bluuebunny/crossref_metadata_2025 huggingface dataset:
Using acoustic velocities and microimaging to probe microstructural changes caused by thermal shocking of tight rocks
Authors: Malenda Margariete , Vanorio Tiziana
Published: January 2023

Introduction: Large scale, Earth processes and bulk rock properties are influenced by underpinning, dynamic, microstructures within rocks and geomaterials. Traditionally, the amount of porosity has been considered the primary control on important bulk rock properties like seismic wave velocities (Vp and Vs) and permeability. However, in tight rocks, velocity and permeability (k) can change substantially despite small changes in the amount of porosity during cracking. Therefore, other microstructural features inherent to given lithologies, such as heterogeneity and anisotropy in mineral properties are considered as factors controlling these bulk rock properties. Understanding which microstructural features control Vp, Vs, and permeability in tight rocks is useful in applications like enhanced geothermal systems (EGS), where thermal shocking is used to increase permeability. Thermal shocking involves injecting surface water into the subsurface to cool mineral crystals, induce contraction of crystals, and cause thermal cracking.

Methods: We tested three tight lithologies with unique microstructures; granodiorite (SWG), basalt (PTB), and carbonate (MSA). We simulated thermal shocking by slowly heating samples to 350°C and then quenching them. We chose a temperature of 350°C because thermal shocking at this temperature is not well documented in literature, and this temperature is relevant to EGS. Using time-lapse microimaging, we assessed how thermal cracking occurs in each lithology and explored how thermal cracks influence connected porosity, Vp, Vs, and k.

Results: Microimaging shows extensive cracking in the SWG and MSA lithologies, and little to no cracking in PTB with thermal shocking treatment. Vp and Vs became more pressure sensitive, and elastic moduli decreased with treatment for all lithologies. This may be caused by reduced stiffness between mineral crystal boundaries with treatment.

Discussion: Lithologies with minerals that have anisotropy of or a wide range in thermal conductivity and/or thermal expansion coefficients can have increased thermal cracking. In thermally shocked SWG and MSA, Vp and Vs are good indicators of thermal cracking and k increases, but less so in PTB. Lithologies like PTB may require multiple thermal shock stimulations to increase permeability. Our results highlight how micro-scale changes influence bulk rock properties and when we can monitor permeability increases and microscale thermal cracking with Vp and Vs.
Rapid construction of Rayleigh wave dispersion curve based on deep learning
Authors: Cui Diyu , Shi Lijing , Gao Kai
Published: January 2023

Introduction:The dispersion curve of the Rayleigh-wave phase velocity (VR) is widely utilized to determine site shear-wave velocity (Vs) structures from a distance of a few metres to hundreds of metres, even on a ten-kilometre crustal scale. However, the traditional theoretical-analytical methods for calculating VRs of a wide frequency range are time-consuming because numerous extensive matrix multiplications, transfer matrix iterations and the root searching of the secular dispersion equation are involved. It is very difficult to model site structures with many layers and apply them to a population-based inversion algorithm for which many populations of multilayers forward modelling and many generations of iterations are essential.

Method:In this study, we propose a deep learning method for constructing the VR dispersion curve in a horizontally layered site with great efficiency. A deep neural network (DNN) based on the fully connected dense neural network is designed and trained to directly learn the relationships between Vs structures and dispersion curves. First, the training and validation sets are generated randomly according to a truncated Gaussian distribution, in which the mean and variance of the Vs models are statistically analysed from different regions’ empirical relationships between soil Vs and its depth. To be the supervised dataset, the corresponding VRs are calculated by the generalized reflection-transmission (R/T) coefficient method. Then, the Bayesian optimization (BO) is designed and trained to seek the optimal architecture of the deep neural network, such as the number of neurons and hidden layers and their combinations. Once the network is trained, the dispersion curve of VR can be constructed instantaneously without building and solving the secular equation.

Results and Discussion:The results show that the DNN-BO achieves a coefficient of determination (R2) and MAE for the training and validation sets of 0.98 and 8.30 and 0.97 and 8.94, respectively, which suggests that the rapid method has satisfactory generalizability and stability. The DNN-BO method accelerates the dispersion curve calculation by at least 400 times, and there is almost no increase in computation expense with an increase in soil layers.
Geochronology and geochemistry of the Shanagen hydrothermal vein-type Mo deposit in Derbugan metallogenic belt of the NE China and their geological significance
Authors: Wu Yunxia , Liu Yu , Liu Aoran , Tian Lifu , Ye Yasheng
Published: January 2023

The Shanagen hydrothermal vein-type Mo deposit belongs to the Derbugan metallogenic belt, which is located in the Ergun block, NE China. The Mo mineralization is mainly developed in sericitized quartz siltstone around alkali-feldspar granite. In this paper, we present Molybdenite Re–Os dating, zircon U–Pb dating and geochemical data with the aim of determining metallogenic epoch and tectonic setting. Molybdenite Re–Os and zircon U–Pb dating of the alkali-feldspar granite indicate that the ore-formation and alkali-feldspar granite emplacement occurred at 143.1 ± 3.8 Ma, and 144.7 ± 0.7 Ma. Both were formed in the early Cretaceous. Chemically, the alkali-feldspar granites are enriched in L rare earth element and LILEs, depleted in H rare earth element and HFSEs, and pronounced negative Eu anomalies, are metaluminous and belong to the high-K calc-alkaline series and highly differentiated I-type granite. Geochemical features and concave upwards rare earth element pattern imply that alkali-feldspar granites were formed from magma generated by partial melting of lower crust. Combining the geochemistry, chronology, and the regional tectonic evolution, we infer that Shanagen hydrothermal vein-type Mo deposit was formed the extensional environment after the closure of the Mongol-Okhotsk Ocean.
The important building blocks of newcomer immigrant students’ education in the Norwegian context
Authors: Norozi Sultana Ali
Published: January 2023

