bluuebunny/crossref_metadata_2025 huggingface dataset:
Nigeria at 62: Quagmire of malaria and the urgent need for deliberate and concerted control strategy
Authors: Oboh Mary A. , Oyebola Kolapo M. , Ajibola Olumide , Thomas Bolaji N.
Published: November 2022

Background

Sub-Saharan Africa (SSA) has disproportionately contributed the majority (95%) of all malaria cases and deaths for more than a decade (2010-2021) and Nigeria contributes the highest in global malaria cases and deaths in the last decade.

Main body

Despite several malaria control initiatives, why is Nigeria still the most endemic malaria country? Published reports have underlined possible reasons for the sustenance of malaria transmission. Malaria transmission pattern in the country is largely and remarkably heterogeneous, hence control measures must take this uniqueness into consideration when designing intervention strategies. Nigeria became 62 years post-independence on the 1st of October, 2022, therefore making positive impacts on all aspects of the country, especially in the health sector becomes imperative more than ever before. To achieve a pre-elimination malaria status, we propose the implementation of focused and calculated research strategies. Such strategies would be consciously geared towards understanding vectorial capacity, susceptibility to approved insecticides, identifying malaria hotspots, and deciphering the genetic structure and architecture of P. falciparum within and between groups and regions. This will provide insight into delineating the inter/intra-regional migration of parasite populations, amongst others.

Conclusion

With regard to malaria elimination, Nigeria still has a long way to go. There is a need for dedicated prioritization of research efforts that would provide a basic understanding of the Plasmodium parasite in circulation. Such information will support the implementation of policies that will drive down malaria transmission in Nigeria.
Remote sensing and buoy based monitoring of chlorophyll a in the Yangtze Estuary reveals nutrient-limited status dynamics: A case study of typhoon
Authors: Xu Yuying , Chen Jianyu
Published: November 2022

Nutrient concentrations and its limited statuses can affect phytoplankton community structure and marine primary productivity. Identifying limiting nutrients under different ocean conditions, the causes, and the nature of such limitations, has important implications for understanding ecosystem changes and interpretation of in situ data. However, there is still a lack of retrieval methods for nutrients in seawater, especially in coastal waters. We propose to characterize the spatiotemporal variability of phytoplankton and nutrient-limited status in the surface ocean with diurnal valuevs of chlorophyll concentration. In this paper, the sediment fronts and plume fronts are used as a reference to select the relative and absolute nutrient-limited status regions. The variance of the six times per day (9:30-14:30) is calculated to represent the diurnal variation of chlorophyll, and the diurnal variation and concentration of chlorophyll combined are used to analyze nutrient-limited status. The results indicate that the diurnal variation of chlorophyll is greater after the typhoon, and the nutrient-limited status is different following each typhoon passing by. The in situ data shows that the highest chlorophyll a concentration reached 20.7 mg/m3 after the typhoon in August 2011.
Effect of chronic ammonia nitrogen stress on the SOD activity and interferon-induced transmembrane protein 1 expression in the clam Cyclina sinensis
Authors: Ge Hongxing , Ni Qian , Liu Jialing , Dong Zhiguo , Chen Shibo
Published: November 2022

Ammonia nitrogen plays a crucial part in oxidative stress in aquatic animals. To elucidate the effect of ammonia nitrogen stress on the superoxide dismutase (SOD) activity and interferon-induced transmembrane protein 1 (IFITM1) expression in the clam Cyclina sinensis, clams were exposed to ammonia nitrogen (8.07 mg/L) for 768 h (32 days) and then challenged with Vibrio parahaemolyticus. The results showed that the SOD activity in the hepatopancreas of C. sinensis exposed to ammonia nitrogen first increased and then decreased with time, returning to the control group’s normal level at 768 h. Following infection with V. parahaemolyticus, the SOD activity in the hepatopancreas fluctuated over time. The SOD activity in clams infected with V. parahaemolyticus at 144 h did not return to the control group’s normal level. The full-length cDNA of CsIFITM1 was 2,434 bases in length, including a 2,301-bp open reading frame (ORF) encoding 714 amino acids, with a putative molecular weight of 83.86 kDa. CsIFITM1 contains an RNA helicase domain (DEXHc_RLR, DR) and a Helicase_C (HC) domain. The transcriptional levels of CsIFITM1 were upregulated by exposure to ammonia nitrogen and were significantly higher from 6 to 768 h compared to the control (0 h) (p < 0.05). Following infection with V. parahaemolyticus, the transcript levels of CsIFITM1 in the hepatopancreas were upregulated and were significantly higher from 6 to 144 h, in contrast to those of the control (0 h) (p < 0.05). The present data provide the first evidence of the SOD activity and CsIFITM1 transcript levels being able to reflect the effect of ammonia on the clam C. sinensis.
Potential roles of MEK1 on aging in Argopecten scallops
Authors: Yuan Ke , Lu Xia , Ning Junhao , Chen Min , Wang Quanchao , Liu Guilong , Xu Xin , Xu He , Wang Chunde
Published: November 2022

