bluuebunny/crossref_metadata_2025 huggingface dataset:
Colorimetric sensing of hydrogen peroxide using capped Morus nigra-sawdust deposited zinc oxide nanoparticles via Trigonella foenum extract
Authors: Nishan Umar , Zahra Tabassum , Badshah Amir , Muhammad Nawshad , Afridi Saifullah , Shah Mohibullah , Khan Naeem , Asad Muhammad , Ullah Riaz , Ali Essam A. , Chen Ke
Published: February 2024

Hydrogen peroxide (H2O2) is one of the main byproducts of most enzymatic reactions, and its detection is very important in disease conditions. Due to its essential role in healthcare, the food industry, and environmental research, accurate H2O2 determination is a prerequisite. In the present work, Morus nigra sawdust deposited zinc oxide (ZnO) nanoparticles (NPs) were synthesized by the use of Trigonella foenum extract via a hydrothermal process. The synthesized platform was characterized by various techniques, including UV-Vis, FTIR, XRD, SEM, EDX, etc. FTIR confirmed the presence of a Zn‒O characteristic peak, and XRD showed the hexagonal phase of ZnO NPs with a 35 nm particle size. The EDX analysis confirmed the presence of Zn and O. SEM images showed that the as-prepared nanoparticles are distributed uniformly on the surface of sawdust. The proposed platform (acetic acid-capped ZnO NPs deposited sawdust) functions as a mimic enzyme for the detection of H2O2 in the presence of 3,3′,5,5′-tetramethylbenzidine (TMB) colorimetrically. To get the best results, many key parameters, such as the amount of sawdust-deposited nanoparticles, TMB concentration, pH, and incubation time were optimized. With a linear range of 0.001–0.360 μM and an R2 value of 0.999, the proposed biosensor’s 0.81 nM limit of quantification (LOQ) and 0.24 nM limit of detection (LOD) were predicted, respectively. The best response for the proposed biosensor was observed at pH 7, room temperature, and 5 min of incubation time. The acetic acid-capped sawdust deposited ZnO NPs biosensor was also used to detect H2O2 in blood serum samples of diabetic patients and suggest a suitable candidate for in vitro diagnostics and commercial purposes.
Complement factor H: a novel innate immune checkpoint in cancer immunotherapy
Authors: Saxena Ruchi , Gottlin Elizabeth B. , Campa Michael J. , Bushey Ryan T. , Guo Jian , Patz Edward F. , He You-Wen
Published: February 2024

The elimination of cancer cells critically depends on the immune system. However, cancers have evolved a variety of defense mechanisms to evade immune monitoring, leading to tumor progression. Complement factor H (CFH), predominately known for its function in inhibiting the alternative pathway of the complement system, has recently been identified as an important innate immunological checkpoint in cancer. CFH-mediated immunosuppression enhances tumor cells’ ability to avoid immune recognition and produce an immunosuppressive tumor microenvironment. This review explores the molecular underpinnings, interactions with immune cells, clinical consequences, and therapeutic possibilities of CFH as an innate immune checkpoint in cancer control. The difficulties and opportunities of using CFH as a target in cancer immunotherapy are also explored.
Innovative Sol-gel functionalized polyurethane foam for sustainable water purification and analytical advances
Authors: Alwael H. , Alsulami A. N. , Abduljabbar T. N. , Oubaha M. , El-Shahawi M. S.
Published: February 2024

Nanomaterial combined polymeric membranes such as polyurethane foams (PUFs) have garnered enormous attention in the field of water purification due to their ease of management and surface modification, cost-effectiveness, and mechanical, chemical, and thermal properties. Thus, this study reports the use of novel Sol-gel impregnated polyurethane foams (Sol-gel/PUFs) as new dispersive solid phase microextractors (d- µ SPME) for the efficient separation and subsequent spectrophotometric detection of Eosin Y (EY) textile dye in an aqueous solution with a pH of 3–3.8. The Sol gel, PUFs, and Sol gel–impregnated PUFs were characterized using scanning electron microscopy (SEM), goniometry measurements, dynamic light scattering (DLS), energy dispersive spectroscopy (EDS), UV-Visible, and FTIR spectra. Batch experiment results displayed a remarkable removal percentage (96% ± 5.4%) of the EY from the aqueous solution, with the total sorption time not exceeding 60 min. These data indicate rate-limited sorption via diffusion and/or surface complex ion associate formations after the rapid initial sorption steps. A pseudo-second order kinetic model thoroughly explained the sorption kinetics, providing a sorption capacity (qe) of 37.64 mg g−1, a half-life time (t1/2) of 0.8 ± 0.01 min, and intrinsic penetration control dye retention. The thermodynamic results revealed a negative value for ΔG⁰ (−78.07 kJ mol−1 at 293 K), clearly signifying that the dye uptake was spontaneous, as well as a negative value for ΔH⁰ (−69.58 kJ mol−1) and a positive value for ΔS⁰ (147.65 J mol−1 K−1), making clear the exothermic nature of EY adsorption onto the sorbent, with a growth in randomness at the molecular level. A ternary retention mechanism is proposed, involving the “weak base anion exchanger” of {(–CH2–OH+ –CH2–) (Dye anion)−}Sol-gel/PUF and/or {(–NH2+ –COO-) (Dye anion)−}Sol-gel/PUF via solvent extraction and “surface adsorption” of the dye anion on/in the Sol-gel/PUFs membranes in addition to H-bonding, including surface complexation and electrostatic π-π interaction, between the dye and the silicon/zirconium oxide (Si-O-Zr) and siloxane (Si-O-Si) groups on the sorbent. Complete extraction and recovery (93.65 ± 0.2, −102.28 ± 2.01) of EY dye with NaOH (0.5 M) as a proper eluting agent was achieved using a sorbent-packed mini column. In addition, the established extractor displayed excellent reusability and does not require organic solvents for EY enrichment in water samples, making it a talented nominee as a novel sorbent for EY sorption from wastewater. This study is of great consequence for expanding the applicatio1n of Sol-gel/PUFs in developing innovative spectrophotometric sensing strategies for dye determination. In view of this, it would also be remarkable to perform future studies to explore the analytical implications of this extractor regarding safety and environmental and public health issues associated to the pollutant.
Elucidating intermolecular forces to improve compatibility of kraft lignin in poly(lactic acid)
Authors: Esakkimuthu Esakkiammal Sudha , Ponnuchamy Veerapandian , Sipponen Mika H. , DeVallance David
Published: February 2024

