bluuebunny/crossref_metadata_2025 huggingface dataset:
Explaining the polarized macrophage pool during murine allergic lung inflammation
Authors: Draijer Christina , Florez-Sampedro Laura , Reker-Smit Catharina , Post Eduard , van Dijk Fransien , Melgert Barbro N.
Published: December 2022

Introduction

Differentially polarized macrophages, especially YM1+ and MHCII+ macrophages, play an important role in asthma development. The origin of these polarized macrophages has not been elucidated yet. We therefore aimed to investigate how proliferation, monocyte recruitment, and/or switching of polarization states contribute to this specific pool of polarized interstitial and alveolar macrophages during development of house dust mite (HDM)-induced allergic lung inflammation in mice.

Methods

Male and female mice were first treated intranasally with PKH26 to label lung-resident macrophages and were then exposed to either HDM or phosphate-buffered saline (PBS) for two weeks. Different myeloid immune cell types were quantified in lung tissue and blood using flow cytometry.

Results

We found that macrophage polarization only starts up in the second week of HDM exposures. Before this happened, unpolarized alveolar and interstitial macrophages transiently increased in HDM-exposed mice. This transient increase was mostly local proliferation of alveolar macrophages, while interstitial macrophages also contained unlabeled macrophages suggesting monocyte contribution. After two weeks of exposures, the number of interstitial and alveolar macrophages was similar between HDM and PBS-exposed mice, but the distribution of polarization states was remarkably different. HDM-exposed mice selectively developed YM1+ alveolar macrophages and MHCII-hi interstitial macrophages while nonpolarized macrophages were lost compared to PBS-exposed mice.

Discussion

In this HDM model we have shown that development of a polarized macrophage pool during allergic inflammation is first dependent on proliferation of nonpolarized tissue-resident macrophages with some help of infiltrating unlabeled cells, presumably circulating monocytes. These nonpolarized macrophages then acquire their polarized phenotype by upregulating YM1 on alveolar macrophages and MHCII on interstitial macrophages. This novel information will help us to better understand the role of macrophages in asthma and designing therapeutic strategies targeting macrophage functions.
A novel ganglioside-related risk signature can reveal the distinct immune landscape of neuroblastoma and predict the immunotherapeutic response
Authors: Yang Jiaxing , Han Lei , Sha Yongliang , Jin Yan , Li Zhongyuan , Gong Baocheng , Li Jie , Liu Yun , Wang Yangyang , Zhao Qiang
Published: December 2022

Introduction

Gangliosides play an essential role in cancer development and progression. However, the involvement of gangliosides in the prognosis and tumor microenvironment (TME) of neuroblastoma is not entirely understood.

Methods

Consensus clustering analysis was performed to identify ganglioside-mediated molecular subtypes. LASSO-Cox analysis was conducted to identify independent prognostic genes, and a novel risk signature was constructed. The risk signature was validated internally and externally. We further explored the independent prognosis value, immune landscape, drug susceptibility, and tumor dedifferentiation of the risk signature. The role of the signature gene B3GALT4 in neuroblastoma was explored in vitro.

Results

Seventeen ganglioside-related genes were differentially expressed between INSS stage 4 and other stages, and two ganglioside-related clusters with distinct prognoses were identified. A novel risk signature integrating ten ganglioside-related prognostic genes was established. Across the train set and external validation sets, the risk signature presented high predictive accuracy and discrimination. The risk signature was an independent prognostic factor and constructed a nomogram combining multiple clinical characteristics. In the high-score group, the deficiency in antigen processing and presenting machinery, lack of immune cell infiltration, and escaping NK cells contributed substantially to immune escape. The low-score group was more responsive to immune checkpoint blockade therapy, while the high-score group showed substantial sensitivity to multiple chemotherapeutic drugs. Besides, the risk score was significantly positively correlated with the stemness index and reduced considerably in all-trans retinoic acid-treated neuroblastoma cell lines, indicating high dedifferentiation in the high-score group. Additionally, neuroblastoma cells with downregulation of B3GALT4 present with increased proliferation, invasion, and metastasis abilities in vitro.

Conclusion

The novel ganglioside-related risk signature highlights the role of ganglioside in neuroblastoma prognosis and immune landscape and helps optimize chemotherapy and immunotherapy for neuroblastoma.
Topical Skullcapflavone II attenuates atopic dermatitis in a mouse model by directly inhibiting associated cytokines in different cell types
Authors: Lee Youngae , Oh Jang-Hee , Li Na , Jang Hyun-Jae , Ahn Kyung-Seop , Oh Sei-Ryang , Lee Dong Hun , Chung Jin Ho
Published: December 2022

