bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of current and future trends in water resources in the Gambia River Basin in a context of climate change
Authors: Séne Serigne Mory Khouma , Faye Cheikh , Pande Chaitanya B.
Published: February 2024

Accurate assessment of water resources at the watershed level is crucial for effective integrated watershed management. While semi-distributed/distributed models require complex structures and large amounts of input data, conceptual models have gained attention as an alternative to watershed modeling. In this paper, the performance of the GR4J conceptual model for runoff simulation in the Gambia watershed at Simenti station is analyzed over the calibration (1981–1990) and validation period (1991–2000 and 2001–2010). The main inputs to conceptual models like GR4J are daily precipitation data and potential evapotranspiration (PET) measured from the same catchment or a nearby location. Calibration of these models is typically performed using the Nash–Sutcliffe daily efficiency with a bias penalty as the objective function. In this case, the GR4J model is calibrated using four optimization parameters. To evaluate the effectiveness of the model's runoff predictions, various statistical measures such as Nash–Sutcliffe efficiency, coefficient of determination, bias, and linear correlation coefficient are calculated. The results obtained in the Gambia watershed at Simenti station indicate satisfactory performance of the GR4J model in terms of forecast accuracy and computational efficiency. The Nash–Sutcliffe (Q) values are 0.623 and 0.711 during the calibration period (1981–1990) and the validation period (1991–2000), respectively. The average annual flow observed during the calibration period is 0.385 mm while it increases with a value of 0.603 mm during the validation period. As for the average flow simulated by the model, it is 0.142 mm during the calibration period (i.e., a delay of 0.142 mm compared to the observed flow), 0.626 mm in the validation period (i.e., an excess of 0.023 mm compared to the observed flow). However, this study is significant because it shows significant changes in all metrics in the watershed sample under different scenarios, especially the SSP245 and SSP585 scenarios over the period 2021–2100. These changes suggest a downward trend in flows, which would pose significant challenges for water management. Therefore, it is clear that sustainable water management would require substantial adaptation measures to cope with these changes.
Bioinformatics analysis and molecular dynamics simulations of azoreductases (AzrBmH2) from Bacillus megaterium H2 for the decolorization of commercial dyes
Authors: Oyewusi Habeebat Adekilekun , Wahab Roswanira Abdul , Akinyede Kolajo Adedamola , Albadrani Ghadeer M. , Al-Ghadi Muath Q. , Abdel-Daim Mohamed M. , Ajiboye Basiru Olaitan , Huyop Fahrul
Published: February 2024

The present study aimed to investigate the decolorization of various commercial dyes by azoreductases (AzrBmH21, AzrBmH22/3, and AzrBmH24/5) through bioinformatics means, comprising molecular docking, molecular dynamics simulation, and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA). Therefore, four commercial dyes, namely acid orange 7, cresol red, methylene blue, and malachite green, were selected as potential targets for degradation by the above said azoreductases derived fromBacillus megateriumH2. The prediction of ligand binding or catalytic sites for AzrBmH21, AzrBmH22/3, and AzrBmH24/5 were performed using a machine learning algorithm based on the Prank Web and DeepSite chemoinformatic tool. This analysis revealed that several amino acids of AzrBmH2 interacted with the tested dyes, indicating the presence of distinct ligand-binding sites for AzrBmH2-dye complexes. Likewise, the binding affinity for AzrBmH21, AzrBmH22/3, and AzrBmH24/5 ranged from − 9.4 to − 5.5 kcal/mol, − 9.2 to − 5.4 kcal/mol, and − 9.0 to − 5.4 kcal/mol, respectively, with each complex stabilized at a minimum of 0–5 hydrogen bonds. MD simulations revealed stable AzrBmH2-dye complexes with RMSD and RMSF values ranging from 0.15 to 0.42 nm and 0.05 to 0.48 nm, respectively, with Rg values between 1.75 and 1.88 nm. MM-PBSA calculations indicated that the AzrBmH2–dye complexes, except for AzrBmH2–malachite green, exhibited the lowest binding energy (− 191.05 ± 7.08 to 314.19 ± 6.88 kcal/mol), with prevalent hydrophobic interactions (− 268.25 ± 12.25 to − 418.92 ± 29.45 kcal/mol) through van der Waals forces. Therefore, this study was able to highlight the potential role of enzymes, specifically azoreductases fromBacillus megateriumH2, in predicting the decolorization of commercial dyes. These findings could contribute to our understanding of the azoreductases’ mechanisms in bioremediation and for biotechnological applications.
Refractive outcomes of immediately sequential bilateral cataract surgery in eyes with long and short axial lengths
Authors: Pollmann André S. , Nguyen Michael Trong Duc , Keyeutat Milime , Danis Éliane , Durr Georges M. , Agoumi Younes , Jabbour Samir
Published: February 2024

Purpose

To report the refractive outcomes of long (≥25.00 mm) and short (≤22.00 mm) axial length (AL) eyes undergoing immediately sequential bilateral cataract surgery (ISBCS).

Methods

In this retrospective cohort study, patients who underwent ISBCS were identified and eyes of patients with bilateral long and short ALs were included. Pre- and postoperative biometry, autorefraction, and ocular comorbidities or complications were recorded. The primary outcome was the mean refractive prediction error.

