accurate placement is essential for maximum effectiveness., Methods: We retrospectively reviewed patients who underwent RFID tag placement via fluoroscopic bronchoscopy under virtual bronchoscopic navigation (VBN) guidance before our institution's sublobar resection of lung lesions. Thirty-one patients with 31 lung lesions underwent RFID lung-marking with fluoroscopic bronchoscopy under VBN guidance., Results: Of the 31 procedures, 26 tags were placed within 10 mm of the target site, 2 were placed more than 10 mm away from the target site, and 3 were placed in a different area from the target bronchus. No clinical complications were associated with RFID tag placement, such as pneumothorax or bleeding. The contribution of the RFID lung-marking system to surgery was high, particularly when the RFID tag was placed at the target site and tumour was located in the intermediate hilar zone., Conclusions: An RFID tag can be placed near the target site using fluoroscopic bronchoscopy in combination with VBN guidance. RFID tag placement under fluoroscopic bronchoscopy with VBN guidance is useful for certain segmentectomies., (© 2024. The Author(s).)

The 2023 International Subarachnoid Hemorrhage Conference identified a need to provide an up-to-date review on prevention methods for delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage and highlight areas for future research. A PubMed search was conducted for key factors contributing to development of delayed cerebral ischemia: anesthetics, antithrombotics, cerebrospinal fluid (CSF) diversion, hemodynamic, endovascular, and medical management. It was found that there is still a need for prospective studies analyzing the best methods for anesthetics and antithrombotics, though inhaled anesthetics and antiplatelets were found to have some advantages. Lumbar drains should increasingly be considered the first line of CSF diversion when applicable. Finally, maintaining euvolemia before and during vasospasm is recommended as there is no evidence supporting prophylactic spasmolysis or angioplasty. There is accumulating observational evidence, however, that intra-arterial spasmolysis with refractory DCI might be beneficial in patients not responding to induced hypertension. Nimodipine remains the medical therapy with the most support for prevention., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To understand the influence of the Fukushima accident on the Northwest Pacific, the distributions and transportations of 134 Cs and 137 Cs in the seawater in the Northwest Pacific in May and September 2015 were studied. The data showed that the Fukushima-derived 134 Cs and 137 Cs at some stations can still be distinguished from background level ~ 4 years later. On the whole, the activities of 137 Cs and 134 Cs in seawater were decreasing from May to Sep 2015. But the increased inventories and the surface activities of 137 Cs imply that there has ever been an extra 137 Cs from offshore water transported to this study area (from 31° N to 27° N, 145° E to 152.5° E) in May 2015. The average activities of 137 Cs in subtropical gyre area in south of KE were the highest and the least were to the east of Luzon Strait in 2015. In vertical direction, 137 Cs in subtropical gyre area were mainly distributed at 100 ~ 500 m layer and 137 Cs only at 500 m layer in this area showed an increasing trend from May to Sep 2015 which reflects more 137 Cs were still penetrating to deeper layer of 500 m from upper water. But they were almost not found below 1000 m layer. It was associated with the subsurface transport of radiocesiums by Northwest Pacific Mode Water (NPMW) and the diffusion of mesoscale eddy. Different distribution characteristics of 137 Cs existed between north of KE and south of KE. The low-temperature-low-salinity water mass likely to be the first Oyashio Intrusion was the main factor that resulted in higher 137 Cs appearing at the upper 100 m layers in north of KE., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the risk factors for delayed postoperative bleeding after endoscopic submucosal dissection (ESD) in patients with gastric precancerous lesions and to construct a risk prediction model., Methods: This retrospective analysis included clinical data from patients with gastric precancerous lesions who underwent ESD at Wuhan University People's Hospital between November 2016 and June 2022. An XGBoost model was built to predict delayed bleeding after ESD using risk factors identified by univariable and multivariate logistic regression analysis. The model was evaluated using receiver operating characteristic curves (ROC), and SHapely Additive exPlanations (SHAP) analysis was used to interpret the model., Results: Seven factors were statistically associated with delayed postoperative bleeding in gastric precancerous lesions after ESD: age, low-grade intraepithelial neoplasia, hypertension, lesion size ≥ 40 mm, operative time ≥ 120 min, female, and nonuse of hemoclips. A risk prediction model was established. In the training cohort, the model achieved an AUC of 0.97 (0.96-0.98), a sensitivity of 0.90, a specificity of 0.94, and an F1 score of 0.91. In the validation cohort, the AUC was 0.94(0.90-0.98), with a sensitivity of 0.85, a specificity of 0.89, and an F1 score of 0.85. In the test cohort, the AUC was 0.94 (0.89-0.99), the sensitivity was 0.80, the specificity was 0.92, and the F1 score was 0.84, indicating strong predictive capability., Conclusion: In this study, an XGBoost prediction model for assessing the risk of delayed postoperative bleeding after ESD in patients with gastric precancerous lesions was developed and validated. This model can be applied in clinical practice to effectively predict the risk of post-ESD bleeding for individual patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nowadays, concurrent attention to economic development and ecological issues is becoming an important trend. In this paper, we measure the eco-efficiency of 285 Chinese cities from 2003 to 2019 using a non-radial directional distance function and the data envelopment analysis method, based on which we analyze the club convergence of cities' eco-efficiency using the logt test; we estimate the impact of open public data platforms on eco-efficiency and its convergence using a multi-period difference in difference model and panel-ordered logit model, respectively. We find that, first, open public data platforms improve cities' eco-efficiency by about 6.5%, and the impact mechanisms include scale efficiency, technical efficiency, and total factor productivity, or, at the micro level, increasing the economic agglomeration degree, boosting the amount of foreign investment used, and increasing green innovation level. Second, there are three convergence clubs of eco-efficiency in China's cities, whose average eco-efficiency trends are above, close to, and below average, respectively. Third, public data platforms significantly increase the probability of cities belonging to the convergence clubs of high and medium eco-efficiency (Clubs 1 and 2) and decrease the probability of belonging to the low one (Club 3). However, the mechanisms only include technical efficiency and total factor productivity, or the amount of foreign investment used and the green innovation level at the micro level., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The miR-497-195 cluster facilitates the occurrence and development of cancer. This study aims to investigate whether the miR-195-497 cluster could regulate the progression of colorectal cancer by regulating the common target gene, FOS-related antigen 1 (FRA1). Overexpression of the miR-195/497 vector was used to evaluate the effect of overexpression of miR-195-497 clusters on the biological behavior of colon cancer cells. In animal experiments, tumor growth and metastasis were recorded by constructing a nude mouse model of a subcutaneously implanted tumor. miR-195 and miR-497 were expressed to varying degrees in Caco-2, LoVo, and HT-29 cells. Overexpression of miR-195/497 and inhibition of FRA1 decreased HT-29 cell proliferation, inhibited cell invasion and migration, and promoted Epithelial-mesenchymal transition (EMT). In vivo experiments showed that the overexpression of miR-195/497 or inhibition of FRA1 inhibited tumor growth, affected EMT in tumor cells, and inhibited the expression of FRA1. Additionally, the aforementioned conditions had the best effect when used together. The miR-195-497 cluster can regulate the proliferation, EMT, invasion, and migration of colorectal cancer cells by regulating the common target gene FRA1, thereby affecting the development of colorectal cancer., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although hyperuricemia is associated with the progression of chronic kidney disease (CKD), a reduction in CKD progression by uric acid (UA)-lowering therapy has been controversial. Recently, dotinurad, a uricosuric drug with selective urate reabsorption inhibitory properties, has been developed. However, its efficacy in lowering serum UA levels and its effects on renal function in patients with severe renal dysfunction are unclear. Thus, this study aimed to determine the effects of dotinurad on renal function in patients with severe renal dysfunction., Methods: Data from 53 outpatients with hyperuricemia who newly received dotinurad between December 2020 and October 2022 were retrospectively analyzed. The mean baseline estimated glomerular filtration rate (eGFR) was 38.7 ± 17.0 mL/min/1.73 m 2 . The patients were divided into three groups based on their baseline eGFR: eGFR < 30 (n = 17), 30 ≤ eGFR < 45 (n = 17), and eGFR ≥ 45 (n = 19)., Results: The mean follow-up period was 9.8 ± 4.5 (range, 3-21) months. Serum UA levels significantly decreased in all groups. Although eGFR did not significantly change in patients with 30 ≤ eGFR < 45 and eGFR ≥ 45 (P = 0.918 and P = 0.535, respectively), it improved significantly in patients with eGFR < 30 (P = 0.032). The proportion of patients with improved eGFR was significantly higher in patients with eGFR < 30 (P = 0.038) than in patients with 30 ≤ eGFR < 45 and eGFR ≥ 45. In the multivariate logistic regression analysis, baseline eGFR < 30 and achieving a serum UA level of ≤ 6.0 mg/dL were significantly associated with improved eGFR (P = 0.033 and P = 0.015, respectively)., Conclusions: Dotinurad may have UA-lowering effects and the potential to improve kidney function in patients with severe renal dysfunction., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Diabetes mellitus (DM) is a chronic disease characterized by elevated blood glucose levels caused by a lack of insulin production (type 1 diabetes) or insulin resistance (type 2 diabetes). It is well known that DM is associated with cognitive deficits and metabolic and neurophysiological changes in the brain. Glutamate is the main excitatory neurotransmitter in the central nervous system that plays a key role in synaptic plasticity, learning, and memory processes. An increasing number of studies have suggested that abnormal activity of the glutamatergic system is implicated in the pathophysiology of DM. Dysfunction of glutamatergic neurotransmission in the central nervous system can provide an important neurobiological substrate for many disorders. Magnetic resonance spectroscopy (MRS) is a non-invasive technique that allows a better understanding of the central nervous system factors by measuring in vivo the concentrations of brain metabolites within the area of interest. Here, we briefly review the MRS studies that have examined glutamate levels in the brain of patients with DM. The present article also summarizes the available data on abnormalities in glutamatergic neurotransmission observed in different animal models of DM. In addition, the role of gut microbiota in the development of glutamatergic alterations in DM is addressed. We speculate that therapeutic strategies targeting the glutamatergic system may be beneficial in the treatment of central nervous system-related changes in diabetic patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management., (© 2023. Asian Pacific Association for the Study of the Liver.)