Dual specificity mitogen-activated protein kinase kinase 1 (MEK1) has been found to regulate aging through the Ras/Raf/MEK/ERK cascade in terrestrial animals. However, few reports have focused on MEK1 promoting aging in marine bivalves. In this study, we aimed to examine the potential roles of MEK1 in the regulation of aging in two Argopecten scallops, the bay scallop A. irradians and the Peruvian scallop A. purpuratus, which are closely related but with distinct lifespan. The complete ORFs of AiiMEK1 and ApuMEK1 were both 1209 bp, encoding 403 identical amino acids but with 41 synonymous SNPs, which may have contributed to the different activities of MEK1 in two scallops. Nutrient restriction, one of the most effective non-genetic means of promoting life span, significantly inhibit the expression of AiiMEK1 and ApuMEK1. The response in hepatopancreas of A. irradians to nutrient restriction was more persistently than that in A. purpuratus. RNAi of AiiMEK1 significantly increased the expression of its downstream genes known to favor longevity, such as FoxO and SOD, while decreased the expression of ERK1/2 and the key genes in the mTOR signaling pathway, as well as the β-GAL activity (a marker for senescence). These results indicated that AiiMEK1 may play a negative role in longevity through Ras/Raf/MEK/ERK pathway. Our results may provide new perspective for understanding of the conservative functions of MEK1 in regulation of aging in animals and benefit the genetic selection of scallops.
Nanomaterials-based vaccines to target intracellular bacterial pathogens
Authors: Files Megan A. , Kristjansson Kadin M. , Rudra Jai S. , Endsley Janice J.
Published: November 2022

Development of novel immunization approaches to combat a growing list of emerging and ancient infectious agents is a global health priority. Intensive efforts over the last several decades have identified alternative approaches to improve upon traditional vaccines that are based on live, attenuated agents, or formulations of inactivated agents with adjuvants. Rapid advances in RNA-based and other delivery systems for immunization have recently revolutionized the potential to protect populations from viral pathogens, such as SARS-CoV-2. Similar efforts to combat bacterial pathogens, especially species with an intracellular niche, have lagged significantly. In the past decade, advances in nanotechnology have yielded a variety of new antigen/adjuvant carrier systems for use in vaccine development against infectious viruses and bacteria. The tunable properties of nanomaterial-based vaccines allow for balancing immunogenicity and safety which is a key hurdle in traditional antigen and adjuvant formulations. In this review, we discuss several novel nanoparticle-based vaccine platforms that show promise for use against intracellular bacteria as demonstrated by the feasibility of construction, enhanced antigen presentation, induction of cell mediated and humoral immune responses, and improved survival outcomes in in vivo models.
Gut microbiota, pathogenic proteins and neurodegenerative diseases
Authors: Wei Wei , Wang Shixu , Xu Chongchong , Zhou Xuemei , Lian Xinqing , He Lin , Li Kuan
Published: November 2022

As the world’s population ages, neurodegenerative diseases (NDs) have brought a great burden to the world. However, effective treatment measures have not been found to alleviate the occurrence and development of NDs. Abnormal accumulation of pathogenic proteins is an important cause of NDs. Therefore, effective inhibition of the accumulation of pathogenic proteins has become a priority. As the second brain of human, the gut plays an important role in regulate emotion and cognition functions. Recent studies have reported that the disturbance of gut microbiota (GM) is closely related to accumulation of pathogenic proteins in NDs. On the one hand, pathogenic proteins directly produced by GM are transmitted from the gut to the central center via vagus nerve. On the other hand, The harmful substances produced by GM enter the peripheral circulation through intestinal barrier and cause inflammation, or cross the blood–brain barrier into the central center to cause inflammation, and cytokines produced by the central center cause the production of pathogenic proteins. These pathogenic proteins can produced by the above two aspects can cause the activation of central microglia and further lead to NDs development. In addition, certain GM and metabolites have been shown to have neuroprotective effects. Therefore, modulating GM may be a potential clinical therapeutic approach for NDs. In this review, we summarized the possible mechanism of NDs caused by abnormal accumulation of pathogenic proteins mediated by GM to induce the activation of central microglia, cause central inflammation and explore the therapeutic potential of dietary therapy and fecal microbiota transplantation (FMT) in NDs.
Production of adaptive movement patterns via an insect inspired spiking neural network central pattern generator
Authors: Steinbeck Fabian , Nowotny Thomas , Philippides Andy , Graham Paul
Published: November 2022

Navigation in ever-changing environments requires effective motor behaviors. Many insects have developed adaptive movement patterns which increase their success in achieving navigational goals. A conserved brain area in the insect brain, the Lateral Accessory Lobe, is involved in generating small scale search movements which increase the efficacy of sensory sampling. When the reliability of an essential navigational stimulus is low, searching movements are initiated whereas if the stimulus reliability is high, a targeted steering response is elicited. Thus, the network mediates an adaptive switching between motor patterns. We developed Spiking Neural Network models to explore how an insect inspired architecture could generate adaptive movements in relation to changing sensory inputs. The models are able to generate a variety of adaptive movement patterns, the majority of which are of the zig-zagging kind, as seen in a variety of insects. Furthermore, these networks are robust to noise. Because a large spread of network parameters lead to the correct movement dynamics, we conclude that the investigated network architecture is inherently well-suited to generating adaptive movement patterns.
Effects of acupuncture on the outcome of tinnitus: An overview of systematic reviews
Authors: Xu Xianpeng , Xie Hui , Liu Zifeng , Guo Tao , Zhang Ying
Published: November 2022

Background

To systematically summarize the evidence for the efficacy of acupuncture in tinnitus treatment, we assessed the methodological quality, reporting quality, and evidence quality of systematic reviews/meta-analyses (SRs/MAs) of acupuncture in the treatment of tinnitus.