Skullcapflavone II (SFII), a flavonoid derived from Scutellaria baicalensis, is an anticancer agent. We aimed to validate SFII for atopic dermatitis (AD) therapy by demonstrating the anti-inflammatory effects of SFII in an AD mouse model produced by the topical application of the vitamin D3 analog MC903. We showed that topical treatment with SFII significantly suppressed MC903-induced serum IgE levels compared with topical hydrocortisone (HC) treatment. Topical SFII also prevents MC903-induced pruritus, skin hyperplasia, and inflammatory immune cell infiltration into lesional skin comparable to topical HC. In addition, MC903-induced immune cell chemoattractants and AD-associated cytokine production in skin lesions were effectively suppressed by topical SFII. The production of MC903-induced effector cytokines influencing T helper (Th)2 and Th17 polarization in lesioned skin is significantly inhibited by topical SFII. Furthermore, we showed that SFII can directly inhibit the production of AD-associated cytokines by human primary keratinocytes, mouse bone marrow-derived cells (BMDCs), and mouse CD4+ T cells in vitro. Lastly, we demonstrated that topical SFII more effectively suppressed serum IgE levels, the production of IL-4 and thymic stromal lymphopoietin (TSLP), and infiltration of CD4+ T cells and Gr-1+ cells (neutrophils) into lesion skin compared to topical baicalein (a flavonoid derived from Scutellaria baicalensis), which has anti-inflammatory effects. Taken together, our findings suggest that SFII may have promising therapeutic potential for this complex disease via the regulation of multiple AD-associated targets.
The HLA class-II immunopeptidomes of AAV capsids proteins
Authors: Brito-Sierra Carlos A. , Lannan Megan B. , Siegel Robert W. , Malherbe Laurent P.
Published: December 2022

Introduction

Gene therapies are using Adeno-associated viruses (AAVs) as vectors, but immune responses against the capsids pose challenges to their efficiency and safety. Helper T cell recognition of capsid-derived peptides bound to human leukocyte antigen (HLA) class II molecules is an essential step in the AAV-specific adaptive immunity.

Methods

Using MHC-associated peptide proteomics, we identified the HLA-DR and HLA-DQ immunopeptidomes of the capsid proteins of three different AAV serotypes (AAV2, AAV6, and AAV9) from a panel of healthy donors selected to represent a majority of allele usage.

Results

The identified sequences span the capsids of all serotypes, with AAV2 having the highest peptide count. For all the serotypes, multiple promiscuous peptides were identified and displayed by both HLA-DR and -DQ. However, despite high sequence homology, there were few identical peptides among AAV2, AAV6, and AAV9 immunopeptidomes, and none were promiscuous.

Discussion

Results from this work represent a comprehensive immunopeptidomics research of potential CD4+ T cell epitopes and provide the basis for immunosurveillance efforts for safer and more efficient AAV-based gene therapies.
Obeticholic acid and 5β-cholanic acid 3 exhibit anti-tumor effects on liver cancer through CXCL16/CXCR6 pathway
Authors: Gou Haoxian , Liu Shenglu , Liu Linxin , Luo Ming , Qin Shu , He Kai , Yang Xiaoli
Published: December 2022

Hepatocellular carcinoma (HCC) is the most common type of liver malignancy with a high incidence and mortality rate. Previous in vitro and in vivo studies have confirmed that liver sinusoidal endothelial cells (LSEC) secrete CXCL16, which acts as a messenger to increase the hepatic accumulation of CXCR6+ natural killer T (NKT) cells and exert potent antitumor effects. However, evidence for this process in humans is lacking and its clinical significance is still unclear. In this study, by dissecting the human HCC single-cell RNA-seq data, we verified this process through cellphoneDB. NKT cells in patients with high expression of CXCL16 exhibited a higher activation state and produced more interferon-γ (IFN-γ) compared with those with low expression. We next investigated the signaling pathways between activated (CD69 high) and unactivated NKT cells (CD69 low) using NKT cell-developmental trajectories and functional enrichment analyses. In vivo experiments, we found that farnesoid X receptor agonist (obeticholic acid) combined with the takeda G protein coupled receptor 5 antagonist (5β-cholanic acid 3) exhibited significant tumor suppressive effects in the orthotopic liver tumor model and this result may be related to the CXCL16/CXCR6 axis. In conclusion, our study provides the basis and potential strategies for HCC immunotherapy based on NKT cells.
Prevalence, antibiotic and heavy metal resistance of Vibrio spp. isolated from the clam Meretrix meretrix at different ages in Geligang, Liaohe estuary in China
Authors: Su Jie , Zhang Yingxue , Hu Tian , Ming Hongxia , Xie Yuyang , Jin Yuan , Shi Tingting , Fan Jingfeng
Published: December 2022

Vibrio as one of the main pathogens of shellfish diseases can cause serious human seafoodborne gastroenteritis and even death. In this study, we analyzed the bacterial communities from the clam, and compared the resistance phenotypes and genotypes of Vibrio spp. from Meretrix meretrix at different growth stages. High-throughput sequencing analysis revealed the predominance of Proteobacteria (50%) in the bacterial community and Vibrio was one of the dominant genera in the clam hepatopancreas in the summer. Vibrio abundance in Meretrix meretrix positively correlated with the water temperature (p<0.05). A total of 73 Vibrio isolates from Meretrix meretrix were classified into 19 species and the dominant strains included V. mediterranei (19%) and V. harveyi (11%), V. algolyticus (10%), and V. parahaemolyticus (8%). The species and abundance of Vibrio spp. were the highest in the 3-year-old of Meretrix meretrix compared with clams of other ages in the summer. Among the 73 isolates, 68 Vibrio strains were resistant to other 15 antibiotics except for sulfamethoxazole-trimethoprim with 57 resistant phenotypes. The most prevalent resistance was toward clindamycin (76%), followed by amikacin (63%), ampicillin (62%), rifampicin (62%), vancomycin (57%), and amoxicillin (50%). The ARI values of Vibrio spp. in different ages ranged from 0.13 to 0.18, and ARI values of 3-year-old (ARI=0.18) clams are higher than that of other ages clam. Approximately 72% of the resistant isolates showed multidrug-resistant phenotypes with maximum resistance to 15 antibiotics. Tolerance to heavy metals including Cd, Zn, and Cu was detected in the majority of antibiotic resistant isolates. In addition to the co-resistance to the same class of antibiotics, resistance to cephalosporin (CFP, CEP, CZ) were significantly correlated with penicillins (AMP, AMC) (p< 0.01), tetracycline (p < 0.001), sulfanilamide (SXT) (p< 0.01) and quinolone (CIP) (p< 0.01). The heavy metal resistance genes copB and nccA were significantly correlated with the clindamycin resistance phenotype (p<0.01). This study revealed that the habitat of Meretrix meretrix is in low exposure to antibiotics, and a link between heavy metal resistance genes and antibiotic resistance.
Application of anticorrosive materials in cement slurry: Progress and prospect
Authors: Zhang Yihang , Wen Jiaxin , Yin Xuejiao , Zhang Xin
Published: December 2022

