bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation and Selection of the Inhaler Device for Treprostinil Palmitil Inhalation Powder
Authors: Gauani Helena , Baker Thomas , Li Zhili , Malinin Vladimir S. , Perkins Walter , Sullivan Eugene , Cipolla David
Published: January 2023

Treprostinil palmitil (TP) is a prodrug of treprostinil that has been formulated as an inhaled powder, termed TPIP, for evaluation in patients with pulmonary arterial hypertension. In these characterization studies we investigated the aerosol performance of TPIP in response to changes in capsule fill, device resistance, and inspiratory flow rate to enable selection of an inhaler for clinical use. Capsules containing 8, 16 or 32 mg of TPIP (80, 160, or 320 μg TP, respectively) were evaluated using four commercially-available, breath-actuated RS01 devices (Plastiape, S. p.A., Osnago, Italy) with low, medium, high or ultra-high inspiratory resistances, creating 12 different capsule and device configurations for evaluation. Aerosol characterization was performed using the next generation impactor at compendial conditions of 23°C and 35% relative humidity and a flow rate corresponding to a 4 kPa pressure drop. The aerosol mass median aerodynamic diameter, geometric standard deviation, fine particle fraction, emitted dose and fine particle dose (FPD) were calculated from the in vitro impactor data. The TP emitted dose at 4 kPa exceeded 75% for all 12 capsule and device configurations. The FPD, an estimate of the respirable dose, varied between 61.0 and 70.6% of the loaded TP dose for all four devices with the 8 and 16 mg TPIP capsule dose. For the 32 mg TPIP capsule dose, the FPD remained above 61.0% for the high and ultra-high resistance devices but decreased to 48.5 and 52.6% for the low and medium resistance devices, respectively. Based on this initial data, the high resistance device was selected for additional characterization studies at 40 and 80 L/min corresponding to pressure drops of 1.4 and 5.4 kPa. The FPD was relatively insensitive to changes in flow rate, providing an expectation of a consistent total lung dose of TP under scenarios simulating variability in how the device is used. Based on these findings, the high resistance device was chosen for further development in human clinical trials.
Self-adaptive seismic data reconstruction and denoising using dictionary learning based on morphological component analysis
Authors: Wang De-Ying , Xu Xing-Rong , Zeng Hua-Hui , Sun Jia-Qing , Xu Xin , Zhang Yi-Kui
Published: January 2023

Data reconstruction and data denoising are two critical preliminary steps in seismic data processing. Compressed Sensing states that a signal can be recovered by a series of solving algorithms if it is sparse in a transform domain, and has been well applied in the field of reconstruction, when, sparse representation of seismic data is the key point. Considering the complexity and diversity of seismic data, a single mathematical transformation will lead to incomplete sparse expression and bad restoration effects. Morphological Component Analysis (MCA) decomposes a signal into several components with outstanding morphological features to approximate the complex internal data structure. However, the representation ability of combined dictionaries is constrained by the number of dictionaries, and cannot be self-adaptively matched with the data features. Dictionary learning overcomes the limitation of fixed base function by training dictionaries that are fully suitable for processed data, but requires huge amount of time and considerable hardware cost. To solve the above problems, a new dictionary library (K-Singluar Value Decomposition learning dictionary and Discrete Cosine Transform dictionary) is hereby proposed based on the efficiency of fixed base dictionary and the high precision of learning dictionary. The self-adaptive sparse representation is achieved under the Morphological Component Analysis framework and is successfully applied to the reconstruction and denoising of seismic data. Real data tests have proved that the proposed method performs better than single mathematical transformation and other combined dictionaries.
DDA simulation study on fracturing failure reproducibility of heterogenous rock
Authors: Chen Dayong , Yang Zheng , Wang Mingke , Jiang Xufei , Ning Youjun
Published: January 2023

The mesoscale heterogeneity of rock determines its macroscale mechanical performance to a large extent. In this paper, a sub-block element discontinuous deformation analysis (DDA) method coupled with a statistic heterogeneity model was used to simulate the fracturing failure of pre-notched rock specimens. The simulation recreated the macroscale whole-process nonlinear deformation and fracturing failure of pre-notched disc and rectangular specimens with some important features explored in experiments or other numerical simulations. Combing intact heterogeneous rock specimen simulations in previous work, the effect of the heterogeneity on the reproducibility of macroscale strength and failure patterns of the specimens were investigated. Results indicate that the influence degree of the heterogeneity on the macroscale equivalent strength and fracturing failure pattern reproducibility varies with the specimen particularities (disc or rectangular, pre-notched or intact, and inclination of the pre-existing flaw), and the reason behind was discussed from the point view of stress concentration. This work is meaningful for the understanding of the result discreteness of rock specimen experiments, and assures the importance to consider the rock heterogeneity in practical rock engineering.
Sequence stratigraphy of the Middle Jurassic Yan’an Formation (NE Ordos Basin, China), relationship with climate conditions and basin evolution, and coal maceral’s characteristics
Authors: Lv Dawei , Shen Yangyang , van Loon A. J. Tom , Raji Munira , Zhang Zhihui , Song Guangzeng , Ren Zhouhe , Wang Yujia , Wang Dongdong
Published: January 2023