Endothelial-to-mesenchymal transition (EndMT), the process by which endothelial cells lose their characteristics and acquire mesenchymal phenotypes, participates in the pathogenic mechanism of idiopathic pulmonary fibrosis. Recently, exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exos) has been introduced as a promising treatment in organ fibrosis. This study aimed to explore the effects as well as the molecular mechanism for hucMSC-Exo in pulmonary fibrosis. The intravenous administration of hucMSC-Exos alleviated bleomycin-induced pulmonary fibrosis in vivo. Moreover, hucMSC-Exos elevated miR-218 expression and restored endothelial properties weakened by TGF-β in endothelial cells. Knockdown of miR-218 partially abrogated the inhibition effect of hucMSC-Exos on EndMT. Our mechanistic study further demonstrated that MeCP2 was the direct target of miR-218. Overexpressing MeCP2 aggravated EndMT and caused increased CpG islands methylation at BMP2 promoter, which lead to BMP2 post-transcriptional gene silence. Transfection of miR-218 mimic increased BMP2 expression as well, which was downregulated by overexpression of MeCP2. Taken together, these findings indicate exosomal miR-218 derived from hucMSCs may possess anti-fibrotic properties and inhibit EndMT through MeCP2/BMP2 pathway, providing a new avenue of preventive application in pulmonary fibrosis., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Many studies have pointed out that inflammation plays a pivotal role in pathophysiology of acute coronary syndromes (ACS) because several inflammatory molecules impair the endothelial functions in the coronary circulation and promote atherothrombotic events. Recently, many clinical/experimental evidences indicate that elevated plasma levels of uric acid (UA) might be considered a risk factor for developing ACS. It has been reported that elevated UA doses impair physiologic functions of endothelial cells, shifting them toward a pro atherothrombotic phenotype. In the present manuscript, we investigated the relationship between UA plasma levels, inflammatory burden, and extension of coronary atherosclerotic disease in patients with ACS. Patients with a clinical presentation of ACS (ST-elevated and non-ST-elevated myocardial infarction) admitted to the Vanvitelli Catheterization Laboratory at Monaldi Hospital in 2019, before the COVID-19 pandemia, were retrospectively analyzed. Biochemical profile, type of ACS presentation, as well as extension of coronary atherosclerosis were assessed. A total of 132 ACS patients were included in the analysis, and grouped into 3 tertiles according to the UA values (UA < 4.72 mg/dl, UA between 4.72 and 6.15 mg/dl, and UA > 6.15 mg/dl). Patients with UA plasma levels ≥ 6.15 mg/dL showed higher levels of C-reactive protein (mean of 5.1 mg/dL) as compared to patients with lower UA plasma levels. Moreover, the former group of patients showed higher levels of cardiac troponin and CPK, and presented more often with multivessel disease and complex coronary stenosis (type C of Ellis classification). Even though monocentric and with limited sample size, the present study shows that plasma levels of UA and hs-CRP are elevated in ACS patients and are associated with a more severe coronary disease, suggesting a potential role of UA in the pathophysiology of acute coronary events., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Purpose: Although a novel deep learning software was proposed using post-processed images obtained by the fusion between X-ray images of normal post-operative radiography and surgical sponge, the association of the retained surgical item detectability with human visual evaluation has not been sufficiently examined. In this study, we investigated the association of retained surgical item detectability between deep learning and human subjective evaluation., Methods: A deep learning model was constructed from 2987 training images and 1298 validation images, which were obtained from post-processing of the image fusion between X-ray images of normal post-operative radiography and surgical sponge. Then, another 800 images were used, i.e., 400 with and 400 without surgical sponge. The detection characteristics of retained sponges between the model and a general observer with 10-year clinical experience were analyzed using the receiver operator characteristics., Results: The following values from the deep learning model and observer were, respectively, derived: Cutoff values of probability were 0.37 and 0.45; areas under the curves were 0.87 and 0.76; sensitivity values were 85% and 61%; and specificity values were 73% and 92%., Conclusion: For the detection of surgical sponges, we concluded that the deep learning model has higher sensitivity, while the human observer has higher specificity. These characteristics indicate that the deep learning system that is complementary to humans could support the clinical workflow in operation rooms for prevention of retained surgical items., (© 2022. CARS.)

