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Este trabajo aplica el Indicador de Rentabilidad Social en Comunicación (IRSCOM) a las emisoras municipales de Castilla-La Mancha, con el fin de medir el estado de salud de su funcionamiento interno. Se estudian 33 variables relacionadas con la gestión, el capital social, la articulación territorial, la programación, el entorno comunicativo y las infraestructuras. El indicador se aplica a las 40 emisoras operativas de la comunidad autónoma a través de un cuestionario telefónico y entrevistas semiestructuradas a personas al cargo de alcaldías, concejalías y de las propias emisoras. Los resultados demuestran la vulnerabilidad del sector, ya que de las 108 licencias concedidas a corporaciones locales en Castilla-La Mancha, sólo un 37% están operativas. Además, la nota obtenida se califica de “muy baja”, y algunas de ellas se encuentran en peligro de extinción. Ante las importantes carencias que presentan en cada una de las variables testadas se proponen caminos de mejora.

Objective: Vesicovaginal fistulas (VVF) are consequences from obstetric and gynecologic surgery. Treatment approach from either abdominal or vaginal route have its own pros and cons. The study aims to present the anatomical, clinical and lower urinary tract symptom outcomes of women with VVF. Materials and methods: A retrospective case series conducted patients with VVF. Data regarding pre-operative evaluation, surgical treatment, and post-operative follow-ups were collected. Surgical approach depended on the cause, type, number, size, location, and time of onset of the fistula. Post-operatively, foley catheter was maintained for at least 1 week with cystoscopy performed prior to removal. Follow-up evaluation included cystoscopy, bladder diary, UDI-6 and IIQ-7 questionnaires and multi-channel urodynamic study. Results: Of the 15 patients that were evaluated, 1 had spontaneous closure, 8 were repaired vaginally and 6 abdominally. Patients repaired vaginally were significantly noted to have a mean age of 50.3 ± 7.1 years with VVFs located adjacent the supra-trigone area having a mean distance of 1.7 ± 0.5 cm from the ureteric orifice. Its operative time and hospital stay were significantly shorter. In contrast, abdominally repaired patients had mean age of 38.0 ± 8.2 years and VVFs with mean distance of 0.4 ± 0.4 cm from the ureteric orifice. Post-operatively, 2 cases (14.2%, 2/14) of VVF recurrence and de novo urodynamic stress incontinence (USI) (25%, 2/8) were noted after vaginal repair and 3 cases (50%, 3/6) of concurrent ureteric injury and overactive bladder after abdominal repair. Conclusion: Treatment outcomes for vaginal and abdominal repair yielded good results. Though the vaginal route had higher incidence of recurrence and de novo USI, its less invasiveness, faster recovery period, and no association with post-op overactive bladder made it more preferable than the abdominal approach. Keywords: Vesicovaginal fistula, Vaginal repair, Abdominal repair, Surgical outcomes, Lower urinary tract symptoms

The troposphere affects Global Navigation Satellite System (GNSS) signals due to the variability of the refractive index. Tropospheric delay is a function of the satellite elevation angle and the altitude of the GNSS receiver and depends on the atmospheric parameters. If the residual tropospheric delay is not modelled carefully a bias error will occur in the vertical component. In order to analyse the precise altimetric positioning based on a local active network, four scenarios in Southern Spain with different topographical, environmental, and meteorological conditions are presented, considering both favourable and non-favourable conditions. The use of surface meteorological observations allows us to take into account the tropospheric conditions instead of a standard atmosphere, but introduces a residual tropospheric bias which reduces the accuracy of precise GNSS positioning. Thus, with short observation times it is recommended not to estimate troposphere parameters, but to use an a priori model together with the standard atmosphere. The results confirm that it is possible to achieve centimetre-scale vertical accuracy and precision with real time kinematic positioning even with large elevation differences with respect to the nearest reference stations. These numerical results may be taken into consideration for improving the altimetric configuration of the local active network.

Objective: To evaluate the outcome of transvaginal mesh surgery as a management of recurrent pelvic organ prolapse, in patients previously treated with sacrocolpopexy. Case report: A series of three patients who developed recurrent pelvic organ prolapse more than 9 years after sacrocolpopexy. A 50-year-old and two 77-year-old patients who presented with recurrent pelvic organ prolapse at 9, 15 and 17 years, respectively after the primary abdominal sacrocolpopexy were managed by transvaginal mesh surgery. Conclusion: Management of recurrent pelvic organ prolapse using transvaginal mesh would be an option for patients treated previously by sacrocolpopexy. Keywords: Vault prolapse, Transvaginal mesh, Abdominal sacrocolpopexy, Sacrospinous ligament

Objective: To know the diagnostic tools and proper management of ureterovaginal fistula following neglected vaginal foreign body in order to achieve optimal outcome. Case report: A case of ureterovaginal fistula associated with a neglected vaginal foreign body. The patient was complaining of a foul-smelling vaginal discharge and lower abdominal pain. On vaginal examination, a hard and large foreign body was found. Examination under anesthesia was performed, and an aerosol cap was removed from her vagina. The patient developed urinary incontinence after removal of the foreign body. Subsequent work-up demonstrated the presence of a right ureterovaginal fistula. The patient underwent an abdominal ureteroneocystostomy. At one year follow up, the patient had fully recovered. Conclusion: Ureterovaginal fistula following neglected vaginal foreign body is a serious condition. Early diagnosis, treatment of infection and proper surgical management can improve the outcome and decrease complications.

Stevia is an important non-caloric sweetener that has health-beneficial properties. The objective is to evaluate growth, development, and rooting of stevia plants during different seasons of the year using growth hormones. Eight experiments were set up in Ciudad Guzman, Jalisco, Mexico, with three treatments (T): T1, indol-3 butyric acid (IBA) 7.4 mM; T2, alphanaphthylacetamide (ANA) 6.4 mM + IBA 0.3 mM; and T3, control. The variables evaluated were rooted plantlets, plant height, root length, number of leaves, stem diameter, leaf dry weight, stem dry weight, root dry weight, leaf area, shoot biomass, total biomass, as well as development and growth indexes. Four samplings were conducted in each experiment. The results show that the most appropriate months for propagating stevia cuttings are February, March, April, May, and July, when 96% to 99% of the cuttings rooted. The hormones had the best results related to production of root development. The control was outstanding only in variables related to production of shoot biomass and not to root development. It is concluded that stevia can be propagated vegetatively using cuttings treated with IBA 7.4 mM or ANA 6.4 mM + IBA 0.3 mM, preferable in the period from February to July, with the exception of June.

ObjectiveTo compare the ultrasonographic positional changes of mid-urethral sling(MUS) tape in relation to symphysis pubis, and the different clinical outcomes among women who underwent MUS insertion with MiniArcTM or MonarcTM for the treatment of stress urinary incontinence 3 years after.Materials and methodsA retrospective follow-up study on patients with clinically confirmed stress urodynamic incontinence and urodynamic stress incontinence who had undergone MiniArc or Monarc surgery. Data regarding preoperative evaluation, intraoperative complications and post-operative follow-ups were collated. Main outcome is to determine the change in position of the sling through measurement of the x- and y-axis at rest and during Valsalva maneuver using the 3D introital ultrasound.ResultsA total of 138 patients were evaluated, 82 belonged to Monarc and 56 to MiniArc. At 3years, objective and subjective cure rates for MiniArc and Monarc were comparable (88%, 91%; p>0.05; 83%, 89%, p>0.05 respectively). Ultrasonographic changes between MiniArc and Monarc from 6 months to 3 years, showed MiniArc to exhibit significant movement in both x- [3.0 ±0.4 mm vs. 2.2 ±0.3 mm (p = 0.02) at rest; 2.6 ±0.3 mm vs. 1.6 ±0.3 mm (pConclusionMaintenance of continence rates of mid-urethral slings depends on the compressive effect of the sling on the urethra, urethral kinking, and sling fixation. From 6months to 3 years, MiniArc changed its position in both x- and y-axis over time, which the authors attribute to loosening of the anchoring mechanism since no clinical relevance could be sought.

