bluuebunny/crossref_metadata_2025 huggingface dataset:
Alloying effect of Ni-Mo catalyst in hydrogenation of N-ethylcarbazole for hydrogen storage
Authors: Wang Bin , Dong Qian , Wang Si-Yao , Li Pei-Ya , Wang Shi-Yuan , Lu Shu-Han , Fang Tao
Published: December 2022

Liquid organic hydrogen storage with N-ethylcarbazole (NEC) as a carrier is a very promising method. The use of precious metal hydrogenation catalysts restricts the development in industrial grade. Efficient and low-cost hydrogen storage catalysts are essential for its application. In this work, a Ni-Mo alloy catalyst supported by commercial activated carbon was synthesized by impregnation method, and the Ni-Mo ratio and preparation conditions were optimized. The catalyst was characterized by XRD, XPS, H2-TPR, SEM, and TEM. The results showed that the doping of Mo could dramatically promote the catalytic hydrogenation of N-ethylcarbazole by the Ni-based catalyst. More than 5.75 wt% hydrogenation could be achieved in 4 h using the Ni-Mo catalyst, and the selectivity of the fully hydrogenated product 12H-NEC could be effectively improved. This result reduces the cost of hydrogenation catalysts by more than 90% and makes liquid organic hydrogen storage a scaled possibility.
Antifungal active ingredient from the twigs and leaves of Clausena lansium Lour. Skeels (Rutaceae)
Authors: Fu Xiaoxiang , Xiao Suling , Cao Duantao , Yuan Minxuan , Xiang Miaolian , Zhou Qinghong , Huang Yingjin , Wei Hongyi , Peng Wenwen
Published: December 2022

Two novel amides, named clauphenamides A and B, and twelve other known compounds were isolated from the twigs and leaves of Clausena lansium Lour. Skeels (Rutaceae). Their structures were elucidated on the basis of extensive spectroscopic analysis and comparison with data reported in the literature. Clauphenamide A (1) featured in the unit of N-2-(4,8-dimethoxyfuro [2,3-b]quinolin-7-yl)vinyl, and clauphenamide B (2) was a unprecedented N-phenethyl cinnamide dimer. Other known compounds belong to pyrrolidone amides (3 and 4), furacoumarins (7–10), simple coumarins (11–14), lignan (5) and sesquiterpene (6). Compounds 5, 6, 10 and 12 were separated from the genus (Clausena) for the first time, while 13 was isolated in the species (C. lansium) for the first time. The antifungal activities of the isolated compounds were assayed. As a result, at the concentration of 100 μg/ml, compared with the control (chlorothalonil, inhibition rate of 83.67%), compounds 1 and 2 were found to exhibit moderate antifungal activity against B. dothidea with inhibition rates of 68.39% and 52.05%, respectively. Compounds 11–14 also exhibited moderate activity against B. dothidea and F. oxysporum, with inhibition rates greater than 40%. In addition, compared with the control (chlorothalonil, inhibition rate of 69.02%), compounds 11–14 showed strong antifungal activity to P. oryzae, with inhibition rates greater than 55%. Among them, compound 14 has the strongest antifungal activity against P. oryzae, and the inhibition rate (65.44%) is close to that of the control chlorothalonil. Additionally, the structure-activity relationships of the separated compounds are also discussed preliminarily in this paper.
Cardiac geometry, as assessed by cardiac magnetic resonance, can differentiate subtypes of chronic thromboembolic pulmonary vascular disease
Authors: McGettrick Michael , Dormand Helen , Brewis Melanie , Johnson Martin K. , Lang Ninian N. , Church Alistair Colin
Published: December 2022

Background

Ventricular septal flattening reflects RV pressure overload in pulmonary arterial hypertension. Eccentricity index (EI) and pulmonary artery distensibility (PAD) correlate with pulmonary artery pressure. We assessed the utility of these using cardiac magnetic resonance (CMR) to assess for pulmonary hypertension (PH) in patients with chronic thromboembolic disease. This may allow non-invasive differentiation between patients who have chronic thromboembolic pulmonary hypertension (CTEPH) and those with pulmonary vascular obstructions without PH at rest, known as chronic thromboembolic pulmonary disease (CTEPD).

Methods

Twenty patients without resting pulmonary hypertension, including ten with chronic thromboembolic disease, and thirty patients with CTEPH were identified from a database at the Scottish Pulmonary Vascular Unit. CMR and right heart catheter had been performed within 96 h of each other. Short-axis views at the level of papillary muscles were used to assess the EI at end-systole and diastole. Pulmonary artery distensibility was calculated using velocity-encoded images attained perpendicular to the main trunk.

Results

Eccentricity index at end-systole and end-diastole were higher in CTEPH compared to controls (1.3 ± 0.5 vs. 1.0 ± 0.01; p ≤ 0.01 and (1.22 ± 0.2 vs. 0.98 ± 0.01; p ≤ 0.01, respectively) and compared to those with CTED. PAD was significantly lower in CTEPH compared to controls (0.13 ± 0.1 vs. 0.46 ± 0.23; p ≤ 0.01) and compared to CTED. End-systolic EI and end-diastolic EI correlated with pulmonary vascular hemodynamic indices and exercise variables, including mean pulmonary arterial pressure (R0.74 and 0.75, respectively), cardiac output (R-value −0.4 and −0.4, respectively) NTproBNP (R-value 0.3 and 0.3, respectively) and 6-min walk distance (R-value −0.7 and −0.8 respectively). Pulmonary artery distensibility also correlated with 6-min walk distance (R-value 0.8).