Results

Thirty-seven patients (74 eyes) with long ALs and 18 patients (36 eyes) with short ALs were included. The means ± standard deviations of the ALs were 26.40 ± 1.38 mm and 21.44 ± 0.46 mm in the long and short AL groups, respectively. In long AL eyes, the mean absolute error from the biometry-predicted refraction was − 0.16 ± 0.46 D, corresponding to 74% of eyes achieving a refraction within ±0.50 D of the predicted value. In short AL eyes, the mean absolute error was − 0.63 ± 0.73 D, corresponding to 44% of eyes achieving a refraction within ±0.50 D of the predicted value. Eight (44.4%) patients with short AL eyes had a myopic deviation greater than ±0.50 D from the predicted result in both eyes.

Conclusions

Compared to patients with long AL eyes, ISBCS in patients with short ALs had a wider variance in refractive outcome and a lower rate of achieving a postoperative refraction within ±0.50 D of the predicted target.
Association between weight-adjusted waist index and non-alcoholic fatty liver disease: a population-based study
Authors: Yu Changhui , He Shiming , Kuang Maobin , Wang Chao , Huang Xin , Sheng Guotai , Zou Yang
Published: February 2024

Background

Obesity is the most important driver of non-alcoholic fatty liver disease (NAFLD); nevertheless, the relationship of weight-adjusted waist index (WWI), a new obesity index, with NAFLD is unclear.

Methods

This retrospective study used data from the NAGALA project from 1994 to 2016. WWI values were calculated using waist circumference (WC) and weight measurements of the participants. Three stepwise adjusted logistic regression models were developed to assess the relationship of WWI with NAFLD in the whole population and in both sexes. Additionally, we also conducted a series of exploratory analysis to test the potential impact of body mass index (BMI), age, smoking status and exercise habits on the association of WWI with NAFLD. Receiver operating characteristic (ROC) curves were used to estimate cut-off points for identifying NAFLD in the entire population and in both sexes.

Results

The current study included a population of 11,805 individuals who participated in health screenings, including 6,451 men and 5,354 women. After adjusting for all non-collinear variables in the multivariable logistic regression model, we found a significant positive correlation of WWI with NAFLD. For each unit increase in WWI, the risk of NAFLD increased by 72% in the entire population, by 84% in men, and by 63% in women. Furthermore, subgroup analyses revealed no significant discrepancies in the correlation of WWI with NAFLD across individuals with varying ages, exercise habits, and smoking status (all P-interaction > 0.05), except for different BMI groups (P-interaction < 0.05). Specifically, compared to the overweight/obese group, the relationship of WWI with NAFLD was significantly stronger in the non-obese group, especially in non-obese men. Finally, based on the results of ROC analysis, we determined that the WWI cut-off point used to identify NAFLD was 9.7675 in men and 9.9987 in women.

Conclusions

This study is the first to establish a positive correlation between WWI and NAFLD. Moreover, assessing the influence of WWI on NAFLD in individuals without obesity may yield more valuable insights compared to those who are overweight or obese.
Factors contributing to the rising prevalence of waterpipe smoking dependence among university students: a cross-sectional study
Authors: Maraqa Beesan , Nazzal Zaher , Baker Noor Abu , Khatib Heyam , Zeyad Marwa , Aburayyan Omar
Published: February 2024

Introduction

Waterpipe smoking (WPS) has been associated with a variety of adverse health effects, consequences, and symptoms of nicotine dependence. This study aims to determine the prevalence of WPS dependence among Palestinian university waterpipe smoking students, their normative beliefs about WPS, and their relationship to dependence.

Methods

A cross-sectional study of current WPS university students at five major Palestinian universities was conducted from September to December 2022. Participants were recruited using convenient sampling, and data collection was carried out via an interviewer-administered questionnaire. We assessed students’ WPS dependence using the Lebanese Waterpipe Dependence Scale. We used the Poisson regression model with robust variance to analyze factors independently associated with high WPS dependence.

Results

The study included 746 current WPS university students. Results revealed a high prevalence of WPS dependence, with 69.4% (95%CI: 66.0-72.7%) exhibiting high dependence. Factors contributing to high WPS dependence included dual cigarette smoking (aPR: 1.18; 95%CI: 1.12–1.25), studying medical sciences (aPR: 1.13; 95%CI: 1.10–1.18), friends’ approval of WPS (aPR: 1.25; 95%CI: 1.17–1.34), daily WPS frequency (aPR: 1.98; 95%CI: 1.39–2.23), spending more than 50% of daily allowance on WPS (aPR: 1.37; 95%CI: 1.10–1.64), and morning WPS sessions (aPR: 1.97; 95%CI: 1.31–2.27). The study highlighted the influence of social factors, such as peers’ approval and perceived prevalence, on WPS dependence.

Conclusions

WPS dependence is prevalent among university students, and it is associated with morning WPS, dual smoking, and increased WPS frequency. Notably, peer and cultural factors are essential primary motivators. As a result, it is critical to incorporate WPS considerations into Palestine’s antismoking health promotion program. Therefore, it is vital to incorporate WPS into the Palestinian antismoking health promotion policy, and the health education of adolescents regarding the dangers of WPS should coincide with antismoking initiatives.
Metabolic engineering of Synechocystis sp. PCC 6803 for the improved production of phenylpropanoids
Authors: Kukil Kateryna , Lindberg Pia
Published: February 2024

Background

Phenylpropanoids are a large group of plant secondary metabolites with various biological functions, derived from aromatic amino acids. Cyanobacteria are promising host organisms for sustainable production of plant phenylpropanoids. We have previously engineered Synechocystis sp. PCC 6803 to produce trans-cinnamic acid (tCA) and p-coumaric acid (pCou), the first intermediates of phenylpropanoid pathway, by overexpression of phenylalanine- and tyrosine ammonia lyases. In this study, we aimed to enhance the production of the target compounds tCA and pCou in Synechocystis.

