bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the interplay between circadian rhythms and prostate cancer: insights into androgen receptor signaling and therapeutic opportunities
Authors: Xia Hongyan , Zhan Yang , Wang Li , Wang Xiaohui
Published: July 2024

Circadian rhythm disruption is closely related to increased incidence of prostate cancer. Incorporating circadian rhythms into the study of prostate cancer pathogenesis can provide a more comprehensive understanding of the causes of cancer and offer new options for precise treatment. Therefore, this article comprehensively summarizes the epidemiology of prostate cancer, expounds the contradictory relationship between circadian rhythm disorders and prostate cancer risk, and elucidates the relationship between circadian rhythm regulators and the incidence of prostate cancer. Importantly, this article also focuses on the correlation between circadian rhythms and androgen receptor signaling pathways, as well as the applicability of time therapy in prostate cancer. This may prove significant in enhancing the clinical treatment of prostate cancer.
Short-term effect of low-dose roxadustat combined with erythropoiesis-stimulating agent treatment for erythropoietin-resistant anemia in patients undergoing maintenance hemodialysis
Authors: Xu Qiaoying , Huang Jingjing , Liu Qingzhen , Wang Xueling , Liu Haiying , Song Yan , Dou Fulin , Lv Shasha , Liu Gang
Published: July 2024

Background

Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week).

Methods

The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50–60% of the recommended dose of roxadustat and higher doses of rhuEPO.

Results

The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased.

Conclusion

Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism.
Association between the AHA life’s essential 8 and prediabetes/diabetes: a cross-sectional NHANES study
Authors: Xu Wei , Feng Yuntao , Abdullah Guzalnur , Li Ling , Fang Ping , Tang Sijing , Yang Huanhuan , Kong Dehong , Huang Hemin , Wang Yang , Xue Ying
Published: July 2024

Background and aims

The American Heart Association (AHA) recently introduced the Life’s Essential 8 (LE8) to improve cardiovascular health (CVH). However, the association between LE8 and the risk of prediabetes or diabetes is not yet fully understood. Consequently, this study aims to assess the association between CVH, as evaluated by LE8, and the risk of prediabetes and diabetes.

Methods and Results

This cross-sectional study encompassed 7,739 participants aged ≥20 years from the 2007-2018 National Health and Nutrition Examination Surveys (NHANES). The CVH of participants was evaluated using the LE8, combining four health behaviors and three health factors. Glucose metabolic status categories included normal glucose metabolism, prediabetes including isolated impaired fasting glucose, isolated impaired glucose tolerance, both IFG and IGT, and diabetes. The associations between CVH and prediabetes and diabetes were analyzed using logistic regression, linear regression, restricted cubic splines, and subgroup analyses. Among 7,739 participants, 1,949 had iIFG, 1,165 were diagnosed with iIGT, 799 were IFG+IGT, and 537 were diagnosed with diabetes. After multivariable adjustments, CVH scores were inversely associated with prediabetes and diabetes, with the most robust inverse association observed between IFG+IGT and CVH across all prediabetes subgroups. Of all CVH components not directly in the causal pathway, body mass index (BMI) had the most robust associations with prediabetes and diabetes. Subgroup analyses indicated that the negative correlation between CVH and prediabetes was stronger among those with university or higher education.

Conclusion

CVH, as defined by LE8, showed a significant negative association with prediabetes and diabetes.
Serum INSL3 measured by LC-MS/MS in pubertal girls and in girls with precocious puberty during GnRH agonist treatment
Authors: Albrethsen Jakob , Hagen Casper P. , Juul Anders
Published: July 2024

Introduction

The peptide hormone Insulin-like Factor 3 (INSL3) is a biomarker of testicular Leydig cells in the male but is also expressed by the theca cells of the ovaries. With the advent of sensitive assays INSL3 can be quantified in female circulation, and we suggest that circulating INSL3 is a novel biomarker for pubertal development in girls. The aim of the study is to quantify INSL3 by LC-MS/MS in sera from normal girls during pubertal transition, and during gonadal suppression by GnRH agonist therapy in girls with central precocious puberty (CPP).

Method

The sensitivity of an established LC-MS/MS-based method for serum INSL3 was improved by switching to a state-of-the-art triple quadruple mass spectrometer (Altis Plus, Thermo).

Results

The limit of detection of the improved LC-MS/MS method for serum INSL3 was 0.01 ug/L (1.5 pM) and the inter-assay CV was < 12%. Serum INSL3 increased during the pubertal transition in healthy girls and changes correlated with the concomitant rise in other measured hormones. In some girls, but not all, INSL3, FSH, inhibin B and estradiol serum concentrations increased prior to first clinical signs of puberty. Serum INSL3 concentrations were increased at baseline in girls with CPP compared to prepubertal controls and decreased during treatment with GnRH agonist followed by a steep rise and normalization after cessation of treatment.

