bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterologous expression of formate dehydrogenase enables photoformatotrophy in the emerging model microalga, Picochlorum renovo
Authors: Dahlin Lukas R. , Meyers Alex W. , Stefani Skylar W. , Webb Ellsbeth G. , Wachter Benton , Subramanian Venkataramanan , Guarnieri Michael T.
Published: August 2023

Rising global greenhouse gas emissions and the impacts of resultant climate change necessitate development and deployment of carbon capture and conversion technologies. Amongst the myriad of bio-based conversion approaches under evaluation, a formate bio-economy has recently been proposed, wherein CO2-derived formate serves as a substrate for concurrent carbon and energy delivery to microbial systems. To date, this approach has been explored in chemolithotrophic and heterotrophic organisms via native or engineered formatotrophy. However, utilization of this concept in phototrophic organisms has yet to be reported. Herein, we have taken the first steps to establish formate utilization in Picochlorum renovo, a recently characterized eukaryotic microalga with facile genetic tools and promising applied biotechnology traits. Plastidial heterologous expression of a formate dehydrogenase (FDH) enabled P. renovo growth on formate as a carbon and energy source. Further, FDH expression enhanced cultivation capacity on ambient CO2, underscoring the potential for bypass of conventional CO2 capture and concentration limitations. This work establishes a photoformatotrophic cultivation regime that leverages light energy-driven formate utilization. The resultant photosynthetic formate platform has widespread implications for applied phototrophic cultivation systems and the bio-economy at large.
Biomechanical properties of a novel cervical spine implant with elastic deformation: a cadaveric study
Authors: Abudouaini Haimiti , Wu Tingkui , Meng Yang , Ding Chen , Liu Hao , Beiyu Wang
Published: August 2023

Introduction: Anterior cervical discectomy and fusion (ACDF) is a most frequently used surgical procedure for treating cervical radiculopathy and myelopathy. However, there is concern about the high adjacent segment degeneration (ASD) rate after ACDF surgery. We creatively designed an elastically deformable cervical implant to reduce the postoperative stress concentration. In this study, we aimed to investigate the biomechanical performance of this novel cervical implant and compare it with the commonly used cervical devices.

Methods: Biomechanical test was conducted on twelve fresh-frozen human cadaveric cervical spines (C2–C7) and randomly divided into four groups according to implant types: intact group, Zero-P VA fusion (ACDF) group, the novel cervical implant group and Pretic-I artificial cervical disc (ACDR) group. An optical tracking system was used to evaluate the segmental range of motion (ROM) of the C4/C5, C5/C6, and C6/C7 segments and micro pressure sensor was used to record the maximum facet joint pressure (FJP), maximum intradiscal pressure (IDP) at the C4-5 and C6-7 segments.

Results: There were no significant differences in the ROM of adjacent segments between the groups. Compared with the intact group, the ACDR group essentially retained the ROM of the operated segment. The novel cervical implant decrease some ROM of the operated segment, but it was still significantly higher than in the fusion group; The maximum FJP and IDP at the adjacent segments in the ACDF group were significantly higher than those values in the other groups, and there were no differences in the other groups.

Conclusion: While the newly developed elastically deformable cervical implant does not completely maintain ROM like the artificial cervical disc, it surpasses the fusion device with regards to biomechanical attributes. After further refinement, this novel implant may be suitable for patients who are prone to severe adjacent segment degeneration after fusion surgery but no indication for artificial cervical disc surgery.
gRNA-SeqRET: a universal tool for targeted and genome-scale gRNA design and sequence extraction for prokaryotes and eukaryotes
Authors: Simirenko Lisa , Cheng Jan-Fang , Blaby Ian
Published: August 2023

High-throughput genetic screening is frequently employed to rapidly associate gene with phenotype and establish sequence-function relationships. With the advent of CRISPR technology, and the ability to functionally interrogate previously genetically recalcitrant organisms, non-model organisms can be investigated using pooled guide RNA (gRNA) libraries and sequencing-based assays to quantitatively assess fitness of every targeted locus in parallel. To aid the construction of pooled gRNA assemblies, we have developed an in silico design workflow for gRNA selection using the gRNA Sequence Region Extraction Tool (gRNA-SeqRET). Built upon the previously developed CCTop, gRNA-SeqRET enables automated, scalable design of gRNA libraries that target user-specified regions or whole genomes of any prokaryote or eukaryote. Additionally, gRNA-SeqRET automates the bulk extraction of any regions of sequence relative to genes or other features, aiding in the design of homology arms for insertion or deletion constructs. We also assess in silico the application of a designed gRNA library to other closely related genomes and demonstrate that for very closely related organisms Average Nucleotide Identity (ANI) > 95% a large fraction of the library may be of relevance. The gRNA-SeqRET web application pipeline can be accessed at https://grna.jgi.doe.gov. The source code is comprised of freely available software tools and customized Python scripts, and is available at https://bitbucket.org/berkeleylab/grnadesigner/src/master/ under a modified BSD open-source license (https://bitbucket.org/berkeleylab/grnadesigner).
Resistance to CLnA-induced ferroptosis is acquired in Caco-2 cells upon differentiation
Authors: Cuvelier Géraldine , Vermonden Perrine , Rousseau Justine , Feron Olivier , Rezsohazy René , Larondelle Yvan
Published: August 2023