Results

We eliminated the 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, which is a competing pathway consuming tyrosine and, possibly, phenylalanine for tocopherol synthesis. Moreover, several genes of the terminal steps of the shikimate pathway were overexpressed alone or in operons, such as aromatic transaminases, feedback insensitive cyclohexadienyl dehydrogenase (TyrC) from Zymomonas mobilis and the chorismate mutase (CM) domain of the fused chorismate mutase/prephenate dehydratase enzyme from Escherichia coli. The obtained engineered strains demonstrated nearly 1.5 times enhanced tCA and pCou production when HPPD was knocked out compared to the parental production strains, accumulating 138 ± 3.5 mg L−1 of tCA and 72.3 ± 10.3 mg L−1 of pCou after seven days of photoautotrophic growth. However, there was no further improvement when any of the pathway genes were overexpressed. Finally, we used previously obtained AtPRM8 and TsPRM8 Synechocystis strains with deregulated shikimate pathway as a background for the overexpression of synthetic constructs with ppd knockout.

Conclusions

HPPD elimination enhances the tCA and pCou productivity to a similar extent. The use of PRM8 based strains as a background for overexpression of synthetic constructs, however, did not promote tCA and pCou titers, which indicates a tight regulation of the terminal steps of phenylalanine and tyrosine synthesis. This work contributes to establishing cyanobacteria as hosts for phenylpropanoid production.
The clustering status of detached gastric cancer cells inhibits anoikis-induced ferroptosis to promote metastatic colonization
Authors: Sun Juan , Li Jie , Pantopoulos Kostas , Liu Yuqin , He Yixuan , Kang Weiming , Ye Xin
Published: February 2024

Background and purpose

Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. Its role in cancer metastasis remains unclear. In this study, we aimed to investigate the potential involvement of ferroptosis in gastric cancer (GC) metastasis.

Methods

GC cells (AGS, MKN45, HGC27) were used to explore the role of ferroptosis in single and clustered cells with extracellular matrix (ECM) detachment in vitro. We overexpressed glutathione peroxidase 4 (GPX4) to inhibit ferroptosis and assessed the changes in cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Then tumor tissues from 54 GC patients with and without lymphatic metastasis were collected for immunohistochemical staining to investigate the expression of ferroptosis and EMT markers. Finally, Kaplan–Meier survival curves were used to investigate the relationship between overall survival and expression of GPX4 in 178 GC patients.

Results

Detached single cells had lower viability than adherent cells, but cell clustering improved their survival under matrix-detached conditions. Detached single cells exhibited an induction of iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of ACSL4, TFRC and HO-1, increased iron levels, and changes in mitochondrial morphology. Opposite effects were observed in detached clustered cells, including the upregulation of the ferroptosis suppressors GPX4 and SLC7A11. Overexpression of GPX4 inhibited ferroptosis and promoted GC cell proliferation, migration, invasion, and EMT. Immunohistochemical analysis of tumor tissues from GC patients indicated that lymphatic metastasis was associated with higher potential for ferroptosis inhibition and EMT induction. Finally, Kaplan–Meier survival curves demonstrated a significant decrease in overall survival among GC patients with high GPX4 expression.

Conclusions

Our study provides the first evidence that inhibition of ferroptosis is a crucial mechanism promoting GC metastasis. GPX4 may be a valuable prognostic factor for GC patients. These findings suggest that targeting ferroptosis inhibition may be a promising strategy for GC patients with metastatic potential.

Trial registration The ethical approval code of this study in Institutional Review Board of Peking Union Medical College Hospital is No: K1447.
Socioeconomic and geographic variations of disabilities in India: evidence from the National Family Health Survey, 2019–21
Authors: Rashmi Rashmi , Mohanty Sanjay K.
Published: February 2024

Background

Increasing disability is of global and national concern. Lack of evidence on disability across socioeconomic groups and geographic levels (especially small areas) impeded interventions for these disadvantaged subgroups. We aimed to examine the socioeconomic and geographic variations in disabilities, namely hearing, speech, visual, mental, and locomotor, in Indian participants using cross-sectional data from the National Family Health Survey 2019–2021.

Methods

Using data from 27,93,971 individuals, we estimated age-sex-adjusted disability rates at the national and sub-national levels. The extent of socioeconomic variations in disabilities was explored using the Erreygers Concentration Index and presented graphically through a concentration curve. We adopted a four-level random intercept logit model to compute the variance partitioning coefficient (VPC) to assess the significance of each geographical unit in total variability. We also calculated precision-weighted disability estimates of individuals across 707 districts and showed their correlation with within-district or between-cluster standard deviation.

Results

We estimated the prevalence of any disability of 10 per 1000 population. The locomotor disability was common, followed by mental, speech, hearing, and visual. The concentration index of each type of disability was highest in the poorest wealth quintile households and illiterate 18 + individuals, confirming higher socioeconomic variations in disability rates. Clusters share the largest source of geographic variation for any disability (6.5%), hearing (5.8%), visual (24.3%), and locomotor (17.4%). However, States/Union Territories (UTs) account for the highest variation in speech (3.7%) and mental (6.5%) disabilities, where the variation at the cluster level becomes negligible. Districts with the highest disability rates were clustered in Madhya Pradesh, Maharashtra, Karnataka, Tamil Nadu, Telangana, and Punjab. Further, we found positive correlations between the district rates and cluster standard deviations (SDs) for disabilities.

