We report on a high-repetition-rate and high-beam-quality all-solid-state nanosecond pulsed deep-red laser source by intracavity second harmonic generation of the actively Q-switched Nd:YVO
/KGW ...Raman laser. The polarization of the 1342 nm fundamental laser was aligned with the Ng and Nm axes of KGW crystal for accessing the eye-safe Raman lasers at 1496 and 1526 nm, respectively. With the aid of the elaborately designed V-shaped resonator and the composite Nd:YVO
crystal, excellent mode matching and good thermal diffusion have been confirmed. Under an optimal pulse repetition frequency of 25 kHz, the average output powers of the Raman lasers at 1496 and 1526 nm were measured to be 3.7 and 4.9 W with the superior beam quality factor of M
= 1.2, respectively. Subsequently, by incorporating a bismuth borate (BIBO) crystal, the deep-red laser source was able to lase separately two different spectral lines at 748 and 763 nm, yielding the maximum average output powers of 2.5 and 3.2 W with the pulse durations of 15.6 and 11.3 ns, respectively. The resulting beam quality was determined to be near-diffraction-limited with M
= 1.28.
is a necrotrophic fungal pathogen with a broad host range that causes widespread and devastating disease in sweet cherry (
). We selected a resistant cultivar (RC) and a susceptible cultivar (SC) of ...cherry and used a combined physiological, transcriptomic, and metabolomic approach to investigate the molecular mechanisms underlying the plant's resistance to
, of which little is known. We found that
infection stimulated the outbreak of reactive oxygen species (ROS) in cherry. The responses of the antioxidant enzymes and chitinase to disease were observed earlier in the RC than in the SC. Moreover, cell wall defense ability was stronger in the RC. Differential genes and metabolites involved in defense responses and secondary metabolism were primarily enriched in the biosynthesis of phenylpropanoids, tropane, piperidine and pyridine alkaloids, flavonoids, amino acids, and α-linolenic acid. Reprogramming the phenylpropanoid pathway and the α-linolenic acid metabolic pathway led to lignin accumulation and early induction of jasmonic acid signaling, respectively, in the RC, which consequently enhanced antifungal and ROS scavenging activity. The RC contained a high level of coumarin, and
tests showed that coumarin significantly inhibited
growth and development and had antifungal effect on cherry leaves. In addition, differentially expressed genes encoding transcription factors from the MYB, NAC, WRKY, ERF, and bHLH families were highly expressed, they could be the key responsive factor in the response of cherry to infection by
. Overall, this study provides molecular clues and a multifaceted understanding of the specific response of cherry to
.
The lacustrine black shales of the Chang 7 member are the main source rocks and the most important unconventional (shale oil) petroleum resources in the Ordos Basin, North China. A series of ...continuous core samples was analysed for main, trace, and rare earth elements. The development of thin or laminar tuffs and tuffaceous mudstones and the enrichment of Fe, Mn, and other elements demonstrate that the Chang 7 member was influenced by event deposition, such as volcanic and hydrothermal activity. The ancient lake had brackish water and a relatively high sedimentation rate during the deposition of the Chang 7 member. The palaeoclimate in the early stage was warmer and wetter than that in the middle-late stage of the Chang 7 period. The geochemical proxies for palaeoproductivity and palaeoredox indicate that the ancient lake had a relatively high primary productivity with an anoxic to euxinic sulphide bottom water in the Chang 73 stage, which decreased to dyoxic-oxic water during the Chang 71+2 periods. A parameter dataset comprising 11 elemental proxies related to the reconstruction or evaluation of the depositional environment and palaeoproductivity was analysed using principal component analysis (PCA). The first principal component (PC1) accounted for 59.88% of the total variance in the original dataset and mainly represented the characteristics of palaeoproductivity and redox conditions; thus, it can be interpreted as an indicator of these factors. Based on the excellent positive linear correlation between the total organic matter content of the Chang 7 samples and the PC1 scores, the enrichment of organic matter in the Chang 7 member was mainly controlled by palaeoproductivity and the preservation environment. PCA is an effective method for dimensionality reduction and visualisation of multi-element geochemical data, which allows for a more comprehensive and in-depth understanding of geological samples. This work provides a practical application of chemometrics in elemental geochemistry. This can serve as a model for other studies.
•Insight into organic matter enrichment by combining PCA with element geochemistry.•The primary paleoproductivity of the Chang 7 member in the Ordos Basin was evaluated.•The paleosedimentary environment of the Chang 7 member was reconstructed.•The organic matter enrichment of Chang 7 member was controlled by paleoproductivity and preservation.
Non-small cell lung cancer is a major lethal subtype of epithelial lung cancer, with high morbidity and mortality. The single-cell sequencing technique plays a key role in exploring the pathogenesis ...of non-small cell lung cancer. We proposed a computational method for distinguishing cell subtypes from the different pathological regions of non-small cell lung cancer on the basis of transcriptomic profiles, including a group of qualitative classification criteria (biomarkers) and various rules. The random forest classifier reached a Matthew’s correlation coefficient (MCC) of 0.922 by using 720 features, and the decision tree reached an MCC of 0.786 by using 1880 features. The obtained biomarkers and rules were analyzed in the end of this study.