In contrast to canonical ferroptosis inducers, highly peroxidable conjugated linolenic acids (CLnA) directly fuel the lipid peroxidation cascade upon their incorporation into membrane phospholipids. Little is known, however, about the cytotoxicity level of CLnAs to normal epithelial cells. Caco-2 cells, derived from colorectal adenocarcinoma, spontaneously differentiate into enterocyte-like cells over a period of 21 days of cell culturing, allowing for graduated phenotypic shift from proliferative, undifferentiated cells to a functional intestinal barrier. We exploited this property to assess the sensitivity of Caco-2 cells to CLnAs at different stages of differentiation. Our results show a significant decrease in CLnA-induced ferroptotic cell death over time. The acquired resistance aligned with decreases in cell proliferation and in the extent of lipid peroxidation, as well as with an increase in the expression of GPX4 upon differentiation. These results highlight that while CLnAs are highly toxic for proliferating cancer cells, differentiated epithelial cells are resistant to CLnA-induced ferroptosis. Therefore, this study gives credential to the therapeutic use of CLnAs as an anticancer strategy and offers a new model study to further investigate the safety of peroxidable fatty acids in differentiated cells.
Deciphering the binding mechanism of an anti-cancer phytochemical plumbagin with calf thymus DNA using biophysical and in silico techniques
Authors: Rahaman Abdul , Anjum Farah , Kumari Aknita , Shafie Alaa , Alee Mahafooj , Badr Omnia , Khan Shaheer Hasan , Ashour Amal Adnan , Hazazi Ali , Arif Sultan , Zeng Xin-An
Published: August 2023

Plumbagin (PLM), a plant derivative, is well known for a wide range of therapeutic effects in humans including anti-cancer, anti-inflammatory, anti-oxidant, and anti-microbial. Cytotoxic and genotoxic potential of this phytochemical has been studied which demands further insight. DNA being a major target for several drugs was taken to study against PLM to understand its effects on the cellular system. UV-Vis spectroscopy has indicated the binding of PLM to ctDNA and dye displacement assays have confirmed the formation of PLM-ctDNA complex. The insignificant changes in circular dichroism spectra suggested that PLM is not affecting the structural makeup of the ctDNA, hence the binding could be peripheral and not intercalating. Further, the relative viscosity and minimal change in melting temperature upon the complex formation supported this finding and confirmed the groove binding of PLM. Molecular docking analysis and simulation studies also show PLM as a minor groove binder to DNA and provide details on the interaction dynamics of PLM-DNA complex. Docking followed by a 100 ns simulation reveals the negative Gibbs free energy change (∆G = −6.6 kcal mol−1), and the formation of a stable complex. The PLM- DNA complex with stable dynamics was further supported by different parameters including RMSD, RMSF, SASA, Rg, and the energy profile of interaction. This study provides an insight into the cytotoxic and genotoxic mechanism of PLM which can be a crucial step forward to exploit its therapeutic potential against several diseases including cancer.
Alterations in the gut microbiome and its metabolites are associated with the immune response to mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 spike epitopes in mice
Authors: Hwang In-Chan , Vasquez Robie , Song Ji Hoon , Engstrand Lars , Valeriano Valerie Diane , Kang Dae-Kyung
Published: August 2023

Lactic acid bacteria (LAB) expressing foreign antigens have great potential as mucosal vaccines. Our previous study reported that recombinant Lactiplantibacillus plantarum SK156 displaying SARS-CoV-2 spike S1 epitopes elicited humoral and cell-mediated immune responses in mice. Here, we further examined the effect of the LAB-based mucosal vaccine on gut microbiome composition and function, and gut microbiota-derived metabolites. Forty-nine (49) female BALB/c mice were orally administered L. plantarum SK156-displaying SARS-CoV-2 spike S1 epitopes thrice (at 14-day intervals). Mucosal immunization considerably altered the gut microbiome of mice by enriching the abundance of beneficial gut bacteria, such as Muribaculaceae, Mucispirillum, Ruminococcaceae, Alistipes, Roseburia, and Clostridia vadinBB60. Moreover, the predicted function of the gut microbiome showed increased metabolic pathways for amino acids, energy, carbohydrates, cofactors, and vitamins. The fecal concentration of short-chain fatty acids, especially butyrate, was also altered by mucosal immunization. Notably, alterations in gut microbiome composition, function, and butyrate levels were positively associated with the immune response to the vaccine. Our results suggest that the gut microbiome and its metabolites may have influenced the immunogenicity of the LAB-based SARS-CoV-2 vaccine.
Can spirometry improve the performance of cardiovascular risk model in high-risk Eastern European countries?
Authors: Court Tatyana , Čapková Naděžda , Pająk Andrzej , Tamošiūnas Abdonas , Bobák Martin , Pikhart Hynek
Published: August 2023

Aims

Impaired lung function has been strongly associated with cardiovascular disease (CVD) events. We aimed to assess the additive prognostic value of spirometry indices to the risk estimation of CVD events in Eastern European populations in this study.

Methods

We randomly selected 14,061 individuals with a mean age of 59 ± 7.3 years without a previous history of cardiovascular and pulmonary diseases from population registers in the Czechia, Poland, and Lithuania. Predictive values of standardised Z-scores of forced expiratory volume measured in 1 s (FEV1), forced vital capacity (FVC), and FEV1 divided by height cubed (FEV1/ht3) were tested. Cox proportional hazards models were used to estimate hazard ratios (HRs) of CVD events of various spirometry indices over the Framingham Risk Score (FRS) model. The model performance was evaluated using Harrell’s C-statistics, likelihood ratio tests, and Bayesian information criterion.