Methods

From inception to March 2022, we conducted a detailed and comprehensive search of eight electronic databases in Chinese and English. The Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were used to assess methodological quality, reporting quality and evidence quality for inclusion in SRs/MAs, respectively.

Results

Fourteen published SRs/MAs met the inclusion criteria and were included in the study. Eleven studies reported that acupuncture was effective in treating tinnitus, and three studies reported that no firm conclusions could be drawn about the effectiveness of acupuncture in treating tinnitus. The results of the AMSTAR-2 assessment showed that the methodological quality of the included studies was relatively low in general, with one being moderate quality and the rest being very low quality. The PRISMA checklist evaluation results showed that no studies fully report checklists, with protocol registration and search strategies being the main reporting weaknesses. The GRADE assessment showed that no results were high-quality evidence, 17 results were moderate-quality evidence, 25 results were low-quality evidence, and 12 results were very low-quality evidence.

Conclusion

Acupuncture seems to be a positive and effective treatment for tinnitus. However, the methodological quality and quality of evidence for SRs/MAs in the included studies were generally low, and this result must be viewed with caution. Therefore, more high-quality, large-scale, multi-center randomized controlled trials are needed in the future to verify the effectiveness of acupuncture in the treatment of tinnitus.
The relationship between aesthetic preferences of people for ceramic tile design and neural responses: An event-related potential study
Authors: Chen Jiayin , Cheng Yue
Published: November 2022

Introduction

The aesthetic preferences of people can determine the success of a design and are often closely related to design features. The discovery of designs that match user preferences can provide a reference for designers. Ceramic tiles are widely used in environmental design; however, little attention has been paid to the aesthetic preferences of people for tiles. This study aimed to explore the relationship between aesthetic preferences for tile design and neural responses.

Materials and methods

In this study, two groups of tiles with different preference levels were randomly presented to 16 participants, and their electroencephalograms were recorded. The mean amplitudes of event-related potentials were analyzed by ANOVA.

Results

The results showed that: (1) the aesthetic preferences of people for tiles could modulate brain activity; (2) tiles that people liked triggered higher N100 amplitudes; and (3) tiles that people disliked triggered higher P200 and late positive potential (LPP) amplitudes.

Discussion

These results suggest that N100, P200, and LPP are significantly related to the aesthetic preferences of people for ceramic tiles. The difference in N100 and P200 amplitudes indicates that participants developed aesthetic perceptions of the tiles in the early and middle stages of vision and formed different attention allocations to tiles with varying levels of aesthetic preference; in the middle and late stages of visual processing, the difference in the LPP amplitude indicates that the impression of people for tiles is further deepened in the later stage, forming a top-down emotion-driven evaluation. Exploring the relationship between the aesthetic preferences of people and neural responses is significant in establishing objective aesthetic judgment indicators for tiles and understanding the process of aesthetic cognition. This study provides relevant information for quantitative aesthetic assessments of environmental design, interior design, and marketing involving ceramic tiles.
Resting-state electroencephalogram microstate to evaluate post-stroke rehabilitation and associate with clinical scales
Authors: Wang Zhongpeng , Liu Zhaoyang , Chen Long , Liu Shuang , Xu Minpeng , He Feng , Ming Dong
Published: November 2022

Introduction

Stroke is usually accompanied by a range of complications, like post-stroke motor disorders. So far, its evaluation of motor function is developed on clinical scales, such as Fugl-Meyer Assessment (FMA), Instrumental Activities of Daily Living (IADL), etc. These scale results from behavior and kinematic assessment are inevitably influenced by subjective factors, like the experience of patients and doctors, lacking neurological correlations and evidence.

Methods

This paper applied a microstate model based on modified k-means clustering to analyze 64-channel electroencephalogram (EEG) from 12 stroke patients and 12 healthy volunteers, respectively, to explore the feasibility of applying microstate analysis to stroke patients. We aimed at finding some possible differences between stroke and healthy individuals in resting-state EEG microstate features. We further explored the correlations between EEG microstate features and scales within the stroke group.

Results and discussion

By statistical analysis, we obtained significant differences in EEG microstate features between the stroke and healthy groups and significant correlations between microstate features and scales within the stroke group. These results might provide some neurological evidence and correlations in the perspective of EEG microstate analysis for post-stroke rehabilitation and evaluation of motor disorders. Our work suggests that microstate analysis of resting-state EEG is a promising method to assist clinical and assessment applications.
The role of [18F]FDG-PET/CT in gram-positive and gram-negative bacteraemia: A systematic review
Authors: Packham Alice , Spence Niamh , Bawa Tanveer , Srinivasan Rohit , Goodman Anna L.
Published: November 2022

Objectives

Bacteraemia is associated with significant morbidity and mortality. [18F]FDG-PET/CT is increasingly used to detect infectious metastatic foci, however there remains international variation in its use. We performed a systematic review assessing the impact of [18F]FDG-PET/CT in adult inpatients with gram-positive and Gram-negative bacteraemia.

Design

The systematic review was performed according to PRISMA guidelines. Studies published between 2009 and December 2021 were searched in MEDLINE, EMBASE and Cochrane clinical trials database. Data extraction and quality assessment was performed using ROBINS-I and GRADE.