During gas well cementing operation, the erosion of acidic formation corrosive medium will destroy the cementation between the cement slurry and the sidewall in the well sealing section, reduce the mechanical properties of the cement paste, cause problems such as sidewall collapse and casing damage, seriously endanger the normal exploitation of oil and gas resources, and cause major safety accidents. Therefore, improving the corrosion resistance of cement paste is the key to ensuring long-term stable cementing of high-temperature sour gas wells. This paper summarizes the influencing factors, corrosion mechanism, corrosion test methods and research status of anti-corrosion oil well cement additives, discusses the advantages and disadvantages of each anti-corrosion additive, summarizes the latest progress and challenges of anti-corrosion oil well cement, and aims to provide some reference for researchers in related fields.
Case report: Eosinophilic fasciitis induced by pembrolizumab with high FDG uptake on 18F-FDG-PET/CT
Authors: Amrane Karim , Le Meur Coline , Thuillier Philippe , Alemany Pierre , Niel Clémence , Renault David , Abgral Ronan
Published: December 2022

Eosinophilic fasciitis (EF) is a rare connective tissue disorder causing inflammation and fibrosing of fascia. In this study, we present a very rare case of an immune checkpoint inhibitor (ICI)-induced EF revealed by 18F-fluorodesoxyglucose positron emission tomography (FDG-PET/CT) 20 months after the initiation of Pembrolizumab treatment of a relapsed non-small cell lung cancer (NSCLC). This study presents a 52-year-old Caucasian woman clinically presenting asthenia, inflammatory muscle, and joint pain associated with subcutaneous nodules and symmetrical edema of the lower limbs. Iterative 18FDG-PET/CT scans allow us to guide the therapeutic strategy due to this atypical ICI adverse event.
Sex differences in the progression of cerebral microbleeds in patients with concomitant cerebral small vessel disease
Authors: Yoon Cindy W. , Rha Joung-Ho , Park Hee-Kwon , Park Soo-Hyun , Kwon Soonwook , Kim Byeong C. , Youn Young Chul , Jeong Jee Hyang , Han Hyun Jeong , Choi Seong Hye
Published: December 2022

Background and purpose

Sex differences in cerebral microbleeds (CMBs) are not well-known. We aimed to assess the impact of sex on the progression of CMBs.

Methods

The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Out of 256 subjects, 189 participants with a follow-up brain scan were included in the analysis. The linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between men and women.

Results

A total of 65 men and 124 women were analyzed. There were no significant differences in the prevalence (70.8 vs. 71.8%; P = 1.000) and the median [interquartile range (IQR)] number of total CMBs [1 (0–7) vs. 2 (0–7); P = 0.810] at baseline between men and women. The median (IQR) increase over 2 years in the number of CMBs was statistically higher in women than in men [1 (0–2) vs. 0 (0–1), P = 0.026]. The multivariate linear mixed-effects model showed that women had a significantly greater increase in the number of total, deep, and lobar CMBs compared to men after adjusting for age and the baseline number of CMBs [estimated log-transformed mean of difference between women and men: 0.040 (P = 0.028) for total CMBs, 0.037 (P = 0.047) for deep CMBs, and 0.047 (P = 0.009) for lobar CMBs].

Conclusion

The progression of CMB over 2 years was significantly greater in women than in men.
Multiparametric magnetic resonance imaging-derived deep learning network to determine ferroptosis-related gene signatures in gliomas
Authors: Zuo Zhichao , Liu Wen , Zeng Ying , Fan Xiaohong , Li Li , Chen Jing , Zhou Xiao , Jiang Yihong , Yang Xiuqi , Feng Yujie , Lu Yixin
Published: December 2022

Introduction

Ferroptosis-related gene (FRG) signature is important for assessing novel therapeutic approaches and prognosis in glioma. We trained a deep learning network for determining FRG signatures using multiparametric magnetic resonance imaging (MRI).

