bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a data science CURE in microbiology using publicly available microbiome datasets
Authors: Sun Evelyn , König Stephan G. , Cirstea Mihai , Hallam Steven J. , Graves Marcia L. , Oliver David C.
Published: October 2022

Scientific and technological advances within the life sciences have enabled the generation of very large datasets that must be processed, stored, and managed computationally. Researchers increasingly require data science skills to work with these datasets at scale in order to convert information into actionable insights, and undergraduate educators have started to adapt pedagogies to fulfill this need. Course-based undergraduate research experiences (CUREs) have emerged as a leading model for providing large numbers of students with authentic research experiences including data science. Originally designed around wet-lab research experiences, CURE models have proliferated and diversified globally to accommodate a broad range of academic disciplines. Within microbiology, diversity metrics derived from microbiome sequence information have become standard data products in research. In some cases, researchers have deposited data in publicly accessible repositories, providing opportunities for reproducibility and comparative analysis. In 2020, with the onset of the COVID-19 pandemic and concomitant shift to remote learning, the University of British Columbia set out to develop an online data science CURE in microbiology. A team of faculty with collective domain expertise in microbiome research and CUREs developed and implemented a data science CURE in which teams of students learn to work with large publicly available datasets, develop and execute a novel scientific research project, and disseminate their findings in the online Undergraduate Journal of Experimental Microbiology and Immunology. Analysis of the resulting student-authored research articles, including comments from peer reviews conducted by subject matter experts, demonstrate high levels of learning effectiveness. Here, we describe core insights from course development and implementation based on a reverse course design model. Our approach to course design may be applicable to the development of other data science CUREs.
A multifunctional enzyme portfolio for α-chaconine and α-solanine degradation in the Phthorimaea operculella gut bacterium Glutamicibacter halophytocola S2 encoded in a trisaccharide utilization locus
Authors: Wang Wenqian , Du Guangzu , Yang Guangyuan , Zhang Ke , Chen Bin , Xiao Guanli
Published: October 2022

Steroidal glycoalkaloids (SGAs) are secondary metabolites commonly found in members of the family Solanaceae, including potatoes, and are toxic to pests and humans. The predominant SGAs in potato are α-chaconine and α-solanine. We previously reported that Glutamicibacter halophytocola S2, a gut bacterium of the pest Phthorimaea operculella (potato tuber moth), can degrade α-chaconine and α-solanine in potatoes, which can improve the fitness of P. operculella to feed on potatoes with a high content of toxic SGAs. Glutamicibacter halophytocola S2 harbored a gene cluster containing three deglycosylase genes—GE000599, GE000600, and GE000601—that were predicted encode α-rhamnosidase (RhaA), β-glucosidase (GluA), and β-galactosidase (GalA). However, there is limited information is available on the enzyme activities of the three enzymes expressed by this gene cluster and how they degrade the major toxic α-chaconine and α-solanine. In the current study, each enzyme of this gene cluster was produced by a prokaryotic expression approach and the activity of the recombinant enzymes for their target substrate and α-chaconine and α-solanine were evaluated by EPOCH microplate spectrophotometer and liquid chromatography mass spectrometry (LC-MS). The three enzymes had multifunctional activities, with RhaA and GluA could hydrolyze α-rhamnose, β-glucose, and β-galactose, while GalA can hydrolyze β-glucose and β-galactose. The degradation of α-chaconine and α-solanine was consistent with the results of the enzyme activity assays. The final product solanidine could be generated by adding RhaA or GluA alone. In conclusion, this study characterized the multifunctional activity and specific degradation pathway of these three enzymes in G. halophytocola S2. The three multifunctional enzymes have high glycosidic hydrolysis activity and clear gene sequence information, which help facilitates understanding the detoxification mechanism of insect gut microbes. The enzymes have a broad application potential and may be valuable in the removal of toxic SGAs from for potato food consumption.
Microbiologically influenced corrosion of stainless steel independent of sulfate-reducing bacteria
Authors: Wakai Satoshi , Eno Nanami , Mizukami Hirotaka , Sunaba Toshiyuki , Miyanaga Kazuhiko , Miyano Yasuyuki
Published: October 2022

The presence and activities of microorganisms on metal surfaces can affect corrosion. Microbial communities after such corrosion incidents have been frequently analyzed, but little is known about the dynamics of microbial communities in biofilms on different types of stainless steels, such as austenitic, martensitic, and duplex stainless steels. Here, we conducted immersion experiments on 10 types of stainless steels in a freshwater environment, where microbiologically influenced corrosion was observed. During 22-month of immersion, severe localized corrosions were observed only on martensitic S40300 stainless steel. Microbial community analysis showed notable differences between non-corroded and corroded stainless steels. On the surfaces of non-corroded stainless steels, microbial communities were slowly altered and diversity decreased over time; in particular, relative abundance of Nitrospira sp. notably increased. Whereas microbial communities in corrosion products on corroded stainless steels showed low diversity; in particular, the family Beggiatoaceae bacteria, iron-oxidizing bacteria, and Candidatus Tenderia sp. were enriched. Furthermore, sulfur enrichment during localized corrosion was observed. Since there was no enrichment of sulfate-reducing bacteria, the sulfur enrichment may be derived from the presence of family Beggiatoaceae bacteria with intracellular sulfur inclusion. Our results demonstrated slow and drastic changes in microbial communities on the healthy and corroded metal surfaces, respectively, and microbial communities on the healthy metal surfaces were not affected by the composition of the stainless steel.
Isolation of SARS-CoV-2-blocking recombinant antibody fragments and characterisation of their binding to variant spike proteins
Authors: Antoine Delphine , Mohammadi Moein , McDermott Chloe E. , Walsh Eithne , Johnson Patrick A. , Wawrousek Karen E. , Wall J. Gerard
Published: October 2022