Background: Evidence on renin-angiotensin system inhibitors (RASis) effect in reducing urinary protein levels in patients with nephrotic syndrome is insufficient. We determined whether RASis can induce complete remission (CR) in patients on immunosuppressive therapy., Methods: This cohort study included 84 adults (median age, 65 years; males, 57%) with primary nephrotic syndrome (excluding minimal change disease) not receiving RASis during enrollment in the Japanese Nephrotic Syndrome Cohort Study from January 2009 to December 2010, and were followed up for 5 years. Exposure and outcome were RASi initiation and first CR, respectively. Marginal structural models and Poisson regression were used to account for time-varying covariates and estimate causal effects of RASis on CR., Results: Overall, 51 (61%), 73 (87%), and 55 (66%) patients had membranous nephropathy, were prescribed immunosuppressive agents at baseline (1-month post-renal biopsy and/or at start of immunosuppressive therapy), and were prescribed RASis during the study period, respectively. Sixty-five patients experienced first CR (incidence rate, 5.05/100 person-months). RASi use was associated with a higher (adjusted incidence rate ratio [aIRR] 2.27, 95% confidence interval [CI] 1.06-4.84), and lower (aIRR: 0.17, 95% CI 0.04-0.68) first CR in patients with membranous nephropathy and other pathologies, respectively., Conclusion: RASis are beneficial as adjuvant therapy for inducing remission in patients with membranous nephropathy., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Although they are organelles without a limiting membrane, nucleoli have an exclusive structure, built upon the rDNA-rich acrocentric short arms of five human chromosomes (nucleolar organizer regions or NORs). This has raised the question: what are the structural features of a chromosome required for its inclusion in a nucleolus? Previous work has suggested that sequences adjacent to the tandemly repeated rDNA repeat units (DJ, distal junction sequence) may be involved, and we have extended such studies by addressing several issues related to the requirements for the association of NORs with nucleoli. We exploited both a set of somatic cell hybrids containing individual human acrocentric chromosomes and a set of Human Artificial Chromosomes (HACs) carrying different parts of a NOR, including an rDNA unit or DJ or PJ (proximal junction) sequence. Association of NORs with nucleoli was increased when constituent rDNA was transcribed and may be also affected by the status of heterochromatin blocks formed next to the rDNA arrays. Furthermore, our data suggest that a relatively small size DJ region, highly conserved in evolution, is also involved, along with the rDNA repeats, in the localization of p-arms of acrocentric chromosomes in nucleoli. Thus, we infer a cooperative action of rDNA sequence-stimulated by its activity-and sequences distal to rDNA contributing to incorporation into nucleoli. Analysis of NOR sequences also identified LncRNA&#95;038958 in the DJ, a candidate transcript with the region of the suggested promoter that is located close to the DJ/rDNA boundary and contains CTCF binding sites. This LncRNA may affect RNA Polymerase I and/or nucleolar activity. Our findings provide the basis for future studies to determine which RNAs and proteins interact critically with NOR sequences to organize the higher-order structure of nucleoli and their function in normal cells and pathological states., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Connexin 43 (Cx43, also known as Gja1) is the most abundant testicular gap junction protein. It has a crucial role in the support of spermatogenesis by Sertoli cells in the seminiferous tubules as well as in androgen synthesis by Leydig cells. The multifunctional family of Ca 2+ /calmodulin-dependent protein kinases (CaMK) is composed of CaMK I, II, and IV and each can serve as a mediator of nuclear Ca 2+ signals. These kinases can control gene expression by phosphorylation of key regulatory sites on transcription factors. Among these, AP-1 members cFos and cJun are interesting candidates that seem to cooperate with CaMKs to regulate Cx43 expression in Leydig cells. In this study, the Cx43 promoter region important for CaMK-dependent activation is characterized using co-transfection of plasmid reporter-constructs with different plasmids coding for CaMKs and/or AP-1 members in MA-10 Leydig cells. Here we report that the activation of Cx43 expression by cFos and cJun is increased by CaMKI. Furthermore, results from chromatin immunoprecipitation suggest that the recruitment of AP-1 family members to the proximal region of the Cx43 promoter may involve another uncharacterized AP-1 DNA regulatory element and/or protein-protein interactions with other partners. Thus, our data provide new insights into the molecular regulatory mechanisms that control mouse Cx43 transcription in testicular Leydig cells., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The native forest of northwestern Argentina, as part of the Chaco region, is a rich and unexploited source of phytochemical compounds for medicinal/cosmetic applications. In the present study, fruit, leaf, branch, and bark organs of the native trees Sarcomphalus mistol (Mistol, M) and Schinopsis lorentzii (Quebracho Colorado santiagueño, QC) were harvested, and aqueous plant extracts (PE) were prepared. The spectroscopic (UV-Vis absorbance, diffuse reflectance, ATR-FTIR) and antioxidant (TEAC, Folin-Ciocalteu) properties of PE were characterized and used as TiO 2 coating material to obtain a series of TiO 2 @PE nanocomposites. These materials showed almost null photocatalytic activity compared to aqueous suspensions of bare TiO 2 , displaying yellowish to brownish coloration and high long-term stability in both freshwater and seawater model solutions. The loss of photocatalytic activity in TiO 2 @PE was associated with the combination of the internal filter effect and the antioxidant/radical capacity exerted by the phytochemicals of the PE coating, with higher broadband photoprotection for the nanocomposites prepared with QC extracts. Thus, this study shows the potential capacity of the forest resources of the Chaco region of Argentina for the development of new cosmetic and/or sun protection formulations., (© 2022. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

