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IntroductionGestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance during pregnancy, estimated to affect approximately 20% of the whole pregnancies and is increasing in prevalence globally. However, there is still a big gap in knowledge about the association between gut microbiota associated metabolism alterations and GDM development.MethodsAll the participants accomplished the validated internet-based dietary questionnaire for Chinese and serum, fecal samples were collected. HFD, control diet or colesevelam intervention was fed to GDM mice models or Fxr-/- mice models, with or without antibiotics cocktail treatment. Fecal microbiota transplantation were used for further validation. Gut microbiota and metabolites were detected by metagenomic sequencing and high-performance liquid chromatography-mass spectrometry, respectively. Bile acids of serum, fecal samples from human and mice were analysised. Body weight, average feed intake, blood glucose, insulin levels and oral glucose tolerance test was performed among each groups. Expression levels of Fxr, Shp and Fgf15 mRNA and protein were detected by quantitative reverse transcription polymerase chain reaction and western blot, respectively.ResultsOur data indicated that high fat diet (HFD) was linked with higher prevalence of GDM, and HFD was positively associated with poor prognosis in GDM patients. Moreover, compared with normal diet (ND) group, GDM patients from HFD group performed a loss of gut microbiota diversity and enrichment of Alistipes onderdonkii, Lachnospiraceae bacterium 1_7_58FAA, and Clostridium aspaaragiforme while ruduction of Akkermansiaceae, Paraprevotell xylaniphila, and Prevotella copri. Additionally, HFD aggravated GDM in mice and gut microbiota depletion by antibiotics crippled the effect of excess fat intake. BAs profile altered in HFD GDM patients and mice models. Fecal microbiota transplantation (FMT) further confirmed that gut microbiota contributed to bile acids (BAs) metabolic dysfunction during HFD-associated GDM development. Mechanically, HFD-FMT administration activated Fxr, Shp, and Fgf15 activity, disturbed the glucose metabolism and aggravated insulin resistance but not in HFD-FMT Fxr−/− mice and ND-FMT Fxr−/− mice. Furthermore, colesevelam intervention alleviated HFD-associated GDM development, improved BAs metabolism, suppressed Fxr, Shp, and Fgf15 activity only in WT mice but not in the Fxr−/− HFD + Colesevelam group and Fxr−/− HFD group. HFD induced GDM and contributed to poor prognosis in GDM parturients through inducing gut microbial dysbiosis and metabolic alteration, especially appeared in BAs profile. Moreover, Fxr pathway participated in regulating HFD-associated gut microbiota disordered BAs metabolites and aggravating GDM in mice.DiscussionModulating gut microbiota and BAs metabolites could be a potential therapeutic strategy in the prevention and treatment of HFD-associated GDM.

Objective Previous studies have revealed functional changes within the cerebral hemispheres of patients with SLE; however the changes between cerebral hemispheres are still unknown. The present study aimed to explore the functional and structural changes between bilateral hemispheres using functional MRI and find their relationship with cognition in patients with SLE.Methods 54 patients with SLE and 32 age-matched and sex-matched healthy controls (HCs) underwent MRI scanning and neuropsychological testing, and clinical data was collected in patients with SLE. Voxel-mirrored homotopic connectivity (VMHC) values and grey matter volume were calculated for all subjects. Correlation analysis was established to determine the relationship between VMHC values, grey matter volume and cognitive scores, blood biochemical markers in patients with SLE.Results Compared with HCs, patients with SLE showed increased VMHC values in the insula and parahippocampal gyrus, while grey matter volume were reduced in these regions. Correlation analysis demonstrated that the increased VMHC values in insula was negatively correlated with decreased orientation function and positively correlated with decreased attention function. The grey matter volume in insula was negatively correlated with decreased attention and abstraction. The VMHC values and grey matter volume in insula and parahippocampal gyrus were negatively associated with lupus-specific antibodies.Conclusion The structural and functional changes of insula and parahippocampal gyrus might be potential neuroimaging markers, and specific antibodies associated with lupus might be involved in the pathophysiological mechanisms of brain dysfunction.Trial registration number NCT06226324.