Setting

Eligible study designs included randomised-controlled trials, clinically-controlled trials, prospective trials, retrospective trials, case-control studies, and non-controlled studies.

Participants

Studies solely assessing adult inpatients with blood-culture confirmed bacteraemia with one cohort of patients receiving [18F]FDG-PET/CT were included.

Main outcome measures

primary outcomes were mortality, identification of metastatic foci and relapse rate. Studies not examining any of the pre-specified outcomes were excluded.

Results

Ten studies were included, of which five had a non-PET/CT control arm. Overall, there was low quality of evidence that [18F]FDG-PET/CT is associated with reduced mortality, improved identification of metastatic foci and reduced relapse rate. Six studies assessed Staphylococcus aureus bacteraemia (SAB) only; nine studies included Gram-positive bacteraemia only, and one study included data from Gram-negative bacteraemia. Two studies compared outcomes between patients with different types of bacteraemia. Four studies identified a statistically significant difference in mortality in [18F]FDG-PET/CT recipients and controls. Relapse rate was significantly reduced in patients with SAB who received [18F]FDG-PET/CT. Studies identified significantly higher detection of metastatic foci in [18F]FDG-PET/CT recipients compared to controls. [18F]FDG-PET/CT was the first to identify an infectious site in 35.5% to 67.2% of overall foci identified.

Conclusions

Further research is required to establish the role of [18F]FDG-PET/CT in bacteraemia, and its impact on management and mortality.
The glucotoxicity protecting effect of honokiol in human hepatocytes via directly activating AMPK
Authors: Liu Hui , Luo Wu , Liu Jiazheng , Kang Xincong , Yan Jianming , Zhang Tingting , Yang Lan , Shen Lu , Liu Dongbo
Published: November 2022

Introduction

Sustained hyperglycemia causes glucotoxicity, which has been regarded as a contributor to hepatocyte damage in type 2 diabetes (T2D) and its metabolic comorbidities. Honokiol is a natural biphenolic component derived from the dietary supplement Magnolia officinalis extract. This study aimed to investigate the effects of honokiol on glucose metabolism disorders and oxidative stress in hepatocytes and the underlying mechanisms.

Methods

HepG2 cells were treated with glucosamines (18 mM) to induce glucotoxicity as a diabetic complication model in vitro.

Results and discussion

Honokiol significantly increased glucose consumption, elevated 2-NBDG uptake, and promoted GLUT2 translocation to the plasma membrane in glucosamine-treated HepG2 cells, indicating that honokiol ameliorates glucose metabolism disorders. Furthermore, glucosamine-induced ROS accumulation and loss of mitochondrial membrane potential were markedly reduced by honokiol, suggesting that honokiol alleviated glucotoxicity-induced oxidative stress. These effects were largely abolished by compound C, an AMPK inhibitor, suggesting an AMPK activation-dependent manner of honokiol function in promoting glucose metabolism and mitigating oxidative stress. Molecular docking results revealed that honokiol could interact with the amino acid residues (His151, Arg152, Lys243, Arg70, Lys170, and His298) in the active site of AMPK. These findings provide new insights into the antidiabetic effect of honokiol, which may be a promising agent for the prevention and treatment of T2D and associated metabolic comorbidities.
Diagnosis and treatment of ectopic thyroid carcinoma: A case report and literature review
Authors: Fu Guiming , Guo Fengli , Zhang Wei , Ruan Xianhui , Zheng Xiangqian , Wang Zhaohui , Gao Ming
Published: November 2022

Introduction

Ectopic thyroid cancer (ETC) is primary thyroid cancer occurring in ectopic thyroid tissue, and its incidence rate is approximately 0.3%–0.5% of thyroid cancer. Only approximately 132 cases of ETC have been diagnosed and treated worldwide in the past 110 years, with most of them being adults. Of note, patients with ETC are prone to misdiagnosis and mistreatment.

Case report

This was a 13-year-old adolescent female who reported having a sensation of swallowing obstruction when eating blocky foods. Color Doppler Ultrasound (CDU) found a 2.3 cm ×1.7 cm × 2.1 cm hypoechoic nodule slightly to the right of the deep surface of the tongue base, with a honeycomb shape. Meanwhile, a mixed echogenic nodule of approximately 2.0 cm × 1.9 cm × 2.3 cm was seen deep in the mouth floor, and a very low echogenic region of 1.4 cm × 1.1 cm × 1.8 cm was observed in the nodule. We then performed a fine needle aspiration biopsy (FNAB) of the thyroid nodules guided by CDU, and the results showed papillary thyroid carcinoma (PTC). Then, a local extended resection of the thyroid carcinoma was performed. Bilateral cervical IA and adjacent subhyoid lymph node dissection was performed through a small anterior cervical incision. The patient recovered well, and was discharged on the fifth day after surgery. The patient only took levothyroxine tablets for replacement therapy after surgery. The patient was followed up for 36 months, and the thyroid function remained in the normal range. Reexamination by CDU showed no tumor recurrence, lymph node enlargement, or obvious change in the tongue base ectopic thyroid.