This article presents a work carried out in Argentina for two years as the result of a public, competitive call for proposals. It was designed jointly by professors from the Universidad Nacional de las Artes (Argentina) and the Universidad de Zaragoza (Spain). The aims were: a) to offer quality musical activities to older adults, and b) to provide university students with the opportunity of participating in concrete actions on social improvement. The influence of this programme has been assessed on both aspects. Within a research-action framework, a programme of activities was designed jointly by university professors and students; a qualitative approach was chosen. Within a general aim to improve older adults’ life quality, some specific differentiated objectives were developed, according to each group. The activities were performed by students from the faculty of Music (piano, singing, strings). Some initial, in-process and final evaluations were carried out. University students have contributed to a substantial improvement of older adults’ life quality through musical activities adapted to each aged group (whether the independent, active community or the dependent one). They have also become aware of their potentiality to contribute to social betterness. This programme has been innovative and has promoted both independent and dependent older adults’ well-being; it has also allowed university students of Music become engaged in societal needs and actively participate in social enhancement.

Comparou-se a acumulação e translocação de elementos vestigiais em duas espécies de plantas espontâneas na área mineira do Chança, Cistus ladanifer L. e Cistus monspeliensis L., e caracterizaram-se os solos da área da rizosfera. Os solos apresentaram diferenças no conteúdo em arsénio, cobre, crómio, manganês, vanádio e zinco e alguns elementos atingiram valores totais (mg kg-1) de: 151 (As); 320 (Cr); 926 (Cu); 1010 (Mn); 235 (V). As concentrações em crómio, manganês e vanádio são diferentes na raiz das duas espécies. Na parte aérea, apenas a concentração de manganês e de níquel é semelhante. As espécies mostraram comportamento acumulador relativamente ao manganês, com excepção do C. monspeliensis numa das zonas de amostragem. Para a maioria dos elementos vestigiais, o C. monspeliensis possui maior capacidade de translocação (raiz-parte aérea) do que o C. ladanifer. Os coeficientes de translocação do crómio, manganês, níquel e zinco são superiores a 1,5 nas duas espécies.Trace elements accumulation and translocation in two spontaneous plants of genus Cistus, Cistus ladanifer L. and Cistus monspeliensis L., growing in the Chança mine area, were compared. Samples of plants and soils from rizosphere were collected and characterized. Soil samples showed different total content of arsenic, chromium, copper, manganese, vanadium and zinc, and some of the trace elements had the following total values (mg kg-1): 151 (As); 320 (Cr); 926 (Cu); 1010 (Mn); 235 (V). The concentrations of chromium, manganese and vanadium in roots were different between species. In the shoots, only manganese and nickel concentrations were similar. The two species were manganese accumulators, with C. mon-speliensis exception in one of the sampled areas. Cistus monspeliensis showed the largest translocation capacity of trace elements from roots to shoots. Both species presented the translocation coefficient of chromium, manganese, nickel and zinc larger than 1,5.

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Peripheral microvascular dysfunction has been documented in patients with heart failure with preserved ejection fraction (HFpEF), which may be related to elevated levels of inflammation and oxidative stress. Unfortunately, few strategies have been identified to effectively ameliorate this disease-related derangement. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10 mg daily) on lower limb microvascular reactivity, functional capacity, and biomarkers of inflammation and oxidative stress in patients with HFpEF (statin, n = 8, 76 ± 6 yr; placebo, n = 8, 68 ± 9 yr). The passive limb movement (PLM)-induced hyperemic response and 6-min walk test (6MWT) distance were evaluated to assess ambulatory muscle microvascular function and functional capacity, respectively. Circulating biomarkers were also measured to assess the contribution of changes in inflammation and redox balance to these outcomes. The total hyperemic response to PLM, assessed as leg blood flow area under the curve (LBF AUC ), increased following the statin intervention (pre, 60 ± 68 mL; post, 164 ± 90 mL; P < 0.01), whereas these variables were unchanged in the placebo group ( P = 0.99). There were no significant differences in 6MWT distance following statin or placebo intervention. Malondialdehyde (MDA), a marker of lipid peroxidation, was significantly reduced following the statin intervention (pre, 0.68 ± 0.10; post, 0.51 ± 0.11; P < 0.01) while other circulating biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to a diminution in oxidative stress. NEW & NOTEWORTHY This was the first study to investigate the impact of statin administration on locomotor muscle microvascular function in patients with HFpEF. In support of our hypothesis, the total hyperemic response to PLM, assessed as leg blood flow area under the curve, increased, and malondialdehyde, a marker of oxidative damage, was reduced following the statin intervention. Together, these data provide new evidence for the efficacy of statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to reduced oxidative stress.

Coronavirus disease 2019 (COVID-19), a kind of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily spreads through the respiratory tract from human to human. Its extensive and rapid spread has led to a global pandemic, causing great harm to human health and economic development all over the world. Current known evidence indicates that SARS-CoV-2 has evolved accumulating multiple mutations, with altered infectivity and viral replication capacity. A better understanding of the complications of COVID-19 and its relationship with underlying diseases is crucial for the prevention and treatment of SARS-CoV-2. This case series reviewed case data of our 4 recent patients with severe or critical COVID-19, including treatment plan, status of pulmonary infection and their microbiology workup with metagenomic next-generation sequencing with bronchoalveolar lavage fluid. This report shed light on the significance of rapid and accurate clinical diagnosis and treatment on COVID-19., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A capillary column coated with 3-aminophenylboronic acid (APBA)-functionalized gold nanoparticles (AuNPs@APBA) was prepared via electrostatic self-assembly. The coated column exhibited anti-nonspecific adsorption of glycoproteins, enabling selective online enrichment during capillary electrophoresis (CE). First, gold nanoparticles (AuNPs) were synthesized using the sodium citrate reduction method. Then, APBA was self-assembled electrostatically on the surface of the AuNPs to obtain AuNPs@APBA. This nanomaterial was bonded to the inner wall of a capillary through ion adsorption to produce a AuNPs@APBA-coated capillary column. Glycoproteins were adsorbed via bond formation with boric acid groups under alkaline conditions (pH 8) to generate borate esters. Under acidic conditions (pH 3), the borate esters dissociated to release the glycoproteins, thereby achieving the selective online enrichment and separation of glycoproteins. The AuNPs and AuNPs@APBA were characterized using Fourier transform infrared spectroscopy, and their sizes and Zeta potentials were determined. In addition, the electroosmotic flow (EOF) of the AuNPs@APBA-coated capillary column was measured. The results showed that the surface of the AuNPs was successfully modified with APBA and that AuNPs@APBA was adsorbed on the inner wall of the capillary. The peak area of ovalbumin (OVA) on the AuNPs@APBA-coated column was 26.46 times higher than that on a bare column via conventional electrophoresis. In contrast, the peak area of bovine serum albumin (BSA) only increased by 8.47 times, indicating that the AuNPs@APBA coated column selectively enriched glycoproteins. Evaluation of the reproducibility and stability of this method revealed that the AuNPs@APBA coated capillary column could be used continually for 33-67 h. The relative standard deviations (RSDs) of the peak areas for intra-day ( n =5) and inter-day ( n =6) analyses were 2.2% and 3.0%, respectively. The developed method was successfully applied to enrich glycoproteins in a 1×10 6 -fold diluted egg white sample. Glycoproteins were not detected using conventional electrophoresis on the bare column, whereas the AuNPs@APBA-coated capillary column effectively enriched and separated glycoproteins, resulting in a peak area of 10469 mAU·ms. Furthermore, the entire enrichment and separation process was completed within 3 min. This new online enrichment and separation method for glycoproteins has the advantages of low sample consumption, simple operation, and high separation efficiency.