Conclusion

Eccentricity index and pulmonary artery distensibility can detect the presence of pulmonary hypertension in chronic thromboembolic disease and differentiate between CTEPH and CTED subgroups. These measures support the use of non-invasive tests including CMR for the detection pulmonary hypertension and may reduce the requirement for right heart catheterization.
Heterogeneous circulating miRNA profiles of PBMAH
Authors: Hara Kazunari , Murakami Masanori , Niitsu Yoshihiro , Takeuchi Akira , Horino Masato , Shiba Kumiko , Tsujimoto Kazutaka , Komiya Chikara , Ikeda Kenji , Tsuiki Mika , Tanabe Akiyo , Tanaka Toshihiro , Yokoyama Minato , Fujii Yasuhisa , Naruse Mitsuhide , Yamada Tetsuya
Published: December 2022

Objective

Primary bilateral macronodular adrenal hyperplasia (PBMAH), a rare cause of Cushing syndrome, is often diagnosed as a bilateral adrenal incidentaloma with subclinical cortisol production. Circulating microRNAs (miRNAs) are a characteristic of adrenocortical adenomas, but miRNA expression in PBMAH has not been investigated. We aimed to evaluate the circulating miRNA expression in patients with PBMAH and compare them with those in patients with non-functioning adrenocortical adenoma (NFA) and cortisol-producing adrenocortical adenoma (CPA).

Methods

miRNA profiling of plasma samples from four, five, and five patients with NFA, CPA, and PBMAH, respectively, was performed. Selected miRNA expressions were validated using quantitative RT-PCR.

Results

PBMAH samples showed distinct miRNA expression signatures on hierarchical clustering while NFA and CPA samples were separately clustered. PBMAH was distinguished from the adenoma group of NFA and CPA by 135 differentially expressed miRNAs. Hsa-miR-1180-3p, hsa-miR-4732-5p, and hsa-let-7b-5p were differentially expressed between PBMAH and adenoma (P = 0.019, 0.006, and 0.003, respectively). Furthermore, PBMAH could be classified into two subtypes based on miRNA profiling: subtype 1 with a similar profile to those of adenoma and subtype 2 with a distinct profile. Hsa-miR-631, hsa-miR-513b-5p, hsa-miR-6805-5p, and hsa-miR-548av-5p/548k were differentially expressed between PBMAH subtype 2 and adenoma (P = 0.027, 0.027, 0.027, and 1.53E-04, respectively), but not between PBMAH, as a whole, and adenoma.

Conclusion

Circulating miRNA signature was identified specific for PBMAH. The existence of subtype-based miRNA profiles may be associated with the pathophysiological heterogeneity of PBMAH.
Persistent hyperparathyroidism secondary to ectopic parathyroid adenoma in lung: Case report
Authors: Valizadeh Majid , Ebadinejad Amir , Amouzegar Atieh , Zakeri Anahita
Published: December 2022

Primary hyperparathyroidism (PHPT) is the most prevalent cause of hypercalcemia, affecting 0.3% of the population. The only curative procedure is parathyroidectomy. Persistent PHPT occurs in 4.7 percent of patients, even in the most skilled hands. Ectopic adenomas are challenging to localize before and during surgery and frequently result in persistent PHPT. We presented a case with persistent PHPT due to lung parathyroid adenoma that was successfully resected with video-assisted thoracoscopic surgery. A 55-year-old female patient was admitted to our endocrinology clinic with persistent PHPT after four neck explorations over 16 years. The last 99m Tc-MIBI scintigraphy with SPECT showed nothing suggestive of parathyroid adenoma, neither in the neck nor the mediastinum, but a solitary nodule as an incidental finding was reported in the lower lobe of the right lung, which was highly probable for a parathyroid adenoma in a fluorodeoxyglucose PET scan. Pathological examination ruled out parathyromatosis and lung malignancy; despite its location outside the anticipated embryonic pathway, pathology revealed the presence of an ectopic parathyroid adenoma. After the surgery, serum parathyroid hormone and calcium levels decreased, and hypoparathyroidism was corrected with calcium carbonate and calcitriol.
Whether it is economical to use combined heat and power (CHP) system for the efficient utilization of associated petroleum gas in oil extraction sites in China: A cost-benefit analysis considering environmental benefits
Authors: Chen Mingjian
Published: December 2022

The efficient use of associated petroleum gas with combined heat and power (CHP) systems in oil extraction sites has proven to be technically feasible, but its economic inefficiency continues to deter oil companies from using CHP, given that simple fuel cost reductions do not yield significant positive returns in the face of large investments in purchasing and maintaining CHP. This research constructs a cost-benefit analysis model, which includes the monetized environmental benefits generated by CHP. A pilot experiment operated in a certain oilfield in Shandong province shows that the annual difference between the reduction in fuel costs and the investment in purchase and maintenance of CHP is only about ¥210,000 per device. However, when environmental benefits including health benefit and low-carbon benefit are included in the model, the annual environmental benefits of a single equipment update can be about ¥760,000, and the overall annual net benefits will reach about ¥970,000. It is concluded that the application of CHP in oil extraction sites is economically efficient, taking into account the environmental benefit it can produce. The research results will help oil companies use CHP to make more contributions to carbon and air pollutant emission reduction. However, considering that a large number of CHP systems can form a distributed energy structure, the proposed model still has limitations.
Secondary metabolites produced by endophytic fungi, Alternaria alternata, as potential inhibitors of the human immunodeficiency virus
Authors: Nzimande Bruce , Kumalo Hezekiel M. , Ndlovu Sizwe I. , Mkhwanazi Nompumelelo P.
Published: December 2022