Conclusion

The improved method allowed for quantification of INSL3 in longitudinally collected serum samples during pubertal transition in healthy girls as well as in girls with CPP before, during and after treatment with GnRH agonist. Future studies are needed to clarify if INSL3 in combination with other biomarkers enhances the predictive value of differentiating between premature thelarche and CPP.
Optimized coordinated control method with virtual inertia based on fractional impedance model for charging stations
Authors: Li Jiang , Hu Jianwei , Liu Bo
Published: July 2024

Due to the EV (Electric Vehicles) charging stations are characterized by weak damping and low inertia, the EV with a high degree of uncertainty can easily have an impact on the stability of the charging station system. Therefore, this paper proposes an optimization control method to improve the system inertia effect based on the fractional order impedance model of the charging station. This paper presents a study on establishing a fractional impedance model for charging stations, using the deviation between theoretical impedance spectra and actual measurements as a criterion. The goal is to enhance system inertia and optimize the parameters of the fractional-order controller to improve the supporting capacity of the charging station system and enhance its dynamic response. Initially, considering the fractional characteristics of the EV load, a fractional impedance model of the charging station is established. The analysis demonstrates that the fractional-order capacitor provides inertia to the system, enhancing its inertia support capability. In addition, a virtual inertia control strategy based on fractional-order PID (FOPID) is designed. Finally, an improved particle swarm optimization algorithm is utilized to optimize the control parameters. Through experimental verification under different operating conditions, it has been demonstrated that the fractional-order control strategy can achieve a dynamic response time of approximately 0.025s and limit the voltage deviation within 5%. Furthermore, the rotational inertia can rapidly increase to the maximum value satisfying the objective function within 0.05s. The results indicate that this control method effectively suppresses the DC voltage and power oscillations in the distribution grid.
The impact of digital economy on China’s green-oriented transition of energy: multiple mediation effects from a spatial perspective
Authors: Hou Jianchao , Ye Shuying
Published: July 2024

With the continuous advancement of the new generation of information technology revolution, digital economy is gradually becoming an important driving force for energy transition while restructuring the new form of the economy. This paper selects panel data of 30 provinces in China from 2011 to 2021, empirically verifies the special impacts of digital economy on green-oriented transition of energy by using the spatial Durbin model, and further constructs a multi-intermediary model to verify its transition pathways. The main findings are as follows: First, the overall level of green-oriented transition of energy in China’s eastern coastal areas is relatively high, and the western regions have been more capable of catching up in recent years. Second, digital economy has played a significant role in promoting green-oriented transition of energy, and there is a positive spatial spillover effect. Third, digital economy could indirectly promote the green-oriented transition of energy by promoting the upgrading of industrial structure, improving the level of technological innovation and strengthening environmental regulations. This study provides empirical insights and reference for policymakers in accelerating the comprehensive green-oriented transition of energy.
Causality of genetically determined metabolites on susceptibility to prevalent urological cancers: a two-sample Mendelian randomization study and meta-analysis
Authors: Dai Xianyu , Wang Hongjie , Zhong Rong , Li Jiajun , Hou Yuchuan
Published: July 2024

Background

Prevalent urological cancers, including kidney, prostate, bladder, and testicular cancers, contribute significantly to global cancer incidence and mortality. Metabolomics, focusing on small-molecule intermediates, has emerged as a tool to understand cancer etiology. Given the knowledge gap in this field, we employ a two-sample Mendelian randomization (MR) analysis to investigate the causal relationships between genetically determined metabolites (GDMs) and the susceptibility to four common urological cancers.

Methods

The study employs genome-wide association studies (GWAS) data from European populations, featuring the most extensive case count available for both blood metabolites and four prevalent urological cancers. Preliminary and secondary MR analyses were separately conducted, employing inverse variance weighted (IVW) as the primary method. Multiple statistical analyses, including the MR-Steiger test, Cochran’s Q test, leave-one-out analysis, MR-Egger intercept analysis, and MR-PRESSO analysis, were executed to ensure robustness. Additionally, a meta-analysis was carried out to consolidate findings. The weighted median (WM) method was utilized for a relatively lenient correction (PWM < 0.05).

Results

After rigorous genetic variation filtering, 645 out of 1,400 metabolites were included in both preliminary and secondary MR analyses. Preliminary MR analysis identified 96 potential causal associations between 94 distinct metabolites and four urological cancers. Secondary analysis based on Finnish outcome data revealed 93 potential causal associations. Cross-database meta-analysis identified 68 blood metabolites associated with four urological cancers. Notably, 31 metabolites remained significant after using WM for correction, with additional 37 suggestive causal relationships. Reverse MR analysis revealed a significant causal association between genetically predicted prostate cancer and elevated 4-hydroxychlorothalonil levels (IVW, combined OR: 1.039, 95% CI 1.014–1.064, p = 0.002; WM, combined OR: 1.052, 95% CI 1.010–1.095, p = 0.014).

Conclusion

This comprehensive MR study provides insights into the causal relationships between blood metabolites and urological cancers, revealing potential biomarkers and therapeutic targets, thereby addressing gaps in understanding and laying the foundation for targeted interventions in urological cancer research and treatment.
m6A mRNA methylation-mediated MAPK signaling modulates the nasal mucosa inflammatory response in allergic rhinitis
Authors: Wang Ruikun , Liang Jieqiong , Wang Qian , Zhang Yiming , Lu Yingxia , Zhan Xiaojun , Wang Shan , Gu Qinglong
Published: July 2024

Background

Allergic rhinitis (AR) is a complex disease in which gene-environment interactions contribute to its pathogenesis. Epigenetic modifications, such as N6-methyladenosine (m6A) modification of mRNA, play important roles in regulating gene expression in multiple physiological and pathological processes. However, the function of m6A modification in AR and the inflammatory response is poorly understood.