Background: Cancer-associated fibroblasts (CAFs) are crucial components of the cervical cancer tumor microenvironment, playing a significant role in cervical cancer progression, treatment resistance, and immune evasion, but whether the expression of CAF-related genes can predict clinical outcomes in cervical cancer is still unknown. In this study, we sought to analyze genes associated with CAFs through weighted gene co-expression network analysis (WGCNA) and to create a predictive model for CAFs in cervical cancer., Methods: We acquired transcriptome sequencing data and clinical information on cervical cancer patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. WGCNA was conducted to identify genes related to CAFs. We developed a prognostic model based on CAF genes in cervical cancer using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Single-cell sequencing data analysis and in vivo experiments for validation of hub genes in CAFs., Results: A prognostic model for cervical cancer was developed based on CAF genes including COL4A1 , LAMC1 , RAMP3 , POSTN , and SERPINF1 . Cervical cancer patients were divided into low- and high-risk groups based on the optimal cutoff value. Patients in the high-risk group had a significantly worse prognosis. Single-cell RNA sequencing data revealed that hub genes in the CAFs risk model were expressed mainly in fibroblasts. The real-time fluorescence quantitative polymerase chain reaction (PCR) results revealed a significant difference in the expression levels of COL4A1 , LAMC1 , POSTN , and SERPINF1 between the cancer group and the normal group ( p < 0.05). Consistently, the results of the immunohistochemical tests exhibited notable variations in COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1 expression between the cancer and normal groups ( p < 0.001)., Conclusion: The CAF risk model for cervical cancer constructed in this study can be used to predict prognosis, while the CAF hub genes can be utilized as crucial markers for cervical cancer prognosis., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

The present study aimed to explore the effect of swimming exercise on vascular calcification in type 2 diabetic rats and its related molecular mechanism. Male Sprague Dawley (SD) rats were randomly divided into normal control (NC), diabetes control (DC) and diabetes+exercise (DE) groups. The DC and DE groups were intraperitoneally injected with streptozotocin (STZ) and fed with high-fat diet to establish type 2 diabetes mellitus model. The NC and DC groups did not exercise, and the DE group performed swimming exercise for 8 weeks. ELISA was used to detect the serum glycated hemoglobin A1c (HbA1c) level. The aortas of rats were taken as sample. Assay kits were used to detect vascular calcium content and alkaline phosphatase (ALP) activity. Von Kossa staining was used to detect calcium deposition. qRT-PCR was used detect the expression of microRNA-145 (miR-145). Western blot was used to detect the protein expression levels of smooth muscle contraction markers, calcification marker and related proteins. The results showed that, compared with the NC group, the blood glucose, serum HbA1c level, vascular calcium content and ALP activity in the DC group were significantly increased, the protein expression levels of smooth muscle contraction markers smooth muscle protein 22α (SM22α) and α-smooth muscle actin (α-SMA) were significantly down-regulated, and the protein expression level of calcification marker osteopontin (OPN) was significantly up-regulated; Compared with the DC group, the serum HbA1c level, vascular calcium content and ALP activity in the DE group were significantly decreased, the protein expression levels of SM22α and α-SMA were significantly up-regulated, and the protein expression level of OPN was significantly down-regulated; Compared with the NC group, the expression of miR-145-5p in the DC group was significantly down-regulated, and the protein expression levels of transforming growth factor-β (TGF-β), SMAD2, ERK1/2 and p-ERK1/2 were significantly up-regulated; Compared with the DC group, the expression of miR-145-5p was significantly up-regulated in the DE group, while the expressions of TGF-β, ERK1/2 and p-ERK1/2 were significantly down-regulated. These results suggest that miR-145/TGF-β signaling is involved in the improving effects of 8-week swimming exercise on glucose metabolism disorder, vascular smooth muscle cell phenotype switching and vascular calcification in type 2 diabetes mellitus.

Background: Heart failure with preserved ejection fraction (HFpEF) is a common, complex syndrome associated with elevated morbidity and mortality. Patients with HFpEF have a high prevalence of comorbidities, including hypertension, diabetes mellitus, and obesity, which are closely related to the underlying mechanisms of the disease. Lifestyle modification with weight loss and physical activity can improve risk factors and functional outcomes in HFpEF. We sought to observe daily physical activity and determine whether utilizing an activity tracker can enhance functional status in HFpEF patients., Methods: We performed a prospective analysis of 57 patients with HFpEF from 2021 to 2023 at a single academic medical center who utilized a Fitbit to record one year of daily step activity. The patients were evaluated in the ambulatory setting for an initial visit and subsequently at intervals of 3, 6, and 12 months to gather vitals, labs, physical exam, and functional measurements, including the Six-Minute Walk Test (6MWT) and Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12). Associations between variables were assessed using Pearson's r correlation using Stata 18.0., Results:  Of the 49 patients who completed the study, the mean age was 68.1 ± 10.2 years, with 67% of patients identifying as female. The average BMI was 36.4 ± 8.6 kg/m 2 . Across each time interval, the median numbers of steps per day were 4,113 (2,517-6,520) (1-3 months), 4,583 (2,532-6,326) (4-6 months), and 3,957 (2,942-5,982) (7-12 months). There was no statistically significant variation in daily step count (p=0.06). We observed a statistically significant increase of 66 (6-200) feet in the 6MWT (p= 0.002) from baseline (1,175 (910-1,400)) to 12 months (1,321 (1,000-1,550)). The daily step count was highly correlated with the 6MWT across all time points (1-3 months: r= .70, p< .001; 4-6 months: r= .61, p< .001; 7-12 months: r= .69, p< .001). The total KCCQ-12 scores increased by 6.8 (-4.2-19.8) points (p=0.005) from baseline (60.1 (41.7-73.4)) to 12 months (69.8 (50-84.4)). Among the sub-categories of the questionnaire, we observed a positive correlation between physical limitation scores and daily step count (1-3 months: r= .47, p=.001; 4-6 months: r= .63, p< .001; 7-12 months: r= .56, p= .001). Of interest, one patient who was taking over 15,000 daily steps scored their physical limitation 10-20 points lower than those taking less than half the steps and had one of the lowest quality of life scores in the cohort, reflecting the subjective nature of heart failure (HF) symptoms., Conclusion: Fitbit technology offers a convenient means to monitor real-time physical activity in patients with HFpEF. Utilizing a Fitbit to record daily step activity enhances health-related quality of life in this population. In contrast to the improved average total KCCQ-12 score, we did not observe a clinically significant increase in the 6MWT over the course of the year. Our findings establish the utility of daily step count as a valuable surrogate for six-minute walk distance., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board, University of Utah Health issued approval 00125670. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kogelschatz et al.)