IntroductionWheat (Triticum aestivum L.) is among themost important crop worldwide. Given a growing population and changing climate, enhancing wheat yield is of great importance. Yield is closely associated with flower and spike development, and E-class genes play important roles in the flower and kernel development of plants. Currently, the absence of systematic analysis on the E gene family hinders our comprehension of their roles in plant growth and development.MethodsIdentify E-class genes based on homologous sequence searches. Analyze the identified E-class genes through a series of gene family analyses. Determine the expression levels of wheat E-class genes by searching public databases. Validate the functions of these genes by transforming them into Arabidopsis. Finally, determine the interactions between the genes through yeast two-hybrid experiments.ResultsFifteen E-class genes (TaEs) were identified in common wheat. Nine E-class genes were detected in five ancestral/closely related species, including one in Aegilops tauschii (AtE), one in T. Urartu (TuEs), two in T. turgidum (TtEs), two in T. dicoccoides (TdEs), and three in T. spelta (TsEs). The 24 E-class genes were classified into three subgroups using a phylogenetic approach. All genes were highly expressed in spikes, and most were only highly expressed at the floret meristem stage. The effects of TaSEP5-A on flowering and growth cycles were confirmed in homologous mutants and transgenic Arabidopsis thaliana. The E-class genes were able to regulate the growth cycle of Arabidopsis. Finally, we confirmed the interactions between TaSEP5-A and other wheat E-class genes based on yeast two-hybrid assays.DiscussionOur findings provide information regarding the E-class genes in wheat and will potentially promote the application of these genes in wheat improvement.

[This corrects the article DOI: 10.1371/journal.pone.0224086.].

The nitrogen vacancy (NV) color centers are a solid-state quantum system with the ability to maintain long coherence times at room temperatures. NV centers have potential applications in quantum detection, which necessitates their positioning at minimal distances from surfaces. However, the existing methods for fabricating NV centers are cumbersome, expensive, and difficult to control. This study investigates the etching mechanism of transition metals on diamond under plasma conditions and develops a method for producing shallow NV centers on the surface of high pressure and high temperature diamond. Our proposed method enables the production of shallow NV centers below the surface in the longitudinal direction, while simultaneously allowing precise control over the lateral distribution. Moreover, the operating costs associated with our technique are significantly lower than those of ion implantation and electron irradiation. This research contributes to the advancement of iron-etching diamond processing technology, and the proposed method facilitates the more portable preparation of shallow color centers in specific regions, enabling the realization of locally controllable and scalable coupled quantum systems.

PurposeObservational studies have revealed that serum minerals and vitamins are associated with cancer. However, the causal relationships between serum minerals and vitamins and renal malignancies remain unclear.MethodsMendelian randomization (MR) was used for causal estimation. Single nucleotide polymorphisms (SNPs) for serum minerals and vitamins were obtained from published genome-wide association studies (GWAS). GWAS for malignant kidney neoplasm was obtained from the FinnGen consortium. Methods of inverse variance weighted (IVW), MR-Egger, and weighted median were carried out for causal inference. F-statistic was calculated to ensure a robust instrumental variable. Cochran’s Q statistics was applied to calculate heterogeneity. MR-Egger regression, MR-pleiotropy residual sum and outlier methods (MR-PRESSO) methods were used to perform pleiotropy analysis. Meanwhile, confounding factors were considered to determine whether causal inference would be biased.ResultsEight different micronutrients were included (zinc, iron, magnesium, calcium, copper, selenium, phosphate, and vitamin B12). After MR analysis, we found a protective effect of serum zinc against malignant kidney neoplasm (IVW: odds ratios (ORs), 0.86; 95% confidence interval (95% CI), 0.78–0.94; p, 0.0016; MR-Egger: OR, 0.80; 95% CI, 0.64–0.97; p, 0.052; weighted median: OR, 0.85; 95% CI, 0.75–0.96; p, 0.011). Causal relationships between other micronutrients and malignant kidney neoplasm were not obtained. No heterogeneity and pleiotropy were detected, while causality was not biased by confounding factors.ConclusionWe considered that serum zinc exerted a protective effect against malignant kidney neoplasm. In clinical practice, for people with high malignant kidney neoplasm risk, an oral zinc supplementation might play a role in a potential therapeutic target.