The education of immigrant students, particularly newcomers, must be considered from a holistic framework. The conceptual article aims to highlight other important aspects of newcomers’ education, in addition to language and subject content learning. The three overlooked yet most important components of holistic education for newcomers are the following: (1) well-being pedagogy, (2) positive and comprehensive collaboration with newcomer parents, and (3) teachers’ positive ideology of newcomers and their families. This article begins with a brief presentation of the issue in newcomers’ education demonstrating an emphasis on some important yet overlooked elements in newcomer education. Consequently, in Norway, despite educational efforts aimed at supporting immigrant students, they continue to perform poorly compared with ethnic Norwegian students. Then, the paper defines what well-being pedagogy is and why well-being should be included in the comprehensive and successful schooling of newcomers. Here, well-being pedagogy is not limited to newcomer students’ well-being; rather, it includes teachers (who work with newcomers) and newcomer parents’ well-being. The why and how of comprehensive and successful collaboration with newcomer parents is discussed as a second important component. The third building block is teachers’ positive ideology of newcomers and their parents. The paper establishes that the positive ideology and perceptions of newcomer students and their families are the core of the holistic education of immigrant students. This paper contributes to knowledge development for the education of newly arrived immigrant students by engaging in a discussion that can foster teacher motivation and commitment, resulting in greater support for newcomer students. Second, even though this paper is framed in the context of Norwegian society, the aim is to inspire the international community of educators and researchers committed to an equitable learning environment for immigrant students to consider the topic for further exploration. The article concludes with teachers’ practice recommendations for schools and some directions for future research.
In vitro beta-cell killing models using immune cells and human pluripotent stem cell-derived islets: Challenges and opportunities
Authors: Halliez Clémentine , Ibrahim Hazem , Otonkoski Timo , Mallone Roberto
Published: January 2023

Type 1 diabetes (T1D) is a disease of both autoimmunity and β-cells. The β-cells play an active role in their own demise by mounting defense mechanisms that are insufficient at best, and that can become even deleterious in the long term. This complex crosstalk is important to understanding the physiological defense mechanisms at play in healthy conditions, their alterations in the T1D setting, and therapeutic agents that may boost such mechanisms. Robust protocols to develop stem-cell-derived islets (SC-islets) from human pluripotent stem cells (hPSCs), and islet-reactive cytotoxic CD8+ T-cells from peripheral blood mononuclear cells offer unprecedented opportunities to study this crosstalk. Challenges to develop in vitro β-cell killing models include the cluster morphology of SC-islets, the relatively weak cytotoxicity of most autoimmune T-cells and the variable behavior of in vitro expanded CD8+ T-cells. These challenges may however be highly rewarding in light of the opportunities offered by such models. Herein, we discuss these opportunities including: the β-cell/immune crosstalk in an islet microenvironment; the features that make β-cells more sensitive to autoimmunity; therapeutic agents that may modulate β-cell vulnerability; and the possibility to perform analyses in an autologous setting, i.e., by generating T-cell effectors and SC-islets from the same donor.
Association of hemoglobin A1c with the incidence of hypertension: A large prospective study
Authors: Huang Xu , Qin Cheng , Guo Xiaoxu , Cao Feng , Tang Chengchun
Published: January 2023

Background

Although hemoglobin A1c (HbA1c) is closely related to diabetes, its relationship with the incidence of hypertension is still unknown, so we aimed to evaluate the relationship between HbA1c and the incidence of hypertension in the general population.

Method

In this large prospective cohort study with a median follow-up of 2 years, we included 4,074 participants from the China Health and Nutrition Survey (CHNS). Multivariate COX regression, subgroup analysis, receiver operator characteristic (ROC) curve and restricted cubic spline (RCS) were used to evaluate the relationship between HbA1c and incidental hypertension.

Results

Compared with participants without incident hypertension, participants with incident hypertension had higher levels of HbA1c (P < 0.05). In univariate COX regression analysis, HbA1c was associated with the risk of hypertension (HR: 1.161, 95% CI: 1.105-1.221, P < 0.001). In multivariate COX regression analysis adjusted for confounding variables, HbA1c was still closely related to the risk of hypertension (HR: 1.102, 95% CI: 1.006-1.206, P = 0.037). And subgroup analysis showed that the relationship between HbA1c and hypertension remained significant in female, lower than high school and non-obese subgroups (P < 0.05). ROC curve also showed that HbA1c could predict the risk of hypertension (AUC = 0.583, 95% CI: 0.568-0.598, P < 0.001). Further RCS analysis showed that HbA1c was positively correlated with the risk of hypertension (P for nonlinearity = 0.642).