Methods

FRGs of patients with glioma were acquired from public databases. FRG-related risk score stratifying prognosis was developed from The Cancer Genome Atlas (TCGA) and validated using the Chinese Glioma Genome Atlas. Multiparametric MRI-derived glioma images and the corresponding genomic information were obtained for 122 cases from TCGA and The Cancer Imaging Archive. The deep learning network was trained using 3D-Resnet, and threefold cross-validation was performed to evaluate the predictive performance.

Results

The FRG-related risk score was associated with poor clinicopathological features and had a high predictive value for glioma prognosis. Based on the FRG-related risk score, patients with glioma were successfully classified into two subgroups (28 and 94 in the high- and low-risk groups, respectively). The deep learning networks TC (enhancing tumor and non-enhancing portion of the tumor core) mask achieved an average cross-validation accuracy of 0.842 and an average AUC of 0.781, while the deep learning networks WT (whole tumor and peritumoral edema) mask achieved an average cross-validation accuracy of 0.825 and an average AUC of 0.781.

Discussion

Our findings indicate that FRG signature is a prognostic indicator of glioma. In addition, we developed a deep learning network that has high classification accuracy in automatically determining FRG signatures, which may be an important step toward the clinical translation of novel therapeutic approaches and prognosis of glioma.
A multicenter randomized trials to compare the bioequivalence and safety of a generic doxorubicin hydrochloride liposome injection with Caelyx ® in advanced breast cancer
Authors: Li Yinjuan , Qi Lu , Wang Yu , Li Yan , Lei Chunpu , Zhang Yingjuan , Cheng Xiaoqiang , Liu Ju , Bai HaiHong , Zhao Xia , Lv Shuzhen , Xiong Bingjun , Liu Juan , Shi Yehui , Zhou Huan , Li Hongtao , Liu Lihong , Jiang Hongchuan , Ouyang Weiwei , Li Xiaowen , Li Yanping , Wang Xinghe
Published: December 2022

Purpose

To compare the pharmacokinetic (PK) bioequivalence (BE) and safety of a generic pegylated liposomal doxorubicin (PLD) formulation with the reference product Caelyx®.

Methods

A multicenter, single-dose, open-label, randomized, two-way crossover study was conducted in patients with breast cancer. For each period, the patients were administered with the test or the reference PLD intravenously at a dose of 50 mg/m2. Cmax, AUC0−t and AUC0−∞ for free, and encapsulated doxorubicin (doxorubicin) and partial AUC (AUC0−48h, AUC48h−t) for encapsulated doxorubicin were evaluated in 17 blood samples taken predose, and increasing time intervals over the following 14 days in each period. A washout period of 28-35 days was observed before crossing over.

Results

48 patients were enrolled and randomised, of which 44 were included and analysed in bioequivalence set (BES). The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of Cmax, AUC0−t and AUC0−∞ for free doxorubicin and encapsulated doxorubicin all fall within the bioequivalent range of 80% to 125%. The 90% CIs of GMR of partial AUC (AUC0−48h, AUC48h−t) for encapsulated doxorubicin also fall within the bioequivalent range. 48 patients were all included in the safety set (SS). The incidence of treatment-emergent adverse events (TEAEs) related to T and R was 95.8% (46/48) and 97.8% (45/46) respectively. The highest incidence of TEAEs was various laboratory abnormalities. 2 patients withdrew due to T-drug-related AEs. Only one patient experienced serious adverse events and no death occurred in this study. There were no significant differences between the safety profiles of the generic formulation and Caelyx®.

Conclusions

Bioequivalence between the test and the reference products was established for free and encapsulated doxorubicin.

Clinical trial registration

http://www.chinadrugtrials.org.cn, identifier [CTR20210375].
Risk factors and prediction model of level II lymph node metastasis in papillary thyroid carcinoma
Authors: Huang Chun , Hu Daixing , Zhuang Yuchen , Su Xinliang
Published: December 2022

Introduction

Surgical management of lateral lymph nodes in papillary thyroid carcinoma, especially at level II, remains controversial. This study aimed to investigate the risk factors for level II lymph node metastasis in patients with papillary thyroid carcinoma and establish a prediction model to estimate the metastatic risk.

Materials and methods

A total of 768 patients with papillary thyroid carcinoma underwent thyroidectomy and central plus lateral lymph node dissection, including levels VI, II, III, and IV, at the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2018. Data on the clinicopathological characteristics were collected and analyzed. Univariate and multivariate analyses were performed to identify risk factors for level II lymph node metastasis. Subsequently, a predictive model was established based on the results of the multivariate analyses.

Results

The level II lymph node metastatic rate was 34.11% with the following features: largest tumor diameter >20 mm (Odds ratio=1.629, P=0.026), located in the upper pole (Odds ratio=4.970, P<0.001), clinical lymph node-positive (clinical central lymph node-positive: Odds ratio=1.797; clinical lateral lymph node-positive: Odds ratio=1.805, P=0.008), vascular invasion (Odds ratio=6.759, P=0.012), and rate of central lymph node metastasis (Odds ratio=2.498, P<0.001). Level III lymph node metastasis (Odds ratio=2.749, P<0.001) and level IV lymph node metastasis (Odds ratio=1.732, P=0.007) were independent of level II lymph node metastasis predictors. The prediction model’s areas under the receiver operating characteristic curve were 0.815 and 0.804, based on bootstrapping validation. Level II lymph node metastasis was associated with the tumor-free survival rate of patients with papillary thyroid carcinoma (P<0.001).

