bluuebunny/crossref_metadata_2025 huggingface dataset:
STAT3-Specific Single Domain Nanobody Inhibits Expansion of Pathogenic Th17 Responses and Suppresses Uveitis in Mice
Authors: Mbanefo Evaristus C. , Yan Ming , Kang Minkyung , Alhakeem Sahar A. , Jittayasothorn Yingyos , Yu Cheng-Rong , Parihar Ashutosh , Singh Sunanda , Egwuagu Charles E.
Published: September 2021

STAT3 activates transcription of genes that regulate cell growth, differentiation, and survival of mammalian cells. Genetic deletion ofStat3in T cells has been shown to abrogate Th17 differentiation, suggesting that STAT3 is a potential therapeutic target for Th17-mediated diseases. However, a major impediment to therapeutic targeting of intracellular proteins such as STAT3 is the lack of efficient methods for delivering STAT3 inhibitors into cells. In this study, we developed a novel antibody (SBT-100) comprised of the variable (V) region of a STAT3-specific heavy chain molecule and demonstrate that this 15 kDa STAT3-specific nanobody enters human and mouse cells, and induced suppression of STAT3 activation and lymphocyte proliferation in a concentration-dependent manner. To investigate whether SBT-100 would be effective in suppressing inflammationin vivo, we induced experimental autoimmune uveitis (EAU) in C57BL/6J mice by active immunization with peptide from the ocular autoantigen, interphotoreceptor retinoid binding protein (IRBP651-670). Analysis of the retina by fundoscopy, histological examination, or optical coherence tomography showed that treatment of the mice with SBT-100 suppressed uveitis by inhibiting expansion of pathogenic Th17 cells that mediate EAU. Electroretinographic (ERG) recordings of dark and light adapted a- and b-waves showed that SBT-100 treatment rescued mice from developing significant visual impairment observed in untreated EAU mice. Adoptive transfer of activated IRBP-specific T cells from untreated EAU mice induced EAU, while EAU was significantly attenuated in mice that received IRBP-specific T cells from SBT-100 treated mice. Taken together, these results demonstrate efficacy of SBT-100 in mice and suggests its therapeutic potential for human autoimmune diseases.
A Correlation Between Differentiation Phenotypes of Infused T Cells and Anti-Cancer Immunotherapy
Authors: Ren Hao , Cao Kunkun , Wang Mingjun
Published: September 2021

T-cell therapy, usually with ex-vivo expansion, is very promising to treat cancer. Differentiation status of infused T cells is a crucial parameter for their persistence and antitumor immunity. Key phenotypic molecules are effective and efficient to analyze differentiation status. Differentiation status is crucial for T cell exhaustion, in-vivo lifespan, antitumor immunity, and even antitumor pharmacological interventions. Strategies including cytokines, Akt, Wnt and Notch signaling, epigenetics, and metabolites have been developed to produce less differentiated T cells. Clinical trials have shown better clinical outcomes from infusion of T cells with less differentiated phenotypes. CD27+, CCR7+ and CD62L+ have been the most clinically relevant phenotypic molecules, while Tscm and Tcm the most clinically relevant subtypes. Currently, CD27+, CD62L+ and CCR7+ are recommended in the differentiation phenotype to evaluate strategies of enhancing stemness. Future studies may discover highly clinically relevant differentiation phenotypes for specific T-cell production methods or specific subtypes of cancer patients, with the advantages of precision medicine.
More Precise Control of the In Vitro Enzymatic Degradation via Ternary Self-Blending of High/Medium/Low Molecular Weight Poly(trimethylene carbonate)
Authors: Cai Guiyang , Hou Zhipeng , Li Peng , Sun Wei , Guo Jing , Yang Liqun , Yang Qing
Published: September 2021

To more precisely control the degradation rate of poly(trimethylene carbonate) (PTMC), self-blending films were prepared via the ternary self-blending of pure PTMC with a molecular weight of 334, 152, and 57 kg/mol. The in vitro enzymolysis degradation of the ternary self-blending films was performed in lipase solutions. The results showed that ternary self-blending could control the degradation of PTMC by adjusting the mass ratio of high/medium/low molecular weight PTMC in the composition, and the PTMC334/PTMC152/PTMC57 films with a mass ratio of 1/4/16 showed mass loss of 85.96% after seven weeks of degradation, while that of PTMC334/PTMC152/PTMC57 films with a mass ratio of 1/1/1 was 96.39%. The former and latter’s degradation rate constant was 13.263 and 23.981%/w, respectively, and the former presented better morphology stability than the latter. The strategy of ternary self-blending could simultaneously bestow PTMC with a lower degradation rate and good morphology stability, indicating that ternary self-blending is an efficient way to control the degradation performance of PTMC more precisely.
Aging Increases Cross-Modal Distraction by Unexpected Sounds: Controlling for Response Speed
Authors: Leiva Alicia , Andrés Pilar , Parmentier Fabrice B. R.
Published: September 2021