Conclusion

HbA1c was linearly and positively associated with the incidence of hypertension.
Study on multicomponent composite anti-corrosion cement slurry system suitable for ultra-high temperature acid gas wells
Authors: Zhang Yihang , Huang Yang
Published: January 2023

In the field of oil cementing, corrosion has always been a major problem that perplexes researchers. In the past, the research mainly focused on solving the corrosion problem of cement stone with temperature below 150°C, and there was a lack of corrosion research cases for ultra-high temperature. In addition, the gas channeling problem in the cementing of ultra-high temperature acid gas wells cannot be ignored, which further increases the difficulty in the design of anti-corrosion cement slurry system. Therefore, from the perspective of anti-corrosion, gas channeling and high temperature resistance, this paper uses hydroxyapatite blast furnace slag and functional temperature resistant and anti-corrosion composite emulsion as anti-corrosion additives to build a multi-component composite ultra-high temperature anti-corrosion cement slurry system with good engineering performance and a density range of 1.9 g/cm3-2.4 g/cm3, and analyzes its microstructure and phase composition. The corrosion inhibition mechanism of multicomponent composite cement paste was discussed.
Research on data mining model of fault operation and maintenance based on electric vehicle charging behavior
Authors: Zhu Bin , Hu Xiaorui , He Min , Chi Lei , Xu Tingting
Published: January 2023

In recent years, with the development of new energy technology and the country’s strong support for electric vehicles, there is a lack of effective electric vehicle charging fault analysis and diagnosis methods at this stage. A comprehensive analysis of the working principle of the charging process of electric vehicles, based on the clarification of the failure mechanism of the power battery and charging equipment, analyzes the fault-related factors affecting the power battery and charging equipment from multiple angles, and summarizes the relationship between the power battery and charging equipment. The feature parameters related to equipment failure are discretized by the k-means clustering algorithm. Using the optimized FP-Growth algorithm based on weights, the association rules between the power battery and charging equipment failures and the characteristic parameters of the failure factors are mined, and the correlation of the failures is analyzed based on the association rules, and the correlation between the failure factors and the failures is obtained relevant level.
Probabilistic power flow calculation using principal component analysis-based compressive sensing
Authors: Wang Tonghe , Liang Hong , Cao Junwei , Zhao Yuming
Published: January 2023

The increasing scale of the injection of renewable energy has brought about great uncertainty to the operation of power grid. In this situation, probabilistic power flow (PPF) calculation has been introduced to mitigate the low accuracy of traditional deterministic power flow calculation in describing the operation status and power flow distribution of power systems. Polynomial chaotic expansion (PCE) method has become popular in PPF analysis due to its high efficiency and accuracy, and sparse PCE has increased its capability of tackling the issue of dimension disaster. In this paper, we propose a principal component analysis-based compressive sensing (PCA-CS) algorithm solve the PPF problem. The l1-optimization of CS is used to tackle the dimension disaster of sparse PCE, and PCA is included to further increase the sparsity of expansion coefficient matrix. Theoretical and numerical simulation results show that the proposed method can effectively improve the efficiency of PPF calculation in the case of random inputs with higher dimensions.
Effects of major and trace elements from the El Kahfa ring complex on fish: Geological, physicochemical, and biological approaches
Authors: Saad Eman , Hamed Mohamed , Elshahawy Abdelnaby M. , Abd El-Aal Mohamed , Sayed Alaa El-Din H.
Published: January 2023

The alkaline rocks are known for enriching rare lithophilic elements, including lithium, uranium, and tin, which negatively impact aquatic life. This study offers an intensive investigation of the influence of alkaline rocks on Nile Tilapia (Oreochromis niloticus). The variation in blood profile, the induction of antioxidant enzymes, morphological erythrocyte, and histological structure have been conducted for the fish after 15 days of exposure to alkaline rocks powder with a dose of 100 μg/L. As a result, there was a pronounced decrease in blood profiles, such as platelets and white blood cell counts. There was a failure in the liver and kidney functions. Moreover, it shows an increase in superoxide dismutase (SOD) and catalase (CAT) activities as antioxidant biomarkers. Also, exposure to alkaline rocks induced DNA mutation and erythrocyte distortion. We concluded that the bulk alkaline rocks induced changes in the hemato-biochemical and antioxidant parameters of Nile tilapia. Additionally, exposure to bulk alkaline rock compounds also caused poikilocytosis and nuclear abnormalities of RBCs. This draws our attention to the seriousness of climatic changes, the erosion of rocks, and their access to water.
Cause analysis of the extreme hourly precipitation and its relationship with the urban heat island intensity in Shenyang, China
Authors: Ao Xue , Zhai Qingfei , Zhao Chunyu , Cui Yan , Zhou Xiaoyu , Li Mingqian , Li Jingwei
Published: January 2023