The gradual ageing of the world population has been accompanied by a dramatic increase in the prevalence of obesity and metabolic diseases, especially type 2 diabetes. The adipose tissue dysfunction associated with ageing and obesity shares many common physiological features, including increased oxidative stress and inflammation. Understanding the mechanisms responsible for adipose tissue dysfunction in obesity may help elucidate the processes that contribute to the metabolic disturbances that occur with ageing. This, in turn, may help identify therapeutic targets for the treatment of obesity and age-related metabolic disorders. Because oxidative stress plays a critical role in these pathological processes, antioxidant dietary interventions could be of therapeutic value for the prevention and/or treatment of age-related diseases and obesity and their complications. In this chapter, we review the molecular and cellular mechanisms by which obesity predisposes individuals to accelerated ageing. Additionally, we critically review the potential of antioxidant dietary interventions to counteract obesity and ageing., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Chlorpyrifos (CPF), an organophosphorus pesticide, is detected commonly in environments, where it is thought to be highly toxic to non-target organisms. However, the mechanism of CYP450s pathway mediated by nuclear receptors on CPF-induced apoptosis and necroptosis at the cellular level and the effect of CPF on the cytotoxicity of the chicken hepatocarcinoma cell line (LMH) has also not been reported in detail. Therefore, this experiment aims to explore whether CPF can improve apoptosis and necroptosis in LMH cells by activating the nuclear receptors/CYP450s axis. LMH cells, the subject of this study, were exposed to 5 μg/mL, 10 μg/mL, and 15 μg/mL doses of CPF. With the increase of CPF concentration, the increase of nuclear receptor level led to the up-regulation of CYP450s activity. With the massive production of ROS, the expression of apoptotic pathway genes (Bax, Caspase9, and Caspase3) enhanced, while Bcl-2 expression dropped sharply. The expression of programmed necroptosis genes (RIPK1, RIPK3, and MLKL) heightened, and Caspase8 reduced considerably. In short, our data suggests that excessive activation of nuclear receptors and CYP450s induced by CPF promotes ROS production, which directs apoptosis and programmed necroptosis in LMH cells., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The current world witnesses a greatly increased prevalence and incidence of hyperuricemia and gout with unfortunately the comparative efficacy and safety of present available uricosuric agents remaining uncertain. We herein aimed to investigate the most appropriate uricosuric agent for gout or hyperuricemia patients., Method: PubMed, Embase, Cochrane Library databases, and ClinicalTrials.gov from inception to 2 July 2022 were searched to retrieve eligible studies assessing efficacy and safety of uricosuric drugs in hyperuricemia or gout patients. Network meta-analysis was carried out using the Stata 16.0 software., Results: Twelve randomized controlled trials comprising 1851 patients were eventually included. Network meta-analysis showed that dotinurad 4 mg once daily, verinurad, dotinurad 2 mg once daily, dotinurad 1 mg once daily, and benzbromarone were the top 5 effective treatments to achieve target serum uric acid. Furthermore, dotinurad 4 mg once daily was more effective at achieving urate-lowering targets (RR of dotinurad 4 mg once daily vs. probenecid: 1.68, 95% CI [1.13; 2.50]) and safer (RR of probenecid vs. dotinurad 4 mg once daily: 1.77, 95% CI [0.69; 4.56]) than probenecid., Conclusions: This network meta-analysis demonstrated an important absolute benefit of dotinurad 4 mg once daily to achieve target serum uric acid and low risk of adverse events for drug treatment of gout or hyperuricemia patients. Additionally, verinurad might be used as an alternative uricosuric therapeutic option to dotinurad. These findings provided further comprehensive insight into the treatment value of current uricosuric agents for gout or hyperuricemia. Key Points 1. This is the first systematic review and network meta-analysis examining the efficacy and safety of currently available uricosuric agents in gout or hyperuricemia patients. 2. Recommended doses of dotinurad 4mg once daily used for the treatment of gout or hyperuricemia patients can significantly decrease serum uric acid levels. 3. The present findings will provide further comprehensive insight into the treatment value of certain uricosuric agents for gout or hyperuricemia., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Purpose: The purpose of this study is to investigate the effect of sildenafil a CYP3A4 substrate and inhibitor on the pharmacokinetics and safety of saxagliptin., Methods: Eighteen healthy volunteers were recruited in sequential; single-center study to determine pharmacokinetic parameters of saxagliptin and sildenafil, and (AUC 0-∞ ), (AUC 0-t ); C max ; t max ; t ½ , k e ; k a were measured using validated LC-MS/MS method. Therapeutic doses were given as follows: Sildenafil 50 mg single dose on day one, then washout period from day two till day eight. Saxagliptin 5 mg once/day was given from day 9 till day 12; then on day 13, the two drugs were co-administered. Blood samples for pharmacokinetic analysis were collected on days 1 and 13 for sildenafil and on days 12 and 13 for saxagliptin., Results: Saxagliptin ratios of T/R and 90% CI were 132.1% (122.7-142.3) for AUC 0-t , and 167.6% (154.6-181.8) for C max . On the other hand, sildenafil pharmacokinetics were not affected. G max changed from 93.7 mg/dl to 95.6 mg/dl (P > 0.001) and AUC g0-t from 512.8 ng.h/ml to 532.75 ng.h/ml (P > 0.001) after co-administration of both drugs., Conclusion: Sildenafil significantly affected the pharmacokinetic parameters of saxagliptin when co-administered., Registration: This trial was registered at clinicaltrials.gov under identifier number: [NCT04170790] in November 2019., (© 2022. The Author(s).)