Background: Laying hens undergo intensive metabolism and are vulnerable to cardiac insults. Previous research demonstrated overt heart disorders of broiler chickens induced by dietary Se deficiency., Objectives: This study aimed to reveal effects and mechanism of dietary Se insufficiency on cardiac injuries of egg-type chicks in their early life., Methods: White Leghorn chicks (0-d-old, female) were fed a corn-soy, Se-insufficient basal diet (BD, 0.05 mg Se/kg; n = 11) or the BD supplemented with 0.3 mg Se/kg (as sodium selenite; n = 8) for 35 d. Cardiac tissues were collected at the end of study for histology and to determine its relationship with heart Se contents, selenoprotein expression profiles, antioxidant and inflammatory status, and the Toll-like receptor 4/extracellular signal-regulated kinases/p38 map kinase/c-Jun N-terminal kinase (TLR4/ERK/P38/JNK) pathway., Results: Compared with those fed 0.35 mg Se/kg, chicks fed BD had significantly lower body weights and average daily gain, and 28% lower heart Se, and developed cardiac mononuclear inflammatory cell infiltration, along with elevated (P < 0.05) serum concentrations of creatine kinase, aldolase, and interleukin-1 (IL-1). The BD decreased (P < 0.05) body weight and heart glutathione contents and expression of selenoproteins but increased (P < 0.05) heart concentrations of malondialdehyde and reactive oxygen species. These changes were associated with increased (P < 0.05) mRNA and/or protein concentrations of cyclooxygenases, lipoxygenase-12, cytokines (IL-1β), nuclear factor (NF) κB subunit, chemokines, and receptors (CCL20, CXCR1, and CXCLI2) and increased (P < 0.1) TLR4/ERK /P38/JNK in the heart of Se-insufficient chicks., Conclusions: Dietary Se insufficiency induces infiltration of mononuclear inflammatory cells in the heart of egg-type chicks. This cardiac injury was mediated by decreased functional expressions of selenoproteins, which resulted in apparent elevated oxidative stress and subsequent activations of the TLR4 pathway and NF κB., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

The unique zigzag-patterned tea plant is a rare germplasm resource. However, the molecular mechanism behind the formation of zigzag stems remains unclear. To address this, a BC1 genetic population of tea plants with zigzag stems was studied using histological observation and bulked segregant RNA-seq. The analysis revealed 1494 differentially expressed genes (DEGs) between the upright and zigzag stem groups. These DEGs may regulate the transduction and biosynthesis of plant hormones, and the effects on the phenylpropane biosynthesis pathways may cause the accumulation of lignin. Tissue sections further supported this finding, showing differences in cell wall thickness between upright and curved stems, potentially due to lignin accumulation. Additionally, 262 single-nucleotide polymorphisms (SNPs) across 38 genes were identified as key SNPs, and 5 genes related to zigzag stems were identified through homologous gene function annotation. Mutations in these genes may impact auxin distribution and content, resulting in the asymmetric development of vascular bundles in curved stems. In summary, we identified the key genes associated with the tortuous phenotype by using BSR-seq on a BC1 population to minimize genetic background noise.

Heart failure with preserved ejection fraction (HFpEF) is characterized by impaired vascular endothelial function that may be improved by hydroxy-methylglutaryl-CoA (HMG-CoA) reductase enzyme inhibition. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10 mg daily) on peripheral vascular function and biomarkers of inflammation and oxidative stress in 16 patients with HFpEF [Statin: n = 8, 74 ± 6 yr, ejection fraction (EF) 52-73%; Placebo: n = 8, 67 ± 9 yr, EF 56-72%]. Flow-mediated dilation (FMD) and sustained-stimulus FMD (SS-FMD) during handgrip (HG) exercise, reactive hyperemia (RH), and blood flow during HG exercise were evaluated to assess conduit vessel function, microvascular function, and exercising muscle blood flow, respectively. FMD improved following statin administration (pre, 3.33 ± 2.13%; post, 5.23 ± 1.35%; P < 0.01), but was unchanged in the placebo group. Likewise, SS-FMD, quantified using the slope of changes in brachial artery diameter in response to increases in shear rate, improved following statin administration (pre: 5.31 e -5  ± 3.85 e -5  mm/s -1 ; post: 8.54 e -5  ± 4.98 e -5  mm/s -1 ; P = 0.03), with no change in the placebo group. Reactive hyperemia and exercise hyperemia responses were unchanged in both statin and placebo groups. Statin administration decreased markers of lipid peroxidation (malondialdehyde, MDA) (pre, 0.652 ± 0.095; post, 0.501 ± 0.094; P = 0.04), whereas other inflammatory and oxidative stress biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve brachial artery endothelium-dependent vasodilation, but not microvascular function or exercising limb blood flow, in patients with HFpEF, which may be due in part to reductions in oxidative stress. NEW & NOTEWORTHY This is the first study to investigate the impact of statin administration on vascular function and exercise hyperemia in patients with heart failure with preserved ejection fraction (HFpEF). In support of our hypothesis, both conventional flow-mediated dilation (FMD) testing and brachial artery vasodilation in response to sustained elevations in shear rate during handgrip exercise increased significantly in patients with HFpEF following statin administration, beneficial effects that were accompanied by a decrease in biomarkers of oxidative damage. However, contrary to our hypothesis, reactive hyperemia and exercise hyperemia were unchanged in patients with HFpEF following statin therapy. These data provide new evidence for the efficacy of low-dose statin administration to improve brachial artery endothelium-dependent vasodilation, but not microvascular reactivity or exercising muscle blood flow in patients with HFpEF, which may be due in part to reductions in oxidative stress.

Objective: To explore the effectiveness of minimally invasive surgical treatment for pancreatic acinar cell carcinoma (PACC). Methods: Six patients with PACC diagnosed in Peking University Third Hospital from January 2010 to September 2022 were retrospectively selected. Preoperative evaluation was performed on whether the lesions were eligible for surgery, including whether radical resection of liver metastases could be performed. Laparoscopic or Da Vinci robot-assisted resection was performed on six patients, and spleen retention was determined according to the original lesions and the relationship with peripheral blood vessels and tissues, while simultaneous resection was performed on cases of peripheral organ tissue invasion. The patients' basic information, preoperative general conditions, preoperative diagnosis and tumor stage, minimally invasive surgery methods, postoperative complications, pathological results, tumor stage and follow-up data were collected and analyzed to explore the effectiveness of minimally invasive surgery. Results: Among the six patients, four were males and two were females, with the age of 25-69 years. Five patients had abdominal pain and distension before surgery, five patients had tumors located at the tail of the pancreatic body, and one patient had tumors located at the head of the pancreas. Preoperative imaging (enhanced CT and MRI) was performed to measure the tumor diameter (2.8-10.0 cm). Tumor markers were elevated in two patients before surgery, and six patients underwent surgery through laparoscopy or robotic platform. No complications such as postoperative pancreatic fistula and bleeding were clinically relevant during and after surgery. There were two cases with concurrent or heterochronous liver metastasis, two cases with lymph node metastasis and nodular metastasis, four cases with tumor invasion of surrounding organs (stomach, spleen or duodenum), and three cases with vascular cancer thrombi. The follow-up time of the six patients was 12 to 165 months, and one patient underwent three operations due to postoperative liver metastasis and residual pancreatic recurrence, and the results were satisfactory. All the six patients survived at the last follow-up. Conclusions: PACC is prone to invade the surrounding organs, and has a large tumor diameter. Radical surgery for PACC can be completed through minimally invasive surgery, and satisfactory oncology prognosis can be obtained. In addition, some PACC patients with recurrence and metastasis can still be treated by surgery.