COVID-19 is a severe acute respiratory disease caused by SARS-CoV-2. From its initial appearance in Wuhan, China in 2019, it developed rapidly into a global pandemic. In addition to vaccines, therapeutic antibodies play an important role in immediately treating susceptible individuals to lessen severity of the disease. In this study, phage display technology was utilised to isolate human scFv antibody fragments that bind the receptor-binding domain (RBD) of SARS-CoV-2 Wuhan-Hu-1 spike protein. Of eight RBD-binding scFvs isolated, two inhibited interaction of RBD with ACE2 protein on VeroE6 cells. Both scFvs also exhibited binding to SARS-CoV-2 Delta variant spike protein but not to Omicron variant spike protein in a Raman spectroscopy immunotest. The study demonstrates the potential of recombinant antibody approaches to rapidly isolate antibody moieties with virus neutralisation potential.
Online recorded data-based finite-time composite neural trajectory tracking control for underactuated MSVs
Authors: Zhao Chunbo , Yan Huaran , Gao Deyi
Published: October 2022

This paper presents an online recorded data-based composite neural finite-time control scheme for underactuated marine surface vessels (MSVs) subject to uncertain dynamics and time-varying external disturbances. The underactuation problem of the MSVs was solved by introducing the line-of-sight (LOS) method. The uncertain dynamics of MSVs are approximated by the composite neural networks (NNs). A modified prediction error signal is designed by virtue of online recorded data. The weight updating law of NN is driven by both tracking error and prediction error, introducing additional correction information to the weights of NN, thus improving the learning ability of the NN. Furthermore, disturbance observers can be devised to estimate the compound disturbances consisting of the approximation errors of NNs and external disturbances. Moreover, the smooth function is inserted into the design of the control scheme, and the finite-time composite neural trajectory tracking control of MSVs is achieved. The stability of the MSVs trajectory tracking closed-loop control system is guaranteed rigorously by the Lyapunov approach, and the tracking error will converge to the set of residuals around zero within a finite time. The simulation tests on an MSV verify the effectiveness of the proposed control scheme.
Learning joints relation graphs for video action recognition
Authors: Liu Xiaodong , Xu Huating , Wang Miao
Published: October 2022

Previous video action recognition mainly focuses on extracting spatial and temporal features from videos or capturing physical dependencies among joints. The relation between joints is often ignored. Modeling the relation between joints is important for action recognition. Aiming at learning discriminative relation between joints, this paper proposes a joint spatial-temporal reasoning (JSTR) framework to recognize action from videos. For the spatial representation, a joints spatial relation graph is built to capture position relations between joints. For the temporal representation, temporal information of body joints is modeled by the intra-joint temporal relation graph. The spatial reasoning feature and the temporal reasoning feature are fused to recognize action from videos. The effectiveness of our method is demonstrated in three real-world video action recognition datasets. The experiment results display good performance across all of these datasets.
Characteristics of initial symptoms in patients with dementia with Lewy body disease
Authors: Fei Min , Wang Fei , Wu Hao , Liu Shuai , Gan Jinghuan , Ji Yong
Published: October 2022

Background

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia. Although DLB is characterized by fluctuating cognitive impairment, some symptoms may appear before cognitive impairment, including rapid eye movement, sleep behavior disorder (RBD), psychiatric symptoms, autonomic symptoms, Parkinson's symptoms, etc. Therefore, DLB may be misdiagnosed as other diseases in its early stage.

Objective

This study aimed to investigate the characteristics of initial symptoms of DLB, which could potentially offer essential clues for the earliest diagnosis of this disorder.

Methods

A total of 239 patients with probable DLB who visited the cognitive impairment outpatient department of Tianjin Huanhu Hospital from September 2015 to March 2021 were consecutively enrolled. We retrospectively evaluated the initial symptoms of all included participants. The time of onset of initial symptoms was also assessed.

Results

The most frequent initial symptom was memory loss (53.9%), followed by psychiatric symptoms (34.7%), RBD (20.9%), parkinsonism (15.1%), and autonomic symptoms (10.1%). Significant gender and age differences existed in the initial symptoms of patients with DLB.

Conclusions

Our study elucidated the initial symptoms in patients with probable DLB. RBD was significantly more reported by men than by women, whereas women showed a higher incidence of visual and auditory hallucinations. A better understanding of the initial symptoms of DLB could lead to a more accurate diagnosis.
Worldwide Meniere's disease research: A bibliometric analysis of the published literature between 2002 and 2021
Authors: Zou Wujun , Li Qian , Peng Fei , Huang Dingqiang
Published: October 2022

Background

In recent years, there has been an increasing number of publications on Meniere's disease. However, there are no bibliometric research on Meniere's disease. The purpose of this study was to find the focus and trends of Meniere's disease research through bibliometric approach.