Results

All spirometry indices had a strong linear relation with the incidence of CVD events (HR ranged from 1.10 to 1.12 between indices). The model stratified by FEV1/ht3 tertiles had a stronger link with CVD events than FEV1 and FVC. The risk of CVD event for the lowest vs. highest FEV1/ht3 tertile among people with low FRS was higher (HR: 2.35; 95% confidence interval: 1.96–2.81) than among those with high FRS. The addition of spirometry indices showed a small but statistically significant improvement of the FRS model.

Conclusions

The addition of spirometry indices might improve the prediction of incident CVD events particularly in the low-risk group. FEV1/ht3 is a more sensitive predictor compared to other spirometry indices.
Burden of untreated transthyretin amyloid cardiomyopathy on patients and their caregivers by disease severity: results from a multicenter, non-interventional, real-world study
Authors: Ponti Lucia , Hsu Kristen , Damy Thibaud , Villacorta Eduardo , Verheyen Nicolas , Keohane Denis , Wang Ronnie , Ines Monica , Kumar Nisith , Munteanu Carmen , Cappelli Francesco
Published: August 2023

Background

The humanistic burden of transthyretin amyloid cardiomyopathy (ATTR-CM) is poorly defined.

Methods

An international study to comprehensively characterize the burden of ATTR-CM on patients naïve to disease-modifying therapy and their unpaid primary caregivers using study-specific and established surveys (patients: Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS], 12-Item Short Form Health Survey [SF-12], Hospital Anxiety and Depression Scale [HADS], Patient-Reported Outcomes Measurement Information System [PROMIS] Fatigue and Dyspnea; caregivers: SF-12, HADS, PROMIS Fatigue, Zarit Burden Interview [ZBI]). All data were summarized descriptively.

Results

208 patient and caregiver pairs were included. 86% of patients were male, median age was 81 years, and 91% (141/155 with genetic testing) had wild-type ATTR-CM. Patient responses characterized the mental and physical burden of ATTR-CM, which was numerically higher among those who were New York Heart Association (NYHA) class III (n = 43) vs. class I/II (n = 156). NYHA class III patients had particularly low KCCQ-OS (36) and SF-12 physical component (27) scores, and 67% had a HADS depression score ≥8. Caregivers (median age 68 years; 85% female; 59% spouse of the patient; median duration of caregiving 1.5 years) reported that NYHA III patients more frequently required help with a range of physical activities than NYHA class I/II patients. 51% of caregivers to NYHA class III patients reported at least a mild-to-moderate burden in the ZBI. A plain language summary of this paper can be found as a supplemental material.

Conclusions

Untreated ATTR-CM is a burden to both patients and their caregivers.
Evaluation of road network slopes susceptibility to seismically-induced landslides in the Granada Basin (S Spain)
Authors: Román-Herrera J. C. , Delgado J. , Rodríguez-Peces M. J. , Peláez J. A. , Garrido J.
Published: August 2023

In this work, a method for the fast evaluation of seismically-induced landslides is applied at regional scale in the Granada Basin (southern Spain). The methodology is based on the concept of rigid block but takes into account the variability in input data (geotechnical properties, failure depth and saturation state of the materials) through the use of a logical tree scheme. Input data were combined and evaluated using five different Newmark displacement empirical relations, which are automatically weighted to obtain a final co-seismic landslide susceptibility map. A Geographic Information System system was used to obtain the resulting maps considering the different branches and weights of the logic tree through an specifically developed automatic code written in Phyton. The landslides induced by the 2021 Mw 4.4 events of the Santa Fe seismic series have been used to validate the methodology. This is later used as input along with the road network to analyze the distribution of areas of different susceptibility level. The results obtained show that 1.73% of the total area is characterized by moderate to high susceptibility, being the southern and eastern sections of the Granada basin were more vulnerable slopes are found. When considering only zones around the road network (50 m buffer), it is found that 2.11% of slopes around highways and 1.33% of road slopes have moderate to high susceptibility, especially the A-92 highway and the A-338 road. These roads traverse areas with steep slopes and a combination of hard and soft materials, which increases the susceptibility of disrupted landslides. On the other hand, in more densely populated areas such as the metropolitan area of Granada, the susceptibility is lower due to their location on terrain with low to negligible slopes. The results are of interest for authorities managing slope stabilities because they allow establishing effective and locally-based seismic forecast works in order to minimize the damage of future events.
Platinum-group elements (PGE) in the New Afton alkalic Cu-Au porphyry deposit, Canadian Cordillera, I: relationships between PGE, accessory metals and sulfur isotopes in pyrite
Authors: Boucher Brandon M. , Robb Samuel J. , Hanley Jacob J. , Kerr Mitchell J. , Mungall James E.
Published: August 2023