Objective: To understand the relationship between unhealthy lifestyle and hyperuricemia, as well as the modification effects of hypertension and dyslipidemia in occupational population and provide a theoretical basis for the prevention of hyperuricemia. Methods: A cross-sectional survey design was adopted, based on baseline data from the Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd., which included the population in 28 prefectures from Sichuan Province and Guizhou Province, and 33 districts (counties) from Chongqing Municipality between October and December 2021. This study collected the information about the demographics characteristics, lifestyles, and prevalence of chronic non-communicable diseases of the study subjects through questionnaire, physical measurement and laboratory biochemical test. The unhealthy lifestyle score was scored based on smoking, alcohol consumption, dietary patterns, physical activity, and low weight or overweight, with higher scores being associated with more unhealthy lifestyles. The multivariate logistic regression model was used to analyze the relationship between unhealthy lifestyle score, smoking, alcohol consumption, other factors and hyperuricemia, and the stratified analysis was used to explore the modification effect of hypertension and other diseases on the relationship between unhealthy lifestyle and hyperuricemia. Results: A total of 11 748 participants were included in this study, the prevalence of hyperuricemia was 34.4%. Multivariate logistic regression model showed that current/previous smoking, current/previous alcohol consumption and BMI abnormality were risk factors for hyperuricemia, and the unhealthy lifestyle score showed a "cumulative" effect on the risk for hyperuricemia, with higher score increasing the risk of hyperuricemia, and the OR increased from 1.64 (95% CI : 1.34-2.00) to 2.89 (95% CI : 2.39-3.50). Stratified analysis showed that unhealthy lifestyles had a greater impact on the risk for hyperuricemia in people with hypertension and dyslipidemia. Conclusions: The coexistence of multiple unhealthy lifestyles might increase the risk of hyperuricemia, and this effect was stronger in participants with hypertension and dyslipidemia. Timely correction of unhealthy lifestyles, and control of hypertension and dyslipidemia might reduce the risk for hyperuricemia.

Objective: To understand the influence of unhealthy lifestyle on diabetic dyslipidemia and the key influencing factors in occupational population and provided scientific evidence for the prevention of diabetic dyslipidemia. Methods: Based on baseline data and follow-up data of Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd. during 2021. Diabetic dyslipidemia was defined as diabetes plus one or more forms of dyslipidemia, and unhealthy lifestyle factors included smoking, alcohol consumption, unhealthy dietary patterns, low physical activity, and abnormal BMI. Multivariate logistic regression model was used to analyze the relationship between unhealthy lifestyle scores and diabetic dyslipidemia, network analysis was used to find and explore the key lifestyles influencing glycolipid metabolism. Results: A total of 25 631 subjects were included. People with unhealthy lifestyle score 2 and 3 were 1.93 (95% CI : 1.31-2.86) times and 2.37 (95% CI : 1.60-3.50) times more likely to have diabetes with ≥1 forms of dyslipidemia than those with scores of 0; People with unhealthy lifestyle score 1, 2 and 3 were 1.98 (95% CI : 1.08-3.61) times, 2.87 (95% CI : 1.60-5.14) times and 3.95 (95% CI : 2.22-7.06) times more likely to have diabetes with ≥2 forms of dyslipidemia than those with score 0. Network analysis found that abnormal BMI and HDL-C were the "bridge nodes" that link unhealthy lifestyles with diabetic dyslipidemia. Conclusion: The higher the score of unhealthy lifestyle, the higher the risk for diabetic dyslipidemia, abnormal BMI and HDL-C are key factors influencing the association between unhealthy lifestyle and diabetic dyslipidemia.

Pathway analysis, including nontopology-based (non-TB) and topology-based (TB) methods, is widely used to interpret the biological phenomena underlying differences in expression data between two phenotypes. By considering dependencies and interactions between genes, TB methods usually perform better than non-TB methods in identifying pathways that include closely relevant or directly causative genes for a given phenotype. However, most TB methods may be limited by incomplete pathway data used as the reference network or by difficulties in selecting appropriate reference networks for different research topics. Here, we propose a gene set correlation enrichment analysis method, Gscore, based on an expression dataset-derived coexpression network to examine whether a differentially expressed gene (DEG) list (or each of its DEGs) is associated with a known gene set. Gscore is better able to identify target pathways in 89 human disease expression datasets than eight other state-of-the-art methods and offers insight into how disease-wide and pathway-wide associations reflect clinical outcomes. When applied to RNA-seq data from COVID-19-related cells and patient samples, Gscore provided a means for studying how DEGs are implicated in COVID-19-related pathways. In summary, Gscore offers a powerful analytical approach for annotating individual DEGs, DEG lists, and genome-wide expression profiles based on existing biological knowledge., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

This study investigated how cold storage affects the nutraceutical diversity and physiological quality of Torreya yunnanensis seeds, using a widely targeted UPLC-MS/MS-based metabolomics analysis. The 373 identified metabolites were divided into nine categories: lipids, phenolic acids, amino acids and derivatives, organic acids, nucleotides, saccharides, vitamins and alcohols. Among them, 49 metabolites showed significant changes after 3 months of cold storage, affecting 28 metabolic pathways. The content of amino acid-related metabolites significantly increased, while the content of sugar-related metabolites decreased during storage. Notably, the content of proline acid, shikimic acid, α-linolenic acid and branched-chain amino acids showed significant changes, indicating their potential role in seed storage. This study deepens our understanding of the nutraceutical diversity and physiological quality of T. yunnanensis seeds during storage, providing insight for conservation efforts and habitat restoration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Although itch and pain have many similarities, they are completely different in perceptual experience and behavioral response. In recent years, we have a deep understanding of the neural pathways of itch sensation transmission. However, there are few reports on the role of non-neuronal cells in itch. Microglia are known to play a key role in chronic neuropathic pain and acute inflammatory pain. It is still unknown whether microglia are also involved in regulating the transmission of itch sensation. In the present study, we used several kinds of transgenic mice to specifically deplete CX3CR1+ microglia and peripheral macrophages together (whole depletion), or selectively deplete microglia alone (central depletion). We observed that the acute itch responses to histamine, compound 48/80 and chloroquine were all significantly reduced in mice with either whole or central depletion. Spinal c-fos mRNA assay and further studies revealed that histamine and compound 48/80, but not chloroquine elicited primary itch signal transmission from DRG to spinal Npr1- and somatostatin-positive neurons relied on microglial CX3CL1-CX3CR1 pathway. Our results suggested that microglia were involved in multiple types of acute chemical itch transmission, while the underlying mechanisms for histamine-dependent and non-dependent itch transmission were different that the former required the CX3CL1-CX3CR1 signal pathway., (© 2023 Wiley Periodicals LLC.)

This study aims to establish an accurate prediction model using artificial neural networks (ANNs) to effectively and efficiently predict the process-induced warpage of a flip-chip chip-scale package (FCCSP). To enhance model performance, a novel subdomain-based sampling strategy and Taguchi hyperparameter optimization are proposed in the ANN algorithm. To simulate the warpage behavior the FCCSP during fabrication, a process modeling approach is proposed, where the viscoelastic behavior of the epoxy molding compound is included, in which the viscoelastic properties are determined using dynamic mechanical measurement. In addition, the temperature-dependent thermal-mechanical properties of the materials in the FCCSP are assessed through thermal-mechanical analysis and dynamic mechanical analysis. The modeled warpage results are verified by the warpage measurement. Next, warpage parametric analysis is performed to identify the key factors most affecting warpage behavior for use in the construction of the warpage prediction model. Moreover, the advantages of the proposed sampling and hyperparameter tuning approaches are proved by comparing with other existing models, and the validity of the developed ANN-based deep learning warpage prediction model is demonstrated through a validation dataset.