Conclusions

Though the growing disability condition in India is itself a concerning issue, wide variations across socioeconomic groups and geographic locations indicate the implementation of several policy-relevant implications focusing on these vulnerable chunks of the population. Further, the critical importance of small-area variations within districts suggests the design of strategies targeting these high-burden areas of disabilities.
Two-dimensional nanomaterials induced nano-bio interfacial effects and biomedical applications in cancer treatment
Authors: Wang Yan , Zhang Xiao , Yue Hua
Published: February 2024

Two-dimensional nanomaterials (2D NMs), characterized by a large number of atoms or molecules arranged in one dimension (typically thickness) while having tiny dimensions in the other two dimensions, have emerged as a pivotal class of materials with unique properties. Their flat and sheet-like structure imparts distinctive physical, chemical, and electronic attributes, which offers several advantages in biomedical applications, including enhanced surface area for efficient drug loading, surface-exposed atoms allowing precise chemical modifications, and the ability to form hierarchical multilayer structures for synergistic functionality. Exploring their nano-bio interfacial interactions with biological components holds significant importance in comprehensively and systematically guiding safe applications. However, the current lack of in-depth analysis and comprehensive understanding of interfacial effects on cancer treatment motivates our ongoing efforts in this field. This study provides a comprehensive survey of recent advances in utilizing 2D NMs for cancer treatment. It offers insights into the structural characteristics, synthesis methods, and surface modifications of diverse 2D NMs. The investigation further delves into the formation of nano-bio interfaces during their in vivo utilization. Notably, the study discusses a wide array of biomedical applications in cancer treatment. With their potential to revolutionize therapeutic strategies and outcomes, 2D NMs are poised at the forefront of cancer treatment, holding the promise of transformative advancements.

Graphical Abstract
Evaluation of serum adiponectin as a marker of insulin resistance in women with polycystic ovarian syndrome: a comparative cross-sectional study
Authors: Runsewe Olugbenga Ojatokunbo , Adewunmi Abiodun Adeniyi , Olorunfemi Gbenga , Ottun Abimbola Tawaqualit , Olumodeji Ayokunle Moses , Ogungbemile Babalola , Runsewe-Abiodun Tamramat Iyabo
Published: February 2024

Background

Insulin resistance (IR) is known to be prevalent amongst women with polycystic ovarian syndrome (PCOS). Its presence has been linked to chronic anovulation and marked long term complications in women. Hence, identification and treatment of IR in women with PCOS is required to prevent the metabolic and reproductive complications of the disease. The aim of this study is to determine if serum adiponectin could be used as a surrogate marker for insulin resistance among women with PCOS.

Materials and methods

A total number of 148 consenting women with PCOS diagnosed using the Rotterdam criteria were recruited for this study. Fifty-two of these women had insulin resistance were compared with 96 of the women who did not have insulin resistance. The serum Adiponectin levels, fasting blood glucose and fasting insulin levels were assayed in all study participants. Insulin resistance was assessed in all the study participants using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Data were analyzed using relevant inferential statistics at 95% confidence interval and p value of < 0.05.

Results

The prevalence of insulin resistance among the study participants was 35.1%. Majority of the women (83.1%) had a high body mass index (BMI). More than half (68.2%) of the participants were in the age range of 21-30years and 76.4% (113) were nulliparous. There was no statistically significant difference in the median adiponectin level among insulin resistant (3.735 ug/ml) and non-insulin resistant participants vs. (3.705 ug/ml) (p = 0.6762). Both univariate and multivariate regression analysis did not show a statistically significant relationship between adiponectin and insulin resistance in PCOS.

Conclusion

The prevalence of insulin resistance in women with PCOS is high and serum adiponectin is not a suitable surrogate marker of insulin resistance in women with PCOS.
RBBP7, regulated by SP1, enhances the Warburg effect to facilitate the proliferation of hepatocellular carcinoma cells via PI3K/AKT signaling
Authors: Fang Yuan , Tang WeiQiang , Qu Siming , Li ZhiTao , Zhang XiaoLi , Miao YingLei , Zeng Zhong , Huang HanFei
Published: February 2024

Background

Hepatocellular carcinoma (HCC) is characterized by aggressive progression and elevated mortality rates. This study aimed to investigate the regulatory effects of RBBP7 on HCC pathogenesis and the underlying mechanisms.

Methods

The expression and clinical feature of RBBP7 were evaluated using bioinformatics analysis and the assessment of clinical HCC samples. CCK8 and colony formation were employed to estimate cell proliferation function of RBBP7. Aerobic glycolysis levels of RBBP7 were evaluated by measuring ATP levels, lactic acid production, glucose uptake capacity, and the expression of relevant enzymes (PFKM, PKM2, and LDHA). The phosphorylation levels in PI3K/AKT signaling were measured by western blotting. The regulatory effect of transcription factors of specificity protein 1 (SP1) on RBBP7 mRNA expression was confirmed in dual-luciferase reporter assays and chromatin immunoprecipitation experiments. The proliferation- and glycolysis-associated proteins were assessed using immunofluorescence staining in vivo.