Owing to its abundant supply from renewable resources, lignin has emerged as a promising functional filler for the development of sustainable composite materials. However, achieving good interfacial compatibility between lignin and synthetic polymers, particularly poly (lactic acid) (PLA), remains a fundamental challenge. To advance the development of high-performance bio-based composites incorporating lignin and PLA, our study has scrutinized to unravel the nuances of interfacial binding interactions with the lignin and PLA composite system. Molecular level and experimental examinations were employed to decipher fundamental mechanisms governing and demonstrating the interfacial adhesion. We synthesized casted films of lignin/PLA and acetylated lignin/PLA at varying weight percentages of lignin (5%, 10%, and 20%) and comprehensively investigated their physicochemical and mechanical properties. The inclusion of acetylated lignin in the composites resulted in improved mechanical strength and Young’s modulus, while the glass transition temperature and melting point were reduced compared to neat PLA. Systematic variations in these properties revealed distinct compatibility behaviors between unmodified lignin and acetylated lignin when incorporated into PLA. Molecular dynamics (MD) simulation results elucidated that the observed changes in material properties were primarily attributed to the acetylation of lignin. Acetylated lignin exhibited lower Coulombic interaction energy and higher van der Waals forces, indicating a stronger affinity to PLA and a reduced propensity for intermolecular aggregation compared to unmodified lignin. Our findings highlight the critical role of controlling intermolecular interactions and lignin aggregation to develop PLA composites with predictable performance for new applications, such as functional packaging materials.
The TRPM2 ion channel regulates metabolic and thermogenic adaptations in adipose tissue of cold-exposed mice
Authors: Benzi Andrea , Heine Markus , Spinelli Sonia , Salis Annalisa , Worthmann Anna , Diercks Björn , Astigiano Cecilia , Pérez Mato Raúl , Memushaj Adela , Sturla Laura , Vellone Valerio , Damonte Gianluca , Jaeckstein Michelle Y. , Koch-Nolte Friedrich , Mittrücker Hans-Willi , Guse Andreas H. , De Flora Antonio , Heeren Joerg , Bruzzone Santina
Published: February 2024

Introduction

During thermogenesis, adipose tissue (AT) becomes more active and enhances oxidative metabolism. The promotion of this process in white AT (WAT) is called “browning” and, together with the brown AT (BAT) activation, is considered as a promising approach to counteract obesity and metabolic diseases. Transient receptor potential cation channel, subfamily M, member 2 (TRPM2), is an ion channel that allows extracellular Ca2+ influx into the cytosol, and is gated by adenosine diphosphate ribose (ADPR), produced from NAD+ degradation. The aim of this study was to investigate the relevance of TRPM2 in the regulation of energy metabolism in BAT, WAT, and liver during thermogenesis.

Methods

Wild type (WT) and Trpm2-/- mice were exposed to 6°C and BAT, WAT and liver were collected to evaluate mRNA, protein levels and ADPR content. Furthermore, O2 consumption, CO2 production and energy expenditure were measured in these mice upon thermogenic stimulation. Finally, the effect of the pharmacological inhibition of TRPM2 was assessed in primary adipocytes, evaluating the response upon stimulation with the β-adrenergic receptor agonist CL316,243.

Results

Trpm2-/- mice displayed lower expression of browning markers in AT and lower energy expenditure in response to thermogenic stimulus, compared to WT animals. Trpm2 gene overexpression was observed in WAT, BAT and liver upon cold exposure. In addition, ADPR levels and mono/poly-ADPR hydrolases expression were higher in mice exposed to cold, compared to control mice, likely mediating ADPR generation.

Discussion

Our data indicate TRPM2 as a fundamental player in BAT activation and WAT browning. TRPM2 agonists may represent new pharmacological strategies to fight obesity.
Effect of traditional Chinese fitness exercises on bone mineral density in postmenopausal women: a network meta-analysis of randomized controlled trials
Authors: Liu Shijie , Wu Sijun , Qi Juancai , Wang Lin
Published: February 2024

We aimed to evaluate the clinical efficacy of five traditional Chinese fitness exercises (Baduanjin, Taijiquan, Wuqinxi, Yijinjing, and Liuzijue), as well as their efficacy when combined with drug therapy, in the treatment of decreased bone mineral density in postmenopausal women

Methods

This study strictly followed the evaluation guidelines of PRISMA and followed the “PICOS” principle outlined in the Cochrane Handbook. We performed a systematic search on Web of Science, Springer Link, Scopus, EMBASE, EBSCO, PubMed, the Cochrane Library, CNKI, Wanfang, CBMdisc, and the VIP Database, and we targeted RCTs studying the effect of TCE on BMD in postmenopausal women published prior to September 2023. The quality of the literature and the risk of bias of the included studies were assessed according to ROB2 and GRADE criteria, and data analysis was performed using Stata 14.