The Yan’an Formation of the Ordos Basin in North China is among the largest and most extensively studied Jurassic coal reservoirs in the world. The lacustrine Yan’an Formation was investigated near Dongsheng (Ordos Basin, China) in its sequence-stratigraphic context, to understand the factors that controlled the peat accumulation and the cyclicity in the coal-bearing strata. Nine facies, grouped into two facies associations, jointly composed two third-order sequences. These represent lowstand system tracts, extended (lacustrine) system tracts and highstand system tracts. The sequence stratigraphic framework could be established on the basis of correlations of cores and logging from several wells. It appears that the coal development was controlled partly by fluctuations of the lake level. The sequence development controlled the vertical distribution of the coal seams, which mainly developed during extended lacustrine system tracts (= during transgressive stages of the lake) and the early stage of highstand system tracts. Sequence stratigraphy and maceral analysis indicate that basin subsidence and climate were the main controlling factors for the development of the coal seams and the coal-bearing succession. A generic model was established to show the lateral and vertical distribution of coal seams in the large, subsiding lacustrine coal basin with no significant folding or faulting. Special attention is paid to the changing climate conditions. The findings are considered to help deepen the theory of coal formation; they will also help increase the efficacy of coal exploitation in basins such as the Ordos Basin.
The possible impact of solar activity on the summer temperature distribution over Eurasia
Authors: Lu Wei , Xiao Ziniu , Feng Xueshang
Published: January 2023

The effect of solar activity on the regional temperature in winter has been widely discussed. However, whether the summer temperature of land in the northern hemisphere is sensitive to solar activity remains to be further investigated. In this study, the empirical orthogonal function (EOF) analysis, spectrum analysis, and correlation analysis are employed to reveal the possible link between the summer temperature distribution over Eurasian land (0–180°E and 20°N−80°N) and solar activity. The results show that the corresponding time series of the second pattern significantly exhibits an 11-year solar periodicity. Its tripolar temperature distribution is similar to the correlation maps between the temperature and sunspot number (SSN). Particularly, Central Asia (50°E−90°E and 30°N−60°N) is the key response region over Eurasia. The temperature of Central Asia shows a weak but significant negative correlation with SSN. Further analysis of atmospheric circulation indicates that the solar-induced cyclonic and negative geopotential height anomalies in Central Asia weaken the high-pressure ridge on the southwest side and strengthen northwesterly winds. At the same time, with the increase in the cloud cover and the decrease of shortwave radiation, the temperature is lowered. Due to the impact of solar activity, the upper atmosphere over Eurasia forms a wave train-like structure, resulting in a tripolar temperature distribution pattern. On the other hand, the 21-year sliding correlation results suggest that the connection between solar activity and the temperature in Central Asia was strong and decadal stable until 1980. Whereas the temperature and atmospheric circulations in high latitudes become more sensitive to solar activity after 1980. Anyway, solar activity still can be considered a non-negligible factor in the prediction of the summer temperature in Eurasia.
The role of earthquakes and storms in the fluvial export of terrestrial organic carbon along the eastern margin of the Tibetan plateau: A biomarker perspective
Authors: Wang Jin , Ma Tian , Zhang Fei , Hilton Robert G. , Feng Xiaojuan , Jin Zhangdong
Published: January 2023

Driven by earthquakes and intense rainfall, steep tectonically active mountains are hotspots of terrestrial organic carbon mobilization from soils, rocks, and vegetation by landslides into rivers. Subsequent delivery and fluvial mobilization of organic carbon from different sources can impact atmospheric CO2 concentrations across a range of timescales. Extreme landslide triggering events can provide insight on processes and rates of carbon export. Here we used suspended sediment collected from 2005 to 2012 at the upper Min Jiang, a main tributary of the Yangtze River on the eastern margin of the Tibetan Plateau, to compare the erosion of terrestrial organic carbon before and after the 2008 Wenchuan earthquake and a storm-derived debris flow event in 2005. To constrain the source of riverine particulate organic carbon (POC), we quantified lignin phenols and n-alkanoic acids in the suspended sediments, catchment soils and landslide deposits. We found that riverine POC had higher inputs of less-degraded, discrete organic matter at high suspended sediment loads, while the source of POC seemed stochastic at low suspended sediment concentrations. The debris flow in 2005 mobilized a large amount of POC, resulting in an export of lignin within a single day equivalent to a normal year. In comparison, the 2008 Wenchuan earthquake increased the flux of POC and particulate lignin, albeit with limited impact on POC sources in comparison to seasonal variations. Our results highlight the important role of episodic events in the fluvial export of terrestrial carbon.
Short-term load forecasting based on CEEMDAN-FE-ISSA-LightGBM model
Authors: Li Zhihao , Chen Zhongli
Published: January 2023

To address the problems of low load forecasting accuracy due to the strong non-stationarity of electric loads, this paper proposes a short-term load forecasting method based on a combination of the complete ensemble empirical modal decomposition adaptive noise method-fuzzy entropy (CEEMDAN-FE) and the Light Gradient Boosting Machine (LightGBM) optimized by the improved sparrow search algorithm (ISSA). First, the original data are decomposed by the complete ensemble empirical modal decomposition adaptive noise algorithm to obtain the eigenmodal components (IMFs) and residual values. Second, the obtained sequences are entropy reorganized by fuzzy entropy, and thus new sequences are obtained. Third, the new sequences are input into the improved sparrow search algorithm-Light Gradient Boosting Machine model for training and prediction. The improved sparrow search algorithm algorithm can realize parameter optimization of the Light Gradient Boosting Machine model to make the data match the model better, and the predicted values of each grouping of the model output are superimposed to obtain the final predicted values. Finally, the effect is compared by the error function, and the comparison results are used to test the performance of the algorithm. The experiments showed that the smallest evaluation metrics were obtained in Case 1 (MAE = 32.251, MAPE = 0.0114,RMSE = 42.386, R2 = 0.997) and Case2 (MAE = 3.866, MAPE = 0.003, RMSE = 5.940, R2 = 0.997).
Strengthening and microbial regulation mechanism of Bacillus on purification device for grass carp culture wastewater
Authors: Li Zhifei , Gao Yan , Lu Zhuoyin , Xie Jun , Liu Yang , Wang Guangjun , Cheng Xiangju
Published: January 2023