It is well-established that task-irrelevant sounds deviating from an otherwise predictable auditory sequence capture attention and disrupt ongoing performance by delaying responses in the ongoing task. In visual tasks, larger distraction by unexpected sounds (deviance distraction) has been reported in older than in young adults. However, past studies based this conclusion on the comparisons of absolute response times (RT) and did not control for the general slowing typically observed in older adults. Hence, it remains unclear whether this difference in deviance distraction between the two age groups reflects a genuine effect of aging or a proportional effect of similar size in both groups. We addressed this issue by using a proportional measure of distraction (PMD) to reanalyze the data from four past studies and used Bayesian estimation to generate credible estimates of the age-related difference in deviance distraction and its effect size. The results were unambiguous: older adults exhibited greater deviance distraction than young adults when controlling for baseline response speed (in each individual study and in the combined data set). Bayesian estimation revealed a proportional lengthening of RT by unexpected sounds that was about twice as large in older than in young adults (corresponding to a large statistical effect size). A similar analysis was carried out on the proportion of correct responses (PC) and produced converging results. Finally, an additional Bayesian analysis comparing data from cross-modal and uni-modal studies confirmed the selective effect of aging on distraction in the first and not the second. Overall, our study shows that older adults performing a visual categorization task do exhibit greater distraction by unexpected sounds than young adults and that this effect is not explicable by age-related general slowing.
Endovascular Device Choice and Tools for Recanalization of Medium Vessel Occlusions: Insights From the MeVO FRONTIERS International Survey
Authors: Kashani Nima , Cimflova Petra , Ospel Johanna M. , Singh Nishita , Almekhlafi Mohammed A. , Rempel Jeremy , Fiehler Jens , Chen Michael , Sakai Nobuyuki , Agid Ronit , Heran Manraj , Kappelhof Manon , Goyal Mayank
Published: September 2021

Background: Endovascular treatment (EVT) for stroke due to medium vessel occlusion (MeVO) can be technically challenging. Devices and tools are rapidly evolving. We aimed to gain insight into preferences and global perspectives on the usage of endovascular tools in treating MeVOs.

Methods: We conducted an international survey with seven scenarios of patients presenting A3, M2/3, M3, M3/4, or P2/3 occlusions. Respondents were asked for their preferred first-line endovascular approach, and whether they felt that the appropriate endovascular tools were available to them. Answers were analyzed by occlusion location and geographical region of practice, using multinomial/binary logistic regression.

Results: A total of 263 neurointerventionists provided 1836 responses. The first-line preferences of physicians were evenly distributed among stent-retrievers, combined approaches, and aspiration only (33.2, 29.8, and 26.8%, respectively). A3 occlusions were more often treated with stent-retrievers (RR 1.21, 95% CI: 1.07–1.36), while intra-arterial thrombolysis was more often preferred in M3 (RR 2.47, 95% CI: 1.53–3.98) and M3/4 occlusions (RR 7.71, 95% CI: 4.16–14.28) compared to M2/3 occlusions. Respondents who thought appropriate tools are currently not available more often chose stent retrievers alone (RR 2.07; 95% CI: 1.01–4.24) or intra-arterial thrombolysis (RR 3.35, 95% CI: 1.26–8.42). Physicians who stated that they do not have access to optimal tools opted more often not to treat at all (RR 3.41, 95% CI: 1.11–10.49). Stent-retrievers alone were chosen more often and contact aspiration alone less often as a first-line approach in Europe (RR 2.12, 95% CI: 1.38–3.24; and RR 0.49, 95% CI 0.34–0.70, respectively) compared to the United States and Canada.

Conclusions: In EVT for MeVO strokes, neurointerventionalists choose a targeted vessel specific first-line approach depending on the occlusion location, region of practice, and availability of the appropriate tools.
Intra-Abdominal Desmoplastic Small Round Cell Tumor: Current Treatment Options and Perspectives
Authors: Wei Guixia , Shu Xinyao , Zhou Yuwen , Liu Xia , Chen Xiaorong , Qiu Meng
Published: September 2021

Intra-abdominal desmoplastic small round cell tumor (IDSRCT) is a rare and highly malignant soft tissue neoplasm, which is characterized by rapid progression and poor prognosis. The mechanism underlying the development of this neoplasm remains elusive, but all cases are characterized by the chromosomal translocation t (11;22) (p13; q12), which results in a formation of EWSR1-WT1 gene fusion. The diagnosis of IDSRCT is often made with core-needle tissue biopsy specimens or laparoscopy or laparotomy. Immunohistochemical analyses have shown the co-expression of epithelial, neuronal, myogenic, and mesenchymal differentiation markers. FISH or reverse transcription polymerase chain reaction detecting EWS-WT1 fusion can be performed to assist in molecular confirmation. There is no standard of care for patients with IDSRCT currently, and majority of newly diagnosed patients received the aggressive therapy, which includes >90% resection of surgical debulking, high-dose alkylator-based chemotherapy, and radiotherapy. More recently, targeted therapy has been increasingly administered to recurrent IDSRCT patients and has been associated with improved survival in clinical conditions. Immunotherapy as a possible therapeutic strategy is being explored in patients with IDSRCT. In this review, we summarize currently available knowledge regarding the epidemiology, potential mechanisms, clinical manifestations, diagnosis, treatment, and prognosis of IDSRCT to assist oncologists in comprehensively recognizing and accurately treating this malignancy.
CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis
Authors: Gao Ling , Xia Tingting , Qin Mingde , Xue Xiaofeng , Jiang Linhua , Zhu Xinguo
Published: September 2021

Background

Gastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical roles in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular mechanism of circRNAs in gastric cancer remain largely unknown.

Methods

CircPTK2 (hsa_circ_0005273) was identified by bioinformatics analysis and validated by RT-qPCR assay. Bioinformatics prediction, dual-luciferase reporter, and RNA pull-down assays were used to determine the interaction between circPTK2, miR-196a-3p, and apoptosis-associated tyrosine kinase 1 (AATK).