Results

A total of 33 RCTs (3658 post-menopausal women) were included. Network meta-analysis showed that Taiji (SMD=0.72, 95% CI: 0.22, 1.21, P<0.01) and Yijinjing (SMD=0.51, 95% CI: 0.03, 0.99, P<0.05) were significantly superior to conventional rehabilitation in lumbar BMD. In terms of improvement of femoral neck BMD, Baduanjin (SMD=1.63, 95% CI: -3.58, 6.85, P<0.001) and Taiji (SMD=0.46, 95% CI: 0.14, 0.79, P<0.05) had statistically different outcomes to conventional rehabilitation. Regarding Ward’s triangle BMD, Taiji (SMD= 0.32, 95% CI: 0.14, 0.50, P< 0.05) had statistically different outcomes to conventional rehabilitation. The results of the SUCRA probability ranking showed that Baduanjin + drug interventions achieved the most significant improvement in lumbar BMD (SUCRA=83.6%) and femoral neck BMD (SUCRA=90.2%). Taiji + drug interventions most effectively improved Ward’s triangle BMD (SUCRA=86.0%). In terms of traditional Chinese fitness exercises alone, Taiji was the most effective in improving lumbar BMD (SUCRA=64.4%) and Ward’s triangle BMD (SUCRA=46.8%), and Baduanjin was the most effective in treating femoral neck BMD (SUCRA=89.9%).

Conclusion

Traditional Chinese fitness exercises can significantly improve the BMD levels of postmenopausal women. Taiji, Yijinjing, and Baduanjin combined with medication showed better intervention effects overall. However, due to the limitations of the number of studies and sample sizes of individual interventions, definitive conclusions need to be verified by more high-quality studies.
Glycemic control in children with type 1 diabetes treated with the advanced hybrid closed loop system 2-year prospective, observational, two-center study
Authors: Seget Sebastian , Chobot Agata , Tarasiewicz Mateusz , Bielawska Anna , Rusak Ewa , Ochab Agnieszka , Polanska Joanna , Jarosz-Chobot Przemysława
Published: February 2024

Background and aims

MiniMed 780G is the first Advanced Hybrid Closed Loop (AHCL) system in Poland, approved in the EU in 2020. To date, observations of glycemic control up to 12 months have been published. This study aimed to analyze glycemic control and anthropometric parameters in children and adolescents with type 1 diabetes (T1D) after two years of using the AHCL system.

Materials and methods

We prospectively collected anthropometric data, pump, and continuous glucose records of fifty T1D children (9.9 ± 2.4 years, 24 (48%) boys, T1D for 3.9 ± 2.56 years) using an AHCL system. We compared the two-week AHCL records obtained after AHCL enrollment with data 6, 12, and 24 months after starting AHCL.

Results

Time in range (70-180 mg/dl) and BMI z-score did not change during the 2 years of observation (p>0.05). The percentage of autocorrection in total daily insulin increased significantly (p<0.005).

Conclusion

Glycemic control in the investigated group of children with T1D treated with the AHCL system for 2 years remained stable. Children in this group maintained weight and optimal metabolic control, most likely due to autocorrection boluses.
Dysregulation of ferroptosis-related genes in granulosa cells associates with impaired oocyte quality in polycystic ovary syndrome
Authors: Huang Jialyu , Fan Hancheng , Li Chenxi , Yang Kangping , Xiong Chaoyi , Xiong Siyi , Feng Shenghui , Chen Shen , Wang Bangqi , Su Yufang , Xu Boyun , Yang Haiyan , Wang Ni , Zhu Jing
Published: February 2024

Background

Poor oocyte quality remains one of the major challenges for polycystic ovary syndrome (PCOS) patients during in vitro fertilization (IVF) treatment. Granulosa cells (GCs) in PCOS display altered functions and could cause an unfavorable microenvironment for oocyte growth and maturation. Ferroptosis is a new form of programmed cell death, but its role in PCOS has been largely unclarified.

Methods

Ferroptosis-related differentially expressed genes (DEGs) of GCs in women with PCOS were identified by bioinformatic analyses of GSE155489 and GSE168404 datasets. Functional enrichment analyses were conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Core ferroptosis-related genes were further screened by random forest, and evaluated for diagnostic value by receiver operating characteristic curve analyses. Gene expression was validated by real-time quantitative polymerase chain reaction of collected GC samples, and analyzed for association with oocyte quality. In addition, gene regulatory network was constructed based on predicted RNA interactions and transcription factors, while potential therapeutic compounds were screened through molecular docking with crystallographic protein structures.

Results

A total of 14 ferroptosis-related DEGs were identified. These DEGs were mainly enriched in reactive oxygen species metabolic process, mitochondrial outer membrane, antioxidant activity as well as ferroptosis and adipocytokine signaling pathways. Eight core ferroptosis-related genes (ATF3, BNIP3, DDIT4, LPIN1, NOS2, NQO1, SLC2A1 and SLC2A6) were further selected in random forest model, which showed high diagnostic performance for PCOS. Seven of them were validated in GC samples, and five were found to be significantly and positively correlated with one or more oocyte quality parameters in PCOS patients, including oocyte retrieval rate, mature oocyte rate, normal fertilization rate, and good-quality embryo rate. Gene regulatory network revealed JUN and HMGA1 as two important transcription factors, while dicoumarol and flavin adenine dinucleotide were predicted as small molecules with therapeutic potential.