Antiretroviral treatment has significantly reduced human immunodeficiency virus infection and mortality. However, the current treatment regimen is limited by adverse side effects, the emergence of drug resistance, and the inability to eliminate viral reservoirs. Here, fifteen endophytic fungi were isolated from Sclerocarya birrea and Hypoxis plants. Crude extracts of Alternaria alternata (strain ID PO4PR1, PO4PR2, and PO2PL1) of the fifteen isolate’s crude extracts showed anti-HIV-1 activity in TZM-bl cell line at inhibitory concentration (IC50) values ranging from 0.017 to 1.170 μg/ml. The three crude extracts also maintained the virus replication inhibition profile on PBMCs and CD4+ T cells at concentrations ranging from 0.3 to 50.2 ng/ml. Partial purification using the solid phase extraction and analysis with Gas Chromatography-Mass spectrophotometry showed a diverse profile. The bioactive compounds were identified based on peak area, retention time, similarity index. The major compounds from GC-MS analysis of A. Alternata revealed the existence of cyclotrisiloxane octamethyl (22.92%); Propaninitrile (16,67%); Pyrrolol[1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methyl propyl) (10.42%); Silane, diethylethoxy(2-ethoxyethyloxy) (4.17%); Coumarin, 3,4-dihydro-4,5,7-trimethyl- 4,5,7-Trimethyl-2-chromanone (13.7%) and 1,2-Cyclobutanedicarbonitrile (2.08%) with previously reported biological activities such as antimicrobial, anti-inflammatory and antioxidant properties. Therefore, these bioactive compounds from A. alternata fungal endophytes could be repurposed as potential anti-HIV agents. This study showed the potential of endophytic fungi, Alternaria alternata from S. birrea, and Hypoxis species as producers of anti-HIV compounds.
A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma
Authors: Deng Yuanyuan , Li Huihuang , Fu Jinglan , Pu Ying , Zhang Ying , Chen Shijing , Tong Shiyu , Liu Huixia
Published: December 2022

Background: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumor derived from the adrenal cortex. Because of its highly aggressive nature, the prognosis of patients with adrenocortical carcinoma is not impressive. Hypoxia exists in the vast majority of solid tumors and contributes to invasion, metastasis, and drug resistance. This study aimed to reveal the role of hypoxia in Adrenocortical carcinoma and develop a hypoxia risk score (HRS) for Adrenocortical carcinoma prognostic prediction.

Methods: Hypoxia-related genes were obtained from the Molecular Signatures Database. The training cohorts of patients with adrenocortical carcinoma were downloaded from The Cancer Genome Atlas, while another three validation cohorts with comprehensive survival data were collected from the Gene Expression Omnibus. In addition, we constructed a hypoxia classifier using a random survival forest model. Moreover, we explored the relationship between the hypoxia risk score and immunophenotype in adrenocortical carcinoma to evaluate the efficacy of immune check inhibitors (ICI) therapy and prognosis of patients.

Results: HRS and tumor stage were identified as independent prognostic factors. HRS was negatively correlated with immune cycle activity, immune cell infiltration, and the T cell inflammatory score. Therefore, we considered the low hypoxia risk score group as the inflammatory immunophenotype, whereas the high HRS group was a non-inflammatory immunophenotype. In addition, the HRS was negatively related to the expression of common immune checkpoint molecules such as PD-L1, CD200, CTLA-4, and TIGIT, suggesting that patients with a lower hypoxia risk score respond better to immunotherapy.

Conclusion: We developed and validated a novel hypoxia risk score to predict the immunophenotype and response of patients with adrenocortical carcinoma to immune check inhibitors therapy. These findings not only provide fresh prognostic indicators for adrenocortical carcinoma but also offer several promising treatment targets for this disease.
Phenotype and genotype analyses of Chinese patients with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations
Authors: Wang Yanxin , Lv Yuqiang , Li Zilong , Gao Min , Yang Xiaomeng , Li Yue , Shi Jianguo , Gao Zaifen , Liu Yi , Gai Zhongtao
Published: December 2022

Background: Autosomal dominant mental retardation type 5 (MRD5), a rare neurodevelopmental disorder (NDD) characterized by intellectual disability (ID), developmental delay (DD), and epilepsy predominantly, is caused by a heterozygous mutation in the SYNGAP1 gene. SYNGAP1 mutations have been rarely reported in the Chinese population. Here, we present an investigation of SYNGAP1 mutations in a clinical cohort with ID and DD in Shandong, a northern province in China, to further explore the genotype and phenotype correlations.

Methods: A retrospective study was conducted on 10 children with SYNGAP1 mutations presenting ID, DD, and epilepsy who were diagnosed between January 2014 and May 2022. Clinical data and genetic tests were collected. Treatment and regular follow-ups were carried out to pay close attention to the prognosis of the patients.

Results: We described 10 unrelated affected individuals with SYNGAP1 mutations, displaying ID, DD, epilepsy, or seizures. All mutations of SYNGAP1 in the 10 patients were de novo, except patient 3 whose father was unavailable, including five nonsense mutations, two frameshift mutations, two splicing mutations, and one codon deletion. Among these mutations, five were novel and the other five were previously reported. Significantly, all patients with epilepsy were sensitive to anti-seizure drugs, especially sodium valproate. Furthermore, rehabilitation training seemed to exert a more improved effect on motor development than language development for the patients.