Based on the hourly temperature and precipitation data from China national meteorological stations and regional automatic weather stations in Shenyang, the relationship between extreme hourly precipitation (ExHP) and urban heat island Intensity (UHII) is analyzed. Results show that the UHII is higher at night and in the early morning. The ExHP events mostly occur at night in summer when the UHII is relatively high. The spatial distribution of UHII in Shenyang is consistent with the economic development and the transportation density. Denser population and transportation, and high-rise buildings in the urban center contribute to higher UHII. There are three types of ExHP, namely the abrupt-type ExHP, the growing-type ExHP and the continuous-type ExHP. The overall variation characteristics of the three types of ExHP are relatively consistent. Their UHII values are positive and relatively stable in 6–12 h before the start of ExHP. The UHII begins to increase dramatically about 6 h before the ExHP, but decreases obviously and turn negative after the precipitation begins. Before the abrupt ExHP, the UHII is relatively high and can rapidly return to positive after the ending of ExHP. The UHII of the abrupt-type ExHP is remarkably larger than that of the growing-type and continuous-type ExHP. The UHII before and after the abrupt-type ExHP differs greatly. Before the abrupt ExHP, the UHII is high in the center and low at both ends, and the high-value areas of UHII are mainly located in the urban area. After the abrupt-type EXHP, the UHII drops and turn negative in the whole area. The UHII is obviously increasing with urbanization. The diurnal variation of UHII is enormous, which is higher at night than during the daytime. The increasing UHII can cause abnormal air pressure in cities and villages. The air in the lower atmospheric layer of the city can be heated and expanded, hence resulting in lower local air pressure. Then, the lower air pressure can promote the convergence and upward movement of air, hence facilitating the establishment of UHII circulation. This phenomenon is particularly distinct at night, which is conducive to the occurrence of ExHP events.
Residue behavior and dietary risk assessment of fluopyram in cowpea and determination in nine foodstuffs
Authors: Ren Saihao , Zhang Yu , Zhang Shanying , Lu Hongwei , Liang Xiaoyu , Wang Lifeng , Wang Meng , Zhang Chenghui
Published: January 2023

Pesticide residues have been one of the food safety problems that plague consumers. It is necessary to develop validated detection methods to monitor pesticide residues in food. In this study, fluopyram was analyzed in fruits (banana, grape, and citrus) and vegetables (tomato, cucumber, cowpea, pepper, eggplant, and potato) by optimizing the QuEChERS in combination with GC-MS/MS. The recoveries of fluopyram in all food matrices ranged from 87.02% to 101.42% with RSD below 9.25%. The matrix effect of fluopyram ranging from −1.41% to 17.67%. Finally, this market investigation resulted in a total of 19 positive samples out of 128 market samples, all of which fell below the MRL with the exception of one tomato sample, which was above the EU MRL. Field trial of fluopyram on cowpea was conducted, the half-lives of fluopyram was 3.03–3.95 days, terminal residues ranged from .031–.596 mg/kg. Dietary risk assessment was performed on cowpea. The result indicates that the dietary risk of fluopyram in cowpeas is acceptable. The method of detection developed in this study could enable better monitoring of fluopyram residues in foodstuffs.
A systems level approach to study metabolic networks in prokaryotes with the aromatic amino acid biosynthesis pathway
Authors: V. K Priya , Sinha Somdatta
Published: January 2023

Metabolism of an organism underlies its phenotype, which depends on many factors, such as the genetic makeup, habitat, and stresses to which it is exposed. This is particularly important for the prokaryotes, which undergo significant vertical and horizontal gene transfers. In this study we have used the energy-intensive Aromatic Amino Acid (Tryptophan, Tyrosine and Phenylalanine, TTP) biosynthesis pathway, in a large number of prokaryotes, as a model system to query the different levels of organization of metabolism in the whole intracellular biochemical network, and to understand how perturbations, such as mutations, affects the metabolic flux through the pathway - in isolation and in the context of other pathways connected to it. Using an agglomerative approach involving complex network analysis and Flux Balance Analyses (FBA), of the Tryptophan, Tyrosine and Phenylalanine and other pathways connected to it, we identify several novel results. Using the reaction network analysis and Flux Balance Analyses of the Tryptophan, Tyrosine and Phenylalanine and the genome-scale reconstructed metabolic pathways, many common hubs between the connected networks and the whole genome network are identified. The results show that the connected pathway network can act as a proxy for the whole genome network in Prokaryotes. This systems level analysis also points towards designing functional smaller synthetic pathways based on the reaction network and Flux Balance Analyses analysis.
Stent placement in pancreatic disease, when, which and why? – a current perspective
Authors: Conrad Claudio C. , Ellrichmann Mark
Published: January 2023

Introduction

Stenting of the pancreas is a challenging task for the interventional gastroenterologist. The indications for pancreatic stent implantation are either prophylactic or therapeutic. We give an overview of currently available literature and techniques for the respective indications of pancreatic stent placement.

Methods

A structured literature research was conducted (Pubmed.gov) primarily using the following key words: interventional endoscopy, pancreatic stenting, post-ERCP pancreatitis, pancreatic Q8 fistulae, pancreas divisum.

Results

Prophylactic stent implantation aims to prevent PEP by using thin (3-5 Fr) and short (3-5 cm) designated pancreatic stents at least in high-risk patients. Therapeutic stent placement is intended to restore the proper flow of pancreatic secretion with stenoses, leaks, fistulas or anatomical malformation of the pancreatic duct. Depending on the etiology, plastic stents or SEMSs are used. Another field of pancreatic stenting represents EUS-guided puncture with stent implantation as an alternative access to the main pancreatic duct when transpapillary access is impossible. In addition to the implantation of plastic stents, which achieve good results, LAMS implantation can be discussed as an alternative access route.

Discussion

The field of pancreatic stenting is complex and belongs in the hands of experienced endoscopists in specialized institutions. This can ensure that the patient receives the optimal treatment with the best possible outcome.
The circadian rhythms regulated by Cx43-signaling in the pathogenesis of Neuromyelitis Optica
Authors: Xue Huiru , Wu Minghui , Wang Yongle , Zhao Yunfei , Zhang Meini , Zhang Hui
Published: January 2023

Introduction

Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). NMO manifests as selective and severe attacks on axons and myelin of the optic nerve and spinal cord, resulting in necrotic cavities. The circadian rhythms are well demonstrated to profoundly impact cellular function, behavior, and disease. This study is aimed to explore the role and molecular basis of circadian rhythms in NMO.