Conclusions

This is the first comprehensive report to study the differential expression of ferroptosis-related genes in GCs of PCOS and their clinical relevance with oocyte quality. Our findings could provide novel insights on the potential role of GC ferroptosis in PCOS pathogenesis, diagnosis, and targeted treatment.
Why germanys energiewende may fail to meet its goals: insights from power system simulation with natural generation
Authors: Redeker Artur
Published: February 2024

In order to achieve the Paris climate targets, the German government has developed phased plans and anchored these in an amendment to the Renewable Energy Sources Act (EEG). This not only defines expansion targets for renewable energy producers, but also the additional amounts of energy that must be available in the electricity grid in future if it is to supply the mobility and building heating sectors, which are currently still powered by fossil fuels. While the lack of grid transport capacities is recognized and discussed in the public debate, another known and critical hurdle is rarely presented here. This is the temporal distribution of power from renewable energies and its effects on the processes involved in controlling the grid balance. By analyzing a target scenario specified in the EEG for 2030 and another for 2040+, which a German economic research institute recommends to policymakers, the aim is to investigate whether their targets can be achieved under the conditions of the natural fluctuations occurring in Germany and the quantities of renewable energy that can be harvested with a reasonable use of resources. The focus is on simulating future generation curves using historical data in such a way that they show the typical weather-driven behaviour to be expected in Germany. Unavoidable Surplus generation is used as efficiently as possible with electricity and hydrogen storage systems. Both scenarios fall considerably short of their targets. CO2-free coverage of the demand specified for the long-term future is only possible with a quantity of generators that is at the limit of what is feasible. The reason for this is that the current plans are obviously based on an unrealistic picture of the temporal distribution of renewable energy output. Achieving the transformation goals in Germany could be much more complex than politicians currently believe and may require a change in strategy sooner or later.
Integrated energy system scheduling optimization considering vertical-axis wind turbines and thermal inertia in oilfield management areas
Authors: Wang Xusheng , Cui Jian , Ren Bingpeng , Liu Yanfeng , Huang Yanfei
Published: February 2024

Traditional horizontal-axis wind turbines (HAWTs) have limited efficiency in low-wind speed regions. In this paper, an integrated energy system (IES) incorporating vertical-axis wind turbines (VAWTs) is proposed; this IES is located in an oilfield management area, which can utilize the low-wind speed resources more efficiently and improve renewable energy consumption, and it also introduces a demand response model based on thermal inertia (TI), thus smoothing out the volatility caused by the VAWT. Typical output scenarios are obtained through stochastic optimization to deal with wind turbine and photovoltaic output uncertainties, and an optimal scheduling model is proposed to minimize the system operating cost. Finally, a simulation study was conducted in a micro-oilfield management area in Shandong Province, China, to demonstrate the performance of the proposed system. The results show that the IES using a VAWT and TI can increase the renewable energy consumption capacity by 87% over the conventional HAWT system, change the user behavior, increase the economic efficiency by 12%, and achieve the smoothing of load-side fluctuation of electric and thermal loads, peak shaving, and valley filling. This paper provides a feasible solution for an IES in low-wind speed areas.
Pore-scale simulation of miscible displacement in an inclined porous medium
Authors: Liu Gaojie , Xu Aoyu , Wang Yongqiang , Lou Qin
Published: February 2024

Introduction: This study investigates the displacement of two miscible fluids within an inclined porous medium at the pore scale, highlighting how the pore-scale microstructure, inclination angle, and viscosity ratio affect the interfacial instability between two fluids during displacement processes.

Methods: The lattice Boltzmann Method (LBM) is employed to solve the governing equations. Two distribution functions are used to simulate the velocity field and the concentration field, respectively.

Results and discussion: An increase in inclination angle exacerbates the interfacial instability between fluids and the viscous fingering phenomenon. This viscous fingering expands the sweep range of displacing fluids, which improves the displacement efficiency. When θ > 50°, further increase in inclination angle will not cause significant changes in displacement efficiency. In addition, the viscosity ratio is a key factor affecting displacement efficiency. The larger the viscosity ratio, the greater the displacement efficiency. Furthermore, the critical viscosity ratio has been found, and any increase in the viscosity ratio above the critical value will not affect the displacement efficiency.
Integrative analysis of potential diagnostic markers and therapeutic targets for glomerulus-associated diabetic nephropathy based on cellular senescence
Authors: Sun Donglin , Wei Shuqi , Wang Dandan , Zeng Min , Mo Yihao , Li Huafeng , Liang Caixing , Li Lu , Zhang Jun Wei , Wang Li
Published: February 2024

Introduction

Diabetic nephropathy (DN), distinguished by detrimental changes in the renal glomeruli, is regarded as the leading cause of death from end-stage renal disease among diabetics. Cellular senescence plays a paramount role, profoundly affecting the onset and progression of chronic kidney disease (CKD) and acute kidney injuries. This study was designed to delve deeply into the pathological mechanisms between glomerulus-associated DN and cellular senescence.

Methods

Glomerulus-associated DN datasets and cellular senescence-related genes were acquired from the Gene Expression Omnibus (GEO) and CellAge database respectively. By integrating bioinformatics and machine learning methodologies including the LASSO regression analysis and Random Forest, we screened out four signature genes. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance of the selected genes. Rigorous experimental validations were subsequently conducted in the mouse model to corroborate the identification of three signature genes, namely LOX, FOXD1 and GJA1. Molecular docking with chlorogenic acids (CGA) was further established not only to validate LOX, FOXD1 and GJA1 as diagnostic markers but also reveal their potential therapeutic effects.