Aquaculture wastewater (AW) poses a threat to natural aquatic environments. Microecological agents are widely used to regulate and purify AW, with Bacillus being the most common. To evaluate the AW purification effect of adding Bacillus subtilis and Bacillus licheniformis to an AW treatment device, we constructed an experimental device including a small grass carp culture pond and three groups of cuboid reactors. The effects of adding the two strains to the AW treatment reactor on the AW purification effect and the microbiota compositions in the AW and packing surface biofilm were analyzed via high-throughput sequencing of the 16S rRNA gene. Our results showed that adding Bacillus bacteria to reactors improved the total nitrogen (TN) removal efficiency and reduced the chemical oxygen demand (COD). Adding both the B. subtillis and B. licheniformis preparations significantly increased the abundance of Firmicutes in the water microbiota of the reactor at the middle and end stages of the experiment. The addition of Bacillus changed the microbiota composition in the water and packing surface biofilm and significantly increased the abundance of Bacillus at the middle and later stages of the experiment. Therefore, the addition of Bacillus improved the TN removal efficiency in the AW grass carp treatment reactors and significantly reduced the COD in the AW by increasing the abundance of Bacillus and changing the microbiota composition in the system. We provide an effective way for improving the purification capacity of biofilm reactor.
Nanobodies in cell-mediated immunotherapy: On the road to fight cancer
Authors: Maali Amirhosein , Gholizadeh Monireh , Feghhi-Najafabadi Saba , Noei Ahmad , Seyed-Motahari Seyedeh Sheila , Mansoori Shafieeh , Sharifzadeh Zahra
Published: January 2023

The immune system is essential in recognizing and eliminating tumor cells. The unique characteristics of the tumor microenvironment (TME), such as heterogeneity, reduced blood flow, hypoxia, and acidity, can reduce the efficacy of cell-mediated immunity. The primary goal of cancer immunotherapy is to modify the immune cells or the TME to enable the immune system to eliminate malignancies successfully. Nanobodies, known as single-domain antibodies, are light chain-free antibody fragments produced from Camelidae antibodies. The unique properties of nanobodies, including high stability, reduced immunogenicity, enhanced infiltration into the TME of solid tumors and facile genetic engineering have led to their promising application in cell-mediated immunotherapy. They can promote the cancer therapy either directly by bridging between tumor cells and immune cells and by targeting cancer cells using immune cell-bound nanobodies or indirectly by blocking the inhibitory ligands/receptors. The T-cell activation can be engaged through anti-CD3 and anti-4-1BB nanobodies in the bispecific (bispecific T-cell engagers (BiTEs)) and trispecific (trispecific T-cell engager (TriTEs)) manners. Also, nanobodies can be used as natural killer (NK) cell engagers (BiKEs, TriKEs, and TetraKEs) to create an immune synapse between the tumor and NK cells. Nanobodies can redirect immune cells to attack tumor cells through a chimeric antigen receptor (CAR) incorporating a nanobody against the target antigen. Various cancer antigens have been targeted by nanobody-based CAR-T and CAR-NK cells for treating both hematological and solid malignancies. They can also cause the continuation of immune surveillance against tumor cells by stopping inappropriate inhibition of immune checkpoints. Other roles of nanobodies in cell-mediated cancer immunotherapy include reprogramming macrophages to reduce metastasis and angiogenesis, as well as preventing the severe side effects occurring in cell-mediated immunotherapy. Here, we highlight the critical functions of various immune cells, including T cells, NK cells, and macrophages in the TME, and discuss newly developed immunotherapy methods based on the targeted manipulation of immune cells and TME with nanobodies.
Analysis of causes for poor persistence of CAR-T cell therapy in vivo
Authors: Kong Yingjie , Tang Ling , You Yong , Li Qing , Zhu Xiaojian
Published: January 2023

Chimeric antigen receptor T-cell (CAR-T-cell) therapy has been well researched to date because of its ability to target malignant tumor cells. The most common CAR-T cells are CD19 CAR-T cells, which play a large role in B-cell leukemia treatment. However, most CAR-T cells are associated with relapse after clinical treatment, so the quality and persistence of CAR-T cells need to be improved. With continuous optimization, there have been four generations of CARs and each generation of CARs has better quality and durability than the previous generation. In addition, it is important to increase the proportion of memory cells in CAR-T cells. Studies have shown that an immunosuppressive tumor microenvironment (TME) can lead to dysfunction of CAR-T cells, resulting in decreased cell proliferation and poor persistence. Thus, overcoming the challenges of immunosuppressive molecules and targeting cytokines in the TME can also improve CAR-T cell persistence. In this paper, we explored how to improve the durability of CAR-T cell therapy by improving the structure of CARs, increasing the proportion of memory CAR-T cells and improving the TME.
Multi-omics analysis of N6-methyladenosine reader IGF2BP3 as a promising biomarker in pan-cancer
Authors: Chen Pin , Xu Jing , Cui Zihan , Wu Silin , Xie Tao , Zhang Xiaobiao
Published: January 2023

Background

Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) has been reported to exhibit an oncogenic effect as an RNA-binding protein (RBP) by promoting tumor cell proliferation, migration and invasion in several tumor types. However, a pan-cancer analysis of IGF2BP3 is not currently available, and the exact roles of IGF2BP3 in prognosis and immunology in cancer patients remain enigmatic. The main aim of this study was to provide visualization of the systemic prognostic landscape of IGF2BP3 in pan-cancer and to uncover the potential relationship between IGF2BP3 expression in the tumor microenvironment and immune infiltration profile.