The n-n-type ZnO-SnO 2 nanocomposite was fabricated using malic acid following a simple one-pot co-precipitation method. The fabricated ZnO-SnO 2 nanocomposite was employed as a photocatalyst in the degradation of Biebrich scarlet dye under UV 254 light. TEM, SAED, XRD, XPS, EDX, FTIR, and UV spectra have been recorded to characterize the synthesized ZnO-SnO 2 nanostructures. TEM studies found that the average particle size was 10-12 nm, and the SAED confirmed the polycrystalline nature of the synthesized nanocomposite. It was found that 97% of 10 mg/L Biebrich scarlet dye was degraded by 25 mg/L of photocatalyst within 40-min irradiation of UV 254 light at an optimum pH of 6. Further studies showed that the degradation followed pseudo-first-order kinetics with a rate constant of 5.48 × 10 -2  min -1 . The fabricated ZnO-SnO 2 nanocomposite was reusable up to 8 times; hence, it proved to be an efficient catalyst for the photodegradation of Biebrich scarlet dye., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to investigate the effectiveness of curcumin (CCM) against gentamicin (GEN) and sodium salicylates (NaS)-induced ototoxic effects in rats. For 15 consecutive days, seven rat groups were given 1 mL/rat physiological saline orally, 1 mL/rat olive oil orally, 50 mg/kg bwt CCM orally, 120 mg/kg bwt GEN intraperitoneally, 300 mg/kg bwt NaS intraperitoneally, CCM+GEN, or CCM+NaS. The distortion product otoacoustic emission measurements were conducted. The rats' hearing function and balance have been behaviorally assessed using auditory startle response, Preyer reflex, and beam balance scale tests. The serum lipid peroxidation and oxidative stress biomarkers have been measured. Immunohistochemical investigations of the apoptotic marker caspase-3 and the inflammatory indicator nuclear factor kappa (NF-κB) in cochlear tissues were conducted. GEN and NaS exposure resulted in deficit hearing and impaired ability to retain balance. GEN and NaS exposure significantly decreased the reduced glutathione level and catalase activity but increased malondialdehyde content. GEN and NaS exposure evoked pathological alterations in cochlear and vestibular tissues and increased caspase-3 and NF-κB immunoexpression. CCM significantly counteracted the GEN and NaS injurious effects. These outcomes concluded that CCM could be a naturally efficient therapeutic agent against GEN and NaS-associated ototoxic side effects., (© 2022. The Author(s).)

Health status depends on multiple genetic and non-genetic factors. Nonheritable factors (such as lifestyle and environmental factors) have stronger impact on immune responses than genetic factors. Firefighters work is associated with exposure to air pollution and heat stress, as well as: extreme physical effort, mental stress, or a changed circadian rhythm, among others. All these factors can contribute to both, short-term and long-term impairment of the physical and mental health of firefighters. Increased levels of some inflammatory markers, such as pro-inflammatory cytokines or C-reactive protein (CRP) have been observed in firefighters, which can lead to local, acute inflammation that promotes a systemic inflammatory response. It is worth emphasizing that inflammation is one of the main hallmarks of cancer and also plays a key role in the development of cardiovascular and respiratory diseases. This article presents possible causes of the development of an inflammatory reaction in firefighters, with particular emphasis on airway inflammation caused by smoke exposure., (© 2022. The Author(s).)

Introduction: The current WHO classification and methylation status help predict meningioma recurrence and prognosis. However, up to date, there is no circulating biomarker showing clinical value in meningioma diagnosis or classification. Circulating miRNAs showed the potential to be used as cancer biomarkers in various tumours. This research evaluated specific miRNAs, miR-497 and miR-219, as convenient and efficient predictors of meningioma grades., Methods: We studied serum and exosomal levels of miR-497 in 74 meningioma samples (WHO grade I = 25, WHO grade II = 25, and WHO grade III = 24) and 53 healthy controls. The serum level of miR-219 was studied in 56 meningioma samples WHO grade I = 22, WHO grade II = 14, and WHO grade III = 20). We used qPCR for miRNA quantification. We also tested two different normalisers, endogenous and external, and evaluated their impact on the diagnostic value of miR-497., Results: The serum and exosomal levels of miR-497 distinguished meningioma from the control samples. Moreover, miR-497 was a suitable identifier for meningioma grade. When we combined miR-497 and miR-219, the efficacy of the combined biomarker was higher than miR-497 or miR-219 when used individually in meningioma classification. Both miR-497 and miR-219 showed a noticeable change with the methylation class of meningioma., Conclusion: This study shows that serum miR-497 is an effective and easy-to-measure biomarker for meningioma diagnosis and classification. Moreover, when we combined miR-497 and miR-219, the combined biomarker showed enhanced accuracy in meningioma classification. Furthermore, this is the first study to evaluate the correlation between serum circulating miRNA and the methylation status in meningioma., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Astaxanthin (3,3'-dihydroxy-β,β-carotene-4,4'-dione) is an orange-red, lipophilic keto-carotenoid pigment. It is majorly found in marine ecosystems particularly in aquatic animals such as salmon, shrimp, trout, krill, crayfish, and so on. It is also synthesized in microalgae Heamatococcus pluvialis, Chlorococcum, Chlorella zofingiensis, red yeast Phaffia rhodozyma and bacterium Paracoccus carotinifaciens. Some aquatic and terrestrial creatures regarded as a primary and secondary sources of the astaxanthin producing and accumulating it through their metabolic pathways. Astaxanthin is the powerful antioxidant, nutritional supplement as well as promising therapeutic compound, observed to have activities against different ravaging diseases and disorders. Researchers have reported remarkable bioactivities of astaxanthin against major non-communicable chronic diseases such as cardiovascular diseases, cancer, diabetes, neurodegenerative, and immune disorders. The current review discusses some structural aspects of astaxanthin. It further elaborates its multiple potencies such as antioxidant, anti-inflammatory, anti-proliferative, anti-cancer, anti-obese, anti-diabetic, anti-ageing, anti-TB, anti-viral, anti-COVID 19, neuro-protective, nephro-protective, and fertility-enhancing properties. These potencies make it a more precious entity in the preventions as well as treatments of prevalent systematic diseases and/or disorders. Also, the review is acknowledging and documenting its powerful bioactivities in relation with the pharmaceutical as well as nutraceutical applicability., (© 2022. The Author(s).)