Results

The level of circPTK2 was markedly downregulated in gastric cancer tissues and gastric cancer cells. Upregulation of circPTK2 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells, while circPTK2 knockdown exhibited opposite effects. Mechanically, circPTK2 could competitively bind to miR-196a-3p and prevent miR-196a-3p to reduce the expression of AATK. In addition, overexpression of circPTK2 inhibited tumorigenesis in a xenograft mouse model of gastric cancer.

Conclusion

Collectively, circPTK2 functions as a tumor suppressor to suppress gastric cancer cell proliferation, migration, and invasion through regulating the miR-196a-3p/AATK axis, suggesting that circPTK2 may serve as a novel therapeutic target for gastric cancer.
Immune-Related Adverse Events Associated With Outcomes in Patients With NSCLC Treated With Anti-PD-1 Inhibitors: A Systematic Review and Meta-Analysis
Authors: Zhao Zhe , Wang Xinfeng , Qu Jinghan , Zuo Wei , Tang Yan , Zhu Huijuan , Chen Xiaoguang
Published: September 2021

Background and Objective

Although anti-programmed cell death protein 1 (PD-1) antibodies have exerted remarkable anticancer activity in non-small cell lung cancer (NSCLC), it remains a challenge to identify patients who can benefit from these treatments. Immune-related adverse events (irAEs) may be associated with improved clinical outcomes after immune checkpoint inhibition. However, no conclusive evidence of this correlation has been summarized in patients with NSCLC receiving PD-1 inhibitors. We performed a systematic review and meta-analysis to evaluate the association between irAEs induced by anti-PD-1 antibodies and clinical outcomes in patients with NSCLC.

Methods

Various databases were searched from their inception to January 9, 2021, followed by screening of eligible studies. Hazard ratios were used for the pooled analysis of overall survival (OS) and progression-free survival (PFS), while odds ratios (ORs) were utilized to pool objective response rates (ORRs) and disease control rates (DCRs). A random-effects model was applied to all analyses.

Results

A total of 26 cohorts, including 8,452 patients with NSCLC receiving anti-PD-1 antibodies, were enrolled in the study. Significantly improved OS (HR: 0.51; 95% CI: 0.44-0.60; P < 0.01) and PFS (HR: 0.50; 95% CI: 0.43-0.58; P < 0.01) were found to be correlated with irAEs. In addition, patients with NSCLC who developed irAEs after PD-1 inhibition demonstrated better responses to therapies, confirmed by pooled ORs of ORRs (OR: 3.41; 95% CI: 2.66-4.35; P < 0.01) and DCRs (OR: 4.08; 95% CI: 2.30-7.24; P < 0.01). Furthermore, subgroup analysis suggested that both skin and endocrine irAEs are closely correlated with a reduced risk of death, whereas pulmonary irAEs showed no association with longer OS.

Conclusions

In patients with NSCLC treated with anti-PD-1 therapies, the presence of irAEs was strongly correlated with better survival and response, suggesting its potential role as a predictive biomarker for outcomes after PD-1 inhibition.
M6A Classification Combined With Tumor Microenvironment Immune Characteristics Analysis of Bladder Cancer
Authors: Zhu Huili , Jia Xiaocan , Wang Yuping , Song Zhijuan , Wang Nana , Yang Yongli , Shi Xuezhong
Published: September 2021

Background

Studies have shown that N6-methyl adenosine (m6A) plays an important role in cancer progression; however, the underlying mechanism of m6A modification in tumor microenvironment (TME) cell infiltration of bladder cancer remains unclear. This study aimed to investigate the role of m6A modification in TME cell infiltration of bladder cancer.

Methods

The RNA expression profile and clinical data of bladder cancer were obtained from The Cancer Genome Atlas and Gene Expression Omnibus. We assessed the m6A modification patterns of 664 bladder cancer samples based on 20 m6A regulators through unsupervised clustering analysis and systematically linked m6A modification patterns to TME cell infiltration characteristics. Gene ontology and gene set variation analyses were conducted to analyze the underlying mechanism based on the assessment of m6A methylation regulators. Principal component analysis was used to construct the m6A score to quantify m6A modification patterns of bladder cancer.

Results

The genetic and expression alterations in m6A regulators were highly heterogeneous between normal and bladder tissues. Three m6A modification patterns were identified. The cell infiltration characteristics were highly consistent with the three immune phenotypes, including immune rejection, immune inflammation, and immune desert. The biological functions of three m6A modification patterns were different. Cox regression analyses revealed that the m6A score was an independent signature with patient prognosis (HR = 1.198, 95% CI: 1.031–1.390). Patients with a low-m6A score were characterized by increased tumor mutation burden, PD-L1 expression, and poorer survival. Patients in the low-m6A score group also showed significant immune responses and clinical benefits in the CTLA-4 immunotherapy cohort (p =0.0069).

Conclusions

The m6A methylation modification was related to the formation of TME heterogeneity and complexity. Assessing the m6A modification pattern of individual bladder cancer will improve the understanding of TME infiltration characteristics.
Focal Prostate Stereotactic Body Radiation Therapy With Correlative Pathological and Radiographic-Based Treatment Planning
Authors: Fredman Elisha , Traughber Bryan , Kharouta Michael , Podder Tarun , Lo Simon , Ponsky Lee , MacLennan Gregory , Paspulati Raj , Ellis Bradley , Machtay Mitchell , Ellis Rodney
Published: September 2021

Introduction

Advances in multiparametric MRI (mpMRI) combining anatomic and functional imaging can accurately identify foci of adenocarcinoma within the prostate, offering the possibility of partial gland therapy. We performed tandem prospective pilot trials to investigate the feasibility of focal prostate SBRT (f-SBRT) based on correlating diagnostic mpMRI and biopsies with confirmatory pathology in treatment planning.