Methods

Raw data on IGF2BP3 expression were obtained from GTEx, CCLE, TCGA, and HPA data portals. We have investigated the expression patterns, diagnostic and prognostic significance, mutation landscapes, functional analysis, and functional states of IGF2BP3 utilizing multiple databases, including HPA, TISIDB, cBioPortal, GeneMANIA, GESA, and CancerSEA. Moreover, the relationship of IGF2BP3 expression with immune infiltrates, TMB, MSI and immune-related genes was evaluated in pan-cancer. IGF2BP3 with drug sensitivity analysis was performed from the CellMiner database. Furthermore, the expression of IGF2BP3 in different grades of glioma was detected by immunohistochemical staining and western blot.

Results

We found that IGF2BP3 was ubiquitously highly expressed in pan-cancer and significantly correlated with diagnosis, prognosis, TMB, MSI, and drug sensitivity in various types of cancer. Besides, IGF2BP3 was involved in many cancer pathways and varied in different immune and molecular subtypes of cancers. Additionally, IGF2BP3 is critically associated with genetic markers of immunomodulators in various cancers. Finally, we validated that IGF2BP3 protein expression was significantly higher in glioma than in normal tissue, especially in GBM.

Conclusions

IGF2BP3 may be a potential molecular biomarker for diagnosis and prognosis in pan-cancer, especially for glioma. It could become a novel therapeutic target for various cancers.
Construction and systematic evaluation of a machine learning-based cuproptosis-related lncRNA score signature to predict the response to immunotherapy in hepatocellular carcinoma
Authors: Lu Dingyu , Liao Jian , Cheng Hao , Ma Qian , Wu Fei , Xie Fei , He Yingying
Published: January 2023

Introduction

Hepatocellular carcinoma (HCC) is a common malignant cancer with a poor prognosis. Cuproptosis and associated lncRNAs are connected with cancer progression. However, the information on the prognostic value of cuproptosis-related lncRNAs is still limited in HCC.

Methods

We isolated the transcriptome and clinical information of HCC from TCGA and ICGC databases. Ten cuproptosis-related genes were obtained and related lncRNAs were correlated by Pearson’s correlation. By performing lasso regression, we created a cuproptosis-related lncRNA prognostic model based on the cuproptosis-related lncRNA score (CLS). Comprehensive analyses were performed, including the fields of function, immunity, mutation and clinical application, by various R packages.

Results

Ten cuproptosis-related genes were selected, and 13 correlated prognostic lncRNAs were collected for model construction. CLS was positively or negatively correlated with cancer-related pathways. In addition, cell cycle and immune related pathways were enriched. By performing tumor microenvironment (TME) analysis, we determined that T-cells were activated. High CLS had more tumor characteristics and may lead to higher invasiveness and treatment resistance. Three genes (TP53, CSMD1 and RB1) were found in high CLS samples with more mutational frequency. More amplification and deletion were detected in high CLS samples. In clinical application, a CLS-based nomogram was constructed. 5-Fluorouracil, gemcitabine and doxorubicin had better sensitivity in patients with high CLS. However, patients with low CLS had better immunotherapeutic sensitivity.

Conclusion

We created a prognostic CLS signature by machine learning, and we comprehensively analyzed the signature in the fields of function, immunity, mutation and clinical application.
Similarities and differences of chemical compositions and physical and functional properties of adjuvant system 01 and army liposome formulation with QS21
Authors: Alving Carl R. , Rao Mangala , Matyas Gary R.
Published: January 2023

A vaccine adjuvant known as Adjuvant System 01 (AS01) consists of liposomes containing a mixture of natural congeners of monophosphoryl lipid A (MPL®) obtained from bacterial lipopolysaccharide, and a tree saponin known as QS21. Two vaccines containing AS01 as the adjuvant have been licensed, including a malaria vaccine (Mosquirix®) approved by World Health. Organization and European Medicines Agency for use in sub-Saharan Africa, and a shingles vaccine (Shingrix®) approved by the U.S. Food and Drug Administration. The success of the AS01 vaccine adjuvant has led to the development of another liposomal vaccine adjuvant, referred to as Army Liposome Formulation with QS21 (ALFQ). Like AS01, ALFQ consists of liposomes containing monophosphoryl lipid A (as a synthetic molecule known as 3D-PHAD®) and QS21 as adjuvant constituents, and the polar headgroups of the liposomes of AS01 and ALFQ are similar. We compare here AS01 with ALFQ with respect to their similar and different liposomal chemical structures and physical characteristics with a goal of projecting some of the likely mechanisms of safety, side effects, and mechanisms of adjuvanticity. We hypothesize that some of the side effects exhibited in humans after injection of liposome-based vaccines might be caused by free fatty acid and lysophospholipid released by enzymatic attack of liposomal phospholipid by phospholipase A2 at the injection site or systemically after injection.
Potential contribution of anti-p200 autoantibodies to mucosal lesions in anti-p200 pemphigoid
Authors: Gao Yangmin , Qian Hua , Hashimoto Takashi , Li Xiaoguang
Published: January 2023