Results and discussion

In conclusion, our findings pinpointed three diagnostic markers of glomerulus-associated DN on the basis of cellular senescence. These markers could not only predict an increased risk of DN progression but also present promising therapeutic targets, potentially ushering in innovative treatments for DN in the elderly population.
DiscoTope-3.0: improved B-cell epitope prediction using inverse folding latent representations
Authors: Høie Magnus Haraldson , Gade Frederik Steensgaard , Johansen Julie Maria , Würtzen Charlotte , Winther Ole , Nielsen Morten , Marcatili Paolo
Published: February 2024

Accurate computational identification of B-cell epitopes is crucial for the development of vaccines, therapies, and diagnostic tools. However, current structure-based prediction methods face limitations due to the dependency on experimentally solved structures. Here, we introduce DiscoTope-3.0, a markedly improved B-cell epitope prediction tool that innovatively employs inverse folding structure representations and a positive-unlabelled learning strategy, and is adapted for both solved and predicted structures. Our tool demonstrates a considerable improvement in performance over existing methods, accurately predicting linear and conformational epitopes across multiple independent datasets. Most notably, DiscoTope-3.0 maintains high predictive performance across solved, relaxed and predicted structures, alleviating the need for experimental structures and extending the general applicability of accurate B-cell epitope prediction by 3 orders of magnitude. DiscoTope-3.0 is made widely accessible on two web servers, processing over 100 structures per submission, and as a downloadable package. In addition, the servers interface with RCSB and AlphaFoldDB, facilitating large-scale prediction across over 200 million cataloged proteins. DiscoTope-3.0 is available at: https://services.healthtech.dtu.dk/service.php?DiscoTope-3.0.
The need for paradigm shift: prognostic significance and implications of standard therapy-related systemic immunosuppression in glioblastoma for immunotherapy and oncolytic virotherapy
Authors: Stepanenko Aleksei A. , Sosnovtseva Anastasiia O. , Valikhov Marat P. , Chernysheva Anastasia A. , Abramova Olga V. , Naumenko Victor A. , Chekhonin Vladimir P.
Published: February 2024

Despite significant advances in our knowledge regarding the genetics and molecular biology of gliomas over the past two decades and hundreds of clinical trials, no effective therapeutic approach has been identified for adult patients with newly diagnosed glioblastoma, and overall survival remains dismal. Great hopes are now placed on combination immunotherapy. In clinical trials, immunotherapeutics are generally tested after standard therapy (radiation, temozolomide, and steroid dexamethasone) or concurrently with temozolomide and/or steroids. Only a minor subset of patients with progressive/recurrent glioblastoma have benefited from immunotherapies. In this review, we comprehensively discuss standard therapy-related systemic immunosuppression and lymphopenia, their prognostic significance, and the implications for immunotherapy/oncolytic virotherapy. The effectiveness of immunotherapy and oncolytic virotherapy (viro-immunotherapy) critically depends on the activity of the host immune cells. The absolute counts, ratios, and functional states of different circulating and tumor-infiltrating immune cell subsets determine the net immune fitness of patients with cancer and may have various effects on tumor progression, therapeutic response, and survival outcomes. Although different immunosuppressive mechanisms operate in patients with glioblastoma/gliomas at presentation, the immunological competence of patients may be significantly compromised by standard therapy, exacerbating tumor-related systemic immunosuppression. Standard therapy affects diverse immune cell subsets, including dendritic, CD4+, CD8+, natural killer (NK), NKT, macrophage, neutrophil, and myeloid-derived suppressor cell (MDSC). Systemic immunosuppression and lymphopenia limit the immune system’s ability to target glioblastoma. Changes in the standard therapy are required to increase the success of immunotherapies. Steroid use, high neutrophil-to-lymphocyte ratio (NLR), and low post-treatment total lymphocyte count (TLC) are significant prognostic factors for shorter survival in patients with glioblastoma in retrospective studies; however, these clinically relevant variables are rarely reported and correlated with response and survival in immunotherapy studies (e.g., immune checkpoint inhibitors, vaccines, and oncolytic viruses). Our analysis should help in the development of a more rational clinical trial design and decision-making regarding the treatment to potentially improve the efficacy of immunotherapy or oncolytic virotherapy.
Exploring genetic associations of Crohn’s disease and ulcerative colitis with extraintestinal cancers in European and East Asian populations
Authors: Yu Chengdong , Xu Jiawei , Xu Siyi , Tang Lei , Han Qinyuan , Zeng Xiaoqiang , Huang Yanxiao , Yu Tenghua , Sun Zhengkui
Published: February 2024

Background

Previous studies have reported associations of Crohn’s disease (CD) and ulcerative colitis (UC) with the risks of extraintestinal cancers, but the causality remains unclear.

Methods

Using genetic variations robustly associated with CD and UC extracted from genome-wide association studies (GWAS) as instrumental variables. Nine types of extraintestinal cancers of European and Asian populations were selected as outcomes. We used the inverse variance weighted method as the primary approach for two-sample Mendelian randomization analysis. Sensitivity analyses were carried out to evaluate the reliability of our findings.