Results

We found that RBBP7 is expressed at high levels in HCC and predicts poor survival. Functional assays showed that RBBP7 promoted HCC proliferation and glycolysis. Mechanistically, it was demonstrated that RBBP7 activates the PI3K/AKT pathway, a crucial pathway in glycolysis, contributing to the progression of HCC. The outcomes of the dual-luciferase assay further confirmed that SP1 is capable of activating the promoter of RBBP7.

Conclusions

RBBP7, which is up-regulated by SP1, promotes HCC cell proliferation and glycolysis through the PI3K/AKT pathway. The findings of this study suggest that RBBP7 is a potential biomarker for HCC.
HuR promotes castration-resistant prostate cancer progression by altering ERK5 activation via posttranscriptional regulation of BCAT1
Authors: You Hang , Song Guojing , Xu Zhizhen , Chen Saipeng , Shen Wenhao , Liu Heting , Deng Bingqian , Li Jun , Huang Gang
Published: February 2024

Background

Castration-resistant prostate cancer (CRPC) is refractory to hormone treatment, and the underlying mechanism has not been fully elucidated. This study aimed to clarify the role and mechanism of Human antigen R (HuR) as a therapeutic target for CRPC progression.

Methods

HuR was knocked out by Cas9 or inhibited by the HuR-specific inhibitor KH-3 in CRPC cell lines and in a mouse xenograft model. The effects of HuR inhibition on tumour cell behaviors and signal transduction were examined by proliferation, transwell, and tumour xenograft assays. Posttranscriptional regulation of BCAT1 by HuR was determined by half-life and RIP assays.

Results

HuR knockout attenuated the proliferation, migration, and invasion of PC3 and DU145 cells in vitro and inhibited tumour progression in vivo. Moreover, BCAT1 was a direct target gene of HuR and mediated the oncogenic effect of HuR on CRPC. Mechanistically, HuR directly interacted with BCAT1 mRNA and upregulated BCAT1 expression by increasing the stability and translation of BCAT1, which activated ERK5 signalling. Additionally, the HuR-specific inhibitor KH-3 attenuated CRPC progression by disrupting the HuR-BCAT1 interaction.

Conclusions

We confirmed that the HuR/BCAT1 axis plays a crucial role in CRPC progression and suggest that inhibiting the HuR/BCAT1 axis is a promising therapeutic approach for suppressing CRPC progression.

Graphical Abstract
Gut microbial metabolites SCFAs and chronic kidney disease
Authors: He Meng , Wei Wenqian , Zhang Yichen , Xiang Zhouxia , Peng Dan , Kasimumali Ayijiaken , Rong Shu
Published: February 2024

The global incidence of Chronic Kidney Disease (CKD) is steadily escalating, with discernible linkage to the intricate terrain of intestinal microecology. The intestinal microbiota orchestrates a dynamic equilibrium in the organism, metabolizing dietary-derived compounds, a process which profoundly impacts human health. Among these compounds, short-chain fatty acids (SCFAs), which result from microbial metabolic processes, play a versatile role in influencing host energy homeostasis, immune function, and intermicrobial signaling, etc. SCFAs emerge as pivotal risk factors influencing CKD’s development and prognosis. This paper review elucidates the impact of gut microbial metabolites, specifically SCFAs, on CKD, highlighting their role in modulating host inflammatory responses, oxidative stress, cellular autophagy, the immune milieu, and signaling cascades. An in-depth comprehension of the interplay between SCFAs and kidney disease pathogenesis may pave the way for their utilization as biomarkers for CKD progression and prognosis or as novel adjunctive therapeutic strategies.
Multi-omic profiling reveals associations between the gut microbiome, host genome and transcriptome in patients with colorectal cancer
Authors: Zou Shaomin , Yang Chao , Zhang Jieping , Zhong Dan , Meng Manqi , Zhang Lu , Chen Honglei , Fang Lekun
Published: February 2024

Background

Colorectal cancer (CRC) is the leading cancer worldwide. Microbial agents have been considered to contribute to the pathogenesis of different disease. But the underlying relevance between CRC and microbiota remain unclear.

Methods

We dissected the fecal microbiome structure and genomic and transcriptomic profiles of matched tumor and normal mucosa tissues from 41 CRC patients. Of which, the relationship between CRC-associated bacterial taxa and their significantly correlated somatic mutated gene was investigated by exome sequencing technology. Differentially expressed functional genes in CRC were clustered according to their correlation with differentially abundant species, following by annotation with DAVID. The composition of immune and stromal cell types was identified by XCELL.

Results

We identified a set of 22 microbial gut species associated with CRC and estimate the relative abundance of KEGG ontology categories. Next, the interactions between CRC-related gut microbes and clinical phenotypes were evaluated. 4 significantly mutated gene: TP53, APC, KRAS, SMAD4 were pointed out and the associations with cancer related microbes were identified. Among them, Fusobacterium nucleatum positively corelated with different host metabolic pathways. Finally, we revealed that Fusobacterium nucleatum modified the tumor immune environment by TNFSF9 gene expression.

Conclusion

Collectively, our multi-omics data could help identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC.
Diffuse large B-cell lymphoma: the significance of CD8+ tumor-infiltrating lymphocytes exhaustion mediated by TIM3/Galectin-9 pathway
Authors: Zhu Qiqi , Yang Yiming , Chen Kexin , Zhang Qiaoyu , Huang Yifan , Jian Shunhai
Published: February 2024

Background

Overexpression of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is related to the exhaustion of CD8+ tumor-infiltrating lymphocytes (TILs) in diffuse large B-cell lymphoma (DLBCL). However, the mechanism of TIM3-mediated CD8+TILs exhaustion in DLBCL remains poorly understood. Therefore, we aimed to clarify the potential pathway involved in TIM3-mediated CD8+TILs exhaustion and its significance in DLBCL.