Groundwater pollution risk assessment is an effective method to manage groundwater resources and prevent groundwater pollution. The DRSTIW model was used to evaluate the groundwater vulnerability in a plain area of the Yarkant River Basin, and factor analysis was used to identify pollution sources for pollution loading evaluation. The functional value of groundwater was estimated by considering both the mining value and the in-situ value. The entropy weight method and the analytic hierarchy process (AHP) were used to determine the comprehensive weight, and a groundwater pollution risk map was generated based on the overlay function of ArcGIS software. The results showed that the natural geological factors such as large groundwater recharge modulus, wide recharge sources, strong permeability of soil surface and unsaturated zone, and shallow groundwater depth facilitated pollutant migration and enrichment, resulting in a higher overall groundwater vulnerability. Very high vulnerability and high vulnerability areas were mainly distributed in Zepu County, Shache County, Maigaiti County, Tumushuke City, and the eastern part of Bachu County. The pollution loading of groundwater was generally low, the main pollution sources were point source pollution caused by water-rock interaction, non-point source pollution caused by pesticides and fertilizers, and point source pollution caused by industry and life. The overall functional value of groundwater was low because of human economic activities, fine water quality, and good habitat quality. Groundwater pollution risk was generally low, and very high and high pollution risk areas accounted for 20.7% of the study area, mainly distributed in Shache County, Zepu County, Maigaiti County, Tumushuke City, and the western part of Bachu County. Natural conditions such as strong aquifer permeability, weak groundwater runoff conditions, large groundwater recharge modulus, low vegetation coverage, and strong water-rock interaction, coupled with frequent human activities such as application of agricultural fertilizers and discharge of industrial and domestic sewage, made the groundwater pollution risk higher in these areas. Groundwater pollution risk assessment provided strong data support for the optimization of the groundwater monitoring network and the prevention of groundwater pollution.

2,5-Diformylfuran, which can be prepared via the oxidation of biobased HMF, has received considerable attention because of its potential applications in producing furan-based chemicals and functional materials, such as biofuels, polymers, fluorescent material, vitrimers, surfactants, antifungal agents and medicines. This work aimed to develop an efficient one-pot process for chemoenzymatic transformation of biobased substrate to 2,5-diformylfuran with deep eutectic solvent (DES) Betaine:Lactic acid ([BA][LA]) catalyst and oxidase biocatalyst in [BA][LA]-H 2 O. Using waste bread (50 g/L) and D-fructose (18.0 g/L) as feedstocks in [BA][LA]-H 2 O (15:85, vol/vol), the yields of HMF were 32.8% (15 min) and 91.6% (90 min) at 150 °C, respectively. These prepared HMF could be biologically oxidized to 2,5-diformylfuran by Escherichia coli pRSFDuet-GOase, achieving a productivity of 0.631 g 2,5-diformylfuran/(g fructose) and 0.323 g 2,5-diformylfuran/(g bread) after 6 h under the mild performance condition. This bioresourced intermediate 2,5-diformylfuran was effectively synthesized from biobased feedstock in an environmentally-friendly system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Pulmonary arterial hypertension (PAH) is a progressive disease that despite advances in therapy is associated with a 7-year survival of approximately 50%. Several risk factors are associated with developing PAH, include methamphetamine use, scleroderma, human immunodeficiency virus, portal hypertension, and genetic predisposition. PAH can also be idiopathic. There are traditional pathways underlying the pathophysiology of PAH involving nitric oxide, prostacyclin, thromboxane A2, and endothelin-1, resulting in impaired vasodilation, enhanced vasoconstriction and proliferation in the pulmonary vasculature. Established PAH medications targets these pathways; however, this paper aims to discuss novel drugs for treating PAH by targeting new and alternative pathways., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Bulk Bi 0.5 Sr 0.5 Fe 0.5 Cr 0.5 O 3 (BSFCO) is a new compound comprising the R3c structure. The structural, magnetic property and exchange bias (EB) details are investigated. The material was in the super-paramagnetic (SP) state at room temperature. Exchange bias usually occurs at the boundary between different magnetic states after field cooling (H FC ) acts on the sample. Here the result shows that changing H FC from 1 to 6 T reduces the H EB value by 16% at 2 K at the same time. Meanwhile, H EB diminishes as the ferromagnetic layer thickness increases. The variation of (the thickness of ferromagnetic layer) t FM with the change of H FC leads to the tuning of H EB by H FC in BSFCO bulk. These effects are obviously different from the phenomenon seen in other oxide types., (© 2023. The Author(s).)

Silicon-based composites are promising candidates as the next-generation anode materials for high-performance lithium-ion batteries (LIBs) due to their high theoretical specific capacity, abundant reserves, and reliable security. However, expensive raw materials and complicated preparation processes give silicon carbon anode a high price and poor batch stability, which become a stumbling block to its large-scale practical application. In this work, a novel ball milling-catalytic pyrolysis method is developed to fabricate a silicon nanosheet@amorphous carbon/N-doped graphene (Si-NSs@C/NG) composite with cheap high-purity micron-size silica powder and melamine as raw materials. Through systematic characterizations such as XRD, Raman, SEM, TEM and XPS, the formation process of NG and a Si-NSs@C/NG composite is graphically demonstrated. Si-NSs@C is uniformly intercalated between NG nanosheets, and these two kinds of two-dimensional (2D) materials are combined in a surface-to-surface manner, which immensely buffers the stress changes caused by volume expansion and contraction of Si-NSs. Attributed to the excellent electrical conductivity of graphene layer and the coating layer, the initial reversible specific capacity of Si-NSs@C/NG is 807.9 mAh g -1 at 200 mA g -1 , with a capacity retention rate of 81% in 120 cycles, exhibiting great potential for application as an anode material for LIBs. More importantly, the simple and effective process and cheap precursors could greatly reduce the production cost and promote the commercialization of silicon/carbon composites.

Heterocyclic Quaternary Phosphonium Salts (HQPS) have emerged as promising chemicals for organic synthesis and medicinal chemistry. However, the present synthetic methodology of this type of compound is still limited. Here, we report a deconstructive reorganization strategy based on Brønsted acid-mediated tandem 1,4 addition/intramolecular cyclization of triphenylphosphine derivatives and in situ generated o -AQMs for the first time. This protocol provides a novel approach to heterocyclic quaternary phosphonium salts. The method also features a non-metal catalyst, mild reaction conditions, high efficiency and wide substrate scope. Moreover, a series of obtained heterocyclic phosphonium salts can be converted to isotopically labelled 2-benzofuran compounds directly by simple deuteration reactions.