The second part of this article can be found here: 10.3389/feart.2023.819109 (DOI). At the late Triassic New Afton alkalic porphyry Cu-Au deposit (British Columbia, Canada), pyrite is a widely distributed minor sulfide phase within hypogene ore where it predates Cu mineralization and hosts significant concentrations of Pd and Pt. Here we characterize pyrite major, minor and trace element composition by EPMA and LA-ICP-MS, and S isotopes (bulk pyrite and in situ SIMS in individual growth zones) to elucidate compositional variations at different stages of pyrite growth with respect to PGE deposition. At least two cycles of zoned Co-Ni-Pd-Pt-Se-As co-enrichment are recorded over two stages of pyrite growth at the New Afton deposit. Concentrations of Co (up to ∼5.5 wt%; highest observed in any reported ore-forming system) and Ni (up to 1 wt%) overlap with pyrite from mafic-ultramafic platinum-group element (PGE) deposits, iron oxide±apatite and iron oxide-copper-gold deposits (IOA-IOCG), and mantle peridotite-associated base metal exhalative deposits. In early hypogene (type I) pyrite, high Pt (up to ∼24 ppm) occurs in crystal cores that have high Co/Ni ratio (>∼7), high Co (>∼ 1 wt%) and are poor in Ni, Se, and As. With progressive growth, early hypogene pyrite rims and late hypogene (type II) cores record an initial Ni-Pd-As-Se (±Co) co-enrichment stage, followed by oscillations in composition (from “barren” to variably Co-Ni-Pd-Pt-As-Se-enriched). Pd in pyrite (up to ∼70 ppm) is inversely correlated to Co/Ni ratio, being enriched when Co/Ni < ∼7 and Ni > ∼1000 ppm. The highest levels of Pd enrichment occur in the most Ni- and Se-enriched growth zones. The transition from early, high Co/Ni (Pt-enriched) to later, low Co/Ni (Pd-enriched) growth zones is accompanied by a decrease in pyrite δ34SVCDT of up to ∼7‰ (4‰ range in single grains) with a total range in composition measured between −5.5‰ and +1.4‰. Subsequent to the shift to lower values, overgrowths of high Co/Ni pyrite formed with values of δ34SVCDT similar to the earliest Co-Pt-rich growth zones. Some combination of fluctuations in temperature and oxygen fugacity related to episodic cooling and hydrothermal recharge involving new pulses of metal-rich magmatic fluids is required to explain the observed metal enrichment patterns and variations in S isotope values. Co-Ni-rich pyrite may be a valuable exploration vector to PGE enrichment in porphyry deposits.
Impact of thyroid-stimulating hormone levels after controlled ovarian hyperstimulation on in vitro fertilization/intracytoplasmic sperm injection outcomes in women with fresh embryo transfer: a prospective cohort study
Authors: Huang Ning , Chen Lixue , Lian Ying , Chi Hongbin , Qiao Jie
Published: August 2023

Objective

Maternal hypothyroidism before and during pregnancy is associated with an increased risk of adverse pregnancy outcomes; many studies have evidenced that controlled ovarian hyperstimulation (COH) triggers a significant increase in the levels of TSH; however, no large-scale prospective studies have evaluated the impact of TSH levels after COH on assisted reproductive technology outcomes. The aim of this prospective study was to investigate whether in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes are affected by TSH levels after COH in women with fresh embryo transfer (ET).

Methods

A total of 664 patients who underwent IVF/ICSI treatment and received fresh ET at the Peking University Third Hospital were included in this study. The rates of clinical pregnancy, miscarriage, live birth, and preterm delivery were analyzed.

Results

The patients were categorized into two groups based on serum TSH levels after COH (0.55 mIU/L < TSH < 2.5 mIU/L: n= 449, 2.5 mIU/L ≤ TSH ≤ 4.78 mIU/L: n= 215). There were no significant differences in the rates of clinical pregnancy, miscarriage, and live birth between the two groups, even after adjusting for age, body mass index (BMI), thyroid antibody positivity, and COH protocols. However, the preterm delivery rate was significantly higher in women with TSH < 2.5 mIU/L than in those with TSH ≥ 2.5 mIU/L, even after adjusting for relevant confounding factors. There was no significant difference in live birth weight between the two groups.

Discussion

Mildly elevated TSH levels (TSH ≥ 2.5 mIU/L) after COH did not affect IVF/ICSI outcomes, and strict control of TSH levels within 2.5 mIU/L after COH might not be necessary. Additionally, strictly controlled TSH levels (TSH < 2.5 mIU/L) may increase preterm delivery risk.
Health related Quality of Life over time in German sarcoma patients. An analysis of associated factors - results of the PROSa study
Authors: Eichler Martin , Hentschel Leopold , Singer Susanne , Hornemann Beate , Richter Stephan , Hofbauer Christine , Hohenberger Peter , Kasper Bernd , Andreou Dimosthenis , Pink Daniel , Jakob Jens , Grützmann Robert , Fung Stephen , Wardelmann Eva , Arndt Karin , Hermes-Moll Kerstin , Schoffer Olaf , Fried Marius , Jambor Helena K. , Weitz Jürgen , Schaser Klaus-Dieter , Bornhäuser Martin , Schmitt Jochen , Schuler Markus K.
Published: August 2023

Introduction

Sarcomas are rare cancers and very heterogeneous in their location, histological subtype, and treatment. Health-Related Quality of Life (HRQoL) of sarcoma patients has rarely been investigated in longitudinal studies.

Methods

Here, we assessed adult sarcoma patients and survivors between September 2017 and February 2020, and followed-up for one year in 39 study centers in Germany. Follow-up time points were 6 (t1) and 12 months (t2) after inclusion. We used a standardized, validated questionnaire (the European Organisation for Research and Treatment of Cancer Quality of Life Core Instrument (EORTC QLQ-C30) and explored predictors of HRQoL in two populations (all patients (Analysis 1), patients in ongoing complete remission (Analysis 2)) using generalized linear mixed models.