Conclusions

Largest tumor diameter >20 mm, located in the upper pole, clinical lymph node-positive, vascular invasion, rate of central lymph node metastasis, and levels III and IV lymph node metastases were independent level II lymph node metastasis predictors. We developed a prediction model for level II lymph node metastasis. Overall, level II lymph node metastasis dissection should be individualized according to clinicopathological data both preoperatively and intraoperatively.
Activated PI3Kδ syndrome 1 mimicking systemic lupus erythematosus and secondary Sjögren's syndrome-like phenotype without recurrent infections: A case report
Authors: Yin Jing , Ma Jijun , Xia Jingyue , Cao Yang , Li Chongwei
Published: December 2022

Activated phosphoinositide 3-kinase-δ syndrome 1 (APDS1) is a combined immunodeficiency caused by a heterozygous gain-of-function mutation in PIK3CD, encoding the p110δ catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). APDS1 is characterized by recurrent sinopulmonary infections, leading to airway damage, chronic herpes viremia, lymphoproliferation, and autoimmune and inflammatory diseases. Several cases of systemic lupus erythematosus (SLE) have been reported in APDS1; however, Sjögren's syndrome (SS) or an SS-like phenotype is rarely described in patients with APDS1. In this study, we report a 4-year-old girl with APDS1 who did not experience recurrent sinopulmonary infections and chronic viremia but presented with cytopenia, proteinuria, hypocomplementemia, and positive antinuclear antibodies that met the classification criteria for SLE. Additionally, the patient also mimicked a secondary SS-like phenotype based on recurrent parotitis and labial salivary gland biopsy. The patient achieved remission after treatment with sirolimus and immunosuppressive therapy. This case report enriches the clinical phenotype of APDS1 and provides a reference for the diagnosis and therapy of patients with APDS1.
A new statistical thermodynamic mechanism for quantum mechanics
Authors: Alpert Martin
Published: December 2022

A new quantum mechanics mechanism theory based on statistical mechanics is introduced. This theory is based on corresponding changes in the number of states with associated energy changes at the observer and observed occurring at observer 1) reset and 2) observation. It is shown that a) the change in the number of states has different consequences than determining the “value” obtained at observation, where each state is a possible interaction between the system and the environment. The number of bits, as a measure of information content, is determined in discrete cell size increments. Two experiments are proposed to validate the introduced mechanism. The first experiment is to determine the spatial and temporal characteristics of energy changes and how they are related to the observer and observed during the entire measurement process. The second experiment is designed to determine timing between changes in the number of states in the system at observer reset. It is anticipated that these experiments will demonstrate no time delay, an entangled process, and, hence, explain delayed choice observations. Moreover, they would demonstrate that bits not stored in the system are transferred to the environment at observer reset, so when the number of inputs is greater than the number of outputs, an energy change occurs and interference is observed (wave characteristics). Conversely, if the number of inputs equals the number of outputs, no energy change occurs and no interference is observed (particle characteristics). It is envisioned that upon validating this mechanism theory, it will further the understanding of the measurement process and entanglement’s involvement in that process.
A heterogeneous integrated self-powered IoT system of an LiNbO3 device and CMOS readout circuit
Authors: Wang Xiuyu , Kang Min , Zhao Yang , Su Yue , Zhang Xu , Mao Xurui
Published: December 2022

A self-powered IoT system with high integration, robust performance, and adaptability to complex environments is one of the current research hotspots. Piezoelectric materials have been widely used in pressure sensing and energy harvesting due to their stable output electrical properties. In this paper, a heterogeneous integrated self-powered IoT system based on a lithium niobate (LiNbO3) piezoelectric device and CMOS readout circuit is proposed. The piezoelectric sensor is fabricated by depositing electrodes on the surface of the 36°Y-cut LiNbO3 piezoelectric material. The sensitivity of the fabricated sensor is 17.5 mV/kPa. Based on the CSMC 0.18 μm BCD process, a ring voltage-controlled oscillator (VCO) based on the current starvation delay element is designed as a wireless data transmission unit. The oscillator has two tuning terminals, which can realize frequency alignment and voltage threshold judgment. Using photolithography, wire bonding technology, etc., the heterogeneous integration of the Si-based chip and LiNbO3 piezoelectric device is realized. The experimental results show that below 1.8 V supply voltage, the oscillation frequency of the chip increases with the increase in the control terminal voltage, which provides an idea for solving the energy supply problem of an IoT system. This system has great application potential in the field of self-powered sensing.
Developing an in vitro validated 3D in silico internal carotid artery sidewall aneurysm model
Authors: Yi Hang , Yang Zifeng , Johnson Mark , Bramlage Luke , Ludwig Bryan
Published: December 2022

Introduction: Direct quantification of hemodynamic factors applied to a cerebral aneurysm (CA) remains inaccessible due to the lack of technologies to measure the flow field within an aneurysm precisely. This study aimed to develop an in vitro validated 3D in silico patient-specific internal carotid artery sidewall aneurysm (ICASA) model which can be used to investigate hemodynamic factors on the CA pathophysiology.