Perampanel is a first-in-class α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist and a novel anti-seizure medication. It is currently used as adjunctive treatment for partial seizures in patients over 12 years of age. With the increasing clinical application of perampanel, monitoring its concentration under certain clinical conditions is important. This study developed a rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry method to quantify perampanel in human plasma. Protein precipitation with acetonitrile was performed for sample preparation. Perampanel and perampanel-d5 (internal standard) were analyzed under gradient conditions using a C18 column. The mobile phase was composed of 0.1% (v/v) formic acid in water (solvent A) and 0.1% (v/v) formic acid in acetonitrile (solvent B) at a flow rate of 0.4 mL/min. Mass detection was performed using multiple reaction monitoring in the positive ionization mode. The proposed method was validated over a range of 0.5-500 ng/mL for perampanel. The linearity (r 2 value) was higher than 0.999, and the linear equation was y = 0.00116x + 0.0116. The accuracy of the low-, middle-, and high-quality control samples was between 103% and 113%, and the intra- and inter-day precisions were below 6.81%. The quality of the proposed method was evaluated in accordance with the US Food and Drug Administration Bioanalytical Method Validation Guidance for Industry. The plasma concentrations of perampanel in 25 patients were successfully determined to be 38.7-577.7 ng/mL using the validated method., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Climate change is an important driver of species distribution and biodiversity. Understanding the response of plants to climate change is helpful to understand species differentiation and formulate conservation strategies. The genus Polyspora (Theaceae) has an ancient origin and is widely distributed in subtropical evergreen broad-leaved forests. Studies on the impacts of climate change on species geographical distribution of Chinese Polyspora can provide an important reference for exploring the responses of plant groups in subtropical evergreen broad-leaved forests with geological events and climate change in China. Based on the environmental variables, distribution records, and chloroplast genomes, we modeled the potential distribution of Chinese Polyspora in the Last Glacial Maximum, middle Holocene, current, and future by using MaxEnt-ArcGIS model and molecular phylogenetic method. The changes in the species distribution area, centroid shift, and ecological niche in each periods were analyzed to speculate the response modes of Chinese Polyspora to climate change in different periods. The most important environmental factor affecting the distribution of Polyspora was the precipitation of the driest month, ranging from 13 to 25 mm for the highly suitable habitats. At present, highly suitable distribution areas of Polyspora were mainly located in the south of 25°N, and had species-specificity. The main glacial refugia of the Chinese Polyspora might be located in the Ailao, Gaoligong, and Dawei Mountains of Yunnan Province. Jinping County, Pingbian County, and the Maguan County at the border of China and Vietnam might be the species differentiation center of the Chinese Polyspora . Moderate climate warming in the future would be beneficial to the survival of P. axillaris , P. chrysandra , and P. speciosa . However, climate warming under different shared socio-economic pathways would reduce the suitable habitats of P. hainanensis and P. longicarpa ., Competing Interests: The authors have no conflict of interest to declare., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background Since the initial description in the 1980s, our understanding of the diversity of pulmonary arterial hypertension (PAH) has continued to evolve. In this study, we report the characteristics of patients seen in an academic medical center for PAH from August 2020 through November 2021 and contrast those with nationally reported data from the United States Pulmonary Hypertension Scientific Registry (USPHSR).  Study Design Investigators at the University of Utah Pulmonary Hypertension Program prospectively enrolled adult patients diagnosed with WHO Group 1 PAH, who were evaluated between August 2020 and November 2021 in a program-specific registry. Patient exposure and health histories were collected through structured interviews and questionnaires, along with clinical data and medication use. A total of 242 patients were enrolled in the University of Utah Pulmonary Hypertension Registry (UUPHR).  Results Of the 242 enrolled patients, the most common etiology was associated PAH (APAH), accounting for 71.1% of the population. The second largest etiology was idiopathic PAH (IPAH) at 26.4%. The remaining patients were distributed between familial PAH (FPAH), pulmonary veno-occlusive disease (PVOD), and others. Of the total population classified as APAH, 39% of cases were noted as secondary to connective tissue disease (CTD) and 33% as toxin-induced. These represented 28% and 24% of the total population, respectively.  Conclusions In this US-based accredited academic medical center, the etiology of PAH in our patient population contrasts with national registry data. In the UUPHR, APAH, specifically CTD-PAH and toxin-associated PAH, accounts for the majority of patients with PAH. This contrasts with IPAH, which nationally is the most reported cause of PAH. Differences in our population may reflect the regional variation of the referral site, but it is noteworthy for its contrast with historically reported phenotypes., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2022, Ingram et al.)

Objectives: The aims of this review were to determine whether positive peritoneal lavage cytology (CY+) precludes radical resection in pancreatic cancer and to propose prospections for future studies., Methods: MEDLINE, Embase, and Cochrane Central were searched for related articles. Dichotomous variables and survival outcomes were analyzed with the estimation of odds ratio and hazards ratio (HR), respectively., Results: A total of 4905 patients were included, of which 7.8% were CY+. Positive peritoneal lavage cytology was correlated with poor overall survival (univariate survival analysis [HR, 2.35; P < 0.00001]; multivariate analysis [HR, 1.62; P < 0.00001]), poor recurrence-free survival (univariate survival analysis [HR, 2.50; P < 0.00001]; multivariate analysis [HR, 1.84; P < 0.00001]), and higher initial peritoneal recurrence rate (odds ratio, 5.49; P < 0.00001)., Conclusions: Although CY+ predicts poor prognosis and a higher risk of peritoneal metastasis after curative resection, it is not sufficient to preclude curative resection based on the current evidence, and high-quality trials should be conducted to assess the prognostic impact of operation among resectable CY+ patients. In addition, more sensitive and accurate methods to detect peritoneal exfoliated tumor cells and more effective comprehensive treatment for resectable CY+ pancreatic cancer patients are clearly warranted., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Five undescribed phenylpropanoids, one undescribed phenolic glucoside, and sixteen known compounds were isolated from Brachybotrys paridiformis Maxim. Ex Oliv. The undescribed compounds were named brachoside B-C, brach acid A-B, brachnan A, and brachin D, respectively. Additionally, the anti-hepatitis B virus activities of all isolated compounds were studied. Among them, brachnan A, brach acid A, globoidnan A, 3-carboxy-6,7-dihydroxy-1-(3',4'-dihydroxy-phenyl)-naphthalene, and 3,4-dihydroxybenzaldehyde showed significant anti-hepatitis B virus activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rivaroxaban, a direct factor Xa inhibitor, is widely used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to conduct a population pharmacokinetic-pharmacodynamic (PK-PD) analysis of rivaroxaban in Chinese patients with NVAF to assess ethnic differences and provide model-based precision dosing. A total of 256 rivaroxaban plasma concentrations and 244 prothrombin time (PT) measurements were obtained from 195 Chinese NVAF patients from a prospective clinical trial. The population PK-PD model was developed using nonlinear mixed effects modeling (NONMEM) software. The PK of rivaroxaban was adequately described using a one-compartment model with first-order adsorption and elimination. Estimated glomerular filtration rate (eGFR) was identified as a major covariate for apparent clearance. No single nucleotide polymorphism was identified as a significant covariate. PT exhibited a linear relationship with rivaroxaban concentration. Total bilirubin (TBIL) and eGFR were identified as significant covariates for baseline PT. According to the Monte Carlo simulation, 15 mg for Chinese patients with eGFR ≥50 mL/min and normal liver function yielded an exposure comparable to 20 mg for Caucasian patients. Patients with moderately impaired renal function may require a lower dose of rivaroxaban to avoid overexposure. Moreover, there was an approximate 26% increase in PT levels in patients with TBIL of 34 μmol/L and eGFR of 30 mL/min, which could increase the risk of major bleeding. The established population PK-PD model could inform individualized dosing for Chinese NVAF patients who are administered rivaroxaban., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Polyspora Sweet (Theaceae) are winter ornamental landscape plants native to southern and southeastern Asia, some of which have medicinal value. The chloroplast (cp) genome data of Polyspora are scarce, and the gene evolution and interspecific relationship are still unclear. In this study, we sequenced and annotated Polyspora chrysandra cp genome and combined it with previously published genomes for other Chinese Polyspora species. The results showed that cp genomes of six Chinese Polyspora varied in length between 156,452 bp (P. chrysandra) and 157,066 bp (P. speciosa), but all contained 132 genes, with GC content of 37.3%, and highly similar genes distribution and codon usage. A total of eleven intergenic spacer regions were found having the highest levels of divergence, and eight divergence hotspots were identified as molecular markers for Phylogeography and genetic diversity studies in Polyspora. Gene selection pressure suggested that five genes were subjected to positive selection. Phylogenetic relationships among Polyspora species based on the complete cp genomes were supported strongly, indicating that the cp genomes have the potential to be used as super barcodes for further analysis of the phylogeny of the entire genus. The cp genomes of Chinese Polyspora species will provide valuable information for species identification, molecular breeding and evolutionary analysis of genus Polyspora., (© 2022. The Author(s).)