Results

In total we included up to 1111 patients at baseline (915 at t1, and 847 at t2), thereof 387 participants were in complete remission at baseline (334 at t1, and 200 at t2). When analyzing all patients, HRQoL differed with regard to tumor locations: patients with sarcoma in lower extremities reported lower HRQoL values than patients with sarcomas in the upper extremities. Treatment which included radiotherapy and/or systemic therapy was associated with lower HRQoL. For patients in complete remission, smoking was associated with worse HRQoL-outcomes. In both analyses, bone sarcomas were associated with the worst HRQoL values. Being female, in the age group 55-<65 years, having lower socioeconomic status, and comorbidities were all associated with a lower HRQoL, in both analyses.

Discussion

HRQoL increased partially over time since treatment and with sporting activities. HRQoL improved with time since treatment, although not in all domains, and was associated with lifestyle and socioeconomic factors. Bone sarcomas were the most affected subgroup. Methods to preserve and improve HRQoL should be developed for sarcoma patients.
A possible genetic association between obesity and colon cancer in females
Authors: Zhang Xiao-li , Zhang Xin-feng , Fang Yuan , Li Meng-li , Shu Ruo , Gong Yi , Luo Hua-you , Tian Yan
Published: August 2023

Object

There is mounting clinical evidence that an increase in obesity is linked to an increase in cancer incidence and mortality. Although studies have shown a link between obesity and colon cancer, the particular mechanism of the interaction between obesity and colon cancer in females remains unknown. The goal of this work is to use bioinformatics to elucidate the genetic link between obesity and colon cancer in females and to investigate probable molecular mechanisms.

Methods

GSE44076 and GSE199063 microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. In the two microarray datasets and healthy controls, the online tool GEO2R was utilized to investigate the differential genes between obesity and colon cancer. The differential genes (DEGs) identified in the two investigations were combined. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were performed on the DEGs. The STRING database and Cytoscape software were then used to build protein-protein interaction (PPI) networks to discover hub genes. NetworkAnalyst was also used to build networks of target microRNAs (miRNAs) and hub genes, as well as networks of transcriptions.

Results

Between the two datasets, 146 DEGs were shared. The DEGs are primarily enriched in inflammatory and immune-related pathways, according to GO analysis and KEGG. 14 hub genes were identified via PPI building using the Cytoscape software’s MCODE and CytoNCA plug-ins: TYROBP, CD44, BGN, FCGR3A, CD53, CXCR4, FN1, SPP1, IGF1, CCND1, MMP9, IL2RG, IL6 and CTGF. Key transcription factors for these hub genes include WRNIP1, ATF1, CBFB, and NR2F6. Key miRNAs for these hub genes include hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-164a-5p and hsa-mir-9-5p.

Conclusion

Our research provides evidence that changed genes are shared by female patients with colon cancer and obesity. Through pathways connected to inflammation and the immune system, these genes play significant roles in the emergence of both diseases. We created a network between hub genes and miRNAs that target transcription factors, which may offer suggestions for future research in this area.
Association between female circulating heavy metal concentration and abortion: a systematic review and meta-analysis
Authors: Ren Meiqi , Wang Liantong , Wen Liqin , Chen Jinghua , Quan Song , Shi Xiao
Published: August 2023

Objective

This study aimed to evaluate the association between blood heavy metal (zinc (Zn), copper (Cu), lead (Pb), and cadmium (Cd)) concentrations and spontaneous abortion (SA) and recurrent pregnancy loss (RPL) and explore the possible endocrine dysfunction associated with it.

Methods

A literature search was performed in the PubMed, Embase, Cochrane Library, and Web of Science databases up to April 2023. The overall effects were expressed as the standard mean difference (SMD). Subgroup analysis was performed according to the type of abortion (SA or RPL). Stata 16.0 was utilized for data analysis.

Results

Based on the integrated findings, abortion women showed significantly lower Zn (SMD = −1.05, 95% CI: −1.74 to −0.36, p = 0.003) and Cu concentrations (SMD = −1.42, 95% CI: −1.97 to −0.87, p <0.001) and higher Pb (SMD = 1.47, 95% CI: 0.89–2.05, p <0.001) and Cd concentrations (SMD = 1.15, 95% CI: 0.45–1.85, p = 0.001) than normal pregnant women. Subgroup analysis showed that Zn and Cu deficiency and Cd and Pb exposure were significantly (p <0.05) associated with RPL, whereas Cu deficiency and Cd and Pb exposure were significantly (p <0.05) associated with SA.

Conclusion

Zn and Cu deficiencies and Pb and Cd exposure were associated with abortion. Endocrine dysfunction, such as insulin resistance, vitamin D insufficiency, and abnormal thyroid and sex hormone concentrations, is thought to be involved in heavy metal-related abortion.
Identification and precision therapy for three maturity-onset diabetes of the young (MODY) families caused by mutations in the HNF4A gene
Authors: Zhang Juan , Jiang Yanyan , Li Jianhua , Zou Haiyin , Yin Li , Yang Yang , Yang Lei
Published: August 2023

Background

Heterozygous pathogenic variants in HNF4A gene cause maturity-onset diabetes of the young type 1 (MODY1). The mutation carriers for MODY1 have been reported to be relatively rare, in contrast to the most frequently reported forms of MODY2 and MODY3.

Methods

Whole exome sequencing (WES) and Sanger sequencing were performed for genetic analysis of MODY pedigrees. Tertiary structures of the mutated proteins were predicted using PyMOL software.