Conclusions

ETC is an extremely rare type of thyroid cancer, which is easy to be misdiagnosed. Preoperative use of CDU, nuclide scanning, computed tomography (CT)/Magnetic resonance imaging (MRI), and FNAB can significantly reduce the misdiagnosis rate of this disease. Surgery is currently the main treatment for ETC. Complete resection still has a high cure rate. For patients with advanced ETC who cannot be completely resected, external radiotherapy and targeted therapy can be tried, but the prognosis needs to be verified with more cases in the future.
An exploratory analysis of the impact of the COVID-19 pandemic on pediatric type 1 diabetes mellitus patient outcomes: A single-center study
Authors: Rajan Raeesha , Athale Uma , Ewusie Joycelyne Efua , McAssey Karen , Thabane Lehana , Samaan M. Constantine
Published: November 2022

Background

The COVID-19 pandemic led to substantial shifts in pediatric diabetes care delivery to virtual and hybrid models. It is unclear if these changes in care delivery impacted short-term patient outcomes.

Objectives

We aimed to explore glycemic control and other diabetes-related outcomes in children living with Type 1 Diabetes Mellitus (T1DM) during the first year of the COVID-19 pandemic at a tertiary pediatric academic center in Canada.

Subjects

Patients <18 years of age with a confirmed diagnosis of T1DM for at least one year were included.

Methods

This was a retrospective chart review. We compared data from two years pre-pandemic (March 15, 2018–March 14, 2020) to the first year of the pandemic (March 15, 2020–March 14, 2021). The data assessed included glycemic control [Hemoglobin A1c (HbA1c)], diabetic ketoacidosis (DKA), hospital attendance and hospitalizations, hypoglycemia, and hyperglycemia. The generalized estimating equation (GEE) analysis was used to model potential factors affecting the HbA1c and diabetes-related morbidities. Multiple imputations were conducted as a sensitivity analysis.

Results

There were 346 eligible patients included in the study. The HbA1c remained stable during the pandemic compared to the pre-pandemic phase (MD-0.14, 95% CI, −0.28, 0.01;p = 0.058). The pandemic saw an increase in the number of newly diagnosed patients (X2 = 16.52,p < 0.001) and a higher number of newly diagnosed patients presenting in DKA (X2 = 12.94,p < 0.001). In patients with established diabetes, there was an increase in hyperglycemia (OR1.38, 95% CI, 1.12,1.71;p = 0.003) and reduced DKA (OR 0.30, 95% CI, 0.12,0.73;p = 0.009) during the pandemic compared to the pre-pandemic phase. Stable rates of hospitalization (OR0.57, 95% CI, 0.31,1.04,p = 0.068) and hypoglycemia (OR1.11, 95% CI, 0.83,1.49;p = 0.484) were noted. These results were retained in the sensitivity analysis.

Conclusions

Glycemic control in children with T1DM remained stable during the first year of the pandemic. There were more newly diagnosed patients during the pandemic compared to the pre-pandemic phase, and more of these new patients presented in DKA. The latter presentation was reduced in those with established diabetes during the same period.

Further studies are needed to assess the ongoing impact of the COVID-19 pandemic on T1DM care pathways and outcomes to allow children, families, and diabetes teams to personalize choices of care models.
Myocardial fibrosis in congenital heart disease
Authors: Gordon Blanca , González-Fernández Víctor , Dos-Subirà Laura
Published: November 2022

Myocardial fibrosis resulting from the excessive deposition of collagen fibers through the myocardium is a common histopathologic finding in a wide range of cardiovascular diseases, including congenital anomalies. Interstitial fibrosis has been identified as a major cause of myocardial dysfunction since it distorts the normal architecture of the myocardium and impairs the biological function and properties of the interstitium. This review summarizes current knowledge on the mechanisms and detrimental consequences of myocardial fibrosis in heart failure and arrhythmias, discusses the usefulness of available imaging techniques and circulating biomarkers to assess this entity and reviews the current body of evidence regarding myocardial fibrosis in the different subsets of congenital heart diseases with implications in research and treatment.
Origin, distribution, and function of three frequent coding polymorphisms in the gene for the human P2X7 ion channel
Authors: Schäfer Waldemar , Stähler Tobias , Pinto Espinoza Carolina , Danquah Welbeck , Knop Jan Hendrik , Rissiek Björn , Haag Friedrich , Koch-Nolte Friedrich
Published: November 2022