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) is a highly adaptive pathogen and has acquired diverse genetic elements, such as genomic islands and prophages, via horizontal gene transfer to promote fitness in vivo. Two-component signaling systems (TCSs) allow bacteria to sense, respond to, and adapt to various environments. This study identified a putative two-component signaling system composed of the histidine kinase EDL5436 (renamed LmvK) and the response regulator EDL5428 (renamed LmvR) in EHEC. lmvK and lmvR along with EDL5429 to EDL5434 (EDL5429–5434) between them constitute the OI167 genomic island and are highly associated with the EHEC pathotype. EDL5429–5434 encode transporters and metabolic enzymes that contribute to growth on mannose and are directly upregulated by LmvK/LmvR in the presence of mannose, as revealed by quantitative PCR (qPCR) and DNase I footprint assays. Moreover, LmvR directly activates the expression of the type III secretion system in response to mannose and promotes the formation of attaching and effacing lesions on HeLa cells. Using human colonoid and mouse infection models, we show that lmvK and lmvR contributed greatly to adherence and microcolony (MC) formation ex vivo and colonization in vivo. Finally, RNA sequencing and chromatin immunoprecipitation coupled with sequencing analyses identified additional direct targets of LmvR, most of which are involved in metabolism. Given that mannose is a mucus-derived sugar that induces virulence and is preferentially used by EHEC during infection, our data revealed a previously unknown mechanism by which EHEC recognizes the host metabolic landscape and regulates virulence expression accordingly. Our findings provide insights into how pathogenic bacteria evolve by acquiring genetic elements horizontally to adapt to host environments. IMPORTANCE The gastrointestinal tract represents a complex and challenging environment for enterohemorrhagic Escherichia coli (EHEC). However, EHEC is a highly adaptable pathogen, requiring only 10 to 100 CFUs to cause infection. This ability was achieved partially by acquiring mobile genetic elements, such as genomic islands, that promote overall fitness. Mannose is an intestinal mucus-derived sugar that stimulates virulence and is preferentially used by EHEC during infection. Here, we characterize the OI167 genomic island of EHEC, which encodes a novel two-component signaling system (TCS) and transporters and metabolic enzymes (EDL5429–5434) involved in mannose utilization. The TCS directly upregulates EDL5429–5434 and genes encoding the type III secretion system in the presence of mannose. Moreover, the TCS contributes greatly to EHEC virulence ex vivo and in vivo. Our data demonstrate an elegant example in which EHEC strains evolve by acquiring genetic elements horizontally to recognize the host metabolic landscape and regulate virulence expression accordingly, leading to successful infections.

ObjectiveTo investigate the effect of Hsp27 and the inhibitory effect of Atractylenolide I (ATL-1) on the proliferation of prostate cancer cell DU145 and PC-3.MethodsMTT assay was used to detect the inhibitory effect of silencing Hsp27 and ATL-1 on DU145 and PC-3 proliferation of prostate cancer cells. TUNEL detected the apoptosis rate of prostate cancer cell DU145 and PC-3 after silencing Hsp27 and ATL-1 treated. qRT-PCR was used to detect the changes of apoptosis related genes caspase-3, PARP, Bax and Bcl-2 in prostate cancer cell DU145 and PC-3 after the effect of silencing Hsp27 and ATL-1 treated. At the same time, the antitumor effect of ATL-1 combined with cabozantinib was analyzed.ResultsHsp27 was highly expressed in human prostate cancer. MTT assay showed that ATL-1 inhibited the proliferation of prostate cancer cells DU145 and PC-3 compared with the control group. TUNEL results showed that silencing Hsp27 and ATL-1 treated could significantly promote the apoptosis of prostate cancer cells DU145 and PC-3 compared with the control group. qRT-PCR results showed that compared with the control group, ATL-1 could promote the expression of caspase-3, PARP and Bax in DU145 and PC-3 prostate cancer cells. Inhibition of Hsp27 by ATL-1 reduced cell viability and induced apoptosis. ATL-1 inhibits the antitumor effect of Hsp27 - enhanced cabozantinib. Hsp27 regulates eIF4E and mediates cell protection.ConclusionSilencing Hsp27 inhibits EMT. ATL-1 can inhibit the malignant evolution of prostate cancer cells by inhibiting Hsp27/eIF4E. ATL-1 also enhanced chemosensitization of cabozantinib in prostate cancer.