Methods

Publications related to Meniere's disease in the Web of Science Core Collection (WOSCC) from 2002 to 2021 were collected. The bibliometric approach was used to estimate the searched data. Research foci of the studies were identified using VOSviewer and CiteSpace software.

Results

A total of 1,987 articles meet the inclusion criteria and are included in the study. In the past 20 years, the number of Meniere's disease publications is gradually increasing, especially in the past 3 years. The country with the largest contribution to Meniere's disease research is the United States, followed by Europe and Japan. High-frequency keywords included Meniere's disease, endolymphaic hydrops, vertigo, meniere-disease, inner ear, dizziness, symptoms, hearing, diagnosis, and tentamicin. The analyses of keyword burst direction indicate that evoked myogenic potential, MRI, and committee are emerging research hotspots.

Conclusion

This study provides an objective, systematic, and comprehensive analysis of Meniere's disease-related literature. In addition, we find a dramatic increase in studies in this field over the past 3 years. Evoked myogenic potentials and MRI may become the research hotspots of Meniere's disease in future. This study will help otolaryngologists, neurologists, and audiologists to clarify the research direction and potential hotspots of Meniere's disease and further help clinicians improve patients' prognosis.
Tortuosity of parent artery predicts in-stent stenosis after pipeline flow-diverter stenting for internal carotid artery aneurysms
Authors: Gao Haibin , You Wei , Wei Dachao , Lv Jian , Sun Wei , Li Youxiang
Published: October 2022

Background and purpose

The relationship between the tortuosity of the parent artery and treatment outcomes is not well established. We investigate the association between parent artery tortuosity and flow diverter (FD) treatment outcomes in patients with internal carotid artery aneurysms in this study.

Methods

A retrospective review study was conducted to identify all patients with internal carotid artery aneurysms who were implanted with Pipeline embolization device (PED) between 2016 and 2020. The relationship between parent artery tortuosity and aneurysm complete occlusion (CO) and in-stent stenosis (ISS) was analyzed. The mathematical parameters “Curvature”, “torsion”, and “DM” extracted from the parent artery were utilized to quantify the parent artery tortuosity. A vascular narrowing of greater than 25% was categorized as ISS. Logistic regression analysis was used to identify significant independent predictors. Furthermore, we compared the performance of four machine learning algorithms and Logistic Regression model in predicting ISS.

Results

This research included 62 patients who with internal carotid artery aneurysms. In 49 (79%) cases, follow-up angiography (mean follow-up duration 11.7 ±7.3 months) revealed CO of the aneurysm. ISS was detected in 22 (35.5%) cases. According to univariate analysis, parent artery tortuosity and other variables were not associated with CO (p > 0.1). Maximum curvature (OR = 1.084; 95% CI, 1.008–1.165; p = 0.03) and DM (OR = 0.01; 95% CI, 0–0.488; p = 0.02) exhibited strong independent associations with ISS in multivariate analysis. The SVM model is superior to the conventional Logistic Regression model and the other models in predicting ISS.

Conclusions

The tortuosity of the parent artery may affect the treatment outcome of FD stenting. We found that parent artery tortuosity was associated with ISS, but not with aneurysm complete occlusion following PED stenting for internal carotid artery aneurysms in this study. Parent arteries with higher maximum curvature and lower DM were more likely to develop ISS.
Associations of circadian rest/activity rhythms with cognition in middle-aged and older adults: Demographic and genetic interactions
Authors: Rabinowitz Jill A. , An Yang , He Linchen , Alfini Alfonso J. , Zipunnikov Vadim , Wu Mark N. , Wanigatunga Sarah K. , Schrack Jennifer A. , Jackson Chandra L. , Ferrucci Luigi , Simonsick Eleanor M. , Resnick Susan M. , Spira Adam P.
Published: October 2022

Objectives

Wrist actigraphs (accelerometers) can record motor activity over multiple days and nights. The resulting data can be used to quantify 24-h activity profiles, known as circadian rest-activity rhythms (CRARs). Actigraphic CRARs have been tied to cognitive performance and decline in older adults; however, little is known about links between CRARs and performance or change in specific cognitive domains, or how individual differences may influence these associations. We investigated associations of actigraphic CRARs with cognitive performance and change in middle-aged and older adults, and explored whether age, sex/gender, race, and apolipoprotein E (APOE) e4 carrier status moderated these associations.

Materials and methods

Participants (N = 422; 47% male) were cognitively healthy adults (i.e., without mild cognitive impairment or dementia) at baseline aged ≥ 50 years from the Baltimore Longitudinal Study of Aging who completed 5.6 ± 0.89 nights of wrist actigraphy and tests of memory, executive function, attention, language, and visuospatial ability at the same visit the actigraph was issued; 292 participants had repeat cognitive testing 3.12 (1.58) years later. Predictors included indices of rhythm strength [i.e., amplitude; relative amplitude (RA); interdaily stability (IS); mesor], delayed timing of the rhythm peak [i.e., later acrophase; midpoint of an individual’s least active 5 h (L5 time); midpoint of an individual’s most active 10 h (M10 time)], and fragmentation [i.e., intradaily variability (IV)].

Results

In main effects, later L5 time was cross sectionally associated with poorer memory, and greater IS predicted slower longitudinal memory decline. Associations of CRARs with cognition differed as a function of age, sex/gender, race, and APOE e4 carrier status.