Methods

We used the ovalbumin (OVA) and aluminum hydroxide to induce an AR mouse model. Nasal symptoms, histopathology, and serum cytokines were examined. We performed combined m6A and RNA sequencing to analyze changes in m6A modification profiles. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and methylated RNA immunoprecipitation sequencing qPCR (MeRIP-qPCR) were used to verify differential methylation of mRNAs and the m6A methylation level. Knockdown or inhibition of Alkbh5 in nasal mucosa of mice was mediated by lentiviral infection or IOX1 treatment.

Results

We showed that m6A was enriched in a group of genes involved in MAPK signaling pathway. Moreover, we identified a MAPK pathway involving Map3k8, Erk2, and Nfκb1 that may play a role in the disrupted inflammatory response associated with nasal inflammation. The m6A eraser, Alkbh5, was highly expressed in the nasal mucosa of AR model mice. Furthermore, knockdown of Alkbh5 expression by lentiviral infection resulted in high MAPK pathway activity and a significant nasal mucosa inflammatory response. Our findings indicate that ALKBH5-mediated m6A dysregulation likely contributes to a nasal inflammatory response via the MAPK pathway.

Conclusion

Together, our data show that m6A dysregulation mediated by ALKBH5, is likely to contribute to inflammation of the nasal mucosa via the MAPK signaling pathway, suggesting that ALKBH5 is a potential biomarker for AR treatment.
Blood immune cell profiling in adults with longstanding type 1 diabetes is associated with macrovascular complications
Authors: He Xuehui , Wang Xinhui , van Heck Julia , van Cranenbroek Bram , van Rijssen Esther , Stienstra Rinke , Netea Mihai G. , Joosten Irma , Tack Cees J. , Koenen Hans J. P. M.
Published: July 2024

Aims/hypothesis

There is increasing evidence for heterogeneity in type 1 diabetes mellitus (T1D): not only the age of onset and disease progression rate differ, but also the risk of complications varies markedly. Consequently, the presence of different disease endotypes has been suggested. Impaired T and B cell responses have been established in newly diagnosed diabetes patients. We hypothesized that deciphering the immune cell profile in peripheral blood of adults with longstanding T1D may help to understand disease heterogeneity.

Methods

Adult patients with longstanding T1D and healthy controls (HC) were recruited, and their blood immune cell profile was determined using multicolour flow cytometry followed by a machine-learning based elastic-net (EN) classification model. Hierarchical clustering was performed to identify patient-specific immune cell profiles. Results were compared to those obtained in matched healthy control subjects.

Results

Hierarchical clustering analysis of flow cytometry data revealed three immune cell composition-based distinct subgroups of individuals: HCs, T1D-group-A and T1D-group-B. In general, T1D patients, as compared to healthy controls, showed a more active immune profile as demonstrated by a higher percentage and absolute number of neutrophils, monocytes, total B cells and activated CD4+CD25+ T cells, while the abundance of regulatory T cells (Treg) was reduced. Patients belonging to T1D-group-A, as compared to T1D-group-B, revealed a more proinflammatory phenotype characterized by a lower percentage of FOXP3+ Treg, higher proportions of CCR4 expressing CD4 and CD8 T cell subsets, monocyte subsets, a lower Treg/conventional Tcell (Tconv) ratio, an increased proinflammatory cytokine (TNFα, IFNγ) and a decreased anti-inflammatory (IL-10) producing potential. Clinically, patients in T1D-group-A had more frequent diabetes-related macrovascular complications.

Conclusions

Machine-learning based classification of multiparameter flow cytometry data revealed two distinct immunological profiles in adults with longstanding type 1 diabetes; T1D-group-A and T1D-group-B. T1D-group-A is characterized by a stronger pro-inflammatory profile and is associated with a higher rate of diabetes-related (macro)vascular complications.
EBV T-cell immunotherapy generated by peptide selection has enhanced effector functionality compared to LCL stimulation
Authors: Cooper Rachel S. , Sutherland Catherine , Smith Linda M. , Cowan Graeme , Barnett Mark , Mitchell Donna , McLean Colin , Imlach Stuart , Hayes Alan , Zahra Sharon , Manchanayake Champa , Vickers Mark A. , Graham Gerry , McGowan Neil W. A. , Turner Marc L. , Campbell John D. M. , Fraser Alasdair R.
Published: July 2024