Results

Three heterozygous missense mutations in the HNF4A gene, I159T, W179C, and D260N, were identified in the probands of three unrelated MODY families using WES, one of which (W179C) was novel. Cascade genetic screening revealed that the mutations co-segregated with hyperglycemic phenotypes in their families. The molecular diagnosis of MODY1 has partly transformed its management in clinical practice and improved glycemic control. The proband in family A successfully converted to sulfonylureas and achieved good glycemic control. Proband B responded well to metformin combined with diet therapy because of his higher body mass index (BMI). The proband in family C, with paternal-derived mutations, had markedly defective pancreatic β-cell function due to the superposition effect of T2DM susceptibility genes from the maternal grandfather, and he is currently treated with insulin. In silico analysis using PyMOL showed that the I159T and D260N mutations altered polar interactions with the surrounding residues, and W179C resulted in a smaller side chain.

Discussion

We identified three heterozygous missense mutations of HNF4A from Chinese MODY families. Structural alterations in these mutations may lead to defects in protein function, further contributing to the hyperglycemic phenotype of mutation carriers.
Changes of androgen and corticosterone metabolites excretion and conversion in cystic fibrosis
Authors: Podgórski Rafał , Sumińska Marta , Rachel Marta , Pikuła Barbara , Fichna Piotr , Bidlingmaier Martin , Fichna Marta
Published: August 2023

Cystic fibrosis (CF) is a life-threatening inherited disease related to a mutation in the CFTR gene, that leads to serious health complications such as chronic pulmonary infections, pancreatic insufficiency, dysfunction of the sweat glands and reproductive system. For the first time, we have described the profile of corticosterone and androgen metabolites in urine, as well as the activity of enzymes involved in steroid genesis and metabolism in people with CF, using gas chromatography/mass spectrometry. A significant reduction in the excretion of most of the measured metabolites in CF was found. These differences were observed in the group of progestagen metabolites, as well as among metabolites of corticosterone and androgens. We revealed higher activities of 17β-hydroxysteroid dehydrogenase and 17,20-lyase in the Δ4 pathway compared with controls, what can promote the androgen synthesis through the backdoor androgen pathway. We have also found the increased conversion activity of 11-oxyganated steroids by 5a-reductase in backdoor pathway. Levels of the most potent and vital androgens (testosterone and dihydrotestosterone) are comparable in both groups. However, the excretion of dehydroepiandrosterone was lower in CF. Decreased cholesterol lipoprotein levels may contribute to limited intracellular cholesterol supply and reduced adrenal steroidogenesis in CF individuals. Changes in the activity of some steroidogenesis enzymes may suggest the presence of some peripheral adaptive mechanisms in CF to maintain androgen balance in the body despite the limited sufficiency of secretion by the adrenal cortex.
Numerical simulation of transient cavitation characteristics of valve-controlled liquid-filled hydrodynamic coupling
Authors: Cui Hongwei , Zhang Jiahua , Li Li , Wang Guoqiang
Published: August 2023

In high-power impeller industries, valve-controlled liquid-filled hydrodynamic couplings are widely used in the soft startup of heavy-duty scraper conveyors for mining. However, the water circulation speed in internal flow fields is higher at lower speed ratios, making the hydrodynamic couplings prone to severe cavitation, which further results in severe performance degradation, noise, vibration, or even erosion failure. Meanwhile, because a hydrodynamic coupling is a piece of closed-loop multicomponent turbomachinery, internal transient cavitation flow behavior cannot be easily controlled. To reasonably predict the characteristics of cavitation and its influence on the working performance of the hydrodynamic coupling, a high-quality structured mesh model of the internal flow field for an impeller was established. Considering the periodic structural characteristics of the impeller, a scale-resolving simulation turbulence model was combined with a Rayleigh–Plesset cavitation model to establish a single-cycle hydrodynamic coupling calculation model. The cavitation distribution characteristics and torque transmission of the flow field under different working conditions were obtained, and the effect of cavitation on the soft startup performance was analyzed. The results demonstrated that cavitation in the hydrodynamic coupling mainly occurred under low speed ratios. The degree of cavitation decreased as speed ratio increased. The worst-case scenario for cavitation occurred when the speed ratio was zero. Most of the cavitation bubbles were generated at the tip of the blades, resulting in unstable variation in torque characteristics and deterioration of the working performance of the hydrodynamic coupling. The analysis reveals that the cavitation process in the impeller is highly unstable and periodic, and the cavitation development near the tip of the blades occurs in four stages: birth, growth, separation, and disintegration. The generated steam accumulates in the inner ring of the impeller. Therefore, a method for accurately predicting the cavitation characteristics of hydrodynamic couplings based on high-precision technology is proposed, and a theoretical basis for coupling design and cavitation suppression technology is provided.
Flow field analysis and noise characteristics of an automotive cooling fan at different speeds
Authors: Ren Kai , Zhang Shuguang , Zhang Huanping , Deng Changming , Sun Haiyang
Published: August 2023