Methods

The expression of TIM3 and its correlation with CD8+TILs exhaustion, the key ligand of TIM3, and the potential pathway of TIM3-mediated CD8+TILs exhaustion in DLBCL were analyzed using single-cell RNA sequencing and validated by RNA sequencing. The biological significance of TIM3-related pathway in DLBCL was investigated based on RNA sequencing, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction data. Finally, the possible regulatory mechanism of TIM3-related pathway in DLBCL was explored using single-cell RNA sequencing and RNA sequencing.

Results

Our results demonstrated that CD8+TILs, especially the terminally exhausted state, were the major clusters that expressed TIM3 in DLBCL. Galectin-9, mainly expressed in M2 macrophages, is the key ligand of TIM3 and can induce the exhaustion of CD8+TILs through TIM3/Galectin-9 pathway. Meanwhile, high TIM3/Galectin-9 enrichment is related to immunosuppressive tumor microenvironment, severe clinical manifestations, inferior prognosis, and poor response to CHOP-based chemotherapy, and can predict the clinical efficacy of immune checkpoint blockade therapy in DLBCL. Furthermore, the TIM3/Galectin-9 enrichment in DLBCL may be regulated by the IFN-γ signaling pathway.

Conclusions

Our study highlights that TIM3/Galectin-9 pathway plays a crucial role in CD8+TILs exhaustion and the immune escape of DLBCL, which facilitates further functional studies and could provide a theoretical basis for the development of novel immunotherapy in DLBCL.
Towards portable MRI in the plant sciences
Authors: Blystone Shannan , Nuixe Magali , Traoré Amidou Sissou , Cochard Hervé , Picon-Cochard Catherine , Pagés Guilhem
Published: February 2024

Plant physiology and structure are constantly changing according to internal and external factors. The study of plant water dynamics can give information on these changes, as they are linked to numerous plant functions. Currently, most of the methods used to study plant water dynamics are either invasive, destructive, or not easily accessible. Portable magnetic resonance imaging (MRI) is a field undergoing rapid expansion and which presents substantial advantages in the plant sciences. MRI permits the non-invasive study of plant water content, flow, structure, stress response, and other physiological processes, as a multitude of information can be obtained using the method, and portable devices make it possible to take these measurements in situ, in a plant’s natural environment. In this work, we review the use of such devices applied to plants in climate chambers, greenhouses or in their natural environments. We also compare the use of portable MRI to other methods to obtain the same information and outline its advantages and disadvantages.
Exploring the impact of light intensity under speed breeding conditions on the development and growth of lentil and chickpea
Authors: Mitache Mohammed , Baidani Aziz , Bencharki Bouchaib , Idrissi Omar
Published: February 2024

The use of high-performant varieties could help to improve the production of food legumes and thus meet the demand of the growing world population. However, long periods needed to develop new varieties through traditional breeding are a major obstacle. Thus, new techniques allowing faster genetic advance are needed. Speed breeding using longer periods of light exposure on plants, appears to be a good solution for accelerating plant life cycles and generation turnover. However, applying extended photoperiod causes plant stress and mortality due to lack of information on the adequate intensity to be used in speed breeding protocol. This study examines the impact of light intensity under speed breeding conditions on the development and growth of lentils and chickpeas, with a keen interest in enhancing genetic gain in these key food legumes. Four distinct levels of light intensity (T1: Green-house: 2000 µmol/m2/s; T2: 148–167 µmol/m2/s; T3: 111–129 µmol/m2/s; T4: 74–93 µmol/m2/s) under a photoperiod of 18 h of light and 6 h of darkness were tested in a growth chamber. Significant variation depending on light intensity was observed for plant height, total biomass, number of secondary stems, pods number, number of seeds per plant, growth rate, green canopy cover, time to flowering, time of pod set, time to maturity, vegetative stage length, reproduction stage length and seed filling stage length. Light intensity significantly influenced flowering/maturity and plant’s stress compared to normal conditions in green-house where flowering/maturity were around 67/97 days for lentil and 79/111 days for chickpea. Therefore, lentils in treatment 2 flowered and reached maturity in 30/45 days respectively, with high stress, while chickpeas in the same treatment did not flower. In contrast, treatment 4 showed interesting results, promoting optimal growth with low stress, and flowering/maturity in 27/46 days and 28/54 days, respectively for lentils and chickpeas. These results underline the crucial importance of light management in speed breeding to accelerate vegetative growth and phenology while allowing healthy growth conditions for plants to produce enough seeds for generation turnover.
Identification of chromosomal abnormalities in miscarriages by CNV-Seq
Authors: Shao Yuqi , Yang Saisai , Cheng Lin , Duan Jie , Li Jin , Kang Jiawei , Wang Fang , Liu Juan , Zheng Fang , Ma Jianhong , Zhang Yuanzhen
Published: February 2024

Objective

The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies.

Methods

This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs).