Adoptive immunotherapy with Epstein–Barr virus (EBV)-specific T cells is an effective treatment for relapsed or refractory EBV-induced post-transplant lymphoproliferative disorders (PTLD) with overall survival rates of up to 69%. EBV-specific T cells have been conventionally made by repeated stimulation with EBV-transformed lymphoblastoid cell lines (LCL), which act as antigen-presenting cells. However, this process is expensive, takes many months, and has practical risks associated with live virus. We have developed a peptide-based, virus-free, serum-free closed system to manufacture a bank of virus-specific T cells (VST) for clinical use. We compared these with standard LCL-derived VST using comprehensive characterization and potency assays to determine differences that might influence clinical benefits. Multi-parameter flow cytometry revealed that peptide-derived VST had an expanded central memory population and less exhaustion marker expression than LCL-derived VST. A quantitative HLA-matched allogeneic cytotoxicity assay demonstrated similar specific killing of EBV-infected targets, though peptide-derived EBV T cells had a significantly higher expression of antiviral cytokines and degranulation markers after antigen recall. High-throughput T cell receptor-beta (TCRβ) sequencing demonstrated oligoclonal repertoires, with more matches to known EBV-binding complementary determining region 3 (CDR3) sequences in peptide-derived EBV T cells. Peptide-derived products showed broader and enhanced specificities to EBV nuclear antigens (EBNAs) in both CD8 and CD4 compartments, which may improve the targeting of highly expressed latency antigens in PTLD. Importantly, peptide-based isolation and expansion allows rapid manufacture and significantly increased product yield over conventional LCL-based approaches.
Maturing neutrophils of lower density associate with thrombocytopenia in Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome
Authors: Cabrera Luz E. , Tietäväinen Johanna , Jokiranta Suvi T. , Mäkelä Satu , Vaheri Antti , Mustonen Jukka , Vapalahti Olli , Kanerva Mari , Strandin Tomas
Published: July 2024

Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUV-HFRS) is characterized by strong neutrophil activation. Neutrophils are the most abundant immune cell type in the circulation and are specially equipped to rapidly respond to infections. They are more heterogenous than previously appreciated, with specific neutrophil subsets recently implicated in inflammation and immunosuppression. Furthermore, neutrophils can be divided based on their density to either low-density granulocytes (LDGs) or “normal density” polymorphonuclear cell (PMN) fractions. In the current study we aimed to identify and characterize the different neutrophil subsets in the circulation of PUUV-HFRS patients. PMNs exhibited an activation of antiviral pathways, while circulating LDGs were increased in frequency following acute PUUV-HFRS. Furthermore, cell surface marker expression analysis revealed that PUUV-associated LDGs are primarily immature and most likely reflect an increased neutrophil production from the bone marrow. Interestingly, both the frequency of LDGs and the presence of a “left shift” in blood associated with the extent of thrombocytopenia, one of the hallmarks of severe HFRS, suggesting that maturing neutrophils could play a role in disease pathogenesis. These results imply that elevated circulating LDGs might be a general finding in acute viral infections. However, in contrast to the COVID-19 associated LDGs described previously, the secretome of PUUV LDGs did not show significant immunosuppressive ability, which suggests inherent biological differences in the LDG responses that can be dependent on the causative virus or differing infection kinetics.
Foraminiferal detoxification breakdown induced by fatal levels of TiO2 nanoparticles
Authors: Inagaki Yuka , Ishitani Yoshiyuki , Tame Akihiro , Uematsu Katsuyuki , Tomioka Naotaka , Ushikubo Takayuki , Ujiié Yurika
Published: July 2024

The increase discharge of titanium dioxide (TiO2) nanoparticles, derived from engineered material waste, exerts a detrimental impact on both the marine ecosystem and public health. The cytotoxicity of TiO2 nanoparticles on marine organisms should be imperatively understood to tackle the urgent concern for the well-being of marine life. Various concentrations of TiO2 nanoparticles have proven to reach fatal levels in aquatic organisms, requiring a deeper exploration of cytotoxicity. Notably, certain benthic foraminifers, such as Ammonia veneta, have been identified as capable of incorporating TiO2 nanoparticles into vesicles. However, these organisms exhibit a detoxification mechanism through exocytosis, as indicated by previous transcriptomic inferences. This presents the advantage of assessing the tolerance of foraminifers to TiO2 nanoparticles as pollutants and investigating the long-term effects of cytotoxicity. In this study, we scrutinized the distribution of TiO2 nanoparticles within cells and the growth rates of individuals in seawater media containing 1, 5, 10, and 50 ppm TiO2 nanoparticles, comparing the results with a control group over a 5-week period, utilizing A. veneta stain. Transmission electron microscopy observations consistently revealed high concentrations of TiO2 nanoparticles in vesicles, and their expulsion from cells was evident even with exposure to 5 ppm TiO2 nanoparticles. Under the control and 1 ppm TiO2 conditions, foraminifers increased their cell volume by adding a calcification chamber to their tests every 1 or 2 days. However, the 5-week culturing experiments demonstrated that foraminifers gradually ceased growing under 5 ppm TiO2 nanoparticle exposure and exhibited no growth at > 10 ppm concentrations, despite an ample food supply. Consequently, these findings with A. veneta suggest that the foraminiferal detoxification system could be disrupted by concentrations exceeding 5 ppm of TiO2 nanoparticles. The toxic effect of TiO2 nanoparticles on meiofauna, such as benthic foraminifers, have been poorly understood, though these organisms play an important role in the marine ecosystem. Environmental accumulation of TiO2 nanoparticles on the coast has already exceeded twenty times more than foraminiferal detoxification level. Future studies focusing on toxic mechanism of TiO2 nanoparticles are crucial to prevent the breakdown of the marine ecosystem through accelerating discharge of TiO2 nanoparticles into the ocean.
Autophagy, apoptosis, and inflammation response of Sebastiscus marmoratus to different concentrations of hydroxychloroquine
Authors: Liu Yifan , Luo Jun , Ren Chuanchen , Chen Long , Zhao Yifeng , Yin Xiaolong , Liu Bingjian
Published: July 2024