Conclusion The 10 patients carrying SYNGAP1 mutations were diagnosed as MRD5. Five novel genetic mutations were found, which expanded the mutational spectrum of the SYNGAP1 gene. The identification of these mutations in this study helps explore the relationship between genotypes and phenotypes and contributes to genetic counseling and therapeutic intervention for patients with MRD5.
Enhanced Spike-specific, but attenuated Nucleocapsid-specific T cell responses upon SARS-CoV-2 breakthrough versus non-breakthrough infections
Authors: Ahmed Mohamed Ibraheem Mahmoud , Diepers Paulina , Janke Christian , Plank Michael , Eser Tabea M. , Rubio-Acero Raquel , Fuchs Anna , Baranov Olga , Castelletti Noemi , Kroidl Inge , Olbrich Laura , Bauer Bernadette , Wang Danni , Prelog Martina , Liese Johannes G. , Reinkemeyer Christina , Hoelscher Michael , Steininger Philipp , Überla Klaus , Wieser Andreas , Geldmacher Christof
Published: December 2022

SARS-CoV-2 vaccine breakthrough infections frequently occurred even before the emergence of Omicron variants. Yet, relatively little is known about the impact of vaccination on SARS-CoV-2-specific T cell and antibody response dynamics upon breakthrough infection. We have therefore studied the dynamics of CD4 and CD8 T cells targeting the vaccine-encoded Spike and the non-encoded Nucleocapsid antigens during breakthrough infections (BTI, n=24) and in unvaccinated control infections (non-BTI, n=30). Subjects with vaccine breakthrough infection had significantly higher CD4 and CD8 T cell responses targeting the vaccine-encoded Spike during the first and third/fourth week after PCR diagnosis compared to non-vaccinated controls, respectively. In contrast, CD4 T cells targeting the non-vaccine encoded Nucleocapsid antigen were of significantly lower magnitude in BTI as compared to non-BTI. Hence, previous vaccination was linked to enhanced T cell responses targeting the vaccine-encoded Spike antigen, while responses against the non-vaccine encoded Nucleocapsid antigen were significantly attenuated.
N6-methyladenosine modification of viral RNA and its role during the recognition process of RIG-I-like receptors
Authors: Li Huanan , Guo Yang , Qi Wenbao , Liao Ming
Published: December 2022

N6‐methyladenosine (m6A) is the most abundant RNA chemical modification in eukaryotes and is also found in the RNAs of many viruses. In recent years, m6A RNA modification has been reported to have a role not only in the replication of numerous viruses but also in the innate immune escape process. In this review, we describe the viruses that contain m6A in their genomes or messenger RNAs (mRNAs), and summarize the effects of m6A on the replication of different viruses. We also discuss how m6A modification helps viral RNAs escape recognition by exogenous RNA sensors, such as retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), during viral invasion. Overall, the goal of our review is to summarize how m6A regulates viral replication and facilitates innate immune escape. Furthermore, we elaborate on the potential of m6A as a novel antiviral target.
Diagnostic gene signatures and aberrant pathway activation based on m6A methylation regulators in rheumatoid arthritis
Authors: Geng Qishun , Cao Xiaoxue , Fan Danping , Gu Xiaofeng , Zhang Qian , Zhang Mengxiao , Wang Zheng , Deng Tingting , Xiao Cheng
Published: December 2022

Purpose

Rheumatoid arthritis (RA) is a chronic autoimmune disease (AD) characterized by persistent synovial inflammation, bone erosion and progressive joint destruction. This research aimed to elucidate the potential roles and molecular mechanisms of N6-methyladenosine (m6A) methylation regulators in RA.

Methods

An array of tissues from 233 RA and 126 control samples was profiled and integrated for mRNA expression analysis. Following quality control and normalization, the cohort was split into training and validation sets. Five distinct machine learning feature selection methods were applied to the training set and validated in validation sets.

Results

Among the six models, the LASSO_λ-1se model not only performed better in the validation sets but also exhibited more stringent performance. Two m6A methylation regulators were identified as significant biomarkers by consensus feature selection from all four methods. IGF2BP3 and YTHDC2, which are differentially expressed in patients with RA and controls, were used to predict RA diagnosis with high accuracy. In addition, IGF2BP3 showed higher importance, which can regulate the G2/M transition to promote RA-FLS proliferation and affect M1 macrophage polarization.

Conclusion

This consensus of multiple machine learning approaches identified two m6A methylation regulators that could distinguish patients with RA from controls. These m6A methylation regulators and their target genes may provide insight into RA pathogenesis and reveal novel disease regulators and putative drug targets.
Immune-mediated inflammatory diseases and risk of venous thromboembolism: A Mendelian randomization study
Authors: Lv Xiaoshuo , Gao Xixi , Liu Jingwen , Deng Yisen , Nie Qiangqiang , Fan Xueqiang , Ye Zhidong , Liu Peng , Wen Jianyan
Published: December 2022

Introduction

Immune-mediated inflammatory diseases (IMIDs) have been associated with an increased risk of venous thromboembolism (VTE) in multiple observational studies. However, a direct causally relation between IMIDs and VTE remains unclear to date. Here, we used Mendelian randomization (MR) analysis to investigate causal associations between IMIDs and VTE.

Methods

We collected genetic data from published genome-wide association studies (GWAS) for six common IMIDs, specifically inflammatory bowel disease (IBD), Crohn’s disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriasis (PSO), and systemic lupus erythematosus (SLE); and summary-level data for VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) from the FinnGen database. Two-sample MR analysis using inverse variance weighting (IVW) was performed to identify causal associations between IMIDs and VTE/DVT/PE, and sensitivity analyses were implemented for robustness.

Results

IVW analysis showed a causal relationship between genetically predicted UC (one type of IBD) and the risk of VTE (OR = 1.043, 95% CI: 1.013-1.073, p = 0.004) and DVT (OR = 1.088, 95% CI: 1.043-1.136, p < 0.001), but we found no evidence of causality between UC and PE (OR = 1.029, 95% CI: 0.986-1.074, p = 0.19). In addition, no associations were observed between total IBD, CD, RA, SLE, or PSO and VTE/DVT/PE. Sensitivity analysis found no evidence for horizontal pleiotropy.