Methods: The validated ICASA model was developed by quantifying and comparing the flow field using particle image velocimetry (PIV) measurements and computational fluid dynamics (CFD) simulations. Specifically, the flow field characteristics, i.e., blood flowrates, normalized velocity profiles, flow streamlines, and vortex locations, have been compared at representative time instants in a cardiac pulsatile period in two designated regions of the ICASA model, respectively. One region is in the internal carotid artery (ICA) inlet close to the aneurysm sac, the other is across the middle of the aneurysmal sac.

Results and Discussion: The results indicated that the developed computational fluid dynamics model presents good agreements with the results from the parallel particle image velocimetry and flowrate measurements, with relative differences smaller than 0.33% in volumetric flow rate in the ICA and relative errors smaller than 9.52% in averaged velocities in the complex aneurysmal sac. However, small differences between CFD and PIV in the near wall regions were observed due to the factors of slight differences in the 3D printed model, light reflection and refraction near arterial walls, and flow waveform uncertainties. The validated model not only can be further employed to investigate hemodynamic factors on the cerebral aneurysm pathophysiology statistically, but also provides a typical model and guidance for other professionals to evaluate the hemodynamic effects on cerebral aneurysms.
Dose-response relationship of Ralstonia solanacearum and potato in greenhouse and in vitro experiments
Authors: Eisfeld Carina , Schijven Jack F. , Kastelein Pieter , van Breukelen Boris M. , Medema Gertjan , Velstra Jouke , Teunis Peter F. M. , van der Wolf Jan M.
Published: December 2022

Ralstonia solanacearum is the causative agent of bacterial wilt of potato and other vegetable crops. Contaminated irrigation water contributes to the dissemination of this pathogen but the exact concentration or biological threshold to cause an infection is unknown. In two greenhouse experiments, potted potato plants (Solanum tuberosum) were exposed to a single irrigation with 50 mL water (non-invasive soil-soak inoculation) containing no or 102 – 108 CFU/mL R. solanacearum. The disease response of two cultivars, Kondor and HB, were compared. Disease development was monitored over a three-month period after which stems, roots and tubers of asymptomatic plants were analyzed for latent infections. First wilting symptoms were observed 15 days post inoculation in a plant inoculated with 5x109 CFU and a mean disease index was used to monitor disease development over time. An inoculum of 5x105 CFU per pot (1.3x102 CFU/g soil) was the minimum dose required to cause wilting symptoms, while one latent infection was detected at the lowest dose of 5x102 CFU per pot (0.13 CFU/g). In a second set of experiments, stem-inoculated potato plants grown in vitro were used to investigate the dose-response relationship under optimal conditions for pathogen growth and disease development. Plants were inoculated with doses between 0.5 and 5x105 CFU/plant which resulted in visible symptoms at all doses. The results led to a dose-response model describing the relationship between R. solanacearum exposure and probability of infection or illness of potato plants. Cultivar Kondor was more susceptible to brown-rot infections than HB in greenhouse experiments while there was no significant difference between the dose-response models of both cultivars in in vitro experiments. The ED50 for infection of cv Kondor was 1.1x107 CFU. Results can be used in management strategies aimed to reduce or eliminate the risk of bacterial wilt infection when using treated water in irrigation.
Synergistic effects of nitrogen metabolites on auxin regulating plant growth and development
Authors: Fu Yu-Fan , Yang Xin-Yue , Zhang Zhong-Wei , Yuan Shu
Published: December 2022

Nitrogen is one of the important nutrients required for plant growth and development. There is increasing evidences that almost all types of nitrogen metabolites affect, at least to some extent, auxin content and/or signaling in plants, which in turn affects seed germination, plant root elongation, gravitropism, leaf expansion and floral transition. This opinion focuses on the roles of nitrogen metabolites, NO3−, NH4+, tryptophan and NO and their synergistic effects with auxin on plant growth and development. Nitrate reductase (NR) converts nitrate into nitrite, and was roughly positive-correlated with the root auxin level, suggesting a crosstalk between nitrate signaling and auxin signaling. Abscisic Acid Responsive Element Binding Factor 3 (AFB3) and Tryptophan Aminotransferase of Arabidopsis 1 (TAA1) are also the key enzymes involved in nitrogen metabolite-regulated auxin biosynthesis. Recent advances in the crosstalk among NO3−, NH4+, tryptophan and NO in regulation to NR, AFB3 and TAA1 are also summarized.
Cloning of TaeRF1 gene from Caucasian clover and its functional analysis responding to low-temperature stress
Authors: Zhang Xiaomeng , Jiang Jingwen , Ma Zewang , Yang Yupeng , Meng Lingdong , Xie Fuchun , Cui Guowen , Yin Xiujie
Published: December 2022

Low temperature (LT) is an important threat to the normal growth of plants. In this study, based on the full-length transcriptome sequencing results, the cold resistance genes were cloned from Caucasian clover with strong cold resistance. We cloned the CDS of TaeRF1, which is 1311 bp in length and encodes 436 amino acids. The molecular weight of the protein is 48.97 kDa, which had no transmembrane structure, and its isoelectric point (pI) was 5.42. We predicted the structure of TaeRF1 and found 29 phosphorylation sites. Subcellular localization showed that TaeRF1 was localized and expressed in cell membrane and chloroplasts. The TaeRF1 gene was induced by stress due to cold, salt, alkali and drought and its expression level was higher in roots and it was more sensitive to LT. Analysis of transgenic A. thaliana plants before and after LT treatment showed that the TaeRF1 gene enhanced the removal of excess H2O2, and increased the activity of antioxidant enzymes, thus improving the plant’s ability to resist stress. Additionally, the OE lines showed increased cold tolerance by upregulating the transcription level of cold-responsive genes (CBF1, CBF2, COR15B, COR47, ICE1, and RD29A). This study demonstrates that TaeRF1 is actively involved in the responses of plants to LT stress. We also provide a theoretical basis for breeding and a potential mechanism underlying the responses of Caucasian clover to abiotic stress.
A study of the factors which influence digital transformation in Kibs companies
Authors: Marino-Romero Jorge Alberto , Palos-Sanchez Pedro Ramiro , Velicia-Martin Félix Antonio , Rodrigues Ricardo Gouveia
Published: December 2022