P2X7, an ion channel gated by extracellular ATP, is widely expressed on the plasma membrane of immune cells and plays important roles in inflammation and apoptosis. Several single nucleotide polymorphisms have been identified in the humanP2RX7gene. In contrast to other members of the P2X family, non-synonymous polymorphisms in P2X7 are common. Three of these occur at overall frequencies of more than 25% and affect residues in the extracellular “head”-domain of P2X7 (155 Y/H), its “lower body” (270 R/H), and its “tail” in the second transmembrane domain (348 T/A). Comparison of the P2X7 orthologues of human and other great apes indicates that the ancestral allele is Y—R—T (at 155–270–348). Interestingly, each single amino acid variant displays lower ATP-sensitivity than the ancestral allele. The originally published reference sequence of human P2X7, often referred to as “wildtype,” differs from the ancestral allele at all three positions, i.e. H—H—A. The 1,000 Genome Project determined the sequences of both alleles of 2,500 human individuals, including roughly 500 persons from each of the five major continental regions. This rich resource shows that the ancestral alleles Y155, R270, and T348 occur in all analyzed human populations, albeit at strikingly different frequencies in various subpopulations (e.g., 25%–59% for Y155, 59%–77% for R270, and 13%–47% for T348). BLAST analyses of ancient human genome sequences uncovered several homozygous carriers of variant P2X7 alleles, possibly reflecting a high degree of inbreeding, e.g., H—R—T for a 50.000 year old Neanderthal, H—R—A for a 24.000 year old Siberian, and Y—R—A for a 7,000 year old mesolithic European. In contrast, most present-day individuals co-express two copies of P2X7 that differ in one or more amino acids at positions 155, 270, and 348. Our results improve the understanding of how P2X7 structure affects its function and suggest the importance of considering P2X7 variants of participants when designing clinical trials targeting P2X7.
Enhanced tumor penetration for efficient chemotherapy by a magnetothermally sensitive micelle combined with magnetic targeting and magnetic hyperthermia
Authors: Wang Yu , Wang Rui , Chen Lixin , Chen Lili , Zheng Yi , Xin Yuanrong , Zhou Xiqiu , Song Xiaoyun , Zheng Jinzhou
Published: November 2022

The high accumulation and poor penetration of nanocarriers in tumor is a contradiction of nanomedicine, which reduces the efficacy of chemotherapy. Due to the positive effect of hyperthermia on in vivo drug diffusion, we designed a magnetothermally sensitive micelle (MTM) by integrating magnetic targeting (MT), magnetic hyperthermia (MH), and magnetothermally responsive drug release to facilitate simultaneous drug accumulation and penetration in tumor. Accordingly, we synthesized a cyanine7-modified thermosensitive polymer with phase transition at 42.3°C, and utilized it to prepare drug-loaded MTMs by encapsulating superparamagnetic MnFe2O4 nanoparticles and doxorubicin (DOX). The obtained DOX–MTM had not only high contents of DOX (9.1%) and MnFe2O4 (38.7%), but also some advantages such as superparamagnetism, high saturation magnetization, excellent magnetocaloric effect, and magnetothermal-dependent drug release. Therefore, DOX–MTM improved in vitro DOX cytotoxicity by enhancing DOX endocytosis under the assistance of MH. Furthermore, MT and MH enhanced in vivo DOX–MTM accumulation and DOX penetration in tumor, respectively, substantially inhibiting tumor growth (84%) with excellent biosafety. These results indicate the development of an optimized drug delivery system with MH and MH-dependent drug release, introducing a feasible strategy to enhance the application of nanomedicines in tumor chemotherapy.
Exploring the pharmacological mechanisms of icaritin against nasopharyngeal carcinoma via network pharmacology and experimental validation
Authors: Liu Minglu , Hu Tong , Gou Wenfeng , Chang Huajie , Li Yanli , Li Yiliang , Zuo Daiying , Hou Wenbin , Jiao Shunchang
Published: November 2022

Background: Icaritin is a natural product with a wide range of anti-tumor effects. However, its anti-tumor mechanism has not been thoroughly studied. This study examined the inhibitory effect of icaritin on nasopharyngeal cancer and its underlying mechanism using network pharmacology along with in vivo and in vitro experiments.

Methods: MTT and clone formation assays were used to detect the effects of icaritin on the viability and proliferation of nasopharyngeal carcinoma cells, followed by the construction of a HONE1 xenograft tumor model to evaluate the anti-tumor efficacy of icaritin in vivo. A public database was used to predict prospective targets, built a protein-protein interaction (PPI) network, and analyze gene enrichment and biological processes. Based on network pharmacological data, cell cycle-related proteins were identified using western blotting. Besides, cell cycle distribution, apoptosis, and intracellular reactive oxygen species (ROS) generation were identified using flow cytometry. In addition, SA-β-Gal staining was performed to detect cellular senescence, and western blotting was performed to detect the expression of P53, P21, and other proteins to verify key signaling pathways.

Results: Icaritin effectively inhibited the viability and proliferation of nasopharyngeal carcinoma cell lines and showed good anti-tumor activity against HONE1 nasopharyngeal carcinoma cells in vivo. Key protein targets, including AKT1, HSP90AA1, CDK4, CCND1, and EGFR, were screened using PPI network topology analysis. GO and KEGG analysis revealed that the cell cycle, p53 signaling, and cell senescence pathways may be the main regulatory pathways. Flow cytometry and western blot experiments showed that icaritin caused S-phase arrest and promoted an increase in ROS. SA-β-Gal staining showed that icaritin significantly induced cellular senescence, and western blotting showed that the expression of senescence-related proteins p53 and P21 increased significantly. Moreover, inhibition of ROS levels by N-Acetylcysteine (NAC) enhanced cell viability, reversed cellular senescence and reduced cellular senescence-associated protein expression.