Methods

We used an Aquaporin 4(AQP4) IgG-induced NMO cell model in isolated astrocytes. The expression of Cx43 and Bmal1 were detected by real-time PCR and Western Blot. TAT-Gap19 and DQP-1105 were used to inhibit Cx43 and glutamate receptor respectively. The knockdown of Bmal1 were performed with the shRNA containing adenovirus. The levels of glutamate, anterior visual pathway (AVP), and vasoactive intestinal peptide (VIP) were quantified by ELISA kits.

Results

We found that Bmal1 and Clock, two essential components of the circadian clock, were significantly decreased in NMO astrocytes, which were reversed by Cx43 activation (linoleic acid) or glutamate. Moreover, the expression levels of Bmal1 and Clock were also decreased by Cx43 blockade (TAT-Gap19) or glutamate receptor inhibition (DQP-1105). Furthermore, adenovirus-mediated Bmal1 knockdown by shRNA (Ad-sh-Bmal1) dramatically decreased the levels of glutamate, AVP, and VIP from neurons, and significantly down-regulated the protein level of Cx43 in NMO astrocytes with Cx43 activation (linoleic acid) or glutamate treatment. However, Bmal1 knockdown did not alter these levels in normal astrocytes with Cx43 blockade (TAT-Gap19) or glutamate receptor inhibition (DQP-1105).

Discussion

Collectively, these results suggest that Cx43-glutamate signaling would be a critical upstream regulator that contributes to the NMO-induced rhythmic damage in SCN astrocytes.
Traffic jam within lymphocytes: A clinician’s perspective
Authors: Hosahalli Vasanna Smitha , Dalal Jignesh
Published: January 2023

With the discovery of novel diseases and pathways, as well as a new outlook on certain existing diseases, cellular trafficking disorders attract a great deal of interest and focus. Understanding the function of genes and their products in protein and lipid synthesis, cargo sorting, packaging, and delivery has allowed us to appreciate the intricate pathophysiology of these biological processes at the molecular level and the multi-system disease manifestations of these disorders. This article focuses primarily on lymphocyte intracellular trafficking diseases from a clinician’s perspective. Familial hemophagocytic lymphohistiocytosis is the prototypical disease of abnormal vesicular transport in the lymphocytes. In this review, we highlight other mechanisms involved in cellular trafficking, including membrane contact sites, autophagy, and abnormalities of cytoskeletal structures affecting the immune cell function, based on a newer classification system, along with management aspects of these conditions.
Fourteen-day vonoprazan and low- or high-dose amoxicillin dual therapy for eradicating Helicobacter pylori infection: A prospective, open-labeled, randomized non-inferiority clinical study
Authors: Hu Yi , Xu Xin , Liu Xiao-Shun , He Cong , Ouyang Yao-Bin , Li Nian-Shuang , Xie Chuan , Peng Chao , Zhu Zhen-Hua , Xie Yong , Shu Xu , Zhu Yin , Graham David Y. , Lu Nong-Hua
Published: January 2023

Background and aim

We previously reported that vonoprazan-amoxicillin (VA) dual therapy for 7 or 10 days is not satisfactorily efficacious for Helicobacter pylori (H. pylori) eradication. We aimed to explore the efficacy of VA dual therapy for 14 days as a first-line treatment for H. pylori infection.

Methods

This was a single center, prospective, open-labeled, randomized non-inferiority clinical study conducted in China. Treatment naïve H. pylori infected patients were randomized into two groups: 20 mg vonoprazan (VPZ) b.i.d. in combination with low-dose (1000 mg b.i.d.) or high-dose (1000 mg t.i.d) amoxicillin for 14 days. 13C-urea breath tests were used to access the cure rate at least 4 weeks after treatment.

Results

A total of 154 patients were assessed and 110 subjects were randomized. The eradication rate of VPZ with b.i.d. amoxicillin or t.i.d. amoxicillin for 14 days was 89.1% and 87.3% by intention-to-treat analysis, respectively, and 94.1% and 95.9% by per-protocol analysis, respectively. The eradication rate and incidence of adverse events were not different between the two groups.

Conclusion

VPZ with b.i.d. or t.i.d. amoxicillin for 14 days provides satisfactory efficacy as a first-line treatment for H. pylori infection in China.
Peripheral blood cellular profile at pre-lymphodepletion is associated with CD19-targeted CAR-T cell-associated neurotoxicity
Authors: De Matteis Serena , Dicataldo Michele , Casadei Beatrice , Storci Gianluca , Laprovitera Noemi , Arpinati Mario , Maffini Enrico , Cortelli Pietro , Guarino Maria , Vaglio Francesca , Naddeo Maria , Sinigaglia Barbara , Zazzeroni Luca , Guadagnuolo Serafina , Tomassini Enrica , Bertuccio Salvatore Nicola , Messelodi Daria , Ferracin Manuela , Bonafè Massimiliano , Zinzani Pier Luigi , Bonifazi Francesca
Published: January 2023

Background

Infusion of second generation autologous CD19-targeted chimeric antigen receptor (CAR) T cells in patients with R/R relapsed/refractory B-cell lymphoma (BCL) is affected by inflammatory complications, such as Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). Current literature suggests that the immune profile prior to CAR-T infusion modifies the chance to develop ICANS.