Materials and Methods

Patients with pathologic focal Gleason 6–7 disease and a corresponding PIRADS 4–5 lesion on mpMRI underwent targeted and comprehensive biopsies using MRI/ultrasound fusion under electromagnetic sensor navigation. After rigorous analysis for imaging biopsy concordance, five of 18 patients were eligible to proceed to f-SBRT. Chi-squared test was used for differences from expected outcomes, and concordance was estimated with binomial distribution theory and Wilson’s method.

Results

Six patients had Gleason 6 and 12 had Gleason 3 + 4 disease (mean PSA: 5.8 ng/ml, range: 2.2–8.4). Absolute concordance was 43.8% (95% CI: 0.20, 0.64). Patterns of discordance included additional sites of ipsilateral disease, bilateral disease, and negative target. Five were upstaged to a new NCCN risk category necessitating treatment escalation. The five patients with concordant pathology completed three-fraction f-SBRT with sparing of the surrounding normal structures (including contralateral neurovascular bundle), with no reported grade 2+ toxicities and favorable PSA responses (mean: 41% decrease).

Conclusions

On our pilot trials of f-SBRT planning using rigorous imaging and pathology concordance, image-guided confirmatory biopsies frequently revealed additional disease, suggesting the need for caution in partial-gland therapy. For truly focal disease, f-SBRT provided excellent dosimetry, minimal toxicity, and encouraging biochemical response. Clinical Trial Registration: www.clinicaltrials.gov, NCT02681614; NCT02163317.
Add-On Effect of Honeysuckle in the Treatment of Coronavirus Disease 2019: A Systematic Review and Meta-Analysis
Authors: Du Xu-Qin , Shi Li-Peng , Cao Wen-Fu , Chen Zhi-Wei , Zuo Biao , Hu Jin-Yuan
Published: September 2021

Background: The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread to become a global emergency since December 2019. Chinese herbal medicine plays an important role in the treatment of COVID-19. Chinese herbal medicine honeysuckle is an extremely used traditional edible and medicinal herb. Many trials suggest that honeysuckle has obtained a good curative effect for COVID-19; however, no systematic evaluation on the clinical efficacy of honeysuckle in the treatment of COVID-19 is reported. This study aimed to evaluate the efficacy and safety of Chinese herbal medicine honeysuckle in the treatment of COVID-19.

Methods: Seven electronic databases (PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and China Biology Medicine) were searched to identify randomized controlled trials (RCTs) of honeysuckle for adult patients (aged ≥ 18 years) with COVID-19. The Cochrane Risk of Bias Tool was applied to assess the methodological quality of trials. Review Manager 5.3 software was used for data analysis.

Results: Overall, nine RCTs involving 1,286 patients were enrolled. Our meta-analyses found that combination therapy of honeysuckle and conventional therapy was more effective than conventional therapy alone in lung computed tomography (CT) [relative risk (RR) = 1.24, 95% confidence interval (95%CI) (1.12, 1.37), P < 0.0001], clinical cure rate [RR = 1.21, 95%CI (1.12, 1.31), P < 0.00001], and rate of conversion to severe cases [RR = 0.50, 95%CI (0.33, 0.76), P = 0.001]. Besides, combination therapy can improve the symptom score of fever, cough reduction rate, symptom score of cough, and inflammatory biomarkers (white blood cell (WBC) count; C-reactive protein (CRP)) (P < 0.05).

Conclusion: Honeysuckle combined with conventional therapy may be beneficial for the treatment of COVID-19 in improving lung CT, clinical cure rate, clinical symptoms, and laboratory indicators and reducing the rate of conversion to severe cases. Besides, combination therapy did not increase adverse drug events. More high-quality RCTs are needed in the future.
Zanthoxylum Species: A Review of Traditional Uses, Phytochemistry and Pharmacology in Relation to Cancer, Infectious Diseases and Sickle Cell Anemia
Authors: Okagu Innocent Uzochukwu , Ndefo Joseph Chinedum , Aham Emmanuel Chigozie , Udenigwe Chibuike. C.
Published: September 2021

The health benefits and toxicity of plant products are largely dependent on their secondary metabolite contents. These compounds are biosynthesized by plants as protection mechanisms against environmental factors and infectious agents. This review discusses the traditional uses, phytochemical constituents and health benefits of plant species in genus Zanthoxylum with a focus on cancer, microbial and parasitic infections, and sickle cell disease as reported in articles published from 1970 to 2021 in peer-reviewed journals and indexed in major scientific databases. Generally, Z. species are widely distributed in Asia, America and Africa, where they are used as food and for disease treatment. Several compounds belonging to alkaloids, flavonoids, terpenoids, and lignans, among others have been isolated from Z. species. This review discusses the biological activities reported for the plant species and their phytochemicals, including anticancer, antibacterial, antifungal, antiviral, anti-trypanosomal, antimalarial and anti-sickling properties. The safety profiles and suggestions for conservation of the Z. species were also discussed. Taken together, this review demonstrates that Z. species are rich in a wide range of bioactive phytochemicals with multiple health benefits, but more research is needed towards their practical application in the development of functional foods, nutraceuticals and lead compounds for new drugs.
Protective Effects of Caesalpinia sappan Linn. and Its Bioactive Compounds on Cardiovascular Organs
Authors: Syamsunarno Mas Rizky AA , Safitri Ratu , Kamisah Yusof
Published: September 2021