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed at night and under water-limited conditions. Elucidating the genetic architecture of natural variation for leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we conducted a genome-wide association study of gc of adult leaves in a maize inbred association panel that was evaluated in four environments (Maricopa, AZ, and San Diego, CA, in 2016 and 2017). Five genomic regions significantly associated with gc were resolved to seven plausible candidate genes (ISTL1, two SEC14 homologs, cyclase-associated protein, a CER7 homolog, GDSL lipase, and β-D-XYLOSIDASE 4). These candidates are potentially involved in cuticle biosynthesis, trafficking and deposition of cuticle lipids, cutin polymerization, and cell wall modification. Laser microdissection RNA sequencing revealed that all these candidate genes, with the exception of the CER7 homolog, were expressed in the zone of the expanding adult maize leaf where cuticle maturation occurs. With direct application to genetic improvement, moderately high average predictive abilities were observed for whole-genome prediction of gc in locations (0.46 and 0.45) and across all environments (0.52). The findings of this study provide novel insights into the genetic control of gc and have the potential to help breeders more effectively develop drought-tolerant maize for target environments.

Bulliform cells comprise specialized cell types that develop on the adaxial (upper) surface of grass leaves, and are patterned to form linear rows along the proximodistal axis of the adult leaf blade. Bulliform cell patterning affects leaf angle and is presumed to function during leaf rolling, thereby reducing water loss during temperature extremes and drought. In this study, epidermal leaf impressions were collected from a genetically and anatomically diverse population of maize inbred lines. Subsequently, convolutional neural networks were employed to measure microscopic, bulliform cell-patterning phenotypes in high-throughput. A genome-wide association study, combined with RNAseq analyses of the bulliform cell ontogenic zone, identified candidate regulatory genes affecting bulliform cell column number and cell width. This study is the first to combine machine learning approaches, transcriptomics, and genomics to study bulliform cell patterning, and the first to utilize natural variation to investigate the genetic architecture of this microscopic trait. In addition, this study provides insight toward the improvement of macroscopic traits such as drought resistance and plant architecture in an agronomically important crop plant.

Directly modulated 850-nm multimode vertical-cavity surface-emitting lasers (MM-VCSELs) with different oxide apertures and transmission microstrip lengths are compared on the transmission performance of the non-return-to-zero on-off keying (NRZ-OOK) and four-level pulse amplitude modulation (PAM-4) data formats. In this work, intrinsic and extrinsic responses of the MM-VCSEL are also discussed concurrently. By tuning the length of the transmission microstrip in VCSEL, the low reflection coefficient and the enhanced 3-dB modulation bandwidth are achieved. The inductance of the transmission microstrip in the series connection with the capacitance in the active region is optimized to reduce the power loss induced by imaginary impedance. The different oxide aperture sizes for MM-VCSEL are also studied to control the capacitance and photon density. More importantly, the 3-dB modulation bandwidth, impedance matching, slope efficiency, relative intensity noise (RIN), and mode partition noise (MPN) for the MM-VCSEL with various designs are discussed to determine the best device with the high-speed transmission capability. The optimal MM-VCSEL with a diameter of 7 µm oxide aperture and a length of 25 µm transmission microstrip successfully demonstrates 50-Gbit/s OOK and 84-Gbit/s PAM4 after using the pre-emphasis technique for future data-center applications.

The sophistication of gene prediction algorithms and the abundance of RNA-based evidence for the maize genome may suggest that manual curation of gene models is no longer necessary. However, quality metrics generated by the MAKER-P gene annotation pipeline identified 17,225 of 130,330 (13%) protein-coding transcripts in the B73 Reference Genome V4 gene set with models of low concordance to available biological evidence. Working with eight graduate students, we used the Apollo annotation editor to curate 86 transcript models flagged by quality metrics and a complimentary method using the Gramene gene tree visualizer. All of the triaged models had significant errors-including missing or extra exons, non-canonical splice sites, and incorrect UTRs. A correct transcript model existed for about 60% of genes (or transcripts) flagged by quality metrics; we attribute this to the convention of elevating the transcript with the longest coding sequence (CDS) to the canonical, or first, position. The remaining 40% of flagged genes resulted in novel annotations and represent a manual curation space of about 10% of the maize genome (~4,000 protein-coding genes). MAKER-P metrics have a specificity of 100%, and a sensitivity of 85%; the gene tree visualizer has a specificity of 100%. Together with the Apollo graphical editor, our double triage provides an infrastructure to support the community curation of eukaryotic genomes by scientists, students, and potentially even citizen scientists.