Eighteen interviews were used in this research to inductively conceptualize the factors that influence digital transformation (DT) in Kibs companies that provide multidisciplinary Knowledge Intensive Business Services. Two main groups were identified: factors of DT and use in the new digital environment. Using the findings obtained, a comparison was made with the existing literature and the most relevant aspects of DT as a disruptive phenomenon which can generate intra-organizational competitive advantage are exposed.

Objective

To identify the factors of innovation-oriented organizational management, generated by the collaboration of the professional grouping of Kibs companies through the systematization of knowledge, which serve to conceptually delimit the DT phenomenon. Ultimately, it is expected to establish recommendations for this type of companies based on providing services with high knowledge value that strive to digitally transform their businesses.

Originality

the paper contributes to advancing the conceptual understanding of DT through the study of Kibs companies, which remain understudied. Likewise, there is no known study that analyzes the factors that give rise to DT in a professional grouping of small Kibs companies. It is clear that this union of small companies generates a strong internal capacity for knowledge absorption, through daily interactions with clients and public administrations, which favors the process of implementing certain technological and strategic components that are beneficial for the development of professional activity and increases the propensity to innovate.

Methodology

qualitative content was analysed using a grounded theory methodology including interviews with experts and the managers of the Kibs companies in the professional sector to obtain a solid basis that can be used to identify the most relevant factors of DT.

Findings/results

as DT is a multidimensional phenomenon of individual companies, this study presents a conceptual framework for the term with the strategic requirements of the market, organizations, public institutions and technological infrastructures of the professional sector. By considering the disruptive factors of digital development in this macroenvironment, conclusions can be made about the basic principles and effects of DT.
Wireless technology is an environmental stressor requiring new understanding and approaches in health care
Authors: McCredden Julie E. , Cook Naomi , Weller Steven , Leach Victor
Published: December 2022

Electromagnetic signals from everyday wireless technologies are an ever-present environmental stressor, affecting biological systems. In this article, we substantiate this statement based on the weight of evidence from papers collated within the ORSAA database (ODEB), focusing on the biological and health effects of electromagnetic fields and radiation. More specifically, the experiments investigating exposures from real-world devices and the epidemiology studies examining the effects of living near mobile phone base stations were extracted from ODEB and the number of papers showing effects was compared with the number showing no effects. The results showed that two-thirds of the experimental and epidemiological papers found significant biological effects. The breadth of biological and health categories where effects have been found was subsequently explored, revealing hundreds of papers showing fundamental biological processes that are impacted, such as protein damage, biochemical changes and oxidative stress. This understanding is targeted toward health professionals and policy makers who have not been exposed to this issue during training. To inform this readership, some of the major biological effect categories and plausible mechanisms of action from the reviewed literature are described. Also presented are a set of best practice guidelines for treating patients affected by electromagnetic exposures and for using technology safely in health care settings. In conclusion, there is an extensive evidence base revealing that significant stress to human biological systems is being imposed by exposure to everyday wireless communication devices and supporting infrastructure. This evidence is compelling enough to warrant an update in medical education and practice.
Thermal Protection Mechanism of a Novel Adjustable Non-Ablative Thermal Protection System for Hypersonic Vehicles
Authors: Chang Bin , Huang Jie , Yao Wei-Xing
Published: December 2022

In order to improve the thermal protection performance of the active thermal protection system (TPS) based on the spike and jet, an adjustable non-ablative thermal protection system, of which the spike can be rotated in the direction of the free stream, is proposed in this paper. The thermal protection mechanism and the optimal installation angle are analyzed by adopting the numerical method. The results show that the angle of attack has great influence on the peak heat flux of hypersonic vehicles, the dangerous point is on the windward side of the vehicles at the non-zero angle of attack. With the increase in angle of attack, the heat flux of the windward side of the vehicles rises rapidly, leading to the decrease in the global thermal protection efficiency. The adjustable non-ablative TPS in this paper greatly reduces the aeroheating of the windward side through the installation angle between the spike and nose cone, thus improving the global thermal protection efficiency. The optimal installation angle can be obtained by numerical or experimental methods in engineering design, and the difference between the angle of attack and the optimal installation angle is about 2.4° for the proposed model. Therefore, the installation angle can be automatically adjusted based on the angle of attack to achieve the highest thermal protection efficiency.
UV-B Radiation as a Novel Tool to Modulate the Architecture of In Vitro Grown Mentha spicata (L.)
Authors: Crestani Gaia , Cunningham Natalie , Badmus Uthman O. , Prinsen Els , Jansen Marcel A. K.
Published: December 2022