Conclusion

This MR study provides new genetic evidence for the causal relationship between IMIDs and the risk of VTE. Our findings highlight the importance of active intervention and monitoring to mitigate VTE risk in patients with IBD, in particular those presenting with UC.
The role of inflammation in immune system of diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications
Authors: Yue Tong , Shi Yu , Luo Sihui , Weng Jianping , Wu Yali , Zheng Xueying
Published: December 2022

Diabetic retinopathy is one of the most common complications of diabetes mellitus and the leading cause of low vision and blindness worldwide. Mounting evidence demonstrates that inflammation is a key mechanism driving diabetes-associated retinal disturbance, yet the pathophysiological process and molecular mechanisms of inflammation underlying diabetic retinopathy are not fully understood. Cytokines, chemokines, and adhesion molecules interact with each other to form a complex molecular network that propagates the inflammatory and pathological cascade of diabetic retinopathy. Therefore, it is important to understand and elucidate inflammation-related mechanisms behind diabetic retinopathy progression. Here, we review the current understanding of the pathology and pathogenesis of inflammation in diabetic retinopathy. In addition, we also summarize the relevant clinical trials to further suggest inflammation-targeted therapeutics for prevention and management of diabetic retinopathy.
Using exergame-based exercise to prevent and postpone the loss of muscle mass, muscle strength, cognition, and functional performance among elders in rural long-term care facilities: A protocol for a randomized controlled trial
Authors: Tuan Sheng-Hui , Chang Ling-Hui , Sun Shu-Fen , Lin Ko-Long , Tsai Yi-Ju
Published: December 2022

Objective

Elderly individuals in long-term care facilities (LTCFs) have a higher prevalence of sarcopenia than those in the community. Exercise is the gold standard for preventing and treating sarcopenia. Regarding exercise, multicomponent exercises, including progressive resistance training (PRT), are beneficial. However, developing routine, structured exercise programs for the elderly in LTCFs is difficult because of a shortage of healthcare providers, particularly in rural regions. Exergame-based exercises can increase a player’s motivation and reduce staff time for an intervention. Nintendo Switch RingFit Adventure (RFA) is a novel exergame that combines resistance, aerobic, and balance exercises. In this study, we aim to investigate the clinical effectiveness of RFA on muscle and functional performance parameters among the elderly in LTCFs.

Methods

The EXPPLORE (using EXergame to Prevent and Postpone the LOss of muscle mass, muscle strength, and functional performance in Rural Elders) trial is a single-center randomized controlled trial involving elderly individuals (≥60 years) living in LTCFs in rural southern Taiwan. The participants will be equally randomized to the intervention group (exergame-based exercise plus standard care) or the control group (standard care alone). Both groups will receive standard care except that the intervention group will receive exergame-based exercises at the time previously scheduled for sedentary activities in the LTCFs. The exergame-based exercise will be performed using RFA in the sitting position with a specialized design, including arm fit skills and knee assist mode. Each session of the exercise lasts 30 mins and will be performed two times per week for 12 weeks. The primary outcomes will be the osteoporotic fracture index, appendicular skeletal muscle mass index, dominant handgrip strength, and gait speed. Meanwhile, the secondary outcomes will be the dexterity and agility, muscle strength and thickness, range of motion of the joints of the dominant upper extremity, Kihon checklist, Medical Outcomes Study 36-Item Short-Form Health Survey, and Brain Health Test.

Discussion

This trial will provide valuable knowledge on whether exergames using RFA can counteract physical decline and improve quality of life and cognition among the elderly in LTCFs.

Clinical trial registration

[www.ClinicalTrials.gov], identifier [NCT05360667].
The effect of disinfectants and antiseptics on co- and cross-selection of resistance to antibiotics in aquatic environments and wastewater treatment plants
Authors: Basiry Daniel , Entezari Heravi Nooshin , Uluseker Cansu , Kaster Krista Michelle , Kommedal Roald , Pala-Ozkok Ilke
Published: December 2022

The outbreak of the SARS-CoV-2 pandemic led to increased use of disinfectants and antiseptics (DAs), resulting in higher concentrations of these compounds in wastewaters, wastewater treatment plant (WWTP) effluents and receiving water bodies. Their constant presence in water bodies may lead to development and acquisition of resistance against the DAs. In addition, they may also promote antibiotic resistance (AR) due to cross- and co-selection of AR among bacteria that are exposed to the DAs, which is a highly important issue with regards to human and environmental health. This review addresses this issue and provides an overview of DAs structure together with their modes of action against microorganisms. Relevant examples of the most effective treatment techniques to increase the DAs removal efficiency from wastewater are discussed. Moreover, insight on the resistance mechanisms to DAs and the mechanism of DAs enhancement of cross- and co-selection of ARs are presented. Furthermore, this review discusses the impact of DAs on resistance against antibiotics, the occurrence of DAs in aquatic systems, and DA removal mechanisms in WWTPs, which in principle serve as the final barrier before releasing these compounds into the receiving environment. By recognition of important research gaps, research needs to determine the impact of the majority of DAs in WWTPs and the consequences of their presence and spread of antibiotic resistance were identified.
Novel modular chimeric antigen receptor spacer for T cells derived from signal regulatory protein alpha Ig-like domains
Authors: Koski Jan , Jahan Farhana , Luostarinen Annu , Schenkwein Diana , Ylä-Herttuala Seppo , Göös Helka , Monzo Hector , Ojala Päivi M. , Maliniemi Pilvi , Korhonen Matti
Published: December 2022

Background: T cells equipped with chimeric antigen receptors (CAR) have shown remarkable efficacy in targeting B lineage malignancies. Improvement of the CAR structure is needed, however, with a view to developing flexibly modifiable spacers that are inert in interactions with unwanted cells. Specifically, binding to cells carrying receptors for IgG’s crystallizable fragment (FcR), that recognize IgG-derived domains in CARs is to be avoided.