Hydroxychloroquine (HCQ) is an important public health therapeutic agent widely used in the prevention and treatment of malaria and autoimmune diseases, with some antiviral effects, as well as a common autophagy inhibitor. Its autophagy-inhibiting effect attracts great research interest in mammals but is still little studied in fish. We even have no idea about the effects of HCQ on different tissues of fish and what concentrations should be used for safety studies. This study investigated the effect of different concentration of HCQ treatments on the survival, tissue structure, and expressions of genes related to autophagy, apoptosis, and inflammation in the gill, spleen, testis, and ovary of Sebastiscus marmoratus. The results showed that the higher HCQ concentration (77.40 and 154.80 mg/mL) led to mass mortality within an hour. The half-lethal concentration (LC50, 24 h) of HCQ for S. marmoratus was approximately 48.95 mg/mL. When exposed to 30.96 mg/mL HCQ for 24 hours, autophagy was blocked as revealed by electron microscopy from gill, spleen and testis of fish. The expressions of autophagy-related genes (LC3/Cx43), apoptosis-related genes (Cas3/p53), and inflammation-related genes (TNF-α/IL8) exhibited tissue-specific and dose-dependent responses. The gonads showed preferential expression of all these genes and were found to be sensitive and regular after HCQ treatment. For example, at a concentration of 30.96 mg/mL, the testis demonstrated a regularity that suggests it is an ideal candidate tissue for studying the role of HCQ or autophagy. This study systematically revealed the response of S. marmoratus to different concentrations of HCQ and provided optional assay concentrations for key tissues, serving as an important reference for the future studies on HCQ and autophagy in S. marmoratus. Furthermore, the potential crosstalk between autophagy, apoptosis, and inflammatory pathways initially identified in this study could be helpful for the future research on autophagy regulation in marine fish.
Interannual variability of air-sea CO2 exchange in the Northern Yellow Sea and its underlying mechanisms
Authors: Lv Jia , Nie Hongtao , Shen Jiawei , Wei Hao , Guo Gang , Zhang Haiyan
Published: July 2024

A three-dimensional (3-D) physical-biogeochemical-carbon cycle coupled model is used to investigate the interannual variability of the air-sea carbon dioxide (CO2) flux (FCO2) in the Northern Yellow Sea (NYS) from 2009 to 2018. The verification of the model indicate that the simulation results for multiple variables exhibit consistency and fit well with the observed data. The study show that although the multi-year average FCO2 in the NYS is close to the source-sink balance, there are obvious interannual differences between different years. In particular, a relatively strong source of atmospheric CO2 (1.0 mmol m–2 d–1) is exhibited in 2014, while a relatively strong sink of atmospheric CO2 (–0.7 mmol m–2 d–1) emerges in 2016. Mechanism analysis indicates that the abnormally high temperature is the main controlling factor for the relatively high CO2 efflux rate in the NYS in 2014, while the abnormally low dissolved inorganic carbon (DIC) concentration is the main factor contributing to the relatively high CO2 influx rate in 2016. Further analysis reveals that the primary reason for the low DIC concentration since the onset of winter in 2016 is the high net decrease rate of DIC in the NYS in 2015, influenced by net community production in the summer and advection processes during the autumn. The abnormally high primary production during the summer of 2015 results in the excessive reduction of DIC concentration through biological processes. In addition, due to the strong northeasterly wind event in November 2015, low-concentration-DIC water from the Yellow Sea (YS) extends into the Bohai Sea (BS). This further leads to higher DIC flux from the NYS into the BS in the upper mixed layer and increases the inflow of low-concentration-DIC water from the Southern Yellow Sea (SYS) into the NYS. These ultimately result in the abnormal reduction of DIC concentration in the upper mixed layer of the NYS during the autumn of 2015. This study enriches our understanding of interannual variability of FCO2 in the NYS, which will not only help to further reveal the variations of FCO2 under human activities and climate change, but also provide useful information for guiding the comprehensive assessment of the carbon budget.
Modeling inherited retinal diseases using human induced pluripotent stem cell derived photoreceptor cells and retinal pigment epithelial cells
Authors: Seah Ivan , Goh Debbie , Banerjee Animesh , Su Xinyi
Published: July 2024

Since the discovery of induced pluripotent stem cell (iPSC) technology, there have been many attempts to create cellular models of inherited retinal diseases (IRDs) for investigation of pathogenic processes to facilitate target discovery and validation activities. Consistency remains key in determining the utility of these findings. Despite the importance of consistency, quality control metrics are still not widely used. In this review, a toolkit for harnessing iPSC technology to generate photoreceptor, retinal pigment epithelial cell, and organoid disease models is provided. Considerations while developing iPSC-derived IRD models such as iPSC origin, reprogramming methods, quality control metrics, control strategies, and differentiation protocols are discussed. Various iPSC IRD models are dissected and the scientific hurdles of iPSC-based disease modeling are discussed to provide an overview of current methods and future directions in this field.
Interplay among manures, vegetable types, and tetracycline resistance genes in rhizosphere microbiome
Authors: Ali Izhar , Naz Beenish , Liu Ziyang , Chen Jingwei , Yang Zi , Attia Kotb , Ayub Nasir , Ali Ikram , Mohammed Arif Ahmed , Faisal Shah , Sun Likun , Xiao Sa , Chen Shuyan
Published: July 2024