Conclusion

Among middle-aged and older adults, delayed circadian phase is associated with poorer memory performance, and greater day-to-day rhythm stability is associated with slower declines in memory. Significant interactions suggest that CRARs are generally more strongly associated with cognitive performance and rate of cognitive decline among women, Black adults, older individuals, and APOE e4 carriers. Replication in independent samples is needed.
The cortisol awakening response at admission to hospital predicts depression severity after discharge in major depressive disorder patients—A replication study
Authors: Neyer Sabrina , Witthöft Michael , Cropley Mark , Pawelzik Markus , Sütterlin Stefan , Lugo Ricardo G.
Published: October 2022

The cortisol awakening response (CAR) is a non-invasive biomarker for hypothalamic-pituitary-adrenal axis (HPA) dysregulation, reflecting accumulated stress over time. In a previous study we reported that a blunted CAR before an inpatient treatment predicted self-reported depressive symptoms six weeks and six months after discharge [Eikeseth, F. F., Denninghaus, S., Cropley, M., Witthöft, M., Pawelzik, M., & Sütterlin, S. (2019). The cortisol awakening response at admission to hospital predicts depression severity after discharge in major depressive disorder (MDD) patients. Journal of Psychiatric Research, 111, 44-50)]. This replication study adopted an improved overall methodology with more stringent assessment protocols and monitoring. The longitudinal design included 122 inpatients from a psychosomatic hospital with a diagnosis of MDD displaying symptoms of moderate to severe major depression (n = 80 females). The CAR was measured at intake. Depression severity was assessed as Beck Depression Inventory II scores at intake, discharge, 6 weeks and 6 months following discharge. Results from the original study were replicated in terms of effect size but did not reach statistical significance (correlation between BDI-II 6 months after discharge and AUCg: r = −0.213; p = 0.054). The replication study yielded nearly identical correlation coefficients as in the original study (BDI-II 6 months and CAR, r = −0.223, p < 0.05). The replication of previously reported effect sizes with a concurrent lack of statistical significance in the more restrictive, larger and better controlled replication study may well inform research on psycho-endocrinological predictors for treatment success, but suggests a rather limited practical relevance for cortisol awakening response measures in this clinical context.
Associations between dietary magnesium intake and handgrip strength were modified by serum vitamin D level among the US elderly
Authors: Han Shuang , Gao Yue , Gan Da
Published: October 2022

Objective

The present study aimed to evaluate the associations between dietary magnesium intake and handgrip strength, and whether these associations were affected by serum vitamin D status.

Methods

A total of 2,127 participants aged 60 and above from the National Health and Nutrition Examination Survey (NHANES) of the 2011–2014 cycles were included in the analyses. Magnesium intake was obtained by 24-h dietary recalls and 30-day dietary supplement. Participants in the lowest sex-specific tertile of magnesium intake were defined as having low magnesium intake. Serum 25-hydroxyvitamin D [25(OH)D)] concentrations were examined by using ultra-high performance liquid chromatography tandem mass spectrometry and categorized into three levels: deficient, suboptimal, and sufficient. Handgrip strength was determined by using a dynamometer. Multivariable linear regression models were used to investigate the associations between dietary magnesium intake and handgrip strength.

Results

Low magnesium intake was not associated with handgrip strength, but interactions between low magnesium intake and serum 25(OH)D level existed on handgrip strength. The stratified analyses found that only in participants with deficient serum 25(OH)D, low magnesium intake was associated with reduced handgrip strength. The combined analyses shown that participants with both low magnesium intake and deficient serum 25(OH)D had highest decrease of handgrip strength.

Conclusion

Findings suggested that low magnesium intake was associated with reduced handgrip strength only in participants with deficient serum 25(OH)D. Increased magnesium intake was recommended for participants with deficient serum 25(OH)D in maintaining muscle strength.
1-methylhistamine as a potential biomarker of food histamine intolerance. A pilot study
Authors: Sánchez-Pérez Sònia , Celorio-Sardà Ricard , Veciana-Nogués M. Teresa , Latorre-Moratalla M. Luz , Comas-Basté Oriol , Vidal-Carou M. Carmen
Published: October 2022

Efforts are currently being directed to identify a non-invasive marker that can serve as a solid and clinically irrefutable diagnostic criterion for histamine intolerance associated with diamine oxidase (DAO) deficiency. Accordingly, the identification of biomarkers of histamine (HA) metabolism in urine is proposed as a possible new diagnostic strategy. It is hypothesized that individuals with histamine intolerance could have a different urinary profile of HA and its metabolites in comparison with the healthy population. Thus, the aim of this study was to assess the urinary excretion of HA and 1-methylhistamine (MHA) in individuals diagnosed with histamine intolerance and in a control group. Levels of HA and MHA were compared between 24 h and first morning spot urine in a subgroup of 14 control individuals. Then, HA and MHA concentrations in spot urine of 32 histamine intolerant and 55 control individuals were determined by ultra-high performance liquid chromatography and fluorometric detection (UHPLC-FL) and normalized by creatinine. No differences were found between HA and MHA levels in 24 h and first morning samples. Overall, histamine intolerant patients presented a distinct urinary excretion profile compared to the control group due to lower levels of MHA. No differences in urinary MHA were observed related to serum DAO activity. Spot urine samples were thus validated as a reliable tool to determine the urinary excretion of HA and MHA. These results constitute a starting point for the study of HA metabolomics as a suitable and non-invasive approach to histamine intolerance diagnosis.
Radiolabeled EGFR TKI as predictive imaging biomarkers in NSCLC patients – an overview
Authors: Van De Stadt Eveline , Yaqub Maqsood , Jahangir A. A. , Hendrikse Harry , Bahce Idris
Published: October 2022