Methods

This is a monocenter prospective study on 53 patients receiving approved CAR T-cell products (29 axi-cel, 24 tisa-cel) for R/R-BCL. Clinical, biochemical, and hematological variables were analyzed at the time of pre-lymphodepletion (pre-LD). In a subset of 21 patients whose fresh peripheral blood sample was available, we performed cytofluorimetric analysis of leukocytes and extracellular vesicles (EVs). Moreover, we assessed a panel of soluble plasma biomarkers (IL-6/IL-10/GDF-15/IL-15/CXCL9/NfL) and microRNAs (miR-146a-5p, miR-21-5p, miR-126-3p, miR-150-5p) which are associated with senescence and inflammation.

Results

Multivariate analysis at the pre-LD time-point in the entire cohort (n=53) showed that a lower percentage of CD3+CD8+ lymphocytes (38.6% vs 46.8%, OR=0.937 [95% CI: 0.882-0.996], p=0.035) and higher levels of serum C-reactive protein (CRP, 4.52 mg/dl vs 1.00 mg/dl, OR=7.133 [95% CI: 1.796-28], p=0.005) are associated with ICANS. In the pre-LD samples of 21 patients, a significant increase in the percentage of CD8+CD45RA+CD57+ senescent cells (median % value: 16.50% vs 9.10%, p=0.009) and monocytic-myeloid derived suppressor cells (M-MDSC, median % value: 4.4 vs 1.8, p=0.020) was found in ICANS patients. These latter also showed increased levels of EVs carrying CD14+ and CD45+ myeloid markers, of the myeloid chemokine CXCL-9, as well of the MDSC-secreted cytokine IL-10. Notably, the serum levels of circulating neurofilament light chain, a marker of neuroaxonal injury, were positively correlated with the levels of senescent CD8+ T cells, M-MDSC, IL-10 and CXCL-9. No variation in the levels of the selected miRNAs was observed between ICANS and no-ICANS patients.

Discussion

Our data support the notion that pre-CAR-T systemic inflammation is associated with ICANS. Higher proportion of senescence CD8+ T cells and M-MDSC correlate with early signs of neuroaxonal injury at pre-LD time-point, suggesting that ICANS may be the final event of a process that begins before CAR-T infusion, consequence to patient clinical history.
Impact of SIV infection on mycobacterial lipid-reactive T cell responses in Bacillus Calmette-Guérin (BCG) inoculated macaques
Authors: Walker Edith M. , Merino Kristen M. , Slisarenko Nadia , Grasperge Brooke F. , Mehra Smriti , Roy Chad J. , Kaushal Deepak , Rout Namita
Published: January 2023

Background

Although BCG vaccine protects infants from tuberculosis (TB), it has limited efficacy in adults against pulmonary TB. Further, HIV coinfection significantly increases the risk of developing active TB. In the lack of defined correlates of protection in TB disease, it is essential to explore immune responses beyond conventional CD4 T cells to gain a better understanding of the mechanisms of TB immunity.

Methods

Here, we evaluated unconventional lipid-reactive T cell responses in cynomolgus macaques following aerosol BCG inoculation and examined the impact of subsequent SIV infection on these responses. Immune responses to cellular lipids of M. bovis and M. tuberculosis were examined ex vivo in peripheral blood and bronchioalveolar lavage (BAL).

Results

Prior to BCG inoculation, innate-like IFN-γ responses to mycobacterial lipids were observed in T cells. Aerosol BCG exposure induced an early increase in frequencies of BAL γδT cells, a dominant subset of lipid-reactive T cells, along with enhanced IL-7R and CXCR3 expression. Further, BCG exposure stimulated greater IFN-γ responses to mycobacterial lipids in peripheral blood and BAL, suggesting the induction of systemic and local Th1-type response in lipid-reactive T cells. Subsequent SIV infection resulted in a significant loss of IL-7R expression on blood and BAL γδT cells. Additionally, IFN-γ responses of mycobacterial lipid-reactive T cells in BAL fluid were significantly lower in SIV-infected macaques, while perforin production was maintained through chronic SIV infection.

Conclusions

Overall, these data suggest that despite SIV-induced decline in IL-7R expression and IFN-γ production by mycobacterial lipid-reactive T cells, their cytolytic potential is maintained. A deeper understanding of anti-mycobacterial lipid-reactive T cell functions may inform novel approaches to enhance TB control in individuals with or without HIV infection.
The immune suppressive tumor microenvironment in multiple myeloma: The contribution of myeloid-derived suppressor cells
Authors: Giannotta Claudia , Autino Federica , Massaia Massimo
Published: January 2023

Myeloid derived suppressors cells (MDSC) play major roles in regulating immune homeostasis and immune responses in many conditions, including cancer. MDSC interact with cancer cells within the tumor microenvironment (TME) with direct and indirect mechanisms: production of soluble factors and cytokines, expression of surface inhibitory molecules, metabolic rewiring and exosome release. The two-way relationship between MDSC and tumor cells results in immune evasion and cancer outgrowth. In multiple myeloma (MM), MDSC play a major role in creating protumoral TME conditions. In this minireview, we will discuss the interplay between MDSC and MM TME and the possible strategies to target MDSC.
Gastropod chemoreception behaviors—Mechanisms underlying the perception and location of targets and implications for shellfish fishery development in aquatic environments
Authors: Yu Zheng-Lin , Yang Mei-Jie , Song Hao , Zhang Tao , Yuan Xiu-Tang
Published: January 2023