The rapid global emergence of antibiotic resistance genes (ARGs) is a substantial public health concern. Livestock manure serves as a key reservoir for tetracycline resistance genes (TRGs), serving as a means of their transmission to soil and vegetables upon utilization as a fertilizer, consequently posing a risk to human health. The dynamics and transfer of TRGs among microorganisms in vegetables and fauna are being investigated. However, the impact of different vegetable species on acquisition of TRGs from various manure sources remains unclear. This study investigated the rhizospheres of three vegetables (carrots, tomatoes, and cucumbers) grown with chicken, sheep, and pig manure to assess TRGs and bacterial community compositions via qPCR and high-throughput sequencing techniques. Our findings revealed that tomatoes exhibited the highest accumulation of TRGs, followed by cucumbers and carrots. Pig manure resulted in the highest TRG levels, compared to chicken and sheep manure, in that order. Bacterial community analyses revealed distinct effects of manure sources and the selective behavior of individual vegetable species in shaping bacterial communities, explaining 12.2% of TRG variation. Firmicutes had a positive correlation with most TRGs and the intl1 gene among the dominant phyla. Notably, both the types of vegetables and manures significantly influenced the abundance of the intl1 gene and soil properties, exhibiting strong correlations with TRGs and elucidating 30% and 17.7% of TRG variance, respectively. Our study delineated vegetables accumulating TRGs from manure-amended soils, resulting in significant risk to human health. Moreover, we elucidated the pivotal roles of bacterial communities, soil characteristics, and the intl1 gene in TRG fate and dissemination. These insights emphasize the need for integrated strategies to reduce selection pressure and disrupt TRG transmission routes, ultimately curbing the transmission of tetracycline resistance genes to vegetables.
Cr(VI) removal performance from wastewater by microflora isolated from tannery effluents in a semi-arid environment: a SEM, EDX, FTIR and zeta potential study
Authors: Aké Aké Henri Joël , Rochdi Nabil , Jemo Martin , Hafidi Mohamed , Ouhdouch Yedir , El Fels Loubna
Published: July 2024

Hexavalent chromium removal from the environment remains a crucial worldwide challenge. To address this issue, microbiological approaches are amongst the straightforward strategies that rely mainly on the bacteria's and fungi's survival mechanisms upon exposure to toxic metals, such as reduction, efflux system, uptake, and biosorption. In this work, scanning electron microscopy, energy-dispersive X-ray spectrophotometry, Fourier transform infrared spectroscopy, and zeta potential measurements were used to investigate the ability of chromium adsorption by Bacillus licheniformis, Bacillus megaterium, Byssochlamys sp., and Candida maltosa strains isolated from tannery wastewater. Scanning electron microscopy combined with energy dispersive X-ray spectroscopy revealed alterations in the cells treated with hexavalent chromium. When exposed to 50 mg/L Cr6+, Bacillus licheniformis and Candida maltosa cells become rough, extracellular secretions are reduced in Bacillus megaterium, and Byssochlamys sp. cells are tightly bound and exhibit the greatest Cr weight percentage. In-depth analysis of Fourier transform infrared spectra of control and Cr-treated cells unveiled Cr-microbial interactions involving proteins, lipids, amino acids, and carbohydrates. These findings were supported by zeta potential measurements highlighting significant variations in charge after treatment with Cr(VI) with an adsorption limit of 100 mg/L Cr6+ for all the strains. Byssochlamys sp. showed the best performance in Cr adsorption, making it the most promising candidate for treating Cr-laden wastewater.
Associations of serum lactate and lactate clearance with delirium in the early stage of ICU: a retrospective cohort study of the MIMIC-IV database
Authors: Qian Xiangfeng , Sheng Yi , Jiang Yinsheng , Xu Yong’an
Published: July 2024

Aim

This study aimed to investigate the associations of serum lactate level [within and after 24 h of the intensive care unit (ICU) admission] and lactate clearance rate with delirium and assess associations of lactate and lactate clearance rate with 30-day mortality in delirium patients.

Methods

Data in this retrospective cohort study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database in 2012–2019. The associations of lactate and lactate clearance rate with delirium were explored through univariable and multivariable logistic regression analyses, whereas the associations of lactate and lactate clearance rate with 30-day mortality in delirium patients were investigated using univariable and multivariable Cox regression analyses. Subgroup analysis was performed for age, gender, sepsis, hypertension, sedative drug, ventilation, antibiotic drug, vasopressors, and the Sequential Organ Failure Assessment (SOFA) score. The evaluation indexes were odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs).