In vitro culturing can generate plants with a distorted morphology. Some distortions affect the plant’s survival after transfer to an ex vitro environment, while others can affect the aesthetic value. Therefore, exogenous hormones are often applied in in vitro cultures to modulate plant architecture. In this study, it was hypothesised that regulatory effects of UV-B radiation on plant morphology can be exploited under in vitro conditions, and that UV exposure will result in sturdier, less elongated plants with more branches and smaller leaves, mediated by changes in plant hormones. Plants were grown in tissue-culture containers and exposed to ~0.22 W m−2 UV-B for 8 days. Subsequently, plants were transferred to soil and monitored for a further 7 days. Results show that UV induced a marked change in architecture with a significant increase in axillary branches, and reductions in leaf area, plant height and root weight. These changes were associated with significant alterations in concentrations of hormones, including IAA, GA7, GA3 and iP–9–G. Changes in hormone concentrations suggest a regulatory, rather than a stress response to UV-B. Therefore, it is proposed that the application of UV in in vitro culture can be an innovative approach to manipulate plant architecture.
Identification of Novel Begomoviruses Associated with Leaf Curl Disease of Papaya (Carica papaya L.) in India
Authors: Udavatha Premchand , Mesta Raghavendra K. , Basavarajappa Mantapla Puttappa , Venkataravanappa Venkataravanappa , Devappa Venkatappa , Narasimha Reddy Lakshminarayana Reddy C. , Shankarappa Kodegandlu Subbanna
Published: December 2022

Papaya (Carica papaya L.) is one of the most important fruit crops grown in tropical and subtropical regions of the world. Papaya leaf curl disease is one of the greatest concerns next to Papaya ring spot disease for India and the world. A survey was conducted during the year 2019 to 2021 for assessing the leaf curl disease incidence in five major papaya-growing districts of Karnataka State, India. The incidence ranged from 10 to 21 percent, with plants expressing typical begomovirus symptoms. Thirty-two virus-infected papaya samples (PLC-1 to PLC-32), collected from different farmer’s fields, gave positive amplification for begomovirus detection. Based on the partial genome analysis, 13 representative papaya leaf curl isolates were selected for complete genome amplification by rolling circle DNA amplification (RCA). The RCA products were cloned, sequenced and analyzed. Based on the analysis and strain classification criteria for begomoviruses, five isolates (PLC-2, 3, 9, 11 and 18) were considered variants of Chilli leaf curl virus (ChiLCV). Isolate PLC-22 is considered a strain of ChiLCV, with 93.5% nt identity sharing. Similarly, isolate PLC-28 is considered a strain of Croton yellow vine mosaic virus (CYVMV), and isolates PLC-25 and PLC-31 were considered as strains of Papaya leaf curl virus (PaLCuV). Among the remaining four isolates, three (PLC-1, PLC-4 and PLC-7) share more than 91% nt identity among them and less than 91% nt identity with all other reported begomovirus isolates. Hence, they are considered to be isolates of the novel begomovirus, and the name Papaya leaf curl Bagalkote virus [India:Karnataka:Bagalkote:Papaya:2021] is proposed. One isolate (PLC-32) is also found to be distinct from all other begomovirus isolates, including the isolates in the current study also considered to be novel begomovirus, for which we propose the name Papaya leaf curl Haveri virus [India:Karnataka:Haveri:Papaya:2021]. The putative recombination analysis of all 13 papaya isolates showed that a major part of the viral genome was likely descended from the begomoviruses reported previously. This is the first report on the diversity and a distribution of the begomoviruses infecting papaya in Karnataka, India. The current investigation results revealed five major papaya-infecting begomoviruses (PaLCuBKV, ChiLCV, PaLCuV, CYVMV and PaLCuHV) in the sampled regions.
Genome-Wide Identification and Phylogenetic Analysis of TRP Gene Family Members in Saurian
Authors: Zhang Lin , Li Ning , Dayananda Buddhi , Wang Lihu , Chen Huimin , Cao Yunpeng
Published: December 2022

The transient receptor potential plays a critical role in the sensory nervous systems of vertebrates in response to various mechanisms and stimuli, such as environmental temperature. We studied the physiological adaptive evolution of the TRP gene in the saurian family and performed a comprehensive analysis to identify the evolution of the thermo-TRPs channels. All 251 putative TRPs were divided into 6 subfamilies, except TRPN, from the 8 saurian genomes. Multiple characteristics of these genes were analyzed. The results showed that the most conserved proteins of TRP box 1 were located in motif 1, and those of TRP box 2 were located in motif 10. The TRPA and TRPV in saurian tend to be one cluster, as a sister cluster with TRPC, and the TRPM is the root of group I. The TRPM, TRPV, and TRPP were clustered into two clades, and TRPP were organized into TRP PKD1-like and PKD2-like. Segmental duplications mainly occurred in the TRPM subfamily, and tandem duplications only occurred in the TRPV subfamily. There were 15 sites to be under positive selection for TRPA1 and TRPV2 genes. In summary, gene structure, chromosomal location, gene duplication, synteny analysis, and selective pressure at the molecular level provided some new evidence for genetic adaptation to the environment. This result provides a basis for identifying and classifying TRP genes and contributes to further elucidating their potential function in thermal sensors.