Methods: Two novel CARs targeting the CD19 antigen where the IgG1-CH2 and -CH3 domains were replaced with Ig-like domains from signal-regulatory protein α (SIRPα) were designed in silico. An IgG1-based CAR and a CAR lacking both SIRPα and IgG1 domains were used as comparators. The phenotype and memory phenotype of the expanded cells were analyzed by flow cytometry, and CAR T cell activation and cytotoxic efficacy were assessed in co-culture experiments in response to CD19+ target cells. Unwanted interactions with FcR-expressing myeloid cells were interrogated in co-culture assays with THP-1 monocytic cells.

Results: T cells carrying the novel SIRPα-based CARs enacted potent in vitro cytotoxicity against CD19 positive B-lineage leukemia cells, comparable to traditional IgG1-based CAR T cells. Co-culture of IgG1-based CAR T cells with FcR-expressing THP-1 monocytic cells led to prominent cell surface expression of CD69 on T cells together with production of Interleukin (IL)-2 and Interferon-γ, and production of IL-1β, indicating activation of the T cells and monocytes, respectively. Longer co-culture led to killing of the monocytes. No signs of T cell nor monocyte activation were detected in co-cultures of SIRPα-based CAR T cells with THP-1 cells. Arming T cells with the SIRPα-based CARs favored differentiation towards CD4+ phenotype during expansion, while the effects on memory phenotype of the T cells were equivalent between the SIRPα- and IgG1-based CARs. In a pilot experiment, T cells modified with one of the SIRPα-based CARs showed dose dependent leukemia cell control.

Conclusion: The novel SIRPα based spacers offer a suitable backbone for developing chimeric antigen receptors that evade the off-target binding to FcR while the cells retain a favorable memory phenotype and efficient cytotoxicity, establishing a promising candidate for future in vivo and clinical testing.
Cancer cell targeting by CAR-T cells: A matter of stemness
Authors: D’Accardo Caterina , Porcelli Gaetana , Mangiapane Laura Rosa , Modica Chiara , Pantina Vincenzo Davide , Roozafzay Narges , Di Franco Simone , Gaggianesi Miriam , Veschi Veronica , Lo Iacono Melania , Todaro Matilde , Turdo Alice , Stassi Giorgio
Published: December 2022

Chimeric antigen receptor (CAR)-T cell therapy represents one of the most innovative immunotherapy approaches. The encouraging results achieved by CAR-T cell therapy in hematological disorders paved the way for the employment of CAR engineered T cells in different types of solid tumors. This adoptive cell therapy represents a selective and efficacious approach to eradicate tumors through the recognition of tumor-associated antigens (TAAs). Binding of engineered CAR-T cells to TAAs provokes the release of several cytokines, granzyme, and perforin that ultimately lead to cancer cells elimination and patient’s immune system boosting. Within the tumor mass a subpopulation of cancer cells, known as cancer stem cells (CSCs), plays a crucial role in drug resistance, tumor progression, and metastasis. CAR-T cell therapy has indeed been exploited to target CSCs specific antigens as an effective strategy for tumor heterogeneity disruption. Nevertheless, a barrier to the efficacy of CAR-T cell-based therapy is represented by the poor persistence of CAR-T cells into the hostile milieu of the CSCs niche, the development of resistance to single targeting antigen, changes in tumor and T cell metabolism, and the onset of severe adverse effects. CSCs resistance is corroborated by the presence of an immunosuppressive tumor microenvironment (TME), which includes stromal cells, cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and immune cells. The relationship between TME components and CSCs dampens the efficacy of CAR-T cell therapy. To overcome this challenge, the double strategy based on the use of CAR-T cell therapy in combination with chemotherapy could be crucial to evade immunosuppressive TME. Here, we summarize challenges and limitations of CAR-T cell therapy targeting CSCs, with particular emphasis on the role of TME and T cell metabolic demands.
Methylmalonic acid levels in serum, exosomes, and urine and its association with cblC type methylmalonic acidemia-induced cognitive impairment
Authors: Sun Shuqi , Jin Hong , Rong Yu , Song Wenqi , Li Qiliang
Published: December 2022

Background

The cblC type methylmalonic acidemia is the most common methylmalonic acidemia (MMA) in China. The biochemical characteristics of this disease include elevated methylmalonic acid and homocysteine (HCY), increased propionylcarnitine (C3), decreased free carnitine (C0). In this study, we aimed to clarify the roles of these biomarkers in cblC-MMA induced cognitive impairment and evaluate the capacity of methylmalonic acid in different fluids or exosomes to distinguish cblC-MMA induced cognitive impairment.

Methods

15 non-inherited hyperhomocysteinemia (HHcy) patients, 42 cblC-MMA patients and 57 age- and sex-matched healthy children were recruited in this study. The levels of HCY were detected by an automatic immune analyzer. The levels of acylcarnitines and methylmalonic acid were detected by tandem mass spectrometer.

Results

The main findings were all biomarkers as HCY, acylcarnitines and methylmalonic acid had capacities for distinguishing patients with cblC-MMA induced cognitive impairment from healthy children. The methylmalonic acid in different fluids or exosomes had good performances for distinguishing patients with cblC-MMA induced cognitive impairment from HHcy patients. The methylmalonic acid in serum exosomes and neuronal-derived exosomes were able to distinguishing cblC-MMA patients with cognitive impairment from patients without cognitive impairment. The methylmalonic acid in neuronal-derived exosomes might be helpful to evaluate the severity of cblC-MMA induced cognitive impairment.