Results

Among 7,812 (14.58%) eligible participants, 4,338 (8.19%) had delirium and 1,903 (24.36%) died within 30 days. After adjusting for covariates, patients with lactic acidosis (lactate level > 5 mmol/L and PH < 7.35) at T0 (within 24 h of the ICU admission) had higher odds of delirium (OR = 1.235, 95%CI: 1.105–1.382). Hyperlactatemia (lactate level 2–5 mmol/L and PH > 7.35) at T1 (after 24 h of the ICU admission) was also associated with higher odds of delirium (OR = 1.277, 95%CI: 1.126–1.447). Lactate clearance rate > 50% was linked to lower odds of delirium (OR = 0.705, 95%CI: 0.613–0.811), and this relationship was also observed in ≥65 years old, female, male, non-sepsis, sepsis, non-hypertension, non-sedative drug use, sedative drug use, ventilation, antibiotic drug use, use of vasopressors, and different SOFA score subgroups (all p < 0.05). Additionally, hyperlactatemia and lactic acidosis (whether at T0 or T1) may be potential risk factors for 30-day mortality in delirium patients, whereas lactate clearance rate ≥ 0 had a potential protective effect on 30-day mortality (all p < 0.05).

Conclusion

Higher serum lactate levels in the early stage of the ICU were associated with a higher risk of delirium and subsequent mortality. Measures taken to increase the lactate clearance rate are necessary to reduce potential delirium or mortality risk in clinical settings. However, more evidence from prospective studies is needed to verify these findings.
Architectural organization and molecular profiling of 3D cancer heterospheroids and their application in drug testing
Authors: Nielsen Boye Schnack , Madsen Natasha Helleberg , Larsen Jesper , Skandorff Isabella , Gad Monika , Holmstrøm Kim
Published: July 2024

3D cancer cell cultures have enabled new opportunities for replacing compound testing in experimental animals. However, most solid tumors are composed of multiple cell types, including fibroblasts. In this study we developed multicellular tumor heterospheroids composed of cancer and fibroblasts cell lines. We developed heterospheroids by combining HT-29, MCF-7, PANC-1 or SW480 with 1BR.3.G fibroblasts, which we have previously reported support spheroid formation. We also tested fibroblast cell lines, MRC-5, GM00498 and HIF, but 1BR.3.G was found to best form heterospheroids with morphological similarity to in vivo tumor tissue. The architectural organization of heterospheroids was based on histological examination using immunohistochemistry. We found that HT-29 and MCF-7 cells developed spheroids with the cancer cells surrounding the fibroblasts, whereas PANC-1 cells interspersed with the fibroblasts and SW480 cells were surrounded by fibroblasts. The fibroblasts also expressed collagen-1 and FAP-α, and whole transcriptomic analysis (WTA) showed abundant ECM- and EMT-related expression in heterospheroids, thus reflecting a representative tumor-like microenvironment. The WTA showed that PANC-1 heterospheroids possess a strong EMT profile with abundant Vimentin and CDH2 expression. Drug testing was evaluated by measuring cytotoxicity of 5FU and cisplatin using cell viability and apoptosis assays. We found no major impact on the cytotoxicity when fibroblasts were added to the spheroids. We conclude that the cancer cell lines together with fibroblasts shape the architectural organization of heterospheroids to form tumor-like morphology, and we propose that the various 3D tumor structures can be used for drug testing directed against the cancer cells as well as the fibroblasts.
From laboratory to clinical practice: an update of the immunological and molecular tools for neurocysticercosis diagnosis
Authors: Toribio Luz M. , Bustos Javier A. , Garcia Hector H.
Published: July 2024

Neurocysticercosis (NCC) is caused by the invasion of Taenia solium larvae in the central nervous system (CNS) and stands as the predominant cause of epilepsy and other neurological disorders in many developing nations. NCC diagnosis is challenging because it relies on brain imaging exams (CT or MRI), which are poorly available in endemic rural or resource-limited areas. Moreover, some NCC cases cannot be easily detected by imaging, leading to inconclusive results. Multiple laboratory assays, principally immunological, have been developed to support the diagnosis and/or monitor the treatment efficacy, but its production can be costly, laborious, and non-globally accessible because they depend on parasite material. Therefore, recent advances have been focused on the implementation of recombinant or synthetic antigens as well as monoclonal antibodies for NCC immunodiagnosis purposes. Similarly, molecular diagnosis has been explored, obtaining promising results. Here we described the recent progress in the development of immunological and molecular diagnostic tools for NCC diagnosis over the past 13 years, discussing their potential application to address important challenges and how to focus future directions to improve NCC diagnosis with emphasis on enhance accessibility and the importance of test validation to provide an adequate support for clinical decisions.
Cardiomyocyte crosstalk with endothelium modulates cardiac structure, function, and ischemia-reperfusion injury susceptibility through erythropoietin
Authors: Marrow Jade P. , Alshamali Razan , Edgett Brittany A. , Allwood Melissa A. , Cochrane Kyla L. S. , Al-Sabbag Sara , Ayoub Anmar , Ask Kjetil , Hare Gregory M. T. , Brunt Keith R. , Simpson Jeremy A.
Published: July 2024