Non-small cell lung cancer (NSCLC) has one of the highest cancer-related mortality rates worldwide. In a subgroup of NSCLC, tumor growth is driven by epidermal growth factor receptors (EGFR) that harbor an activating mutation. These patients are best treated with EGFR tyrosine kinase inhibitors (EGFR TKI). Identifying the EGFR mutational status on a tumor biopsy or a liquid biopsy using tumor DNA sequencing techniques is the current approach to predict tumor response on EGFR TKI therapy. However, due to difficulty in reaching tumor sites, and varying inter- and intralesional tumor heterogeneity, biopsies are not always possible or representative of all tumor lesions, highlighting the need for alternative biomarkers that predict tumor response. Positron emission tomography (PET) studies using EGFR TKI-based tracers have shown that EGFR mutational status could be identified, and that tracer uptake could potentially be used as a biomarker for tumor response. However, despite their likely predictive and monitoring value, the EGFR TKI-PET biomarkers are not yet qualified to be used in the routine clinical practice. In this review, we will discuss the currently investigated EGFR-directed PET biomarkers, elaborate on the typical biomarker development process, and describe how the advances, challenges, and opportunities of EGFR PET biomarkers relate to this process on their way to qualification for routine clinical practice.
Clinical characteristics and prognosis of 16 relapsed/refractory B-cell malignancy patients with CAR T-cell-related hyperferritinaemia
Authors: Zhou Lanlan , Yu Nanzhou , Li Tongjuan , Ji Hongyan , Jiang Lijun , Wang Di , Xu Bin , Zhou Xiaoxi
Published: October 2022

With the success of chimeric antigen receptor-modified (CAR) T-cell therapy for relapsed/refractory (r/r) B-cell malignancies, severe complications after CAR T-cell infusion have emerged as nonnegligible prognosis-related factors. However, the prognosis of patients with CAR T-cell-related hyperferritinaemia (HFA) is unclear. We report the efficacy and safety of CAR T-cell therapy in 16 r/r B-cell malignancy patients with CAR T-cell-related HFA. The rates of serum ferritin levels above 10,000 ng/ml during CAR T-cell therapy were 6.2% and 14.3% in B-cell non-Hodgkin’s lymphoma (B-NHL) and acute B lymphocyte leukemia (B-ALL), respectively. These patients were characterized by an extremely high tumor burden and a high rate of extranodal involvement. In lymphoma, the complete remission (CR) rate was 37.5% (3/8), which was lower than that in the control group with the lowest value of ferritin (CR was 87.5% (7/8), P=0.0406), and it could also be seen that the OS of the control group (1-year OS rate 100%) had a better trend than HFA group (1-year OS rate 50%). In the B-ALL patients, the OS of the control group (1-year OS rate 100%) was higher than HFA group (1-year OS rate 45%, P=0.0189), although there was no significant difference in CR rate. High-grade CRS (≥3) occurred in 56.25% of the patients, and the mortality rate was 56.25%, which was significantly higher than control group (12.5% and 12.5%, P=0.009). The peak serum ferritin level in the patients who died of CRS was significantly higher than others (P=0.0168). Regardless of whether the CAR T-related MAS diagnostic criteria were met, there was no significant difference in ORR and OS in HFA group, however patients with MAS showed a higher rate of high-grade CRS. Interestingly, in our study, glucocorticoid intervention in HFA group showed little impact on expansion of CAR-T cells, whether compared with control group or compared within HFA group by dividing patients into high and low dosage subgroups based on the median dose of glucocorticoid. High mortality was observed in patients with CAR T-cell-related HFA. Early glucocorticoid intervention might be worth trying to improve the safety of CAR T therapy in these patients.
The role of BCL-2 family proteins in regulating apoptosis and cancer therapy
Authors: Qian Shanna , Wei Zhong , Yang Wanting , Huang Jinling , Yang Yinfeng , Wang Jinghui
Published: October 2022

Apoptosis, as a very important biological process, is a response to developmental cues or cellular stress. Impaired apoptosis plays a central role in the development of cancer and also reduces the efficacy of traditional cytotoxic therapies. Members of the B-cell lymphoma 2 (BCL-2) protein family have pro- or anti-apoptotic activities and have been studied intensively over the past decade for their importance in regulating apoptosis, tumorigenesis, and cellular responses to anticancer therapy. Since the inflammatory response induced by apoptosis-induced cell death is very small, at present, the development of anticancer drugs targeting apoptosis has attracted more and more attention. Consequently, the focus of this review is to summarize the current research on the role of BCL-2 family proteins in regulating apoptosis and the development of drugs targeting BCL-2 anti-apoptotic proteins. Additionally, the mechanism of BCL-2 family proteins in regulating apoptosis was also explored. All the findings indicate the potential of BCL-2 family proteins in the therapy of cancer.
Lung ultrasound to guide the administration of exogenous pulmonary surfactant in respiratory distress syndrome of newborn infants: A retrospective investigation study
Authors: Liu Jing , Fu Wei , Qin Shen-Juan
Published: October 2022

Background

Respiratory distress syndrome (RDS) is a common disease that seriously endangers the life and safety of newborns, especially premature infants. Exogenous pulmonary surfactant (PS) is the specific agent for the treatment of neonatal RDS. Lung ultrasound (LUS) has been successfully used in the diagnosis of RDS, but its value in guiding the application of PS is still unclear. This paper explored whether the application of PS under LUS monitoring has some advantages, including (1) decreasing the misdiagnosis rate of RDS and decreasing probability of using PS, and (2) reducing the dose of PS without reducing the therapeutic effect.