Results

Of 580 miscarriage cases, three were excluded as maternal cell contamination, 357 cases showed abnormal chromosomal results, and the remaining 220 were normal, with a positive detection rate of 61.87% (357/577). In the 357 miscarriage cases, 470 variants were discovered, of which 65.32% (307/470) were pathogenic. Among all variants detected, 251 were numerical chromosomal abnormalities, and 219 were structural abnormalities. With advanced maternal age, the proportion of numerical abnormalities increased, but the proportion of structural abnormalities decreased. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis revealed that eleven pathways and 636 biological processes were enriched in pCNVs region genes. Protein–protein interaction analysis of 226 dosage-sensitive genes showed that TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 might be significant in the development of miscarriages.

Conclusion

Our study provides evidence that chromosomal abnormalities contribute to miscarriages, and emphasizes the significance of microdeletions or duplications in causing miscarriages apart from numerical abnormalities. Essential genes found in pCNVs regions may account for miscarriages which need further validation.
Biosynthesis of melatonin from l-tryptophan by an engineered microbial cell factory
Authors: Wang Lijuan , Deng Yongdong , Gao Jianjie , Wang Bo , Han Hongjuan , Li Zhenjun , Zhang Wenhui , Wang Yu , Fu Xiaoyan , Peng Rihe , Yao Quanhong , Tian Yongsheng , Xu Jing
Published: February 2024

Background

The demand for melatonin is increasing due to its health-promoting bioactivities such as antioxidant and sleep benefits. Although melatonin is present in various organisms, its low content and high extraction cost make it unsustainable. Biosynthesis is a promising alternative method for melatonin production. However, the ectopic production of melatonin in microorganisms is very difficult due to the low or insoluble expression of melatonin synthesis genes. Hence, we aim to explore the biosynthesis of melatonin using Escherichia coli as a cell factory and ways to simultaneously coordinated express genes from different melatonin synthesis pathways.

Results

In this study, the mXcP4H gene from Xanthomonas campestris, as well as the HsAADC, HsAANAT and HIOMT genes from human melatonin synthesis pathway were optimized and introduced into E. coli via a multi-monocistronic vector. The obtained strain BL7992 successfully synthesized 1.13 mg/L melatonin by utilizing L-tryptophan (l-Trp) as a substrate in a shake flask. It was determined that the rate-limiting enzyme for melatonin synthesis is the arylalkylamine N-acetyltransferase, which is encoded by the HsAANAT gene. Targeted metabolomics analysis of l-Trp revealed that the majority of l-Trp flowed to the indole pathway in BL7992, and knockout of the tnaA gene may be beneficial for increasing melatonin production.

Conclusions

A metabolic engineering approach was adopted and melatonin was successfully synthesized from low-cost l-Trp in E. coli. This study provides a rapid and economical strategy for the synthesis of melatonin.
Genotype data for 60 SNP genetic markers associated with eye, hair, skin color, ABO blood group, sex, core Y-chromosome haplogroups in Kazakh population
Authors: Bukayev Alizhan , Aidarov Baglan , Fesenko Denis , Saidamarova Viktoriya , Ivanovsky Ivan , Maltseva Elina , Naizabayeva Dinara , Bukayeva Ayagoz , Faizov Bekzhan , Pylev Vladimir , Darmenov Akynkali , Skiba Yuriy , Balanovska Elena , Zhabagin Maxat
Published: February 2024

Objectives

The collection of genotype data was conducted as an essential part of a pivotal research project with the goal of examining the genetic variability of skin, hair, and iris color among the Kazakh population. The data has practical application in the field of forensic DNA phenotyping (FDA). Due to the limited size of forensic databases from Central Asia (Kazakhstan), it is practically impossible to obtain an individual identification result based on forensic profiling of short tandem repeats (STRs). However, the pervasive use of the FDA necessitates validation of the currently employed set of genetic markers in a variety of global populations. No such data existed for the Kazakhs. The Phenotype Expert kit (DNA Research Center, LLC, Russia) was used for the first time in this study to collect data.

Data description

The present study provides genotype data for a total of 60 SNP genetic markers, which were analyzed in a sample of 515 ethnic Kazakhs. The dataset comprises a total of 41 single nucleotide polymorphisms (SNPs) obtained from the HIrisPlex-S panel. Additionally, there are 4 SNPs specifically related to the AB0 gene, 1 marker associated with the AMELX/Y genes, and 14 SNPs corresponding to the primary haplogroups of the Y chromosome. The aforementioned data could prove valuable to researchers with an interest in investigating genetic variability and making predictions about phenotype based on eye color, hair color, skin color, AB0 blood group, gender, and biogeographic origin within the male lineage.
MRI-based synthetic CT for assessment of the bony elements of the sacroiliac joints in children
Authors: Schiettecatte Eva , Vereecke Elke , Jaremko Jacob L. , Morbée Lieve , Vande Walle Caroline , Jans Lennart , Herregods Nele
Published: February 2024

Objectives

The purpose of this study is to assess the equivalency of MRI-based synthetic CT (sCT) to conventional CT for sacroiliac joint bony morphology assessment in children.

Methods

A prospective study was performed. Children who had (PET-)CT-scan underwent additional MRI. sCT-CT image quality was analyzed by two readers subjectively overall, semi-quantitatively in terms of cortical delineation, joint facet defects, growth plate fusion, ossified nuclei, lumbosacral transitional anomaly, and bony bridges, and quantitatively for disc space height, spinal canal width, and sacral vertebrae width and height. Cohen’s kappa and equivalence analyses with Bland–Altman plots were calculated for categorical and continuous measures respectively.