Chemoreception is one of the most important senses and it plays a key role in the survival and adaptation of animals to their environments. Many gastropods, such as Rapana venosa and Neptunea cumingii, have emerged as economically important shellfish. Meanwhile, invasive gastropods have destroyed commercial shellfisheries in many countries. Given the importance of chemoreception in the behavior of aquatic gastropods, the mechanism of their chemical perception has recently garnered attention. To provide a foundation for understanding the chemoreception of aquatic gastropods, we reviewed recent studies and summarized the chemoreception behaviors and mechanisms that gastropods use to perceive and locate targets in aquatic environments, along with relevant molecular and genetic insights. We highlight several of the implications of these studies for chemoreception-related research and shellfish fishery development. This review should aid in the rational development and utilization of gastropod resources as well as in controlling the populations of invasive species.
Time-frequency analysis framework for understanding non-stationary and multi-scale characteristics of sea-level dynamics
Authors: Liang Xindan , Lin Yinyi , Wu Renguang , Li Gang , Khan Nicole , Liu Rui , Su Hua , Wei Shan , Zhang Hongsheng
Published: January 2023

Rising sea level caused by global climate change may increase extreme sea level events, flood low-lying coastal areas, change the ecological and hydrological environment of coastal areas, and bring severe challenges to the survival and development of coastal cities. Hong Kong is a typical economically and socially developed coastal area. However, in such an important coastal city, the mechanisms of local sea-level dynamics and their relationship with climate teleconnections are not well explained. In this paper, Hong Kong tide gauge data spanning 68 years was documented to study the historical sea-level dynamics. Through the analysis framework based on Wavelet Transform and Hilbert Huang Transform, non-stationary and multi-scale features in sea-level dynamics in Hong Kong are revealed. The results show that the relative sea level (RSL) in Hong Kong has experienced roughly 2.5 cycles of high-to-low sea-level transition in the past half-century. The periodic amplitude variation of tides is related to Pacific Decadal Oscillation (PDO) and El Niño-Southern Oscillation (ENSO). RSL rise and fall in eastern Hong Kong often occur in La Niña and El Niño years, respectively. The response of RSL to the PDO and ENSO displays a time lag and spatial heterogeneity in Hong Kong. Hong Kong's eastern coastal waters are more strongly affected by the Pacific climate and current systems than the west. This study dissects the non-stationary and multi-scale characteristics of relative sea-level change and helps to better understand the response of RSL to the global climate system.
Gonad transcriptome analysis reveals the differences in gene expression related to sex-biased and reproduction of clam Cyclina sinensis
Authors: Liu Meimei , Ni Hongwei , Rong Zichao , Wang Zi , Yan Susu , Liao Xiaoting , Dong Zhiguo
Published: January 2023

Sexual differentiation and gonad development are important biological processes for bivalve species. The clam Cyclina sinensis is an important cultured marine bivalve widely distributed along with the coastal areas of China. However, the information related to sexual determination/differentiation and gonadal development of C. sinensis almost has no reported. To study the molecular mechanisms of its sexual determination/differentiation and gonadal development, transcriptome analysis was performed in the gonad of C. sinensis, and the potential biological functions of reproduction-related gene were also investigated in this study. The results showed that 1 013 and 427 genes were differentially expressed in the ovary and testis, respectively. KEGG enrichment analysis showed that the DEGs in the gonad were significantly clustered in progesterone-mediated oocyte maturation, cell cycle and oocyte meiosis. Further analysis showed that 23 genes were mainly involved in sex determination/differentiation, including Dmrt1, Sox2/4/9, Foxl2, β-catenin and GATA-type zinc finger protein 1-like. Twenty key genes were mainly involved in the process of spermatogenesis, and five genes encode steroid biosynthesis and metabolism. Fifteen genes related to ovarian development were also identified in this study, such as Vitellogenin, MAM and LDL-receptor class A domain-containing protein 1 and Cell division cycle protein 20 homolog. Moreover, 50µg/L estradiol treatment significantly up-regulated the expression levels of CsVg in the ovary and hepatopancreas. These results highlight the genes involved in sexual determination/differentiation and gonadal development, which enhance our understanding for further studies of reproduction and breeding of C. sinensis and other marine bivalves.
Genetic characterization and virulence determinants of multidrug-resistant NDM-1-producing Aeromonas caviae
Authors: Hu Xinjun , Zhang Huanran , Liu Yi , Liu Xiaojing , Qiao Jie , Ge Haoyu , Zhao Junhui , Ma Xiaohan , Chen Mantao , Liu Ruishan
Published: January 2023