Methods

This study included two parts. Part 1: To decide whether the LUS is good to differentiate RDS from other lung diseases in the premature infants. All patients who were diagnosed with RDS and required PS treatment based on conventional criteria were routinely examined by LUS. Then, according to LUS findings, we decided whether they needed to receive PS treatment. Part 2: To see the dose reduction of surfactant is applicable. In RDS patients diagnosed based on LUS presentation and treated with Curosurf (Chiesi Pharmaceutical, Parma, Italy), the dose of Curosurf was compared with that recommended by the European RDS management guidelines.

Results

(1) Since March 2017, 385 newborn infants admitted to our neonatal intensive care unit met the traditional diagnostic criteria of RDS. Of these, only 269 cases were diagnosed with RDS and needed PS treatment according to LUS manifestations. The other 116 infants who did not meet the criteria for ultrasound diagnosis of RDS did not receive PS supplementation but obtained good outcomes, that is LUS findings decreased a misdiagnosis rate of RDS by 30.1% and subsequently resulted in a 30.1% reduction in PS use. (2) Among the 269 RDS patients diagnosed based on LUS findings, 148 were treated with Curosurf (another 121 RDS infants who received domestic PS treatment were not included in the study group), and the average dose was 105.4 ± 24.3 mg/kg per time, which is significantly lower than the dose of 200 mg/kg per time recommended by the European RDS guidelines. (3) The mortality rate of RDS patients was 0%, and no patients had ventilator-associated pneumonia or bronchopulmonary dysplasia in this study.

Conclusion

LUS can decrease the misdiagnosis rate of RDS, thereby decreasing the probability of using PS and decreasing the dose of PS, and can help RDS infants to achieve better outcomes.
The thiophene α-terthienylmethanol isolated from Tagetes minuta inhibits angiogenesis by targeting protein kinase C isozymes α and β2
Authors: Llorens de los Ríos María C. , Lanza Priscila A. , Barbieri Cecilia L. , González María L. , Chabán Macarena Funes , Soria Gastón , Vera D. Mariano A. , Carpinella María C. , Joray Mariana B.
Published: October 2022

Background: Tumor angiogenesis is considered as a crucial pathologic feature of cancer with a key role in multidrug resistance (MDR). Adverse effects of the currently available drugs and the development of resistance to these remain as the hardest obstacles to defeat.

Objetive: This work explores flora from Argentina as a source of new chemical entities with antiangiogenic activity.

Methods: Tube formation assay using bovine aortic endothelial cells (BAECs) was the experiment of choice to assess antiangiogenic activity. The effect of the pure compound in cell invasiveness was investigated through the trans-well migration assay. The inhibitory effect of the pure compound on VEGFR-2 and PKC isozymes α and β2 activation was studied by molecular and massive dynamic simulations. Cytotoxicity on peripheral blood mononuclear cells and erythrocyte cells was evaluated by means of MTT and hemolysis assay, respectively. In silico prediction of pharmacological properties (ADME) and evaluation of drug-likeness features were performed using the SwissADME online tool.

Results: Among the plants screened, T. minuta, showed an outstanding effect with an IC50 of 33.6 ± 3.4 μg/ml. Bio-guided isolation yielded the terthiophene α-terthienylmethanol as its active metabolite. This compound inhibited VEGF-induced tube formation with an IC50 of 2.7 ± 0.4 μM and significantly impaired the invasiveness of bovine aortic endothelial cells (BAECs) as well as of the highly aggressive breast cancer cells, MDA-MB-231, when tested at 10 μM. Direct VEGFR-2 and PKC inhibition were both explored by means of massive molecular dynamics simulations. The results obtained validated the inhibitory effect on protein kinase C (PKC) isozymes α and β2 as the main mechanism underlying its antiangiogenic activity. α-terthienylmethanol showed no evidence of toxicity against peripheral blood mononuclear and erythrocyte cells.