Discussion

Methylmalonic acid levels in serum exosomes, especially in serum neuronal-derived exosomes, serve as potential biomarkers for distinguishing cblC-MMA induced cognitive impairment.
Grasping the semantic of actions: a combined behavioral and MEG study
Authors: Visani Elisa , Garofalo Gioacchino , Rossi Sebastiano Davide , Duran Dunja , Craighero Laila , Riggio Lucia , Buccino Giovanni
Published: December 2022

There is experimental evidence that the brain systems involved in action execution also play a role in action observation and understanding. Recently, it has been suggested that the sensorimotor system is also involved in language processing. Supporting results are slower response times and weaker motor-related MEG Beta band power suppression in semantic decision tasks on single action verbs labels when the stimulus and the motor response involve the same effector. Attenuated power suppression indicates decreased cortical excitability and consequent decreased readiness to act. The embodied approach forwards that the simultaneous involvement of the sensorimotor system in the processing of the linguistic content and in the planning of the response determines this language-motor interference effect. Here, in a combined behavioral and MEG study we investigated to what extent the processing of actions visually presented (i.e., pictures of actions) and verbally described (i.e., verbs in written words) share common neural mechanisms. The findings demonstrated that, whether an action is experienced visually or verbally, its processing engages the sensorimotor system in a comparable way. These results provide further support to the embodied view of semantic processing, suggesting that this process is independent from the modality of presentation of the stimulus, including language.
Mesenchymal stem cells for regenerative medicine in central nervous system
Authors: Li Man , Chen Hong , Zhu Mingxin
Published: December 2022

Mesenchymal stem cells (MSCs) are multipotent stem cells, whose paracrine and immunomodulatory potential has made them a promising candidate for central nervous system (CNS) regeneration. Numerous studies have demonstrated that MSCs can promote immunomodulation, anti-apoptosis, and axon re-extension, which restore functional neural circuits. The therapeutic effects of MSCs have consequently been evaluated for application in various CNS diseases including spinal cord injury, cerebral ischemia, and neurodegenerative disease. In this review, we will focus on the research works published in the field of mechanisms and therapeutic effects of MSCs in CNS regeneration.
Crocin: Functional characteristics, extraction, food applications and efficacy against brain related disorders
Authors: Ali Anwar , Yu Liang , Kousar Safura , Khalid Waseem , Maqbool Zahra , Aziz Afifa , Arshad Muhammad Sajid , Aadil Rana Muhammad , Trif Monica , Riaz Sakhawat , Shaukat Horia , Manzoor Muhammad Faisal , Qin Hong
Published: December 2022

Crocin is a bioactive compound that naturally occurs in some medicinal plants, especially saffron and gardenia fruit. Different conventional and novel methods are used for its extraction. Due to some control conditions, recent methods such as ultrasonic extraction, supercritical fluid extraction, enzyme-associated extraction, microwave extraction, and pulsed electric field extraction are widely used because these methods give more yield and efficiency. Crocin is incorporated into different food products to make functional foods. However, it can also aid in the stability of food products. Due to its ability to protect against brain diseases, the demand for crocin has been rising in the pharmaceutical industry. It also contain antioxidant, anti-inflammatory, anticancer and antidepressant qualities. This review aims to describe crocin and its role in developing functional food, extraction, and bioavailability in various brain-related diseases. The results of the literature strongly support the importance of crocin against various diseases and its use in making different functional foods.
The cause analysis of benign uretero-ileal anastomotic stricture after radical cystectomy and urinary diversion
Authors: Liu Zhenghong , Zheng Bin , Hu Yuqi , Li Haichang , Qin Xiaowen , Hu Xuanhan , Wang Shuai , Wang Heng , Zhang Pu , Wo Qijun , Sun Li , Mou Yixuan , Liu Feng , Cui Jianxin , Zhang Dahong
Published: December 2022

Background

Benign uretero-ileal anastomotic stricture (UIAS) is a major complication following radical cystectomy (RC) and ileal orthotopic bladder substitution, and it can occur in combination with other complications. But risk factors for patients with UIAS have not been well described.

Material and methods

We retrospectively reviewed 198 patients treated with RC for bladder cancer from 2014 to 2019 at the Zhejiang Provincial People’s Hospital. Patient demographic and clinical variables were examined to determine the risk factors associated with UIAS by univariate and multivariate logistic regression analysis.

Results

A total of 180 patients into the group standards and in all 360 uretero-ileal anastomoses. Among the above cases, 22 patients developed UIAS, including 10 cases of left UIAS, nine cases of right UIAS, and three cases of bilateral UIAS. There was no difference in demographic, operative, or perioperative variables between patients with and without UIAS. In a multivariate analysis, after adjusting for gender, age, surgical methods, and underlying diseases, intraoperative or postoperative blood transfusion (HR = 0.144, P <0.01), postoperative urinary tract infection (HR = 3.624, P <0.01), and extracorporeal bladder anastomosis (HR = 3.395, P = 0.02) significantly increased the risk of UIAS.

Conclusions

In our experience, intraoperative or postoperative blood transfusion, postoperative urinary tract infection, and extracorporeal neobladder anastomoses increased the risk of UIAS after radical cystectomy and ileal orthotopic bladder substitution surgery. Further studies with larger samples are necessary to validate this result.
Circulating messenger RNA variants as a potential biomarker for surveillance of hepatocellular carcinoma
Authors: Block Timothy , Zezulinski Daniel , Kaplan David E. , Lu Jingqiao , Zanine Samantha , Zhan Tingting , Doria Cataldo , Sayeed Aejaz
Published: December 2022

Background and rationale

Liver derived messenger ribonucleic acid (mRNA) transcripts were reported to be elevated in the circulation of hepatocellular carcinoma (HCC) patients. We now report the detection of high-risk mRNA variants exclusively in the circulation of HCC patients. Numerous genomic alleles such as single nucleotide polymorphisms (SNPs), nucleotide insertions and deletions (called Indels), splicing variants in many genes, have been associated with elevated risk of cancer. Our findings potentially offer a novel non-invasive platform for HCC surveillance and early detection.