Results

In the European population, we found that CD showed a potential causal relationship with pancreatic cancer (OR: 1.1042; 95% CI: 1.0087-1.2088; P=0.0318). Meanwhile, both CD (outliers excluded: OR: 1.0208; 95% CI: 1.0079-1.0339; P=0.0015) and UC (outliers excluded: OR: 1.0220; 95% CI: 1.0051-1.0393; P=0.0108) were associated with a slight increase in breast cancer risk. Additionally, UC exhibited a potential causal effect on cervical cancer (outliers excluded: OR: 1.1091; 95% CI: 1.0286-1.1960; P=0.0071). In the East Asian population, CD had significant causal effects on pancreatic cancer (OR: 1.1876; 95% CI: 1.0741-1.3132; P=0.0008) and breast cancer (outliers excluded: OR: 0.9452; 95% CI: 0.9096-0.9822; P=0.0040). For UC, it exhibited significant causal associations with gastric cancer (OR: 1.1240; 95% CI: 1.0624-1.1891; P=4.7359×10–5), bile duct cancer (OR: 1.3107; 95% CI: 1.0983-1.5641; P=0.0027), hepatocellular carcinoma (OR: 1.2365; 95% CI: 1.1235-1.3608; P=1.4007×10–5) and cervical cancer (OR: 1.3941; 95% CI: 1.1708-1.6599; P=0.0002), as well as a potential causal effect on lung cancer (outliers excluded: OR: 1.1313; 95% CI: 1.0280-1.2449; P=0.0116).

Conclusions

Our study provided evidence that genetically predicted CD may be a risk factor for pancreatic and breast cancers in the European population, and for pancreatic cancer in the East Asian population. Regarding UC, it may be a risk factor for cervical and breast cancers in Europeans, and for gastric, bile duct, hepatocellular, lung, and cervical cancers in East Asians. Therefore, patients with CD and UC need to emphasize screening and prevention of site-specific extraintestinal cancers.
Carbon and cost accounting for liner shipping under the European Union Emission Trading System
Authors: Sun Ling , Wang Xinghe , Hu Zijiang , Ning Zhong
Published: February 2024

Excessive CO2 emissions and increased total costs of liner shipping are the two main problems affecting the environmental and economic benefits of liner companies under the European Union Emission Trading System (EU ETS). To address the upcoming EU ETS, we propose a carbon and cost accounting model for liner shipping that accurately calculates CO2 emissions and total cost of liner shipping. We conduct a case study that a containership operates on the liner route from the Far East to Northwest Europe. The results show that the sailing stage plays a pivotal role in CO2 emissions from liner shipping, accounting for 94.70% of CO2 emissions. Among four types of fuel, CO2 emissions from liner shipping using MGO is the largest, while CO2 emissions from liner shipping using methanol is the smallest. Methanol, as an alternative fuel, proves to be a better choice than LNG for CO2 control of liner shipping. The relationship between sailing speed and CO2 emissions follows a U-shaped curve for the selected containership. Notably, speed reduction is effective in carbon control of liner shipping only when the sailing speed exceeds 8.29 knots. Under the EU ETS, sailing speed is a key variable affecting the total cost of liner shipping. Speed reduction may not always be cost-effective. When keeping the total cost of liner shipping unchanged, sailing speed should be reduced as the EU allowance (EUA) price rises within a certain range. For the selected containership using MGO and HFO, the most economical sailing speed is 8.29 knots, corresponding to the increase in EUA price of 304.95% and 261.21%, respectively. If EUA price continues to rise, speed reduction will become ineffective in controlling the total cost of liner shipping. This model can enhance the environmental and economic benefits of liner companies, meet compliance requirements of the EU ETS, and provide a new perspective for carbon and cost control of liner shipping.
Social-ecological vulnerability to environmental extremes and adaptation pathways in small-scale fisheries of the southern California Current
Authors: Micheli Fiorenza , Saenz-Arroyo Andrea , Aalto Emilius , Beas-Luna Rodrigo , Boch Charles A. , Cardenas Juan Camilo , De Leo Giulio A. , Diaz Eduardo , Espinoza-Montes Antonio , Finkbeiner Elena , Freiwald Jan , Fulton Stuart , Hernández Arturo , Lejbowicz Amanda , Low Natalie H. N. , Martinez Ramon , McCay Bonnie , Monismith Stephen , Precoma-de la Mora Magdalena , Romero Alfonso , Smith Alexandra , Torre Jorge , Vazquez-Vera Leonardo , Woodson C. Brock
Published: February 2024

Coastal ecosystems and human communities are threatened worldwide by climate change, and shocks from social, market and political change. There is an urgent global need to promote resilient food production and livelihoods in the face of these shocks. Small-scale fisheries (SSF) in rural settings can be particularly vulnerable as they frequently lack the resources, rights and infrastructure to respond to shocks originating outside the focal systems. We examined ecological and social outcomes of environmental extremes in a SSF socio-ecological system (SES) by using long-term oceanographic (between 2010-2019) and ecological (2006-2018) data tracking change in a kelp forest ecosystem of Baja California, Mexico, and concurrent documentation of proactive and reactive actions of a fishing community organized in a cooperative. Results indicate a complex landscape of ‘winners’ and ‘losers’ among species and fisheries exposed to unprecedented environmental extremes, including marine heat waves and prolonged hypoxia, and a suite of adaptive actions by the local fishing cooperative, and others in the region, that have helped confront these rapid and drastic changes. Cooperatives have established voluntary marine reserves to promote recovery of affected populations and have invested in diversification of activities enabled by access rights, collective decision-making, and participatory science programs. Results indicate that local actions can support social and ecological resilience in the face of shocks, and that enabling locally-driven adaptation pathways is critical to resilience. This case study highlights the crucial importance of strengthening and supporting rights, governance, capacity, flexibility, learning, and agency for coastal communities to respond to change and sustain their livelihoods and ecosystems in the long run.
Sirolimus treatment for intractable lymphatic anomalies: an open-label, single-arm, multicenter, prospective trial
Authors: Ozeki Michio , Endo Saori , Yasue Shiho , Nozawa Akifumi , Asada Ryuta , Saito Akiko M. , Hashimoto Hiroya , Fujimura Takumi , Yamada Yohei , Kuroda Tatsuo , Ueno Shigeru , Watanabe Shoji , Nosaka Shunsuke , Miyasaka Mikiko , Umezawa Akihiro , Matsuoka Kentaro , Maekawa Takanobu , Hirakawa Satoshi , Furukawa Taizo , Fumino Shigehisa , Tajiri Tatsuro , Takemoto Junkichi , Souzaki Ryota , Kinoshita Yoshiaki , Fujino Akihiro
Published: February 2024