Rhizobacteria are root-associated bacteria that influence plant growth by various direct and indirect mechanisms. In quest of efficient plant growth-promoting rhizobacteria (PGPR) with multiple plant growth-promoting traits, a total of 52 rhizobacterial isolates were isolated from the rhizospheric soil collected at Pohang beach, Republic of Korea. The bacterial isolates were evaluated in vitro for their plant growth-promoting traits like production of 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase, indole-3-acetic acid (IAA), siderophore, and phosphate solubilization activities. More than 28% of the isolates revealed all of the multi-trait plant growth-promoting activities, whereas 11.54% exhibited robust results for producing IAA, ACC deaminase, siderophore, and phosphate solubilization activities. Similarly, 36% isolates were capable for the production of IAA, siderophore, and ACC deaminase, while 32% revealed phosphate solubilization and siderophore production. The isolates with prominent multi-trait plant growth-promoting activities were identified based on 16S rRNA gene sequences and matched to Pseudomonas koreensis-(S4T10), Pseudomonas fluorescens-(S3B1), Serratia fonticola-(S1T1), Sphingobacterium multivorum-(S1B1), Brevundimonas vesicularis-(S1T13), and Arthrobacter sp.-(S2T9) with 99-100% similarity. Our results confirm that further evaluation of these PGPR (exhibiting multi-traits for plant growth promotion) is required on crop plants to reveal their pragmatic role under normal and abiotic stress conditions and add into the consortium of biofertilizers for sustainable agriculture., (© 2022. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Background: Information on whether there is a relationship between hospital volume and bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is limited. This study aimed to compare the bleeding rates after ESD for EGC according to the hospital volume., Methods: Patients who underwent ESD for EGC at 33 institutions in Japan between November 2013 and October 2016 were included in this multicenter retrospective study. Hospital volume was categorized into three groups, based on the average annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). The bleeding rate after ESD for EGC was compared between the three hospital volume groups after propensity score matching., Results: A total of 10,320 patients, including 2797 patients in the LMVG, 4646 patients in the HVG, and 2877 patients in the VHVG, were identified. Propensity score matching yielded 2002 patients in each hospital volume group, with an improved balance of confounding variables between the three groups. The bleeding rates in the LMVG, HVG, and VHVG were 4.3%, 3.7%, and 4.9%, respectively, and no significant difference was noted between the three groups., Conclusions: The bleeding rate after ESD for EGC did not differ between hospitals in Japan. The finding indicated that ESD for EGC is equally feasible across Japanese hospitals of different volumes regarding bleeding after ESD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse., Methods: This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors., Results: Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively)., Conclusion: The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Purpose: Intravenous and intra-arterial milrinone as a rescue measure for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been adopted by several groups, but so far, evidence for the clinical benefit is unclear and effect on brain perfusion is unknown. The aim of the actual analysis was to define cerebral hemodynamic effects and outcome of intravenous milrinone plus norepinephrine supplemented by intra-arterial nimodipine as a rescue strategy for DCI following aneurysmal SAH., Methods: Of 176 patients with aneurysmal SAH treated at our neurosurgical department between April 2016 and March 2021, 98 suffered from DCI and were submitted to rescue therapy. For the current analysis, characteristics of these patients and clinical response to rescue therapy were correlated with hemodynamic parameters, as assessed by CT angiography (CTA) and perfusion CT. Time to peak (TTP) delay in the ischemic focus and the volume with a TTP delay of more than 4 s (T4 volume) were used as hemodynamic parameters., Results: The median delay to neurological deterioration following SAH was 5 days. Perfusion CT at that time showed median T4 volumes of 40 cc and mean focal TTP delays of 2.5 ± 2.1 s in these patients. Following rescue therapy, median T4 volume decreased to 10 cc and mean focal TTP delay to 1.7 ± 1.9 s. Seventeen patients (17% of patients with DCI) underwent additional intra-arterial spasmolysis using nimodipine. Visible resolution of macroscopic vasospasm on CTA was observed in 43% patients with DCI and verified vasospasm on CTA, including those managed with additional intra-arterial spasmolysis. Initial WFNS grade, occurrence of secondary infarction, ischemic volumes and TTP delays at the time of decline, the time to clinical decline, and the necessity for additional intra-arterial spasmolysis were identified as the most important features determining neurological outcome at 6 months., Conclusion: The current analysis shows that cerebral perfusion in the setting of secondary cerebral ischemia following SAH is measurably improved by milrinone and norepinephrine-based hyperdynamic therapy. A long-term clinical benefit by the addition of milrinone appears likely. Separation of the direct effect of milrinone from the effect of induced hypertension is not possible based on the present dataset., (© 2022. The Author(s).)