Conclusion: The results of network pharmacological analysis and in vivo and in vitro experiments showed that icaritin effectively inhibited the growth of nasopharyngeal carcinoma cells, promoted ROS production, induced cellular senescence, and inhibited tumor cells, which are related to the regulation of P53/P21 signal pathway.
The risk assessment of landslide hazards in the Badong section of Three Gorges using the variable fuzzy set theory
Authors: Li Y. , Wang Y. H. , Wu Q. H. , Gu X. B.
Published: November 2022

The risk assessment of landslide hazards has a tremendous influence on people’s lives and property safety; therefore, its investigation is significant. The stratigraphic lithology, degree of weathering, relationship between the structural plane and slope direction, cohesive force, angle of internal friction, severity, average slope degree, height of slope, and type of landslide are adopted as the evaluation factors first. Second, an assessment model is developed based on the variable fuzzy set theory. In addition, the proposed model is utilized to assess the landslide hazards in the Badong section of Three Georges in China. Finally, the results demonstrate that the results derived from the proposed model are consistent with the current specifications; the accuracy rate reaches 83%. The method can determine the risk level of landslide hazards and provide an alternative scheme. Hence, this study can accurately present a new approach for assessing landslide hazards in the future.
Design of quasi-phase-matching nonlinear crystals based on quantum computing
Authors: Zheng Zihua , Yang Sijie , Reid Derryck T. , Wei Zhiyi , Sun Jinghua
Published: November 2022

Quasi-phase-matching (QPM) makes it possible to design domain engineered nonlinear crystals for highly efficient and multitasking nonlinear frequency conversion. However, finding the optimal crystal domain arrangement in a meaningful time is very challenging sometimes impossible by classical computing. In this paper, we proposed a quantum annealing computing method and used D-Wave superconducting quantum computer to design aperiodically poled lithium niobate (APPLN) for coupled third harmonic generation (CTHG). We converted the optical transformation efficiency function to an Ising model which can be solved by D-Wave quantum computer. The crystal design results were simulated by using nonlinear envelope equation (NEE), which showed very similar conversion efficiencies to the crystals designed by using simulated annealing (SA) method, demonstrating that quantum annealing computing is a powerful method for QPM crystal design.
Temperature modulates systemic and central actions of thyroid hormones on BAT thermogenesis
Authors: Rial-Pensado Eva , Rivas-Limeres Verónica , Grijota-Martínez Carmen , Rodríguez-Díaz Amanda , Capelli Valentina , Barca-Mayo Olga , Nogueiras Rubén , Mittag Jens , Diéguez Carlos , López Miguel
Published: November 2022

Thyroid hormones (THs) play a major role regulating energy balance and brown adipose tissue (BAT) thermogenesis, as well as body temperature, as shown in hyperthyroid patients. However, the current landscape of preclinical thyroid hormone models is complex. For example, while rats become catabolic after TH administration, mice gain weight; so, these differences in species need to be analyzed in detail and specially whether temperature could be a factor. Here, we aimed to investigate the effect of environmental temperature on those actions. Rats were subcutaneously treated with L-thyroxine (T4) or stereotaxically within the ventromedial nucleus of the hypothalamus (VMH) with triiodothyronine (T3) and housed at 23°C, 4°C or 30°C; energy balance, BAT thermogenesis and AMP-activated protein kinase (AMPK) in the VMH were analyzed. Our data showed that the effect of both systemic T4 of central T3 on energy balance and BAT thermogenesis was dependent upon environmental temperature. This evidence is of interest in the design of experimental settings highlighting the species-specific metabolic actions of THs, and in understanding its physiological role in the adaptation to temperature.
A deep learning based framework for the classification of multi- class capsule gastroscope image in gastroenterologic diagnosis
Authors: Xiao Ping , Pan Yuhang , Cai Feiyue , Tu Haoran , Liu Junru , Yang Xuemei , Liang Huanling , Zou Xueqing , Yang Li , Duan Jueni , Xv Long , Feng Lijuan , Liu Zhenyu , Qian Yun , Meng Yu , Du Jingfeng , Mei Xi , Lou Ting , Yin Xiaoxv , Tan Zhen
Published: November 2022

Purpose: The purpose of this paper is to develop a method to automatic classify capsule gastroscope image into three categories to prevent high-risk factors for carcinogenesis, such as atrophic gastritis (AG). The purpose of this research work is to develop a deep learning framework based on transfer learning to classify capsule gastroscope image into three categories: normal gastroscopic image, chronic erosive gastritis images, and ulcer gastric image.

Method: In this research work, we proposed deep learning framework based on transfer learning to classify capsule gastroscope image into three categories: normal gastroscopic image, chronic erosive gastritis images, and ulcer gastric image. We used VGG- 16, ResNet-50, and Inception V3 pre-trained models, fine-tuned them and adjust hyperparameters according to our classification problem.

Results: A dataset containing 380 images was collected for each capsule gastroscope image category, and divided into training set and test set in a ratio of 70%, and 30% respectively, and then based on the dataset, three methods, including as VGG- 16, ResNet-50, and Inception v3 are used. We achieved highest accuracy of 94.80% by using VGG- 16 to diagnose and classify capsule gastroscopic images into three categories: normal gastroscopic image, chronic erosive gastritis images, and ulcer gastric image. Our proposed approach classified capsule gastroscope image with respectable specificity and accuracy.