Introduction

Intractable lymphatic anomalies (LAs) include cystic lymphatic malformation (LM; macrocystic, microcystic, or mixed), generalized lymphatic anomaly, and Gorham–Stout disease. LAs can present with severe symptoms and poor prognosis. Thus, prospective studies for treatments are warranted. We conducted a prospective clinical trial of sirolimus for intractable LAs.

Methods

This was an open-label, single-arm, multicenter, prospective trial involving five institutions in Japan. All patients with LAs received oral sirolimus once daily, and the dose was adjusted to ensure that the trough concentration remained within 5–15 ng/mL. We prospectively assessed the drug response (response rate for radiological volumetric change in target lesion), performance state, change in respiratory function, visceral impairment (pleural effusion, ascites, bleeding, pain), laboratory examination data, quality of life (QOL), and safety at 12, 24, and 52 weeks of administration.

Results

Eleven patients with LAs (9 generalized lymphatic anomaly, 1 cystic LM, 1 Gorham–Stout disease) were treated with sirolimus, of whom 6 (54.5%; 95% confidence interval: 23.4–83.3%) demonstrated a partial response on radiological examination at 52 weeks of administration. No patients achieved a complete response. At 12 and 24 weeks of administration, 8 patients (72.7%) already showed a partial response. However, patients with stable disease showed minor or no reduction after 12 weeks. Adverse events, such as stomatitis, acneiform dermatitis, diarrhea, and fever, were common with sirolimus. Sirolimus was safe and tolerable.

Conclusion

Sirolimus can reduce the lymphatic tissue volume in LAs and may lead to improvements in clinical symptoms and QOL.
The causal effect of triglyceride and high blood pressure on IgA nephropathy: a Mendelian randomization study
Authors: Yang Yijun , Li Yang , Feng Xinshun , Ding Chenguang , Zhang Jing , Liu Zunwei
Published: February 2024

Background

It has been reported that high blood pressure (HBP) and triglyceride (TG) are considered risk factors in immunoglobulin A nephropathy (IgAN). This study aimed to explore the causalities between HBP and TG, and IgAN on the basis of Mendelian randomization (MR) analysis.

Methods

Firstly, the genome-wide association study (GWAS) summary data of IgAN (GCST90018866) and two exposure factors, TG (ukb-d-30870_raw) and HBP (ukb-a-437), were sourced from the GWAS Catalog and Integrative Epidemiology Unit (IEU) OpenGWAS databases, respectively. In this study, five methods were utilized to perform MR analysis after picking out single nucleotide polymorphisms (SNPs) as instrumental variables, including MR-Egger, weighted median, simple mode, weighted mode, and inverse variance weighted (IVW), followed by the sensitivity analysis containing the heterogeneity, horizontal pleiotropy test and leave-one-out (LOO) analysis. Finally, the enrichment analysis and interaction network construction of genes corresponding to SNPs of HBP and TG were performed.

Results

The univariate MR results revealed that HBP and TG regarded as risk factors were causally related to IgAN [TG: p = 0.046, odds ratio (OR) = 1.065, 95% confidence interval (CI) = 1.001–1.133; HBP: p = 7.09 × 10−7, OR = 1.970, 95% CI = 1.507–2.575] based on random-effect IVM method, of which TG had a weaker impact. The reliability of these univariate MR results was certified by the sensitivity analysis, in which there was no horizontal pleiotropy and exaggerated influence of each SNP. Furthermore, HBP was markedly causally related to IgAN (p = 0.000512) with the help of multivariate MR analysis, rather than TG (p = 0.332). Therefore, when HBP and TG occur simultaneously, HBP is a direct influencing factor on IgAN. Ultimately, a total of 208 and 153 genes separately corresponding to SNPs of TG and HBP were included in enrichment analysis, and thereinto, genes relevant to TG were mainly enriched in lipid homeostasis and cholesterol metabolism, while genes concerned with HBP played their roles in regulation of cell growth, aldosterone synthesis and secretion and so forth.

Conclusion

TG and HBP as risk factors were causally connected with IgAN, of which HBP was strongly related to the onset of IgAN, providing more reliable evidence for further exploring the relationship between TG and HBP and IgAN.
Whole genome sequencing and characterization of Pantoea agglomerans DBM 3797, endophyte, isolated from fresh hop (Humulus lupulus L.)
Authors: Patakova Petra , Vasylkivska Maryna , Sedlar Karel , Jureckova Katerina , Bezdicek Matej , Lovecka Petra , Branska Barbora , Kastanek Petr , Krofta Karel
Published: February 2024

Background

This paper brings new information about the genome and phenotypic characteristics of Pantoea agglomerans strain DBM 3797, isolated from fresh Czech hop (Humulus lupulus) in the Saaz hop-growing region. Although P. agglomerans strains are frequently isolated from different materials, there are not usually thoroughly characterized even if they have versatile metabolism and those isolated from plants may have a considerable potential for application in agriculture as a support culture for plant growth.