An integral component of neural ontogeny and plasticity is the ongoing generation of new neurons from precursor cells throughout the lifespan in virtually all animals with a nervous system. In mammals, postnatal neurogenesis has been documented in the cerebellum, olfactory bulb, hippocampus, striatum, substantia nigra, hypothalamus, and amygdala. Germinal centers of new neuron production in the adult brain have been identified in the neuroepithelium of the subventricular zone and the dentate gyrus. One of the earliest lines of evidence gathered came from studies on the production of cerebellar microneurons in the external germinal layer of rodents and carnivores in the 1960s and 1970s. The undeniable pioneer of that research was the insightful developmental neurobiologist Joseph Altman (1925-2016). This Cerebellar Classic is devoted to the groundbreaking work of Altman and his graduate student and, subsequently, fellow faculty member, Gopal Das (1933-1991), on postnatal neurogenesis using tritiated thymidine autoradiography to tag newly formed neurons in the cerebellum of cats. Perseverant to their ideas and patiently working in West Lafayette (Indiana), they were the founders of two fields that brought about paradigm shifts and led to an explosive growth in brain research: adult neurogenesis and neural tissue transplantation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting not only the synovial joints but also multiple extra-articular sites, including ankle and foot soft tissue. Hindfoot abnormalities usually follow those in the forefoot, with up to 4 out of 10 patients experiencing talalgia during their disease course. Enthesophytosis, retrocalcaneal bursitis, and plantar fasciitis are among the most common etiologies, while heel fat pad abnormalities like subcalcaneal bursitis are rare. Here, we report two cases of subcalcaneal bursitis, and the first case of heel fat pad and subcalcaneal bursa herniation in patients with established RA, along with a comprehensive literature review of subcalcaneal bursitis and other heel fat pad abnormalities in RA. Subcalcaneal bursitis, also referred to as panniculitis, inflammatory-edematous lesion, or adventitial (adventitious) bursitis has been reported in up to 10% of patients with RA. It appears as a compressible, heterogeneous, and hypoechoic subcalcaneal mass on ultrasound (US), with peripheral vascularization on Doppler US. Patients may present with heel discomfort. Ultrasonographic assessment is usually sufficient to confirm the presence of heel fat pad pathologies. Rest, analgesics, and mechanical aids with or without addition of disease-modifying antirheumatic drugs are usually employed, while intervention is rarely required., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background: We reported favorable short-term results of laparoscopic surgery in a randomized study comparing open and laparoscopic surgery for elderly patients with colorectal cancer (CRC). The purpose of this study is to clarify the long-term outcomes of the laparoscopic surgery for elderly patients with CRC., Methods: The inclusion criteria were ≥ 75 years, adenocarcinoma, ≤ T4a, M0 and elective surgery. The patients were randomly allocated to open or laparoscopic surgery according to the tumor location. The survival rates, recurrence and reasons for death were compared., Result: One hundred patients (right colon 43, left colon 28, rectum 29) were included in each group. Eight patients who underwent open surgery and 2 patients who underwent laparoscopic surgery were excluded from the analysis because of metastatic diseases and other malignancies found during the operations. One hundred ninety patients (98 open, 98 laparoscopic) were analyzed. There was no difference in the backgrounds excluding more patients with vascular invasion in the laparoscopic rectal cancer. There were no differences in the 5-year overall survival rate (open vs. laparoscopic; 78.9% vs. 82.1%, p = 0.638), 5-year disease-free survival rate (70.5% vs. 62.8%, p = 0.276), 5-year recurrence-free survival rate (76.1% vs. 72.1%, p = 0.419), or 5-year cancer-specific survival rate (86.1% vs. 80.5%, p = 0.208). No differences in survival were detected in the analyses of stage and tumor location. There was no significant difference in the overall recurrence rate or recurrence site. However, distant lymph node metastases and local recurrences were more common after laparoscopic surgery than after open surgery. There was no difference in the cause of death. More than half of the patients died from other diseases in both groups (57.9% vs. 52.6%, p = 0.765)., Conclusion: Laparoscopic surgery showed similar long-term results compared to open surgery in elderly patients with CRC. Laparoscopic surgery is an effective surgical procedure for elderly patients with CRC., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Eucalyptus is the main species for the forestry industry in Brazil. Biotechnology and, more recently, gene editing offer significant opportunities for rapid improvements in Eucalyptus breeding programs. However, the recalcitrance of Eucalyptus species to in vitro culture is also a major limitation for commercial deployment of biotechnology techniques in Eucalyptus improvement. We evaluated various clones of Eucalyptus urophylla for their in vitro regeneration potential identified a clone, BRS07-01, with considerably higher regeneration rate (85%) in organogenesis, and significantly higher than most works described in literature. Endophytic bacteria are widely reported to improve in vitro plant growth and development. Hence, we believe that inclusion of endophytic plant growth promoting bacteria enhanced was responsible for the improved plantlets growth and development of this clone under in vitro culture. Metagenomic analysis was performed to isolate and characterize the prominent endophytic bacteria on BRS07-01 leaf tissue in vitro micro-cultures, and evaluate their impact on plant growth promotion. The analysis revealed the presence of the phyla Firmicutes (35%), Proteobacteria (30%) and much smaller quantities of Actinobacteria, Bacteroidetes, Gemmatimonadetes, Crenarchaeota, Euryarchaeota and Acidobacteria. Of the thirty endophytic bacterial strains isolated, eleven produced indole-3-acetic acid. Two of the isolates were identified as Enterobacter sp. and Paenibacillus polymyxa, which are nitrogen-fixing and capable of phosphate and produce ammonium. These isolates also showed similar positive effects on the germination of common beans (Phaseolus spp.). The isolates will now be tested as a growth promoter in Eucalyptus in vitro cultures. Graphical abstract for the methodology using cultivation independent and dependent methodologies to investigate the endophytic bacteria community from in vitro Eucalyptus urophylla BRS07-01., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

The objective of this research is to investigate the enzymatic activities between protein disulfide isomerase (PDI) found in animals and plants and the properties found in a commonly used Chinese medicine called Sijunzi Tang. During the investigation, PDI, which is a monomer with a molecular mass of 57.0 kDa, was used to reactivate malate dehydrogenase (MDH). However, with the interference of polycyclic aromatic hydrocarbons (PAHs), evidence indicates that such chemicals are carcinogenic, mutagenic, and toxic to humans. The enzymatic activity of PDI found in animal's liver and plant was 1657 folds of purification; 0.284 unit/mg of enzyme activity, and 5694.4 folds of purification; 1.00 unit/mg of enzyme activity, respectively. PDI extracted in treated animal and plant tissue revealed 2.40% and 80.44% of regaining MDH enzymatic activity, respectively. Although in its initial phase of investigation, it is assumed that the properties found in Sijunzi Tang can help regain enzymatic activity in those affected by xenobiotic substances, thus, making it a potential ingredient in assisting with PDI functions.