As the core component of the automotive air conditioning cooling system, the automotive cooling fan directly affects the cooling performance of the entire system. Therefore, it is necessary to study the flow field and noise of the automotive cooling fan. This study focuses on the analysis off low field characteristics and noise generation in an automotive air conditioning systems, specifically related to an automobile cooling fan at different speeds. The flow field properties of the fan are examined through the distribution off low line trajectory, pressure distribution on the blade surface, and velocity distribution characteristics at various speeds. The analysis reveals that the maximum air velocity occurs at the point where the fan blade meets the wind guard, while the maximum pressure is observed at this point and at the edge where the fan blade cuts through the cavity. Furthermore, a monitoring point located 1 m in front of the fan is selected to study the average value of fan pneumatic noise pulsation and generate a noise cloud map, aiming to identify the main noise source of the fan. To better understand the noise distribution and variation at different speeds, various noise metrics are utilized, including noise Sound Pressure Level (SPL) spectrum, 1/3-octave SPL spectrum, and 1/3-octave A-weighted SPL spectrum. The noise characterization results indicate that the primary areas of fan noise generation are located at the tip of the leaf margin of the forward swept wing. This research provides valuable insights for the improvement and optimization of the cooling fan design, as well as subsequent noise reduction efforts.
Interference effect of configuration parameters of vertical sand-obstacles on near-surface sand transport
Authors: Luo Xiangying , Li Jinrong , Tang Guodong , Li Yingkun , Wang Ru , Han Zhaoen , Feng Jiaxin , Ren Tingjie
Published: August 2023

This study investigates the impacts of height (H) and porosity (P) on the structural properties of wind-driven sand flux in vertical sunflower straw sand-obstacles. We conducted an experiment on sand transport within barriers of various configurations within a 1 m proximity to the surface. In tandem, we monitored wind velocity and direction within the barriers, analyzed total sand transport rate, sand-blocking effects, and cumulative sediment transport rate heights for various parameter configurations, and devised a best sand transport flux model for use within the sand-obstacle. The efficacy of vertical sunflower stalk sand-obstacles in mitigating sand movement has been demonstrated to fall within the range of 37.26%–92.31%. This study reveals a significant correlation between barrier height and porosity in achieving this effect (p < 0.05). High and densely configured sand-obstacles lead to an accumulation of intercepted sand material in front of the front row of the sand-obstacle. In contrast, low and sparsely arranged sand-obstacles exhibit a delayed state of sand material accumulation. Furthermore, with an increase in the height of the obstacle and a decrease in porosity, there is a diminishing trend in the sand transport rate within the obstacle. Concurrently, the height of sand transport within the barrier exhibits an upward trend. A three-parameter exponential function has been employed to more precisely simulate the wind-sand flow structure characteristics within a 1-m height range of the barrier. These research findings contribute to an enhanced understanding of the impact of different vertical sand-obstacle configurations on near-surface wind-driven sand transport patterns in active desert areas. Moreover, they furnish both theoretical underpinnings and practical guidance for the scientific configuration of vertical sand-obstacles.
Optimal fertilizer rates towards the improvement of nitrogen use efficiency and reduction of nitrogen export in paddy rice-wheat intensive farming
Authors: Legesse Nebiyou , Sheng Wu , Yao Wang , Manqin Gan , Peishi Liu , Yu Huang , Hongjun Xu , HongXiang Hu , Youhua Ma
Published: August 2023

Introduction: Fertilizer application above plant nitrogen (N) requirements, leading to N use inefficiency, has become the primary source of N surplus, posing nonpoint pollution threats. Chao Lake has received N loadings, primarily from the agroecosystem that surrounds it. Based on 10 years of field monitoring and experiment, this study used optimum fertilizer rates (30% N reduction) to evaluate nitrogen use efficiency (NUE) and N export in the Chao Lake watershed of paddy rice-wheat rotational farming.

Methods: Five treatments were tested, namely, the Blank Treatment (CK), Conventional Fertilization Treatment (CFT), High Fertilization Treatment (HFT), Reduced Fertilization Treatment (CFT), Reduced Fertilization Treatment plus Straw addition (RFTS). The parameters employed to measure NUE were 1) by calculating NUE indicators; Agronomic efficiency (kg kg-1), recovery efficiency (%), and partial factor productivity (kg kg-1) 2) using the European Union NUE framework as a comparison tool. N export was measured using N export parameters, namely, nitrogen loading (kg ha-1yr-1), nitrogen runoff loss ratio (%), and net nitrogen runoff loss ratio (%).

Results and discussion: Results revealed that optimum N fertilizer input levels maintained high crop and biomass yields. The empirical model of y = y0 + a * exp (−0.5 * (x-x0)/b2) explains the relationships between input N fertilizer and corresponding yield returns. Low yield responses to increased N input beyond certain limits were observed, which may lead to N accumulations. N export was much lower from the reduced fertilization treatments than other treatments. N export increased in 10 years for both paddy rice and wheat seasons. Runoff volume influenced N export more than any other environmental factor studied.

Conclusion: Overall, optimal fertilizer levels produced high NUE, maintained high economic yield, and produced lesser N exports; NUE was in the order of reduced > high > conventional fertilization treatments, while it decreased in 10 years (2008–2018) across all treatments. Such strategies that further reduce fertilizer levels by accounting for excess supplies are vital for consolidating effective N control measures.
A study on the influence of environmental responsible leadership on employee pro-environmental behavior
Authors: Zhao Cundong , Liang Liping
Published: August 2023