Results

Ten patients were included (6 boys; aged 9–16 years; mean age 14 years). Overall sCT image quality was rated good. Semi-quantitative assessment of cortical delineation of sacroiliac joints, bony bridges, and joint facet defects on the right iliac and sacral sides showed perfect agreement. Correlation was good to excellent (kappa 0.615–1) for the presence of lumbosacral transitional anomaly, fusion of sacral growth plates, joint facet defect, and presence of ossified nuclei. sCT-CT measurements were statistically equivalent and within the equivalence margins (–1–1 mm) for intervertebral disc space height and spinal canal width.

Intra- and inter-reader reliability was excellent for quantitative assessment (0.806 < ICC < 0.998). For categorical scoring, kappa ranged from substantial to excellent (0.615–1).

Conclusion

sCT appears to be visually equivalent to CT for the assessment of pediatric sacroiliac joints. sCT may aid in visualizing sacroiliac joints compared to conventional MRI, with the benefit that no ionizing radiation is used, especially important in children.

Critical relevance statement

MRI-based synthetic CT, a new technique that generates CT-like images without ionizing radiation, appears to be visually equivalent to CT for assessment of normal pediatric sacroiliac joints and can potentially assess structural damage as it clearly depicts bony cortex.

Key points

• MRI-based sCT is a new image technique that can generate CT-like images.

• We found that sCT performs similarly to CT in displaying bony structures of pediatric sacroiliac joints.

• sCT has already been clinically validated in the sacroiliac joints in adults.

• sCT can potentially assess structural damage from erosions or ankylosis as it clearly depicts bony cortex.

Graphical Abstract
Intraoperative vascular air embolism and intracardiac thrombosis complicating liver transplantation: a case report
Authors: Sinclair De Frías Jorge , Olivero Lorenzo , Fleissner Zachary , Burns Justin , Chadha Ryan , Moreno Franco Pablo
Published: February 2024

Background

Intracardiac thrombus and vascular air embolism represent rare complications in the context of orthotopic liver transplantation. While isolated reports exist for intracardiac thrombus and vascular air embolism during orthotopic liver transplantation, this report presents the first documentation of their simultaneous occurrence in this surgical setting.

Case presentation

This case report outlines the clinical course of a 60-year-old white female patient with end-stage liver disease complicated by portal hypertension, ascites, and hepatocellular carcinoma. The patient underwent orthotopic liver transplantation and encountered concurrent intraoperative complications involving intracardiac thrombus and vascular air embolism. Transesophageal echocardiography revealed the presence of air in the left ventricle and a thrombus in the right atrium and ventricle. Successful management ensued, incorporating hemodynamic support, anticoagulation, and thrombolytic therapy, culminating in the patient’s discharge after a week.

Conclusions

This report highlights the potential for simultaneous intraoperative complications during orthotopic liver transplantation, manifesting at any phase of the surgery. It underscores the critical importance of vigilant monitoring throughout orthotopic liver transplantation to promptly identify and effectively address these rare yet potentially catastrophic complications.
Prolonged versus intermittent β-lactam infusion in sepsis: a systematic review and meta-analysis of randomized controlled trials
Authors: Zhao Yang , Zang Bin , Wang Qian
Published: February 2024

Background

The two latest studies on prolonged versus intermittent use of β-lactam antibiotics in patients with sepsis did not reach consistent conclusions, further contributing to the controversy surrounding the effectiveness of the prolonged β-lactam antibiotics infusion strategy. We conducted a systemic review and meta-analysis to evaluate the efficacy and safety of prolonged and intermittent β-lactam infusion in adult patients with sepsis.

Methods

We systematically searched PubMed, EMBASE, and Cochrane Library databases for original randomized controlled trials comparing prolonged and intermittent β-lactam infusion in sepsis patients. A random-effects model was used to evaluate mortality, clinical success, microbiological success, and adverse events. We also conducted subgroup analyses to explore the impact of various factors on the mortality rates. Relative risk (RR) and corresponding 95% confidence intervals (CIs) were used to calculate the overall effect sizes for dichotomous outcomes. This meta-analysis was registered in PROSPERO (CRD42023463905).

Results

We assessed 15 studies involving 2130 patients. In our comprehensive assessment, we found a significant reduction in all-cause mortality (RR, 0.83; 95% CI 0.72–0.97; P = 0.02) and a notable improvement in clinical success (RR, 1.16; 95% CI 1.03–1.31; P = 0.02) in the prolonged infusion group compared to the intermittent infusion group, whereas microbiological success did not yield statistically significant results (RR, 1.10; 95% CI 0.98–1.23; P = 0.11). No significant differences in adverse events were observed between the two groups (RR, 0.91; 95% CI 0.64–1.29; P = 0.60). Additionally, remarkable conclusions were drawn from subgroup analyses including studies with sample sizes exceeding 20 individuals per group (RR, 0.84; 95%CI 0.72–0.98; P = 0.03), research conducted post-2010 (RR, 0.84; 95%CI 0.72–0.98; P = 0.03), cases involving infections predominantly caused by Gram-negative bacteria (RR, 0.81; 95%CI 0.68–0.96; P = 0.02), as well as the administration of a loading dose (RR, 0.84; 95% CI 0.72–0.97; P = 0.02) and the use of penicillin (RR, 0.61; 95% CI 0.38–0.98; P = 0.04).

Conclusions

Compared to intermittent infusion, prolonged infusion of β-lactam antibiotics significantly decreases all-cause mortality among patients with sepsis and enhances clinical success without increasing adverse events.