Conclusion: These findings support this thiophene as a promising antiangiogenic phytochemical to fight against several types of cancer mainly those with MDR phenotype.
Potential hepatoprotective effects of Cistanche deserticola Y.C. Ma: Integrated phytochemical analysis using UPLC-Q-TOF-MS/MS, target network analysis, and experimental assessment
Authors: Wang Haichao , Li Yaying , Bian Yifei , Li Xue , Wang Yubei , Wu Ke , Liu Chuanguo , Liu Yuhong , Wang Xiaoming
Published: October 2022

Cistanche deserticola Y.C. Ma (CD) possesses hepatoprotective activity, while the active ingredients and involved mechanisms have not been fully explored. The objective of this study was to investigate the chemical composition and hepatoprotective mechanisms of CD. We primarily used ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) to identify the phenylethanoid glycoside (PhG) components of CD. Then, network analysis was used to correlate and predict the pharmacology of the identified active components of PhGs with hepatoprotection. Next, the mechanisms of the core components and targets of action were explored by cellular assays and toll-like receptor 4 (TLR4) target competition assays. Finally, its hepatoprotective effects were further validated in in vivo experiments. The results showed that a total of 34 PhGs were identified based on the UPLC-Q-TOF-MS/MS method. Echinacoside (ECH) was identified as the key ingredient, and TLR4 and nuclear factor-kappa B (NF-κB) were speculated as the core targets of the hepatoprotective effect of CD via network analysis. The cellular assays confirmed that PhGs had significant anti-inflammatory activity. In addition, the real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot indicated that ECH notably reduced the levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), as well as the mRNA expression of TLR4, TNF-α, and IL-6, and decreased the high expression of the TLR4 protein, which in turn downregulated the myeloid differentiation factor 88 (MyD88), p-P65 and TNF-α proteins in the inflammatory model. The target competition experiments suggested that ECH and LPS could competitively bind to the TLR4 receptor, thereby reducing the expression of TLR4 downstream proteins. The results of in vivo studies showed that ECH significantly ameliorated LPS-induced hepatic inflammatory infiltration and liver tissue damage and reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice. Moreover, ECH remarkably inhibited the release of inflammatory factors such as TNF-α, IL-6, IL-1β, and MCP-1 in the serum of mice, exerting the hepatoprotective effect by the TLR4/NF-κB signaling pathway. More importantly, ECH could act as a potential inhibitor of TLR4 and deserves further in-depth study. Our results could provide a basis for exploring the hepatoprotective properties of CD.
Photothermal effects of CuS-BSA nanoparticles on H22 hepatoma-bearing mice
Authors: Dun Xinyu , Liu Shuliang , Ge Nan , Liu Meng , Li Ming , Zhang Jun , Bao Hongxu , Li Benying , Zhang Hua , Cui Lianhua
Published: October 2022

The objective of this study was to evaluate the in vivo application and photothermal ablation effects and mechanism of copper sulfide nanoparticles (CuS NPs) in hepatocellular carcinoma (HCC). Sheet-like CuS-BSA NPs with a particle size of 30 nm were synthesized using bovine serum albumin (BSA) as a biological modifier, and were physically characterized. To provide a reference range for the biosafety dose of CuS-BSA NPs, 36 male Kunming mice were randomly assigned into six groups. Different one-time doses of CuS-BSA NPs were injected via tail vein injection, and the potential damages of liver, kidney and spleen were observed 14 days later. To evaluate the in vivo photothermal effect of CuS-BSA NPs, 48 male Kunming mice were used to establish the H22 hepatoma-bearing mouse model and were randomly assigned into six groups. CuS-BSA NPs (600 μg/kg) were injected via tail vein or intratumoral injection. Irradiations were performed 30 min after injection, with a 980 nm near-infrared laser (2.0 W/cm2) for 10 min once a week for 3 weeks. The results indicated that the CuS-BSA NPs had good dispersibility in three different solvents and had a strong absorption peak at 980 nm. The heating curves demonstrated that the photothermal effects of CuS-BSA NPs aqueous solution exhibited concentration dependence and power density dependence. In the in vivo experiment, when the doses of CuS-BSA NPs were in the range of 1800–7,200 μg/kg, the thymus index and spleen index of mice were not significantly different from those of the control group, and the structures of liver, kidney and spleen were intact without remarkable pathological changes. A lower dose of CuS-BSA NPs (600 μg/kg) could effectively inhibit tumor growth in H22 hepatoma-bearing mice at 980 nm NIR. Moreover, under the near-infrared laser irradiation, both in the tail vein injection group and the intratumoral injection group, a large area of necrosis in the tumor tissue, as well as the up-regulation of apoptotic proteins including cleaved caspase-3 and cleaved caspase-9 were observed. CuS-BSA NPs are promising photothermal agents in the photothermal therapy of cancer.
Numerical optimization of the extra-cavity diamond Raman laser in the multi-phonon absorption band
Authors: Shao Zhenhua , Li Bei , Chen Hongzhi , Cao Jun
Published: October 2022

The physical process of stimulated Raman scattering (SRS) in the diamond and the performance of the Raman laser in the multi-phonon absorption band of 2.5–3 μm were theoretically studied. A theoretical model for the external-cavity diamond Raman laser emitting at the waveband was built based on the Raman coupled-wave equation and boundary conditions. Raman laser output characteristics such as lasing threshold, input–output, and temporal behavior of Stokes conversion were investigated and theoretically simulated by varying the values of the length of the diamond and the transmittance of the output coupler. The numerical modeling shows that to reduce the impact of the multi-phonon absorption and obtain a higher conversion efficiency, it is necessary to appropriately increase the output coupling of the cavity. Taking the 3 μm diamond Raman laser optimization as an example, it is predicted that the conversion efficiency of 10% could be obtained with a diamond length of 1 cm, a transmittance of 69%, and a pump intensity of 1.2 GWcm−2. The theoretical model also could be used to investigate other wavelengths of the external-cavity diamond Raman laser and be helpful for the optimum design of diamond Raman lasers in the mid-infrared band.
BOARD-AI: A goal-aware modeling interface for systems engineering, combining machine learning and plan recognition
Authors: Castellanos-Paez Sandra , Hili Nicolas , Albore Alexandre , Pérez-Sanagustín Mar
Published: October 2022