Objective: To investigate the effect of different maintenance to target on radiologic outcomes in patients with rheumatoid arthritis (RA) in real-world setting., Methods: RA patients enrolled were screened from a longitudinal cohort. The radiographies were evaluated at baseline, after 1-2 years and thereafter every 2 years. An increase of mTSS > 3 from baseline was taken as the primary outcome and accelerated annual radiological progression as the secondary outcome of radiological progression. The maintenance rate (MR) to target was calculated as the proportion of the year fulfilling preset criteria of target over the whole follow-up period. COX regression and logistic analysis were used to determine the effect of variables on radiological outcomes., Results: Two hundred forty-three patients were enrolled, with median follow-up of 2 years (3.00). Radiological progression was observed in 43 (17.7%) patients, with annual increase of mTSS 0.20 (1.33). In multivariate analysis, MR was the only independent protective factor of both primary and secondary radiological outcomes in two models [HR 0.09, 95% CI (0.04, 0.22), p < 0.001, model 1; OR 0.21, 95% CI (0.09, 0.49), p < 0.001, model 2]. ACPA positivity was another independent risk factor of secondary outcome [OR 2.96, 95% CI (1.27, 6.86), p = 0.012]. Higher MR was also associated with less radiological progression in established RA patients. Partial MR was not inferior to full maintenance within 4 years in terms of halting radiological progression., Conclusion: Low MR and ACPA positivity were independent risk factors of poor radiological outcomes in RA patients. No significant difference in radiological progression could be detected between partial and full maintenance group within 4 years in daily practice., Key Points: • The first study showing that maintenance to target is beneficial to bone protection in established RA patients in real-world setting • No difference in radiological outcomes between partial and full maintenance group within 4 years.

Purpose: Older people are at risk of anticholinergic side effects due to changes affecting drug elimination and higher sensitivity to drug's side effects. Anticholinergic burden scales (ABS) were developed to quantify the anticholinergic drug burden (ADB). We aim to identify all published ABS, to compare them systematically and to evaluate their associations with clinical outcomes., Methods: We conducted a literature search in MEDLINE and EMBASE to identify all published ABS and a Web of Science citation (WoS) analysis to track validation studies implying clinical outcomes. Quality of the ABS was assessed using an adapted AGREE II tool. For the validation studies, we used the Newcastle-Ottawa Scale and the Cochrane tool Rob2.0. The validation studies were categorized into six evidence levels based on the propositions of the Oxford Center for Evidence-Based Medicine with respect to their quality. At least two researchers independently performed screening and quality assessments., Results: Out of 1297 records, we identified 19 ABS and 104 validations studies. Despite differences in quality, all ABS were recommended for use. The anticholinergic cognitive burden (ACB) scale and the German anticholinergic burden scale (GABS) achieved the highest percentage in quality. Most ABS are validated, yet validation studies for newer scales are lacking. Only two studies compared eight ABS simultaneously. The four most investigated clinical outcomes delirium, cognition, mortality and falls showed contradicting results., Conclusion: There is need for good quality validation studies comparing multiple scales to define the best scale and to conduct a meta-analysis for the assessment of their clinical impact.

Rapid development of gene sequencing technologies has led to an exponential increase in microbial sequencing data. Genome research of a single organism does not capture the changes in the characteristics of genetic information within a species. Pan-genome analysis gives us a broader perspective to study the complete genetic information of a species. Paenibacillus polymyxa is a Gram-positive bacterium and an important plant growth-promoting rhizobacterium with the ability to produce multiple antibiotics, such as fusaricidin, lantibiotic, paenilan, and polymyxin. Our study explores the pan-genome of 14 representative P. polymyxa strains isolated from around the world. Heap's law model and curve fitting confirmed an open pan-genome of P. polymyxa. The phylogenetic and collinearity analyses reflected that the evolutionary classification of P. polymyxa strains are not associated with geographical area and ecological niches. Few genes related to phytohormone synthesis and phosphate solubilization were conserved; however, the nif cluster gene associated with nitrogen fixation exists only in some strains. This finding is indicative of nitrogen fixing ability is not stable in P. polymyxa. Analysis of antibiotic gene clusters in P. polymyxa revealed the presence of these genes in both core and accessory genomes. This observation indicates that the difference in living environment led to loss of ability to synthesize antibiotics in some strains. The current pan-genomic analysis of P. polymyxa will help us understand the mechanisms of biological control and plant growth promotion. It will also promote the use of P. polymyxa in agriculture.

The main role of vitamin D is to control mineral homeostasis. However, recent studies suggested the existence of a number of extraskeletal effects. Among the latter, preclinical studies provided consistent data on the involvement of vitamin D in innate and adaptive immunity and autoimmunity. Molecular biology studies showed that both vitamin D receptor and vitamin D enzymatic complexes are expressed in a large number of cells and tissues unrelated to mineral homeostasis. In contrast, only a few randomized clinical trials in humans investigated the possible role of vitamin D in the prevention or treatment of immunological disorders. In this regard, low serum vitamin D levels have been reported in observational trials in human autoimmune disorders. The aim of the present paper was to review the potential implications of vitamin D in immune modulation, with special focus on thyroid autoimmune disorders.

To investigate the effects of short-term discontinuation of methotrexate (MTX) on disease activity in patients with rheumatoid arthritis (RA) taking a stable dose of MTX. A post-hoc analysis of two randomized controlled trials was used to investigate the effects of temporary MTX discontinuation (for 2 weeks or 4 weeks) on responses to seasonal influenza vaccination. The impact of MTX discontinuation on the RA disease activity score (DAS28) and RA flare rate during discontinuation and after reintroduction was examined. The DAS28 increased during the 4-week MTX discontinuation period, before returning to baseline after reintroduction. The overall flare-free survival period did not differ between the groups (log rank p = 0.142). However, during the 4-week MTX discontinuation period, more patients in the MTX-hold group than in the MTX-continue group experienced a flare (20.5% vs. 7.4%, respectively; p = 0.058). After resumption of MTX, the flare rate did not differ between groups. The flare rates in the MTX-continue group and the 2-week and 4-week MTX-hold groups were 5.8%, 10.8% and 20.5%, respectively (p < 0.01). The change in the DAS28 from baseline did not differ significantly between the MTX-continue and the 2-week MTX-discontinue groups. However, there was a significant difference between the 4-week MTX-hold group and the MTX-continue group (p = 0.005). Short-term discontinuation of MTX for up to 2 weeks is safe, whereas discontinuation for 4 weeks is associated with a transient increase in disease flares and activity in RA patients taking a stable MTX dose.Key Points• Methotrexate discontinuation for 2 weeks is safe.• Methotrexate discontinuation for 4 weeks transiently increases flare risk and disease activity.• Disease flare risk and disease activity return to baseline after restarting methotrexate treatment.

Author(s): Kazuyoshi Hirota [sup.1] Author Affiliations: (1) grid.257016.7, 0000 0001 0673 6172, Department of Anesthesiology, Hirosaki University Graduate School of Medicine, , 036-8562, Hirosaki, Japan Remimazolam is a member of [...]