Anti-p200 pemphigoid is a relatively rare subepidermal autoimmune bullous disease (AIBD), which was firstly reported by Detlef Zillikens, Takashi Hashimoto and others in 1996. Skin lesions are considered as the major clinical features of this disease, with occasional involvement of mucosal lesions. The mechanism of mucosal lesions involved in anti-p200 pemphigoid is still unclear. In the present study, we aimed to analyze published data on cases and case series of anti-p200 pemphigoid with mucosal lesions and explored the potential contribution of anti-p200 autoantibodies to mucosal lesions. A total of 32 papers that comprised 52 anti-p200 pemphigoid patients with various mucosal lesions were included in this review. Oral lesions were involved in 75.0% patients, followed by genital lesions (26.9%) and ocular lesions (11.54%). Only one patient had psoriasis, 26.9% patients had multiple mucosal lesions, and 30.8% cases had comorbidity of other AIBDs, particularly anti-laminin (LM) 332-type mucous membrane pemphigoid (MMP). In comparison with anti-LM332-type MMP, anti-BP180-type MMP and epidermolysis bullosa acquisita, higher frequency of genital lesions was identified as a unique character of anti-p200 pemphigoid with mucosal lesions. These results indicated that anti-p200 autoantibodies might contribute to mucosal lesions in a pattern different from other MMP-related autoantibodies, although its pathogenetic mechanisms are still unclear.
Active hydrothermal vent ecosystems in the Indian Ocean are in need of protection
Authors: van der Most Naomi , Qian Pei-Yuan , Gao Yan , Gollner Sabine
Published: January 2023

Deep-sea hydrothermal vent fields are among the most pristine and remarkable ecosystems on Earth. They are fueled by microbial chemosynthesis, harbor unique life and can be sources of precipitated mineral deposits. As the global demand for mineral resources rises, vent fields have been investigated for polymetallic sulfides (PMS) and biological resources. The International Seabed Authority (ISA) has issued 7 contracts for PMS exploration, including 4 licenses for vent fields in the Indian Ocean. Here, we provide a summary of the available ecological knowledge of Indian vent communities and we assess their vulnerability, sensitivity, ecological and biological significance. We combine and apply scientific criteria for Vulnerable Marine Ecosystems (VMEs) by FAO, Particular Sensitive Sea Areas (PSSAs) by IMO, and Ecologically or Biologically Significant Areas (EBSAs) by CBD. Our scientific assessment shows that all active vent fields in the Indian Ocean appear to meet all scientific criteria for protection, and both the high degree of uniqueness and fragility of these ecosystems stand out.
Quantifying the effects of extreme events and oceanographic variability on the spatiotemporal biomass and distribution of two key euphausiid prey species
Authors: Evans Rhian , English Philina A. , Gauthier Stéphane , Robinson Clifford L.K.
Published: January 2023

Euphausiids form a critical component of oceanic food chains and individual species vary in their responses to perturbation events. We aimed to establish if patterns of fine scale oceanographic variability and larger-scale climate events such as marine heatwaves (MHWs) could be linked with spring variability in the biomass of two key forage species in the northeast Pacific Ocean, Euphausia pacifica and Thysanoessa spinifera. To achieve this, we used long-term datasets from the west coast of Vancouver Island Canada, an important commercial fishing area, to first quantify interannual signals of variability in fine-scale oceanographic conditions using multivariate analysis. We then used geostatistical spatiotemporal modelling to quantify the effects on species-specific euphausiid biomass. Oceanographic data showed that the effects of warm events are not always observable, and effects vary across small spatial scales. Warming due to the 2014-2016 MHW was relatively mild on the continental shelf during spring (<1°C above climatology). Spring biomass of euphausiids, particularly E. pacifica, peaked in 2015, and all euphausiid groups analysed (E. pacifica, T. spinifera and total euphausiids) exhibited significant correlations with positive phases of the Pacific Decadal Oscillation. These results have implications for marine predators as euphausiids may act as system stabilisers in the northeast Pacific, thereby potentially increasing ecosystem resilience during extreme events.
Senescent renal tubular epithelial cells activate fibroblasts by secreting Shh to promote the progression of diabetic kidney disease
Authors: Wang Dan , Yin Ling , Chen Rongyu , Tan Wanlin , Liang Luqun , Xiang Jiayi , Zhang Huifang , Zhou Xingcheng , Deng Huaqing , Guo Bing , Wang Yuanyuan
Published: January 2023

Introduction

Diabetic kidney disease (DKD) is one of the complications of diabetes; however, the pathogenesis is not yet clear. A recent study has shown that senescence is associated with the course of DKD. In the present study, we explored whether senescent renal tubular cells promote renal tubulointerstitial fibrosis by secreting Sonic hedgehog (Shh) which mediates fibroblast activation and proliferation in DKD.

Methods

A 36-week-old db/db mice model and the renal tubular epithelial cells were cultured in high glucose (HG, 60 mmol/L) medium for in vivo and in vitro experiments.