Methods

P. agglomerans DBM 3797 was cultured under aerobic and anaerobic conditions, its metabolites were analyzed by HPLC and it was tested for plant growth promotion abilities, such as phosphate solubilization, siderophore and indol-3-acetic acid productions. In addition, genomic DNA was extracted, sequenced and de novo assembly was performed. Further, genome annotation, pan-genome analysis and selected genome analyses, such as CRISPR arrays detection, antibiotic resistance and secondary metabolite genes identification were carried out.

Results and discussion

The typical appearance characteristics of the strain include the formation of symplasmata in submerged liquid culture and the formation of pale yellow colonies on agar. The genetic information of the strain (in total 4.8 Mb) is divided between a chromosome and two plasmids. The strain lacks any CRISPR-Cas system but is equipped with four restriction-modification systems. The phenotypic analysis focused on growth under both aerobic and anaerobic conditions, as well as traits associated with plant growth promotion. At both levels (genomic and phenotypic), the production of siderophores, indoleacetic acid-derived growth promoters, gluconic acid, and enzyme activities related to the degradation of complex organic compounds were found. Extracellular gluconic acid production under aerobic conditions (up to 8 g/l) is probably the result of glucose oxidation by the membrane-bound pyrroloquinoline quinone-dependent enzyme glucose dehydrogenase. The strain has a number of properties potentially beneficial to the hop plant and its closest relatives include the strains also isolated from the aerial parts of plants, yet its safety profile needs to be addressed in follow-up research.
Genistein is effective in inhibiting Orf virus infection in vitro by targeting viral RNA polymerase subunit RPO30 protein
Authors: Lv Pin , Fang Ziyu , Guan Jiyu , Lv Lijun , Xu Mengshi , Liu Xingyuan , Li Zhuomei , Lan Yungang , Li Zi , Lu Huijun , Song Deguang , He Wenqi , Gao Feng , Wang Dacheng , Zhao Kui
Published: February 2024

Orf virus (ORFV), a typical member of the genus Parapoxvirus, Poxvirus family, causes a contagious pustular dermatitis in sheep, goats, and humans. Poxviruses encode a multisubunit DNA-dependent RNA polymerase (vRNAP) that carries out viral gene expression in the host cytoplasm, which is a viral factor essential to poxvirus replication. Due to its vital role in viral life, vRNAP has emerged as one of the potential drug targets. In the present study, we investigated the antiviral effect of genistein against ORFV infection. We provided evidence that genistein exerted antiviral effect through blocking viral genome DNA transcription/replication and viral protein synthesis and reducing viral progeny, which were dosedependently decreased in genistein-treated cells. Furthermore, we identified that genistein interacted with the vRNAP RPO30 protein by CETSA, molecular modeling and Fluorescence quenching, a novel antiviral target for ORFV. By blocking vRNAP RPO30 protein using antibody against RPO30, we confirmed that the inhibitory effect exerted by genistein against ORFV infection is mediated through the interaction with RPO30. In conclusion, we demonstrate that genistein effectively inhibits ORFV transcription in host cells by targeting vRNAP RPO30, which might be a promising drug candidate against poxvirus infection.
Integrated metabolome and microbiome analysis reveals the effect of rumen-protected sulfur-containing amino acids on the meat quality of Tibetan sheep meat
Authors: Liu JiQian , Han Lijuan , Hou Shengzhen , Gui Linsheng , Yuan Zhenzhen , Sun Shengnan , Wang Zhiyou , Yang Baochun
Published: February 2024

Introduction

This study investigated the effects of rumen-protected sulfur-containing amino acids (RPSAA) on the rumen and jejunal microbiota as well as on the metabolites and meat quality of the longissimus lumborum (LL) in Tibetan sheep.

Methods

By combining 16S rDNA sequencing with UHPLC-Q-TOF MS and Pearson correlation analysis, the relationship between gastrointestinal microbiota, muscle metabolites and meat quality was identified.

Results

The results showed that feeding RPSAA can increase the carcass weight, abdominal fat thickness (AP-2 group), and back fat thickness (AP-2 and AP-3 group) of Tibetan sheep. The water holding capacity (WHC), texture, and shear force (SF) of LL in the two groups also increased although the fatty acids content and brightness (L*) value significantly decreased in the AP-2 group. Metabolomics and correlation analysis further showed that RPSAA could significantly influence the metabolites in purine metabolism, thereby affecting L* and SF. In addition, RPSAA was beneficial for the fermentation of the rumen and jejunum. In both groups, the abundance of Prevotella 1, Lachnospiraceae NK3A20 group, Prevotella UCG-003, Lachnospiraceae ND3007 group in the rumen as well as the abundance of Eubacterium nodatum group and Mogibacterium group in the jejunum increased. In contrast, that of Turicibacter pathogens in the jejunum was reduced. The above microorganisms could regulate meat quality by regulating the metabolites (inosine, hypoxanthine, linoleic acid, palmitic acid, etc.) in purine and fatty acids metabolism.

Discussion

Overall, reducing the levels of crude proteins in the diet and feeding RPSAA is likely to improve the carcass quality of Tibetan sheep, with the addition of RPMET (AP-2) yielding the best edible quality, possibly due to its ability to influence the gastrointestinal microbiota to subsequently regulate muscle metabolites.