Cardiovascular diseases are the leading cause of death worldwide. The long-term aim of cardiovascular disease therapy is to reduce the mortality rate and decelerate the progression of cardiovascular organ damage. Current therapies focus on recovering heart function and reducing risk factors such as hyperglycemia and dyslipidemia. However, oxidative stress and inflammation are important causes of further damage to cardiovascular organs. Caesalpinia sappan Linn. (Fabaceae), a flowering tree native to tropical Asia, has antioxidant and anti-inflammatory properties. It is used as a natural dye to color food and beverages and as a traditional treatment for diarrhea, diabetes, and blood stasis. The phytochemical compounds in C. sappan, mainly the homoisoflavonoids brazilin, sappanone A, protosappanin, and hematoxylin, can potentially be used to protect cardiovascular organs. This review aims to provide updates on recent developments in research on C. sappan in relation to treatment of cardiovascular diseases. Many studies have reported protective effects of the plant’s bioactive compounds that reduce cardiac damage and enhance vasorelaxation. For example, brazilin and sappanone A have an impact on molecular and cellular changes in cardiovascular disease pathogenesis, mainly by modulating oxidative, inflammatory, and apoptotic signaling pathways. Therefore, bioactive compounds of C. sappan have the potential to be developed as therapeutic agents to combat cardiovascular diseases like myocardial infarction and vascular disease. This review could help further the understanding of the possible modulatory role of the compounds in cardiovascular diseases, thereby facilitating future studies.
Sacubitril/Valsartan Alleviates Experimental Autoimmune Myocarditis by Inhibiting Th17 Cell Differentiation Independently of the NLRP3 Inflammasome Pathway
Authors: Liang Wei , Xie Bai-Kang , Ding Pei-Wu , Wang Min , Yuan Jing , Cheng Xiang , Liao Yu-Hua , Yu Miao
Published: September 2021

Sacubitril/valsartan (Sac/Val) is a recently approved drug that is commonly used for treatment of heart failure. Several studies indicated that Sac/Val also regulated the secretion of inflammatory factors. However, the effect and mechanism of this drug modulation of inflammatory immune responses are uncertain. In this study, an experimental autoimmune myocarditis (EAM) mouse model was established by injection of α-myosin-heavy chain peptides. The effect of oral Sac/Val on EAM was evaluated by histological staining of heart tissues, measurements of cardiac troponin T and inflammatory markers (IL-6 and hsCRP). The effects of Sac/Val on NLRP3 inflammasome activation and Th1/Th17 cell differentiation were also determined. To further explore the signaling pathways, the expressions of cardiac soluble guanylyl cyclase (sGC) and NF-κB p65 were investigated. The results showed that Sac/Val downregulated the inflammatory response and attenuated the severity of EAM, but did not influence NLRP3 inflammasomes activation. Moreover, Sac/Val treatment inhibited cardiac Th17 cell differentiation, and this might be associated with sGC/NF-κB p65 signaling pathway. These findings indicate the potential use of Sac/Val for treatment of myocarditis.
COVID-19 Impacts on Historic Soundscape Perception and Site Usage
Authors: Jordan Pamela , Fiebig André
Published: September 2021

The ISO 12913 standards acknowledge the primacy of context in perceiving acoustic environments. In soundscape assessments, context is constituted by both physical surroundings and psychological, social, and cultural factors. Previous studies have revealed similarities in people’s soundscape assessments in comparable physical surroundings, such as urban or national parks, despite differing individual associative contexts. However, these assessments were found to be capable of shifting in the historic setting of the Berlin Wall Memorial. Providing contextual information from the past appears to have some bearing on soundscape perception. The COVID-19 lockdown measures enacted since March 2020 in Germany have prevented most tourist activity at the memorial, and a resulting shift in user activity has been observed in the otherwise open and accessible memorial landscape. Building on previous soundscape investigations conducted at the memorial, this paper investigates what effect the restrictions have had on the soundscape context and its perception by visitors. Informal interviews paired with comparative measurements indicated context pliability for local stakeholders. In contrast to site programming alone, tourist presence also appears to affect context perception for local users. This holds repercussions for soundscape and heritage site designs serving local and tourist populations—and their divergent perceptions—alike. The impacts of soundscape assessments being neither static nor generalizable across stakeholders are discussed with suggestions for further research.
VHF Omnidirectional Range (VOR) Experimental Positioning for Stratospheric Vehicles
Authors: Frezza Lorenzo , Marzioli Paolo , Santoni Fabio , Piergentili Fabrizio
Published: September 2021

The usage of aeronautical radio-frequency navigational aids can support the future stratospheric aviation as back-up positioning systems. Although GNSS has been extensively redundant in the last years of space operations, radio NavAids can still be supportive of navigation and tracking for novel mission profiles. As an example, in 2016, VHF Omnidirectional Range (VOR) has been proven to work well above its standard service volume limit on a stratospheric balloon flight with the STRATONAV experiment. While VOR provides the “radial” measurement, i.e., the angle between the Magnetic North and the line between the receiver and the transmitting ground station, the intersection of two or more radials at a time allows to perform ground track reconstruction for the vehicle to be tracked. This paper reports the results from the data re-processing from STRATONAV: the acquired radials have been intersected in order to achieve positioning. The radials interfacing method, the position calculation methodology, and the data acquisition strategies from STRATONAV are reported together with the data analysis results.
The Influence of New Agricultural Business Entities on the Economic Welfare of Farmer’s Families
Authors: Cheng Lingjuan , Zou Wei , Duan Kaifeng
Published: September 2021