Results

Compared to db/m mice, blood glucose, microalbuminuria, serum creatinine, urea nitrogen, and UACR (microalbuminuria/urine creatinine) were markedly increased in db/db mice. Collagen III, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α) were also increased in db/db mice kidneys, suggesting fibrosis and inflammation in the organ. Moreover, the detection of SA-β-galactosidase (SA-β-Gal) showed that the activity of SA-β-Gal in the cytoplasm of renal tubular epithelial cells increased, and the cell cycle inhibition of the expression of senescence-related gene cell cycle inhibitor p16INK4A protein and p21 protein increased, indicating that renal fibrosis in db/db mice was accompanied by cell senescence. Furthermore, Shh is highly expressed in the injured renal tubules and in the kidney tissue of db/db mice, as detected by enzyme-linked immunosorbent assay (ELISA). The results of immunofluorescence staining showed increased positive staining for Shh in renal tubular epithelial cells of db/db mice and decreased positive staining for Lamin B1, but increased positive staining for γH2A.X in cells with high Shh expression; similar results were obtained in vitro. In addition, HG stimulated renal tubular epithelial cells to secrete Shh in the supernatant of the medium. D-gal treatment of renal tubular epithelial cells increased the protein levels of Shh and p21. We also found enhanced activation and proliferation of fibroblasts cultured with the supernatant of renal tubular epithelial cells stimulated by HG medium but the proliferative effect was significantly diminished when co-cultured with cyclopamine (CPN), an inhibitor of the Shh pathway.

Discussion

In conclusion, HG induces renal tubular epithelial cell senescence, and the secretion of senescence-associated proteins and Shh mediates inflammatory responses and fibroblast activation and proliferation, ultimately leading to renal fibrosis.
Case report: 11 years on hemodialysis with a 4-year-old baby girl: A success story
Authors: Mambap Alex Tatang , Bechem Efuetnkeng , Kan Kate Mafor , Laah Sylvain Njoyo , Sunjoh Frida , Ashuntantang Gloria Enow
Published: January 2023

Despite advances in clinical management and dialysis care, the outcome of unplanned pregnancy in women on maintenance hemodialysis (MHD) remains a difficult journey for the patient, fetus, and healthcare staff, particularly in low-resource countries. We report the successful outcome of a pregnancy in an anuric woman on twice-weekly maintenance hemodialysis for chronic glomerulonephritis since November 2012 in Cameroon. She was discovered pregnant at 18 weeks of gestation. The pregnancy was maintained until 36 weeks when a healthy 2,270 g female baby was delivered by elective cesarean section for tight nuchal cords and intrauterine growth retardation. The mother’s post-partum period was uneventful. Except for hypoglycemia shortly after birth, the baby was fine. The patient is still on hemodialysis after 4 years, and the child is healthy and attending school.
Infection-specific PET imaging with 18F-fluorodeoxysorbitol and 2-[18F]F-ρ-aminobenzoic acid: An extended diagnostic tool for bacterial and fungal diseases
Authors: Rua Marta , Simón Jon Ander , Collantes María , Ecay Margarita , Leiva José , Carmona-Torre Francisco , Ramos Rocío , Pareja Félix , Pulagam Krishna R. , Llop Jordi , Del Pozo José Luis , Peñuelas Iván
Published: January 2023

Introduction

Suspected infectious diseases located in difficult-to-access sites can be challenging due to the need for invasive procedures to isolate the etiological agent. Positron emission tomography (PET) is a non-invasive imaging technology that can help locate the infection site. The most widely used radiotracer for PET imaging (2-deoxy-2[18F] fluoro-D-glucose: [18F]FDG) shows uptake in both infected and sterile inflammation. Therefore, there is a need to develop new radiotracers able to specifically detect microorganisms.

Methods

We tested two specific radiotracers: 2-deoxy-2-[18F]-fluoro-D-sorbitol ([18F]FDS) and 2-[18F]F-ρ-aminobenzoic acid ([18F]FPABA), and also developed a simplified alternative of the latter for automated synthesis. Clinical and reference isolates of bacterial and yeast species (19 different strains in all) were tested in vitro and in an experimental mouse model of myositis infection.

Results and discussion

Non-lactose fermenters (Pseudomonas aeruginosa and Stenotrophomonas maltophilia) were unable to take up [18F]FDG in vitro. [18F]FDS PET was able to visualize Enterobacterales myositis infection (i.e., Escherichia coli) and to differentiate between yeasts with differential assimilation of sorbitol (i.e., Candida albicans vs. Candida glabrata). All bacteria and yeasts tested were detected in vitro by [18F]FPABA. Furthermore, [18F]FPABA was able to distinguish between inflammation and infection in the myositis mouse model (E. coli and Staphylococcus aureus) and could be used as a probe for a wide variety of bacterial and fungal species.
Grass-microbial inter-domain ecological networks associated with alpine grassland productivity
Authors: Wang Yingcheng , Dang Ning , Feng Kai , Wang Junbang , Jin Xin , Yao Shiting , Wang Linlin , Gu Songsong , Zheng Hua , Lu Guangxin , Deng Ye
Published: January 2023