Objective: To explore and establish the preparation system of human intestinal fluid transplantation (HIFT) and HIFT capsule, and to preliminarily apply it to clinic. Methods: Strict standards for donor screening and management were established. The nasojejunal tube was catheterized into the distal jejunum, and then it was connected with an improved disposable sterile negative pressure collection device for the collection of human intestinal fluid. After that, it was prepared into capsules by filtering, adding 10% glycerin protectant and freeze-drying method. The amount of living bacteria was used as the standard of therapeutic dose. The living bacteria amount in fluid is ≥ 5.0×10 8 /mL and the living bacteria proportion is ≥ 83%; the living bacteria amount in powder is ≥ 2.0×10 6 /g and the living bacteria proportion is ≥ 81%; The observational indicators included: (1) the basic information of the donor, the amount of living bacteria in the HIF and powder. (2) Preliminary analysis of the treatment for ASD, which combined HIFT capsule with standard FMT capsule, from February to December 2021 (Clinical trial Registration Number: ChiCTR2100043929). Evaluation criteria: Trypan blue staining method was used to detect the living bacteria amount in fluid and powder. The Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to evaluate the efficacy. Results: Compared with the parent donor, the standard donor was younger [(25.4±0.9) y vs. (30.7±3.2) y, t =-19.097, P =0.001] and had a lower body mass index [(19.7±0.5) kg/m 2 vs. (20.8±1.3) kg/m 2 , t =-8.726, P =0.001], more in the living bacteria amount in powder [(7.47±1.52)×10 6 /g vs. (5.03±1.38)×10 6 /g, t =11.331, P =0.031], Chao index (205.4±6.8 vs. 194.2±7.2, t =10.415, P =0.001), and Shannon index (3.25±0.14 vs 2.72±0.27, t =19.465, P =0.001). The differences were statistically significant (all P <0.05). However, there were no significant differences in gender, drainage volume and total number of bacterial liquid colonies between the two groups (all P >0.05). Both the standard donor and the parent donor met the donor screening criteria, and the preparation fluid and powder met the treatment criteria. Eight patients received the treatment of HIFT combined with fecal microbiota transplantation (FMT). Preliminary statistical results showed that HIFT combined with FMT improved ABC and CARS at the 1st, 2nd, 3rd and 4th months. The differences were statistically significant (all P <0.05). No severe adverse reaction occurred. Conclusion: Based on the previous research on FMT preparation system and the clinical technology in our center, this study developed a high standard HIFT preparation system, and explored the clinical study of HIFT combined with FMT, in order to provide an innovative therapy for the treatment of diseases.

Background: Currently, case studies or clinical trials in different patient populations remain the main resource underlying the understanding of disorder of consciousness (DoC). This provides a low efficacy for the derivation of data and the implementation of associated controlled experimental designs. Preclinical models provide precise controls, reduced variability, rich data output and limited ethical complexity. Nonhuman primates are suitable model animals for disorders of consciousness due to their brain structure being very similar to that of humans. Behavioral tests remain the primary standard for assessing the consciousness status of humans. However, there is currently no behavioral assessment scale available for evaluation of the state of consciousness disorder in nonhuman primates. This presents a significant challenge for the establishment of different models of consciousness disorder. Therefore, there is considerable motivation to focus on the development of a proper tool for assessment of the state of consciousness associated with nonhuman primate models that are based on clinically common consciousness assessment scales., Methods: It is assumed that the Delphi and level analysis methods based on clinical consciousness disorder assessment scales may provide an effective way to select and include assessment indexes for levels of consciousness in nonhuman primates., Results: 8 first-level indicators with 41 second-level indexes were selected preliminary as a pool of evaluation entries of state of consciousness of nonhuman primates., Conclusions: It may be practicable to extract appropriate indicators for non-human primates from the clinical consciousness disorder assessment scales. Besides, a combination of Delphi method, behavioral analysis, electroencephalography, neuroimaging (such as positron emission tomography-computed tomography) and functional magnetic resonance imaging is necessary to test the reliability and validity of the novel scale reported here., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

In this work, a luminescent metal-organic framework (Eu-MOF {[Eu 6 L 6 (μ 3 -OH) 8 (H 2 O) 3 ] 8 ·H 2 O} n ) was constructed by a solvothermal method with a linear organic ligand L (10-[(2-amino-4-carboxyl-phenyl)ethynyl]anthracene-9-carboxylic acid) based on anthracene and alkyne groups and using Eu 3+ as the metal center. The MOF exhibits a stable UiO-66 crystal structure, and a six-core cluster twelve-linked secondary structural unit was successfully synthesized using 2-fluorobenzoic acid as a modulator, forming a classical fcu topology. Moreover, it exhibits good chemical stability. Interestingly, Eu-MOF exhibited high selectivity and sensitive fluorescence burst properties towards Fe 3+ ions and 2,4,6-trinitrophenol (TNP) in DMF solution. For Fe 3+ , the K SV value is 5.06 × 10 5 M -1 and the LOD value is 5.1 × 10 -7 M. For TNP, the K SV value is 1.92 × 10 4 M -1 and the LOD value is 1.93 × 10 -6 M. In addition, Eu-MOF showed good anti-interference ability and fast response. This work provides an excellent fluorescent sensor for the detection of Fe 3+ and 2,4,6-trinitrophenol (TNP) residues in contaminants., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

The right ventricle (RV) and pulmonary arterial (PA) tree are inextricably linked, continually transferring energy back and forth in a process known as RV-PA coupling. Healthy organisms maintain this relationship in optimal balance by modulating RV contractility, pulmonary vascular resistance, and compliance to sustain RV-PA coupling through life's many physiologic challenges. Early in states of adaptation to cardiovascular disease-for example, in diastolic heart failure-RV-PA coupling is maintained via a multitude of cellular and mechanical transformations. However, with disease progression, these compensatory mechanisms fail and become maladaptive, leading to the often-fatal state of "uncoupling." Noninvasive imaging modalities, including echocardiography, magnetic resonance imaging, and computed tomography, allow us deeper insight into the state of coupling for an individual patient, providing for prognostication and potential intervention before uncoupling occurs. In this review, we discuss the physiologic foundations of RV-PA coupling, elaborate on the imaging techniques to qualify and quantify it, and correlate these fundamental principles with clinical scenarios in health and disease. © 2022 American Physiological Society. Compr Physiol 12: 1-26, 2022., (Copyright © 2022 American Physiological Society. All rights reserved.)

The active sites of [FeFe]-hydrogenase promoted by Fe/E (E = S, Se) clusters have attracted considerable interest due to their significance in understanding the interconversion of hydrogen with protons and electrons. As an extension of the study on Fe/Se clusters related to H-cluster model compounds of [FeFe]-hydrogenase, a series of tertiary phosphine substituted Fe/Se carbonyls were successfully prepared. The treatment of Fe 2 (μ-SePh) 2 (CO) 6 (A) and excess PR 3 resulted in the ferrous bis(selenolate) carbonyls Fe(SePh) 2 (CO) 2 (PR 3 ) 2 (PR 3 = PPhMe 2 , 1; PMe 3 , 2) in moderate yields. In striking contrast, the reaction of Fe 2 (μ-SeCH 2 Ph) 2 (CO) 6 (B) with the same PR 3 ligand resulted in the PR 3 -disubstituted models Fe 2 (μ-SeCH 2 Ph) 2 (CO) 4 (PR 3 ) 2 (PR 3 = PPhMe 2 , 3; PMe 3 , 4) as the principal products. The more interesting finding is that two independent isomers ( anti - and syn -) can be isolated according to different reaction temperatures. Further reactions of 3 or 4 with PR 3 under UV irradiation afforded the first PR 3 -trisubstituted 2Fe2Se derivatives Fe 2 (μ-SeCH 2 Ph) 2 (CO) 3 (PR 3 ) 3 (PR 3 = PPhMe 2 , 5; PMe 3 , 6). 6 could be further converted into the tetrasubstituted product Fe 2 (μ-SeCH 2 Ph) 2 (CO) 2 (PMe 3 ) 4 (7), while no further substitution was observed with 5 and excess of PPhMe 2 . All the prepared compounds were fully characterized by elemental analysis, various spectroscopic techniques and X-ray crystallography. In addition, some electrochemical properties of these models were studied by cyclic voltammetry (CV) in MeCN. Compounds 4, 6 and 7 were found to be catalysts for the H 2 evolution reaction under electrochemical conditions.