Promoting the coordinated development of new agricultural business entities and small farmers is an important way to realize rural revitalization. It is undoubtedly of great significance to clarify the impact and its mechanism of new agricultural business entities on the economic welfare of farmers’ families. Based on the 2015 China Household Finance Survey (CHFS) data, this paper builds a theoretical analytical framework of “new agricultural business entities—non-agricultural employment and agricultural output—economic welfare of farmers’ family”. From the intermediary perspective of the non-agricultural employment and agricultural output, it empirically tests the impact of new agricultural business entities on the economic welfare of farmers’ families by combining the analysis methods of the benchmark regression and intermediary effect. The research shows that: (1) New agricultural business entities promote the improvement of the economic welfare of farmers’ families. The specific manifestation is that the existence of new agricultural business entities can not only increase the per capita annual income of farmers’ families, but also promote the per capita consumption expenditure of farmers’ families in the village. (2) Non-agricultural employment and agricultural output have a significant mediating effect in the impact of new agricultural business entities on the economic welfare of farmers’ families. (3) In addition to key variables, variables such as education, political status, and family status are also key factors affecting the economic welfare of farmers’ families. Finally, this paper puts forward some policy recommendations such as cultivating high-quality new agricultural business entities, strengthening farmers’ technical training, and optimizing rural residents’ policies.
Soil Response to Agricultural Land Abandonment: A Case Study of a Vineyard in Northern Italy
Authors: Sciubba Luigi , Mazzon Martina , Cavani Luciano , Baldi Elena , Toselli Moreno , Ciavatta Claudio , Marzadori Claudio
Published: September 2021

Agricultural land abandonment is an emerging problem in European Union (EU), and about 11% of agricultural EU land is at high risk of abandonment in the coming 10 years. Land abandonment may have both positive and negative effects in ecosystems. Due to the potential for land abandonment to increase soil fertility, the study of vegetation succession effects on soil quality is of great importance. In this study, we investigated an abandoned vineyard where, after a period of 30 years, rows and alleys were characterized by two different forms of vegetation succession: natural recolonization by trees along the rows and by herbaceous vegetation in the alleys. No-tilled alleys covered by herbaceous vegetation of a neighboring conventionally cultivated vineyard were used as a comparison. Soil samples were chemically characterized (pH, extractable element, and available and total metals), and analyzed for the determination of carbon (C) and nitrogen (N) pools; hydrolytic and phenol oxidizing (PO) enzyme activities involved in C, N, and phosphorus (P) cycles; and the enzyme ratios. Results highlighted that natural recolonization by trees increased the organic C and N soil pools by 58% and 34%, respectively, compared to the natural recolonization by herbaceous vegetation. Moreover, natural recolonization by trees reduced β-glucosidase by 79%, urease by 100%, alkaline phosphastase by 98%, acid phosphatase specific hydrolytic activities by 50%, and catechol oxidase and laccase specific oxidative activities by 127% and 119%, respectively, compared to the renaturalization by herbaceous vegetation. In addition, the natural recolonization by trees reduced the C (βglu):C (PO) enzymes ratio by 16% compared to that of the conventional vineyard. Comparing the natural recolonization by herbaceous vegetation with that of the conventional vineyard revealed little significant difference (15% of the measured and calculated parameters); in particular, PO activities significantly decreased in the renaturalized vineyard with herbaceous vegetation by 49% (catechol oxidase) and 52% (laccase), and the C (βglu):C (PO) enzyme ratio showed a reduction (−11%) in the vineyard naturally recolonized by herbaceous vegetation compared to the conventional vineyard. This highlights that the type of vegetation succession that takes place after land abandonment may have a significant impact in terms of soil fertility and C accrual potential. These results help to focus attention on the practices used in agro-forestry that should be adopted in abandoned agro-ecosystems to increase their biodiversity, soil C stock, and soil quality, because these indicators are affected by the type of vegetative coverage.
Detection of Cacao Mild Mosaic Virus (CaMMV) Using Nested PCR and Evidence of Uneven Distribution in Leaf Tissue
Authors: Puig Alina S.
Published: September 2021

Distribution of improved germplasm of Theobroma cacao is essential for meeting the increased demand for cocoa beans. In cacao, the introduction of new diseases is prevented by exchanging material through a national and international quarantine system. In 2020, virus symptoms were observed on plants in a quarantine greenhouse, and Cacao mild mosaic virus (CaMMV) was detected in one plant using published diagnostic primers. However, no virus was detected in other symptomatic plants. To address high pathogen diversity and low virus titer in recently infected plants, a nested PCR test was developed based on 15 CaMMV sequences from Trinidad and Puerto Rico. The test was validated on a subset (n = 30) of plants in the greenhouse, of which 29 tested positive. Most infections are thought to have occurred during the later stage of the quarantine period, possibly due to spread by mealybugs. However, phylogenetic analysis revealed the presence of three strains, suggesting that it was introduced on scionwood from multiple sources. Results of PCR assays on different leaf tissues indicate that the virus is unevenly distributed and that petiole tissue should be used in molecular diagnostics. The movement of infected scionwood is a major dissemination pathway for CaMMV but can be managed through careful screening.
How Mineral Fertilization and Soil-Climate Conditions Affect Spring Barley Grain Yield and Soil Chemical Properties
Authors: Hlisnikovský Lukáš , Křížová Kateřina , Menšík Ladislav , Kunzová Eva
Published: September 2021