Erythropoietin (EPO) exerts non-canonical roles beyond erythropoiesis that are developmentally, structurally, and physiologically relevant for the heart as a paracrine factor. The role for paracrine EPO signalling and cellular crosstalk in the adult is uncertain. Here, we provided novel evidence showing cardiomyocyte restricted loss of function in Epo in adult mice induced hyper-compensatory increases in Epo expression by adjacent cardiac endothelial cells via HIF-2α independent mechanisms. These hearts showed concentric cellular hypertrophy, elevated contractility and relaxation, and greater resistance to ischemia-reperfusion injury. Voluntary exercise capacity compared to control hearts was improved independent of any changes to whole-body metabolism or blood O2 content or delivery (i.e., hematocrit). Our findings suggest cardiac EPO had a localized effect within the normoxic heart, which was regulated by cell-specific EPO-reciprocity between cardiomyocytes and endothelium. Within the heart, hyper-compensated endothelial Epo expression was accompanied by elevated Vegfr1 and Vegfb RNA, that upon pharmacological pan-inhibition of VEGF-VEGFR signaling, resulted in a paradoxical upregulation in whole-heart Epo. Thus, we provide the first evidence that a novel EPO-EPOR/VEGF-VEGFR axis exists to carefully mediate cardiac homeostasis via cardiomyocyte-endothelial EPO crosstalk.
New population of Solanum pimpinellifolium backcross inbred lines as a resource for heat stress tolerance in tomato
Authors: Bashary Neta , Miller Golan , Doitsch-Movshovits Tzion , Beery Avital , Ouyang Bo , Lieberman-Lazarovich Michal
Published: July 2024

The occurring temperature increase in crop production areas worldwide is generating conditions of heat stress that negatively affect crop productivity. Tomato (Solanum lycopersicum), a major vegetable crop, is highly susceptible to elevated temperatures. Under such conditions, fruit set is dramatically reduced, leading to significant yield losses. Solanum pimpinellifolium, a wild species closely related to the cultivated tomato, was shown to have beneficial attributes under various abiotic stress growth conditions. We have utilized a new population of backcross inbred lines originated from a cross between S. pimpinellifolium and S. lycopersicum, in order to evaluate its potential as a new genetic resource for improvement of reproductive performance of cultivated tomato under heat stress conditions. This population was screened for various heat stress-related traits, under controlled heat stress and non-stress conditions. Our results show that significant variation exists for all the heat stress related traits that were examined and point at individual lines with better reproductive performance under heat stress conditions that share a common introgression from the wild S. pimpinellifolium parent, suggesting several candidate genes as potential drivers of thermotolerance. Thus, our results place this population as a valuable new resource for the discovery of heat stress related genetic loci for the future development of heat stress tolerant tomato cultivars.
Genome-wide analysis of soybean hypoxia inducible gene domain containing genes: a functional investigation of GmHIGD3
Authors: Geng Xiaoyan , Dong Lu , Zhu Tiantian , Yang Chunhong , Zhang Jianhua , Guo Binhui , Chen Huatao , Zhang Qun , Song Li
Published: July 2024

The response of Hypoxia Inducible Gene Domain (HIGD) proteins to hypoxia plays a crucial role in plant development. However, the research on this gene family in soybean has been lacking. In this study, we aimed to identify and comprehensively analyze soybean HIGD genes using the Glycine max genome database. As a result, six GmHIGD genes were successfully identified, and their phylogeny, gene structures, and putative conserved motifs were analyzed in comparison to Arabidopsis and rice. Collinearity analysis indicated that the HIGD gene family in soybean has expanded to some extent when compared to Arabidopsis. Additionally, the cis-elements in the promoter regions of GmHIGD and the transcription factors potentially binding to these regions were identified. All GmHIGD genes showed specific responsiveness to submergence and hypoxic stresses. Expression profiling through quantitative real-time PCR revealed that these genes were significantly induced by PEG treatment in root tissue. Co-expressed genes of GmHIGD were primarily associated with oxidoreductase and dioxygenase activities, as well as peroxisome function. Notably, one of GmHIGD genes, GmHIGD3 was found to be predominantly localized in mitochondria, and its overexpression in Arabidopsis led to a significantly reduction in catalase activity compared to wild-type plants. These results bring new insights into the functional role of GmHIGD in terms of subcellular localization and the regulation of oxidoreductase activity.
Costs over benefits: mind wandering in sporting performance
Authors: Li Jieling , Liu Yafang , Xue Shuangpeng , Tian Bao
Published: July 2024

Introduction

Athletes’ mind wandering during competition has positive and negative effects. The purpose of this study was to explore the reason for these bidirectional effects.

Methods

We recruited 51 athletes from China to take part in semi-structured interviews in which we explored their experiences of mind wandering in competition. We used grounded theory combined with systems thinking to complete the data analysis and theoretical construction.

Results

Results showed that the influence of mind wandering on sporting performance was dynamically influenced by “mind wandering source,” “competition anxiety,” “content of mind wandering,” “attentional resources” and “attentional control,” resulting in our development of the theory of “mind wandering in sporting performance (MWSP).” The above factors determine how mind wandering occurs and how it affects the competition.

Discussion

Although the occurrence of mind wandering during competition has positive effects, its negative effects cannot be ignored, which may lead to athletes losing the race (costs over benefits). Potential strategies focusing on the mitigation of negative effects and promotion of positive effects of mind wandering are discussed.