Associations between grasses and soil microorganisms can strongly influence plant community structures. However, the associations between grass productivity and diversity and soil microbes, as well as the patterns of co-occurrence between grass and microbes remain unclear. Here, we surveyed grass productivity and diversity, determined soil physicochemical, and sequenced soil archaea, bacteria and fungi by metabarcoding technology at 16 alpine grasslands. Using the Distance-decay relationship, Inter-Domain Ecological Network (IDEN), and Mantel tests, we investigated the relationship between grass productivity, diversity and microbial diversity, and the patterns of co-occurrence between grass and microbial inter-domain network in alpine grassland. We found the archaea richness, bacteria richness and Shannon, and fungi α-diversity were significantly negatively correlation with grass diversity, but archaea and bacteria diversity were positively correlation with grass productivity. Moreover, an increase in microbial β-diversity was observed along with increased discrepancy in grass diversity and productivity and soil variables. Variance partitioning analysis suggested that the contribution of grass productivity on microbial community was higher than that of soil variables and grass diversity, which implies that microbial community was more related to grass productivity. Inter-Domain Ecological Network showed that the grass species formed complex and stable ecological networks with some bacterial, archaeal, and fungal species, and the grass-fungal ecological networks showed the highest robustness, which indicated that soil fungi could better co-coexist with aboveground grass in alpine grasslands. Besides, the connectivity degrees of the grass-microbial network were significantly positively correlated with grass productivity, suggesting that the coexistence pattern of grasses and microbes had a positive feedback effect on the grass productivity. The results are important for establishing the regulatory mechanisms between plants and microorganisms in alpine grassland ecosystems.
PIN1 and PIN4 inhibition via parvulin impeders Juglone, PiB, ATRA, 6,7,4′-THIF, KPT6566, and EGCG thwarted hepatitis B virus replication
Authors: Saeed Umar , Piracha Zahra Zahid
Published: January 2023

Introduction

Human parvulin peptidyl prolyl cis/trans isomerases PIN1 and PIN4 play important roles in cell cycle progression, DNA binding, protein folding and chromatin remodeling, ribosome biogenesis, and tubulin polymerization. In this article, we found that endogenous PIN1 and PIN4 were upregulated in selected hepatocellular carcinoma (HCC) cell lines.

Methods

In this study, we inhibited PIN1 and PIN4 via parvulin inhibitors (Juglone, PiB, ATRA, 6,7,4′-THIF, KPT6566, and EGCG). The native agarose gel electrophoresis (NAGE) immunoblotting analysis revealed that upon PIN1 and/ or PIN4 inhibition, the HBc protein expression and core particle or capsid synthesis reduced remarkably. The effects of PIN4 inhibition on hepatitis B virus (HBV) replication were more pronounced as compared to that of PIN1. The Northern and Southern blotting revealed reduced HBV RNA and DNA levels.

Results

During the HBV course of infection, Juglone, PiB, ATRA, 6,7,4′-THIF, KPT6566, and EGCG-mediated inhibition of PIN1 and PIN4 significantly lowered HBV transcriptional activities without affecting total levels of covalently closed circular DNA (cccDNA). Similar to the inhibitory effects of PIN1 and PIN4 on HBV replication, the knockdown of PIN1 and PIN4 in HBV infection cells revealed significantly reduced amounts of intracellular HBc, HBs, HBV pgRNA, SmRNAs, core particles, and HBV DNA synthesis. Similarly, PIN1 and PIN4 KD abrogated extracellular virion release, naked capsid levels, and HBV DNA levels. In comparison with PIN1 KD, the PIN4 KD showed reduced HBc and/or core particle stabilities, indicating that PIN4 is more critically involved in HBV replication. Chromatin immunoprecipitation (ChIP) assays revealed that in contrast to DNA binding PIN4 proteins, the PIN1 did not show binding to cccDNA. Similarly, upon PIN1 KD, the HBc recruitment to cccDNA remained unaffected. However, PIN4 KD significantly abrogated PIN4 binding to cccDNA, followed by HBc recruitment to cccDNA and restricted HBV transcriptional activities. These effects were more pronounced in PIN4 KD cells upon drug treatment in HBV-infected cells.

Conclusion

The comparative analysis revealed that in contrast to PIN1, PIN4 is more critically involved in enhancing HBV replication. Thus, PIN1 and PIN4 inhibition or knockdown might be novel therapeutic targets to suppress HBV infection. targets to suppress HBV infection.
Cognitive impairment in diffuse axonal injury patients with favorable outcome
Authors: Chen Weiliang , Yao Chunyu , Li Shengwen , Huang Hongguang , Zhu Zujian , Chen Rui , Su Wen , Huang Xiao , Xu Lisheng , Sun Kaijie , Song Jiannan , Jiang Rongcai , Wang Guanjun
Published: January 2023

Background and purpose

Traumatic brain injury (TBI), especially the severe TBI are often followed by persistent cognitive sequalae, including decision-making difficulties, reduced neural processing speed and memory deficits. Diffuse axonal injury (DAI) is classified as one of the severe types of TBI. Part of DAI patients are marginalized from social life due to cognitive impairment, even if they are rated as favorable outcome. The purpose of this study was to elucidate the specific type and severity of cognitive impairment in DAI patients with favorable outcome.

Methods

The neurocognition of 46 DAI patients with favorable outcome was evaluated by the Chinese version of the Montreal Cognitive Assessment Basic (MoCA-BC), and the differences in the domains of cognitive impairment caused by different grades of DAI were analyzed after data conversion of scores of nine cognitive domains of MoCA-BC by Pearson correlation analysis.

Results

Among the 46 DAI patients with favorable outcome, eight had normal cognitive function (MoCA-BC ≥ 26), and 38 had cognitive impairment (MoCA-BC < 26). The MoCA-BC scores were positively correlated with pupillary light reflex (r = 0.361, p = 0.014), admission Glasgow Coma Scale (GCS) (r = 0.402, p = 0.006), and years of education (r = 0.581, p < 0.001). Return of consciousness (r = −0.753, p < 0.001), Marshall CT (r = −0.328, p = 0.026), age (r = −0.654, p < 0.001), and DAI grade (r = −0.403, p = 0.006) were found to be negatively correlated with the MoCA-BC scores. In patients with DAI grade 1, the actually deducted scores (Ads) of memory (r = 0.838, p < 0.001), abstraction (r = 0.843, p < 0.001), and calculation (r = 0.782, p < 0.001) were most related to the Ads of MoCA-BC. The Ads of nine cognitive domains and MoCA-BC were all proved to be correlated, among patients with DAI grade 2. However, In the DAI grade 3 patients, the highest correlation with the Ads of MoCA-BC were the Ads of memory (r = 0.904, p < 0.001), calculation (r = 0.799, p = 0.006), orientation (r = 0.801, p = 0.005), and executive function (r = 0.869, p = 0.001).