Barley is one of the most important cereals growing in the Czech Republic. In this paper, we have evaluated how different fertilizer treatments (Control, N1—30 kg ha−1 N, N2—60 kg ha−1 N, NPK1—30, 60, 80 kg ha−1, respectively, NPK2—60, 60, 80, and NPK3—90, 60, 80) affected spring barley grain yield under different soil-climate conditions (Caslav-degraded Chernozem, Ivanovice-Chernozem, Lukavec-Cambisol) between the years 2013 and 2016. The agronomic efficiency (AE) and the effect of the fertilizer treatments (Control, N2, NPK2) on soil properties (pH, P, K, Ca, Mg, Cox, Nt) were also evaluated. The spring barley grain yield was significantly affected by the fertilizer treatment and soil-climate conditions. Two different models (quadratic and linear-plateau) provided the maximum and reasonable doses of N, according to the soil-climate conditions. Application of mineral P and K slightly increased the AE. The regular application of mineral P and K fertilizers led to an increase in the P and K concentration in the soil, which maintains soil fertility and prevents soil depletion.
Characterization of Streptomyces spp. from Rice Fields as a Potential Biocontrol Agent against Burkholderia glumae and Rice Plant Growth Promoter
Authors: Ngalimat Mohamad Syazwan , Mohd Hata Erneeza , Zulperi Dzarifah , Ismail Siti Izera , Ismail Mohd Razi , Mohd Zainudin Nur Ain Izzati , Saidi Noor Baity , Yusof Mohd Termizi
Published: September 2021

The usage of plant growth-promoting (PGP) Streptomyces to improve plant growth is an alternative to existing strategies of chemical fertilizers that commonly caused environmental pollution. The aim of this study was to isolate and characterize PGP Streptomyces from Malaysian rice fields with antagonistic activity against Bacterial Panicle Blight disease in rice caused by Burkholderia glumae. A total of 50 bacterial isolates were recovered from the soil, rhizosphere, and endosphere; 22% showed antagonistic activity against B. glumae. Molecular identification using 16S rRNA amplification and phylogenetic tree analyses revealed that the antagonistic isolates belonged to the genus Streptomyces. Among the antagonistic isolates, Streptomyces sp. TBS5 (26.35 ± 0.14 mm) demonstrated the most antagonistic activity (p < 0.05) against B. glumae. Through API® ZYM analysis, the antagonistic isolates were revealed to have phosphoric hydrolase, ester hydrolase, peptide hydrolase, and glycosidase activities that play a crucial role in plant growth promotion. The antagonistic isolates demonstrated the highest (80%) PGP traits including able to fix nitrogen and solubilize phosphate, as well as produce siderophore and indole-3-acetic acid. Plant growth promotion assay under laboratory and greenhouse conditions were analyzed with the treatment of rice, Oryza sativa, seeds with the antagonistic isolates. Seeds treated with Streptomyces sp. TBS5, JAS2, R2-7, and TKR8 showed improvement in vigor index by more than 100% compared to water-treated control plants under both conditions. Augmentation of root length showed an overall increment of more than 101.5% under laboratory condition and 151.9% under greenhouse condition using Streptomyces sp. TBS5, JAS2, R2-7, and TKR8 treatments. Results suggest that Streptomyces sp. TBS5, JAS2, R2-7, and TKR8 are a good candidate to be developed as both biocontrol agent against B. glumae and PGP agent in rice.
Do Water and Nitrogen Management Practices Impact Grain Quality in Maize?
Authors: Correndo Adrian A. , Fernandez Javier A. , Vara Prasad P.V. , Ciampitti Ignacio A.
Published: September 2021

Concomitantly pursuing superior maize (Zeamays L.) productivity with grain quality is essential for food security. Therefore, this study provides a meta-analysis of 21 studies assembled from the scientific literature to tackle the effect of the two most limiting factors for maize production, water and nitrogen (N), and their impacts on grain quality composition, herein focused on protein, oil, and starch concentrations. Water stress levels resulted in erratic responses both in direction and magnitude on all the grain quality components, plausibly linked to a different duration, timing, and intensity of water stress treatments. Nitrogen fertilization more consistently affected the grain protein concentration, with a larger effect size for protein as fertilizer N levels increased (protein change of +14% for low, ≤70 kg N ha−1; +21% for medium, >70–150 kg N ha−1; and +24% for high, >150 kg N ha−1). Both starch and oil grain concentrations presented less variation to fertilizer N levels. The positive protein–oil correlation (r = 0.49) permitted to infer that although the oil concentration may reach a plateau (8%), further increases in protein are still possible. Augmented research on grain quality is warranted to sustain food production but with both high nutritional and energetic value for the global demand.
Analysis of Weather-Related Growth Differences in Winter Wheat in a Three-Year Field Trial in North-East Germany
Authors: Künzel Alice , Münzel Sandra , Böttcher Falk , Spengler Daniel
Published: September 2021

Winter wheat is the most important crop in Germany, which is why a three-year field trial (2015–2017) investigated the effects of weather on biometric parameters in relation to the phenological growth stage of the winter wheat varieties Opal, Kerubino, Edgar. In Brandenburg, there have been frequent extreme weather events in the growth phases that are relevant to grain yields. Two winter wheat varieties were grown per trial year and parts of the experimental field areas were irrigated. In addition, soil physical, biometric and meteorological data were collected during the growing season (March until end of July). There were five dry periods in 2015, six in 2016, and two in 2017 associated with low soil moisture. Notably, in 2016 the plant height was 5 cm lower and the cover was 15% lower than on irrigated plots. The grain yield was increased by 19% and 31% respectively by irrigation. However, due to irrigation costs, the net grain yield on irrigated plots was lower than on the unirrigated plots. It turned out that in dry years there were hardly any differences between winter wheat varieties. Multiple regression analysis showed a strong correlation between the biometric parameters considered here and the grain yield.
Effects of Probiotics and Wheat Bran Supplementation of Broiler Diets on the Ammonia Emission from Excreta
Authors: Such Nikoletta , Csitári Gábor , Stankovics Petra , Wágner László , Koltay Ilona Anna , Farkas Valéria , Pál László , Strifler Patrik , Dublecz Károly
Published: September 2021