As the public’s call for corporate green development grows, more and more companies are joining the green development team. Environmental responsible leadership, as a leadership style focused on the construction of enterprises, has attracted widespread attention from the corporate and academic communities. Meanwhile, the pro-environmental behavior of employees is the key link in the implementation of green policies in enterprises. To clarify the mechanism of environmental responsible leadership on employee pro-environmental behavior, a moderated mediation model was constructed. This model examined the mediating role of employment relationship atmosphere between environmental responsible leadership and employee pro-environmental behavior, and examined the moderating role of social distance on the relationship between environmental responsible leadership and employment relationship atmosphere. The employment relationship atmosphere focuses on the level of trust, respect, and cooperation between managers and employees. Within a good employment relationship atmosphere, employees find that environmental responsible leaders treat them positively, and according to social exchange theory, in order to give back to the leaders, employees will take the initiative to perform the behaviors expected by the leaders, such as employee pro-environmental behaviors. We conducted a study on employees of five enterprises in Shanxi Province, and analyzed the questionnaire data using SPSS and AMOS. The results showed that environmental responsible leadership has a significant positive effect on employee pro-environmental behavior; employment relationship atmosphere plays a mediating role between environmental responsible leadership and employee pro-environmental behavior; social distance plays a moderating role in the relationship between environmental responsible leadership and employment relationship atmosphere, that is, the closer the social distance, the stronger the impact of environmental responsible leadership on employment relationship atmosphere.
The global potential of log-driven trees for reconstructing forest ecosystems dynamics
Authors: Labrecque-Foy Julie-Pascale , Montoro Girona Miguel
Published: August 2023

The composition and structure of modern forest ecosystems result from past and present climate as well as centuries of anthropic and natural disturbances. Concerns related to the integrity and resilience of forests in the context of climate change have led to novel ecosystem-based management methods that require extensive knowledge about the preindustrial state of forests and past disturbance regimes. At the beginning of industrial forest exploitation, waterways were used as the main conduits to transport wood, but the timing and impacts of this log driving remain understudied. Given that an estimated 15% to 50% of log-driven logs sank during their transport, this accumulation of subfossil wood can serve as a proxy tool for reconstructing the dynamics and structure of preindustrial forests and inform modern forest management practices. This review provides a global overview of log driving and highlights the significant value of these submerged logs for disturbance ecology. We demonstrate that log driving was used on most continents, implying that proxy records from subfossil logs may be available from numerous boreal and mountainous regions. Our review is one of the first to illustrate the paleoecological value of log-driving remnants and explain how such a resource provides a valuable tool for understanding past forest ecosystems. Such knowledge is crucial for informing forest management in the face of climate change.
Information fusion for online estimation of the behavior of traffic participants using belief function theory
Authors: Benciolini Tommaso , Zhang Xuhui , Wollherr Dirk , Leibold Marion
Published: August 2023

Motion planning algorithms for automated vehicles need to assess the intended behavior of other Traffic Participants (TPs), in order to predict the likely future trajectory of TPs and plan the motion consequently. Information resulting from several sources, like sensors, must be gathered and combined into a reliable estimate of the intended behavior of TPs. Such estimates must be sufficiently steady and quantify the inherent uncertainty around the assessment. We present a novel information fusion algorithm to combine information from different sources into a coherent and reliable estimate. To explicitly account for the uncertainty of estimates, we leverage the Belief Function Theory and evaluate and handle possible disagreements between estimates individually provided by the sources. The algorithm is flexible and can also handle sources that do not discern between some of the considered behaviors and are only capable of assessing the probability of unions or clusters of different behaviors. We discuss the strengths of the approach through simulations in SUMO, comparing it to the Interactive Multiple Model algorithm.
A meta-analysis of microarray datasets to identify biological regulatory networks in Alzheimer’s disease
Authors: Hashemi Kimia Sadat , Aliabadi Mohadese Koohi , Mehrara Arian , Talebi Elham , Hemmati Ali Akbar , Rezaeiye Radin Dabbagh , Ghanbary Mohammad Javad , Motealleh Maryam , Dayeri Behnaz , Alashti Shayan Khalili
Published: August 2023

Background: Alzheimer’s Disease (AD) is an age-related progressive neurodegenerative disorder characterized by mental deterioration, memory deficit, and multiple cognitive abnormalities, with an overall prevalence of ∼2% among industrialized countries. Although a proper diagnosis is not yet available, identification of miRNAs and mRNAs could offer valuable insights into the molecular pathways underlying AD’s prognosis.

Method: This study aims to utilize microarray bioinformatic analysis to identify potential biomarkers of AD, by analyzing six microarray datasets (GSE4757, GSE5281, GSE16759, GSE28146, GSE12685, and GSE1297) of AD patients, and control groups. Furthermore, this study conducted gene ontology, pathways analysis, and protein-protein interaction network to reveal major pathways linked to probable biological events. The datasets were meta-analyzed using bioinformatics tools, to identify significant differentially expressed genes (DEGs) and hub genes and their targeted miRNAs’.

Results: According to the findings, CXCR4, TGFB1, ITGB1, MYH11, and SELE genes were identified as hub genes in this study. The analysis of DEGs using GO (gene ontology) revealed that these genes were significantly enriched in actin cytoskeleton regulation, ECM-receptor interaction, and hypertrophic cardiomyopathy. Eventually, hsa-mir-122-5p, hsa-mir-106a-5p, hsa-mir-27a-3p, hsa-mir16-5p, hsa-mir-145-5p, hsa-mir-12-5p, hsa-mir-128-3p, hsa-mir 3200-3p, hsa-mir-103a-3p, and hsa-mir-9-3p exhibited significant interactions with most of the hub genes.

Conclusion: Overall, these genes can be considered as pivotal biomarkers for diagnosing the pathogenesis and molecular functions of AD.