Conclusion: The primary technique and industry standard for diagnosing and treating numerous stomach problems is gastroscopy. Capsule gastroscope is a new screening tool for gastric diseases. However, a number of elements, including image quality of capsule endoscopy, the doctors’ experience and fatigue, limit its effectiveness. Early identification is necessary for high-risk factors for carcinogenesis, such as atrophic gastritis (AG). Our suggested framework will help prevent incorrect diagnoses brought on by low image quality, individual experience, and inadequate gastroscopy inspection coverage, among other factors. As a result, the suggested approach will raise the standard of gastroscopy. Deep learning has great potential in gastritis image classification for assisting with achieving accurate diagnoses after endoscopic procedures.
Understanding plant–microbe interaction of rice and soybean with two contrasting diazotrophic bacteria through comparative transcriptome analysis
Authors: Saini Manish Ranjan , Chandran Latha P. , Barbadikar Kalyani Makarand , Sevanthi Amitha Mithra V. , Chawla Gautam , Kaushik Megha , Mulani Ekta , Phule Amol Sarjerao , Govindannagari Rajani , Sonth Bandeppa , Sinha Subodh Kumar , Sundaram Raman Meenakshi , Mandal Pranab Kumar
Published: November 2022

Understanding the beneficial plant–microbe interactions is becoming extremely critical for deploying microbes imparting plant fitness and achieving sustainability in agriculture. Diazotrophic bacteria have the unique ability to survive without external sources of nitrogen and simultaneously promote host plant growth, but the mechanisms of endophytic interaction in cereals and legumes have not been studied extensively. We have studied the early interaction of two diazotrophic bacteria, Gluconacetobacter diazotrophicus (GAB) and Bradyrhizobium japonicum (BRH), in 15-day-old seedlings of rice and soybean up to 120 h after inoculation (hai) under low-nitrogen medium. Root colonization of GAB in rice was higher than that of BRH, and BRH colonization was higher in soybean roots as observed from the scanning electron microscopy at 120 hai. Peroxidase enzyme was significantly higher at 24 hai but thereafter was reduced sharply in soybean and gradually in rice. The roots of rice and soybean inoculated with GAB and BRH harvested from five time points were pooled, and transcriptome analysis was executed along with control. Two pathways, “Plant pathogen interaction” and “MAPK signaling,” were specific to Rice-Gluconacetobacter (RG), whereas the pathways related to nitrogen metabolism and plant hormone signaling were specific to Rice-Bradyrhizobium (RB) in rice. Comparative transcriptome analysis of the root tissues revealed that several plant–diazotroph-specific differentially expressed genes (DEGs) and metabolic pathways of plant–diazotroph-specific transcripts, viz., chitinase, brassinosteroid, auxin, Myeloblastosis (MYB), nodulin, and nitrate transporter (NRT), were common in all plant–diazotroph combinations; three transcripts, viz., nitrate transport accessory protein (NAR), thaumatin, and thionin, were exclusive in rice and another three transcripts, viz., NAC (NAM: no apical meristem, ATAF: Arabidopsis thaliana activating factor, and CUC: cup-shaped cotyledon), ABA (abscisic acid), and ammonium transporter, were exclusive in soybean. Differential expression of these transcripts and reduction in pathogenesis-related (PR) protein expression show the early interaction. Based on the interaction, it can be inferred that the compatibility of rice and soybean is more with GAB and BRH, respectively. We propose that rice is unable to identify the diazotroph as a beneficial microorganism or a pathogen from an early response. So, it expressed the hypersensitivity-related transcripts along with PR proteins. The molecular mechanism of diazotrophic associations of GAB and BRH with rice vis-à-vis soybean will shed light on the basic understanding of host responses to beneficial microorganisms.
Seed size, endosperm and germination variation in sexual and apomictic Boechera
Authors: Paczesniak Dorota , Pellino Marco , Goertzen Richard , Guenter Devan , Jahnke Siegfried , Fischbach Andreas , Lovell John T. , Sharbel Timothy F.
Published: November 2022

Asexual reproduction results in offspring that are genetically identical to the mother. Among apomictic plants (reproducing asexually through seeds) many require paternal genetic contribution for proper endosperm development (pseudogamous endosperm). We examined phenotypic diversity in seed traits using a diverse panel of sexual and apomictic accessions from the genus Boechera. While genetic uniformity resulting from asexual reproduction is expected to reduce phenotypic diversity in seeds produced by apomictic individuals, pseudogamous endosperm, variable endosperm ploidy, and the deviations from 2:1 maternal:paternal genome ratio in endosperm can all contribute to increased phenotypic diversity among apomictic offspring. We characterized seed size variation in 64 diploid sexual and apomictic (diploid and triploid) Boechera lineages. In order to find out whether individual seed size was related to endosperm ploidy we performed individual seed measurements (projected area and mass) using the phenoSeeder robot system and flow cytometric seed screen. In order to test whether individual seed size had an effect on resulting fitness we performed a controlled growth experiment and recorded seedling life history traits (germination success, germination timing, and root growth rate). Seeds with triploid embryos were 33% larger than those with diploid embryos, but no average size difference was found between sexual and apomictic groups. We identified a maternal effect whereby chloroplast lineage 2 had 30% larger seeds than lineage 3, despite having broad and mostly overlapping geographic ranges. Apomictic seeds were not more uniform in size than sexual seeds, despite genetic uniformity of the maternal gametophyte in the former. Among specific embryo/endosperm ploidy combinations, seeds with tetraploid (automomous) endosperm were on average smaller, and the proportion of such seeds was highest in apomicts. Larger seeds germinated more quickly than small seeds, and lead to higher rates of root growth in young seedlings. Seed mass is under balancing selection in Boechera, and it is an important predictor of several traits, including germination probability and timing, root growth rates, and developmental abnormalities in apomictic accessions.