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed. Dissecting the genetic architecture of natural variation for maize (Zea mays L.) leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we performed an integrated genome- and transcriptome-wide association studies (GWAS and TWAS) to identify candidate genes putatively regulating variation in leaf gc. Of the 22 plausible candidate genes identified, 4 were predicted to be involved in cuticle precursor biosynthesis and export, 2 in cell wall modification, 9 in intracellular membrane trafficking, and 7 in the regulation of cuticle development. A gene encoding an INCREASED SALT TOLERANCE1-LIKE1 (ISTL1) protein putatively involved in intracellular protein and membrane trafficking was identified in GWAS and TWAS as the strongest candidate causal gene. A set of maize nested near-isogenic lines that harbor the ISTL1 genomic region from eight donor parents were evaluated for gc, confirming the association between gc and ISTL1 in a haplotype-based association analysis. The findings of this study provide insights into the role of regulatory variation in the development of the maize leaf cuticle and will ultimately assist breeders to develop drought-tolerant maize for target environments. [ABSTRACT FROM AUTHOR]

Background: Extrahepatic Cholangiocarcinoma (EHCC) is one of the uncommon malignancies in the digestive system which is characterized by a poor prognosis. Aberrations of miRNAs have been shown involved in the progression of this disease. In this study, we evaluated the expression and effects of miR-34a on EHCC. Methods: miR-34a expression levels were detected in EHCC tissues, adjacent non-tumor tissues, normal bile duct (NBD) specimens of patients and cholangiocarcinoma (CC) cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Relationships between miR-34a with clinical characteristics of EHCC patients were further analyzed. Computational search, functional luciferase assay and western blot were further used to demonstrate the downstream target of miR-34a in CC cells. Immunohistochemistry was carried on to identify the downstream target gene of miR-34a in EHCC patients. Cell morphology, invasion and migration assays were further applied to confirm the anti-carcinogenic effects of miR-34a through the downstream target. Results: miR-34a expression was significantly decreased in human EHCC tissues and CC cell lines when compared with the adjacent non-tumor tissues and normal bile duct tissues. miR-34a was found correlated with the migration and invasion in EHCC patients. Smad4 was over-expressed in most of the EHCC patients and was further demonstrated as one of the downstream targets of miR-34a, which was involved in the progression of EHCC. Moreover, activation of miR-34a suppressed invasion and migration through TGF-beta/Smad4 signaling pathway by epithelial-mesenchymal transition (EMT) in vitro. Conclusions: Taken together, our results suggest that miR-34a inhibits invasion and migration by targeting Smad4 to suppress EMT through TGF- beta/Smad signaling pathway in human EHCC. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of different extracts of Cremastra appendiculata (D. Don) Makino on apoptosis of A549 cells, and the underlying mechanism. Methods: The contents of colchicine in ethyl acetate and n-butanol extracts of Cremastra appendiculata (D. Don) Makino were determined using high performance liquid chromatography (HPLC). Lung cancer A549 cells cultured in vitro were divided into blank control, standard colchicine and Cremastra appendiculata (D. Don) Makino extract groups. The effect of different extract concentrations on proliferation of the cells was determined using methyl thiazolyl diphenyl-tetrazolium (MTT) assay, while apoptosis of A549 cells induced by the extracts was evaluated by flow cytometry (FC). Results: Compared with the standard colchicine group, there was no colchicine in the n-butanol and ethyl acetate extracts of Cremastra appendiculata. Results from MTT assay showed that the extract inhibited the proliferation of A549 cells (p < 0.05). Flow cytometry results showed that ethyl acetate extract significantly enhanced apoptosis in A549 cells (p < 0.05). However, n-butanol extract had no significant effect on the apoptosis of A549 cells (p < 0.05). Conclusion: The ethyl acetate extract of Cremastra appendiculata (D. Don) Makino induces apoptosis in lung cancer A549 cells. Therefore, there is a need for further research and development of antitumor drugs from the extract of Cremastra appendiculata (D. Don) Makino. [ABSTRACT FROM AUTHOR]

Heterostructures like InAs/GaSb superlattices (SLs) are distinctly different from well-studied ones like GaAs/AlAs SLs in terms of band alignment, common interface atom, and phonon spectrum overlapping of the constituents, which manifests as stark differences in their electronic and vibrational properties. This paper reports a comprehensive examination of all four types of phonon modes (confined, quasiconfined, extended, and interface) that have long been predicted for the InAs/GaSb SL, with the observation and interpretation of a set of phonon modes by performing cleaved edge μ-Raman study with polarization analysis. Furthermore, we show a signature of symmetry reduction from D2d for GaAs/AlAs SL to C2v for InAs/GaSb SL revealed as a phonon-polariton effect. [ABSTRACT FROM AUTHOR]