Ammonia emission is a concern for the poultry industry from both environmental and animal welfare points of view. The objective of this research was to determine whether probiotics or wheat bran supplementation of broiler diets can modify the N composition of the excreta and the dynamics of ammonia volatilisation emission from the manure. A total of 120-day-old Ross 308 broiler chickens were fed six different diets. The treatments included a corn and soybean meal-based control diet (C) and diets containing wheat bran (WB). Both diets were fed alone and with supplementation of a lactic acid (Lactobacillus farciminis, LAB) and a butyric acid (Clostridium butyricum, BAB) producing bacterial strain. Treatment BAB had a significant effect on the dry matter content of the excreta and both probiotics decreased the amount of excreted uric acid. Treatment WB resulted in a significantly lower NH+4-N concentration of excreta and a tendency toward reduced uric acid content. Treatment LAB reduced the urinary N ratio of excreta. Among dietary treatments, WB resulted in the highest urease producing cell numbers in the excreta, but this difference was not significant. Based on our results, similar to pigs, the soluble fibre fraction of poultry diets can also modify the urinary to faecal N ratio of the excreta.
The Biology of Colicin M and Its Orthologs
Authors: Chérier Dimitri , Patin Delphine , Blanot Didier , Touzé Thierry , Barreteau Hélène
Published: September 2021

The misuse of antibiotics during the last decades led to the emergence of multidrug resistant pathogenic bacteria. This phenomenon constitutes a major public health issue. Consequently, the discovery of new antibacterials in the short term is crucial. Colicins, due to their antibacterial properties, thus constitute good candidates. These toxin proteins, produced by E. coli to kill enteric relative competitors, exhibit cytotoxicity through ionophoric activity or essential macromolecule degradation. Among the 25 colicin types known to date, colicin M (ColM) is the only one colicin interfering with peptidoglycan biosynthesis. Accordingly, ColM develops its lethal activity in E. coli periplasm by hydrolyzing the last peptidoglycan precursor, lipid II, into two dead-end products, thereby leading to cell lysis. Since the discovery of its unusual mode of action, several ColM orthologs have also been identified based on sequence alignments; all of the characterized ColM-like proteins display the same enzymatic activity of lipid II degradation and narrow antibacterial spectra. This publication aims at being an exhaustive review of the current knowledge on this new family of antibacterial enzymes as well as on their potential use as food preservatives or therapeutic agents.
Betulinic Acid–Doxorubicin-Drug Combination Induced Apoptotic Death via ROS Stimulation in a Relapsed AML MOLM-13 Cell Model
Authors: Vu Milan , Kassouf Nick , Appiah Sandra
Published: September 2021

In this study, cell death regulation and induction in AML cell line from a relapsed MLL-rearranged cell model (MOLM-13) was investigated with doxorubin (Dox) and betulinic acid (BetA), singly and in combination. CyQUANT Direct® and Annexin V/propidium iodide double staining were used to measure the cytotoxic and cell death induction effects of the compounds, respectively. Reactive oxygen species (ROS) generation was measured using 2′,7′-dichlorofluorescin diacetate staining. Expressions of proteins and genes were examined by Western blot and reverse transcription polymerase chain reaction analysis, respectively. BetA (20 μM) and Dox (1 μM) indicated a synergistic growth inhibitory effect on MOLM-13 cells. The combined drug caused more cells to reside in irreversible late apoptotic stage compared to the single treatments (p < 0.05). Elevation in ROS may be the synergistic mechanism involved in MOLM-13 cell death since ROS can directly disrupt mitochondrial activity. In contrast, in leukaemic U-937 cells, the combination treatments attenuated Dox-induced cell death. Dox and the drug combination selectively reduced (p < 0.05) a recently reported anti-apoptotic Bcl-2 protein isoform p15-20-Bcl-2 in MOLM-13 by our group, without affecting the usually reported p26-Bcl-2-α. Further studies using known inhibitors of apoptosis are required to confirm the potential of Dox-BetA combination to modulate these pathways.
Iron–Sulfur Cluster Biogenesis as a Critical Target in Cancer
Authors: Petronek Michael S. , Spitz Douglas R. , Allen Bryan G.
Published: September 2021

Cancer cells preferentially accumulate iron (Fe) relative to non-malignant cells; however, the underlying rationale remains elusive. Iron–sulfur (Fe–S) clusters are critical cofactors that aid in a wide variety of cellular functions (e.g., DNA metabolism and electron transport). In this article, we theorize that a differential need for Fe–S biogenesis in tumor versus non-malignant cells underlies the Fe-dependent cell growth demand of cancer cells to promote cell division and survival by promoting genomic stability via Fe–S containing DNA metabolic enzymes. In this review, we outline the complex Fe–S biogenesis process and its potential upregulation in cancer. We also discuss three therapeutic strategies to target Fe–S biogenesis: (i) redox manipulation, (ii) Fe chelation, and (iii) Fe mimicry.