The emergence of carbapenemase significantly threatens public health. It is prevalent worldwide but rare in Aeromonas caviae. Unlike most bacterial species, A. caviae has two distinct flagella systems, which are closely related to biofilm formation. The ability to form biofilms on host tissues or inert surfaces constitutes an important cause of many persistent infections, which causes difficulties in clinical treatment. Here, we report on a multidrug-resistant (MDR) A. caviae carrying blaNDM–1 with a novel sequence type 1,416. The strong ability of biofilm formation of FAHZZU2447 was verified by a crystal violet assay. The resistome profile and location of the blaNDM–1 gene were determined by antimicrobial susceptibility testing, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), and Southern blot analysis. Moreover, the strain underwent whole-genome sequencing to identify its genomic characteristics. In addition, the blaNDM–1 gene was located on a ∼243 kb plasmid with genetic context IS1R-blaNDM–1-ble-trpF-dsbD-hp-sul1-qacE. Phylogenetic analysis indicated the transmission of A. caviae in China, Japan, and Thailand. Our study aimed to elucidate the genomic features of blaNDM–1-producing A. caviae, thereby clarifying the distribution of A. caviae worldwide and emphasizing the harmfulness of biofilm formation to the clinic. Further comprehensive surveillance of this species is needed to control further dissemination.
Pseudomonas aeruginosa GidA modulates the expression of catalases at the posttranscriptional level and plays a role in virulence
Authors: Srimahaeak Thanyaporn , Thongdee Narumon , Chittrakanwong Jurairat , Atichartpongkul Sopapan , Jaroensuk Juthamas , Phatinuwat Kamonwan , Phaonakrop Narumon , Jaresitthikunchai Janthima , Roytrakul Sittiruk , Mongkolsuk Skorn , Fuangthong Mayuree
Published: January 2023

Pseudomonas aeruginosa gidA, which encodes a putative tRNA-modifying enzyme, is associated with a variety of virulence phenotypes. Here, we demonstrated that P. aeruginosa gidA is responsible for the modifications of uridine in tRNAs in vivo. Loss of gidA was found to have no impact on the mRNA levels of katA and katB, but it decreased KatA and KatB protein levels, resulting in decreased total catalase activity and a hydrogen peroxide-sensitive phenotype. Furthermore, gidA was found to affect flagella-mediated motility and biofilm formation; and it was required for the full virulence of P. aeruginosa in both Caenorhabditis elegans and macrophage models. Together, these observations reveal the posttranscriptional impact of gidA on the oxidative stress response, highlight the complexity of catalase gene expression regulation, and further support the involvement of gidA in the virulence of P. aeruginosa.
Engineering a mevalonate pathway in Halomonas bluephagenesis for the production of lycopene
Authors: Su Qixuan , Cheng Ping , Sun Jiyuan , Zhang Yulin , Zheng Yang , Jiang Xiao-Ran , Rao Xiancai
Published: January 2023

Introduction

Red-colored lycopene has received remarkable attention in medicine because of its antioxidant properties for reducing the risks of many human cancers. However, the extraction of lycopene from natural hosts is limited. Moreover, the chemically synthesized lycopene raises safety concerns due to residual chemical reagents. Halomonas bluephagenesis is a versatile chassis for the production of fine chemicals because of its open growth property without sterilization.

Methods

A heterologous mevalonate (MVA) pathway was introduced into H. bluephagenesis strain TD1.0 to engineer a bacterial host for lycopene production. A pTer7 plasmid mediating the expression of six MVA pathway genes under the control of a phage PMmp1 and an Escherichia coli Ptrc promoters and a pTer3 plasmid providing lycopene biosynthesis downstream genes derived from Streptomyces avermitilis were constructed and transformed into TD1.0. The production of lycopene in the engineered H. bluephagenesis was evaluated. Optimization of engineered bacteria was performed to increase lycopene yield.

Results

The engineered TD1.0/pTer7-pTer3 produced lycopene at a maximum yield of 0.20 mg/g dried cell weight (DCW). Replacing downstream genes with those from S. lividans elevated the lycopene production to 0.70 mg/g DCW in the TD1.0/pTer7-pTer5 strain. Optimizing the PMmp1 promoter in plasmid pTer7 with a relatively weak Ptrc even increased the lycopene production to 1.22 mg/g DCW. However, the change in the Ptrc promoter in pTer7 with PMmp1 did not improve the yield of lycopene.

Conclusion

We first engineered an H. bluephagenesis for the lycopene production. The co-optimization of downstream genes and promoters governing MVA pathway gene expressions can synergistically enhance the microbial overproduction of lycopene.
Pigments of aminophenoxazinones and viridomycins produced by termite-associated Streptomyces tanashiensis BYF-112
Authors: Zhang Shuxiang , Wu Jun , Jiang Zhou , Zhang Le , Song Tao , Liu Xinhua , Yin Caiping , Zhang Yinglao
Published: January 2023

Termite-associated Streptomyces tanashiensis BYF-112 was found as a potential source for yellow and green pigments, which were stable under the tested temperature, light and metal ions. Eight metabolites (1–8), including four new natural yellow pigments aminophenoxazinones (1–4), and two rarely iron dependent green pigments viridomycin A and F (9–10) were isolated from BYF-112 cultured in YMS and YMS treated with FeSO4, respectively. The metabolites 2–4 displayed a significant safety performance on the normal liver cell line L-02, while the metabolite 1 showed weak cytotoxicity against the L-02 and several cancer cells. Especially, in the filter paper disc tests, the compound 1 possessed strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) with the zone of inhibition (ZOI) of 15.3 mm, which was equal to that of referenced levofloxacin (ZOI = 15.2 mm). And the metabolite 1 also showed moderate antibacterial activities against Micrococcus teragenus and S. aureus, with the ZOI values of 15.3 and 17.2 mm. In addition, by the minimum inhibitory concentration (MIC) assay, the compound 1 displayed potential antibacterial activities against M. teragenus, S. aureus and MRSA, with the MIC values of 12.5, 12.5, and 25.0 μg/ml, respectively. The present results indicate that BYF-112 may be a promising source for safe and bioactive pigments, which can be used for further development and industrial applications.