Approach

RNAseq analysis was carried out in the plasma of 14 individuals with a diagnosis of HCC, 8 with LC and no HCC, and 6 with no liver disease diagnosis. RNA from 6 matching tumors and 5 circulating extracellular vesicle (EV) samples from 14 of those with HCC was also analyzed. Specimens from two cholangiocarcinoma (CCA) patients were also included in our study. HCC specific SNPs and Indels referred as “variants” were identified using GATK HaplotypeCaller and annotated by SnpEff to filter out high risk variants.

Results

The variant calling on all RNA samples enabled the detection of 5.2 million SNPs, 0.91 million insertions and 0.81 million deletions. RNAseq analyses in tumors, normal liver tissue, plasma, and plasma derived EVs led to the detection of 5480 high-risk tumor specific mRNA variants in the circulation of HCC patients. These variants are concurrently detected in tumors and plasma samples or tumors and EVs from HCC patients, but none of these were detected in normal liver, plasma of LC patients or normal healthy individuals. Our results demonstrate selective detection of concordant high-risk HCC-specific mRNA variants in free plasma, plasma derived EVs and tumors of HCC patients. The variants comprise of splicing, frameshift, fusion and single nucleotide alterations and correspond to cancer and tumor metabolism pathways. Detection of these high-risk variants in matching specimens from same subjects with an enrichment in circulating EVs is remarkable. Validation of these HCC selective ctmRNA variants in larger patient cohorts is likely to identify a predictive set of ctmRNA with high diagnostic performance and thus offer a novel non-invasive serology-based biomarker for HCC.
Neuroprotective effects of a medium chain fatty acid, decanoic acid, isolated from H. leucospilota against Parkinsonism in C. elegans PD model
Authors: Sanguanphun Tanatcha , Sornkaew Nilubon , Malaiwong Nawaphat , Chalorak Pawanrat , Jattujan Prapaporn , Niamnont Nakorn , Sobhon Prasert , Meemon Krai
Published: December 2022

Sea cucumbers are marine organism that have long been used for food and traditional medicine in Asian countries. Recently, we have shown that ethyl acetate fraction (HLEA) of the crude extract of the black sea cucumber, Holothuria leucospilota, could alleviate Parkinsonism in Caenorhabditis elegans PD models. In this study, we found that the effective neuroprotective activity is attributed to HLEA-P1 compound chemically isolated and identified in H. leucospilota ethyl acetate. We reported here that HLEA-P1 could attenuate DAergic neurodegeneration, improve DAergic-dependent behaviors, reduce oxidative stress in 6-OHDA-induced C. elegans. In addition, HLEA-P1 reduced α-synuclein aggregation, improved behavior deficit and recovered lipid deposition in transgenic C. elegans overexpressing α-synuclein. We also found that HLEA-P1 activates nuclear localization of DAF-16 transcription factor of insulin/IGF-1 signaling (IIS) pathway. Treatment with 25 μg/ml of HLEA-P1 upregulated transcriptional activity of DAF-16 target genes including anti-oxidant genes (such as sod-3) and small heat shock proteins (such as hsp16.1, hsp16.2, and hsp12.6) in 6-OHDA-induced worms. In α-synuclein-overexpressed C. elegans strain, treatment with 5 μg/ml of HLEA-P1 significantly activated mRNA expression of sod-3 and hsp16.2. Chemical analysis demonstrated that HLEA-P1 compound is decanoic acid/capric acid. Taken together, our findings revealed that decanoic acid isolated from H. leucospilota exerts anti-Parkinson effect in C. elegans PD models by partly modulating IIS/DAF-16 pathway.
Identification and drug metabolic characterization of four new CYP2C9 variants CYP2C9*72-*75 in the Chinese Han population
Authors: Zhao Fang-Ling , Zhang Qing , Wang Shuang-Hu , Hong Yun , Zhou Shan , Zhou Quan , Geng Pei-Wu , Luo Qing-Feng , Yang Jie-Fu , Chen Hao , Cai Jian-Ping , Dai Da-Peng
Published: December 2022

Cytochrome 2C9 (CYP2C9), one of the most important drug metabolic enzymes in the human hepatic P450 superfamily, is required for the metabolism of 15% of clinical drugs. Similar to other CYP2C family members, CYP2C9 gene has a high genetic polymorphism which can cause significant racial and inter-individual differences in drug metabolic activity. To better understand the genetic distribution pattern of CYP2C9 in the Chinese Han population, 931 individuals were recruited and used for the genotyping in this study. As a result, seven synonymous and 14 non-synonymous variations were identified, of which 4 missense variants were designated as new alleles CYP2C9*72, *73, *74 and *75, resulting in the amino acid substitutions of A149V, R150C, Q214H and N418T, respectively. When expressed in insect cell microsomes, all four variants exhibited comparable protein expression levels to that of the wild-type CYP2C9 enzyme. However, drug metabolic activity analysis revealed that these variants exhibited significantly decreased catalytic activities toward three CYP2C9 specific probe drugs, as compared with that of the wild-type enzyme. These data indicate that the amino acid substitution in newly designated variants can cause reduced function of the enzyme and its clinical significance still needs further investigation in the future.