Paper and pens remain the most commonly used tools by systems engineers to capture system models. They improve productivity and foster collaboration and creativity as the users do not need to conform to formal notations commonly present in Computer-Aided Systems Engineering (CASE) tools for system modeling. However, digitizing models sketched on a whiteboard into CASE tools remains a difficult and error-prone activity that requires the knowledge of tool experts. Over the past decade, switching from symbolic reasoning to machine learning has been the natural choice in many domains to improve the performance of software applications. The field of natural sketching and online recognition is no exception to the rule and most of the existing sketch recognizers rely on pre-trained sets of symbols to increase the confidence in the outcome of the recognizers. However, that performance improvement comes at the cost of trust. The lack of trust directly stems from the lack of explainability of the outcomes of the neural networks, which hinders its acceptance by systems engineering teams. A solution shall not only combine the performance and robustness but shall also earn unreserved support and trust from human users. While most of the works in the literature tip the scale in favor of performance, there is a need to better include studies on human perception into the equation to restore balance. This study presents an approach and a Human-machine interface for natural sketching that allows engineers to capture system models using interactive whiteboards. The approach combines techniques from symbolic AI and machine learning to improve performance while not compromising explainability. The key concept of the approach is to use a trained neural network to separate, upstream from the global recognition process, handwritten text from geometrical symbols, and to use the suitable technique (OCR or automated planning) to recognize text and symbols individually. Key advantages of the approach are that it does not resort to any other interaction modalities (e.g., virtual keyboards) to annotate model elements with textual properties and that the explainability of the outcomes of the modeling assistant is preserved. A user experiment validates the usability of the interface.
Defective ryanodine receptor N-terminus inter-subunit interaction is a common mechanism in neuromuscular and cardiac disorders
Authors: Zhang Yadan , Rabesahala de Meritens Camille , Beckmann Astrid , Lai F. Anthony , Zissimopoulos Spyros
Published: October 2022

The ryanodine receptor (RyR) is a homotetrameric channel mediating sarcoplasmic reticulum Ca2+ release required for skeletal and cardiac muscle contraction. Mutations in RyR1 and RyR2 lead to life-threatening malignant hyperthermia episodes and ventricular tachycardia, respectively. In this brief report, we use chemical cross-linking to demonstrate that pathogenic RyR1 R163C and RyR2 R169Q mutations reduce N-terminus domain (NTD) tetramerization. Introduction of positively-charged residues (Q168R, M399R) in the NTD-NTD inter-subunit interface normalizes RyR2-R169Q NTD tetramerization. These results indicate that perturbation of NTD-NTD inter-subunit interactions is an underlying molecular mechanism in both RyR1 and RyR2 pathophysiology. Importantly, our data provide proof of concept that stabilization of this critical RyR1/2 structure-function parameter offers clear therapeutic potential.
Alternative splicing reprogramming in fungal pathogen Sclerotinia sclerotiorum at different infection stages on Brassica napus
Authors: Cheng Xiaohui , Zhao Chuanji , Gao Lixia , Zeng Lingyi , Xu Yu , Liu Fan , Huang Junyan , Liu Lijiang , Liu Shengyi , Zhang Xiong
Published: October 2022

Alternative splicing (AS) is an important post-transcriptional mechanism promoting the diversity of transcripts and proteins to regulate various life processes in eukaryotes. Sclerotinia stem rot is a major disease of Brassica napus caused by Sclerotinia sclerotiorum, which causes severe yield loss in B. napus production worldwide. Although many transcriptome studies have been carried out on the growth, development, and infection of S. sclerotiorum, the genome-wide AS events of S. sclerotiorum remain poorly understood, particularly at the infection stage. In this study, transcriptome sequencing was performed to systematically explore the genome-scale AS events of S. sclerotiorum at five important infection stages on a susceptible oilseed rape cultivar. A total of 130 genes were predicted to be involved in AS from the S. sclerotiorum genome, among which 98 genes were differentially expressed and may be responsible for AS reprogramming for its successful infection. In addition, 641 differential alternative splicing genes (DASGs) were identified during S. sclerotiorum infection, accounting for 5.76% of all annotated S. sclerotiorum genes, and 71 DASGs were commonly found at all the five infection stages. The most dominant AS type of S. sclerotiorum was found to be retained introns or alternative 3′ splice sites. Furthermore, the resultant AS isoforms of 21 DASGs became pseudogenes, and 60 DASGs encoded different putative proteins with different domains. More importantly, 16 DASGs of S. sclerotiorum were found to have signal peptides and possibly encode putative effectors to facilitate the infection of S. sclerotiorum. Finally, about 69.27% of DASGs were found to be non-differentially expressed genes, indicating that AS serves as another important way to regulate the infection of S. sclerotiorum on plants besides the gene expression level. Taken together, this study provides a genome-wide landscape for the AS of S. sclerotiorum during infection as well as an important resource for further elucidating the pathogenic mechanisms of S. sclerotiorum.