Conclusion

DAI patients with favorable outcome may still be plagued by cognitive impairment, and different grades of DAI cause different domains of cognitive impairment.
Extra cup of tea intake associated with increased risk of Alzheimer’s disease: Genetic insights from Mendelian randomization
Authors: Sun Yuxuan , Liang Zixin , Xia Xiaoxuan , Wang Maggie Haitian , Zhu Chengming , Pan Yihang , Sun Rui
Published: January 2023

Background

Observational studies report inconclusive effects of tea consumption on the risk of Alzheimer’s disease (AD), and the mechanisms are unclear. This study aims to investigate the effects of genetically predicted tea intake (cups of tea consumed per day) on AD, brain volume, and cerebral small vessel disease (CSVD) using the two-sample Mendelian randomization (MR) method.

Methods

Summary statistics of tea intake were obtained from UK Biobank (N = 447,485), and AD was from the International Genomics of Alzheimer’s Project (N = 54,162). Genetic instruments were retrieved from UK Biobank using brain imaging-derived phenotypes for brain volume outcomes (N > 33,224) and genome-wide association studies for CSVD (N: 17,663–48,454).

Results

In the primary MR analysis, tea intake significantly increased the risk of AD using two different methods (ORIVW = 1.48, 95% CI: [1.14, 1.93]; ORWM = 2.00, 95% CI: [1.26, 3.18]) and reached a weak significant level using MR-Egger regression (p < 0.1). The result passed all the sensitivity analyses, including heterogeneity, pleiotropy, and outlier tests. In the secondary MR analysis, per extra cup of tea significantly decreased gray matter (βWM = −1.63, 95% CI: [−2.41, −0.85]) and right hippocampus volume (βWM = −1.78, 95% CI: [−2.76, −0.79]). We found a nonlinear association between tea intake and AD in association analysis, which suggested that over-drinking with more than 13 cups per day might be a risk factor for AD. Association analysis results were consistent with MR results.

Conclusion

This study revealed a potential causal association between per extra cup of tea and an increased risk of AD. Genetically predicted tea intake was associated with a decreased brain volume of gray matter and the right hippocampus, which indicates that over-drinking tea might lead to a decline in language and memory functions. Our results shed light on a novel possible mechanism of tea intake to increase the risk of AD by reducing brain volume.
A LASSO-based model to predict central lymph node metastasis in preoperative patients with cN0 papillary thyroid cancer
Authors: Zhao Feng , Wang Ping , Yu Chaoran , Song Xuefei , Wang Hui , Fang Jun , Zhu Chenfang , Li Yousheng
Published: January 2023

Introduction

Central lymph node metastasis (CLNM) is common in papillary thyroid carcinoma (PTC). Prophylactic central lymph node dissection (PCLND) in clinically negative central compartment lymph node (cN0) PTC patients is still controversial. How to predict CLNM before the operation is very important for surgical decision making.

Methods

In this article, we retrospectively enrolled 243 cN0 PTC patients and gathered data including clinical characteristics, ultrasound (US) characteristics, pathological results of fine-needle aspiration (FNA), thyroid function, eight gene mutations, and immunoenzymatic results. Least absolute shrinkage and selection operator (LASSO) analysis was used for data dimensionality reduction and feature analysis.

Results

According to the results, the important predictors of CLNM were identified. Multivariable logistic regression analysis was used to establish a new nomogram prediction model. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) curve were used to evaluate the performance of the new prediction model.

Discussion

The new nomogram prediction model was a reasonable and reliable model for predicting CLNM in cN0 PTC patients, but further validation is warranted.
Hybrid A* path search with resource constraints and dynamic obstacles
Authors: Cortez Alán , Ford Bryce , Nayak Indranil , Narayanan Sriram , Kumar Mrinal
Published: January 2023

This paper considers path planning with resource constraints and dynamic obstacles for an unmanned aerial vehicle (UAV), modeled as a Dubins agent. Incorporating these complex constraints at the guidance stage expands the scope of operations of UAVs in challenging environments containing path-dependent integral constraints and time-varying obstacles. Path-dependent integral constraints, also known as resource constraints, can occur when the UAV is subject to a hazardous environment that exposes it to cumulative damage over its traversed path. The noise penalty function was selected as the resource constraint for this study, which was modeled as a path integral that exerts a path-dependent load on the UAV, stipulated to not exceed an upper bound. Weather phenomena such as storms, turbulence and ice are modeled as dynamic obstacles. In this paper, ice data from the Aviation Weather Service is employed to create training data sets for learning the dynamics of ice phenomena. Dynamic mode decomposition (DMD) is used to learn and forecast the evolution of ice conditions at flight level. This approach is presented as a computationally scalable means of propagating obstacle dynamics. The reduced order DMD representation of time-varying ice obstacles is integrated with a recently developed backtracking hybrid A∗ graph search algorithm. The backtracking mechanism allows us to determine a feasible path in a computationally scalable manner in the presence of resource constraints. Illustrative numerical results are presented to demonstrate the effectiveness of the proposed path-planning method.