Type 2 diabetes (T2D) is a systematic chronic metabolic condition with abnormal sugar metabolism dysfunction, and its complications are the most harmful to human beings and may be life-threatening ...after long-term durations. Considering the high incidence and severity at late stage, researchers have been focusing on the identification of specific biomarkers and potential drug targets for T2D at the genomic, epigenomic, and transcriptomic levels. Microbes participate in the pathogenesis of multiple metabolic diseases including diabetes. However, the related studies are still non-systematic and lack the functional exploration on identified microbes. To fill this gap between gut microbiome and diabetes study, we first introduced eggNOG database and KEGG ORTHOLOGY (KO) database for orthologous (protein/gene) annotation of microbiota. Two datasets with these annotations were employed, which were analyzed by multiple machine-learning models for identifying significant microbiota biomarkers of T2D. The powerful feature selection method, Max-Relevance and Min-Redundancy (mRMR), was first applied to the datasets, resulting in a feature list for each dataset. Then, the list was fed into the incremental feature selection (IFS), incorporating support vector machine (SVM) as the classification algorithm, to extract essential annotations and build efficient classifiers. This study not only revealed potential pathological factors for diabetes at the microbiome level but also provided us new candidates for drug development against diabetes.
A novel fluorescent sensor based on thiooxorhodamine B has been prepared to detect Hg
2+ in aqueous buffer solution. It demonstrates high selectivity for sensing Hg
2+ with about 383-fold enhancement ...in fluorescence emission intensity and micromolar sensitivity (
K
d
=
7.5
×
10
−6
mol
L
−1) in comparison with alkali and alkaline earth metal ions (K
+, Na
+, Mg
2+, Ca
2+) and other transition metal ions (Mn
2+, Ni
2+, Co
2+, Cu
2+, Zn
2+, Cd
2+, Ag
+, Pb
2+, Cr
3+, Fe
3+). Meanwhile the distinct color changes and rapid switch-on fluorescence also provide ‘naked eyes’ detection for Hg
2+ over a broad pH range. Moreover, such sensor is cell-permeable and can visualize the changes of intracellular mercury ions in living cells using fluorescence microscopy.
ThioRh-1 can monitor mercury ions both in solution by naked-eyes and in living cells by fluorescence microscopy.
Display omitted
► A new fluorescent sensor for Hg
2+ is based on thiooxorhodamine structure. ► Hg
2+-chelation induces significant fluorescence enhancement in HEPES buffer. ► It shows high affinity for Hg
2+ over other metal ions. ► This cell-permeable sensor can visualize the changes of intracellular mercury ions.
The loss of dopaminergic neurons in the substantia nigra and the abnormal accumulation of synuclein proteins and neurotransmitters in Lewy bodies constitute the primary symptoms of Parkinson's ...disease (PD). Besides environmental factors, scholars are in the early stages of comprehending the genetic factors involved in the pathogenic mechanism of PD. Although genome-wide association studies (GWAS) have unveiled numerous genetic variants associated with PD, precisely pinpointing the causal variants remains challenging due to strong linkage disequilibrium (LD) among them. Addressing this issue, expression quantitative trait locus (eQTL) cohorts were employed in a transcriptome-wide association study (TWAS) to infer the genetic correlation between gene expression and a particular trait. Utilizing the TWAS theory alongside the enhanced Joint-Tissue Imputation (JTI) technique and Mendelian Randomization (MR) framework (MR-JTI), we identified a total of 159 PD-associated genes by amalgamating LD score, GTEx eQTL data, and GWAS summary statistic data from a substantial cohort. Subsequently, Fisher's exact test was conducted on these PD-associated genes using 5,152 differentially expressed genes sourced from 12 PD-related datasets. Ultimately, 29 highly credible PD-associated genes, including CTX1B, SCNA, and ARSA, were uncovered. Furthermore, GO and KEGG enrichment analyses indicated that these genes primarily function in tissue synthesis, regulation of neuron projection development, vesicle organization and transportation, and lysosomal impact. The potential PD-associated genes identified in this study not only offer fresh insights into the disease's pathophysiology but also suggest potential biomarkers for early disease detection.
Abstract The discovery of novel oncotargets for glioma is of immense significance. We here explored the expression patterns, biological functions, and underlying mechanisms associated with ORC6 ...(origin recognition complex 6) in glioma. Through the bioinformatics analyses, we found a significant increase in ORC6 expression within human glioma tissues, correlating with poorer overall survival, higher tumor grade, and wild-type isocitrate dehydrogenase status. Additionally, ORC6 overexpression is detected in glioma tissues obtained from locally-treated patients and across various primary/established glioma cells. Further bioinformatics scrutiny revealed that genes co-expressed with ORC6 are enriched in multiple signaling cascades linked to cancer. In primary and immortalized (A172) glioma cells, depleting ORC6 using specific shRNA or Cas9-sgRNA knockout (KO) significantly decreased cell viability and proliferation, disrupted cell cycle progression and mobility, and triggered apoptosis. Conversely, enhancing ORC6 expression via a lentiviral construct augmented malignant behaviors in human glioma cells. ORC6 emerged as a crucial regulator for the expression of key oncogenic genes, including Cyclin A2 , Cyclin B2 , and DNA topoisomerase II ( TOP2A ), within glioma cells. Silencing or KO of ORC6 reduced the mRNA and protein levels of these genes, while overexpression of ORC6 increased their expression in primary glioma cells. Bioinformatics analyses further identified RBPJ as a potential transcription factor of ORC6 . RBPJ shRNA decreased ORC6 expression in primary glioma cells, while its overexpression increased it. Additionally, significantly enhanced binding between the RBPJ protein and the proposed ORC6 promoter region was detected in glioma tissues and cells. In vivo experiments demonstrated a significant reduction in the growth of patient-derived glioma xenografts in the mouse brain subsequent to ORC6 KO. ORC6 depletion, inhibited proliferation, decreased expression of Cyclin A2/B2/TOP2A, and increased apoptosis were detected within these ORC6 KO intracranial glioma xenografts. Altogether, RBPJ-driven ORC6 overexpression promotes glioma cell growth, underscoring its significance as a promising therapeutic target.
An embryo develops from a single-celled zygote, which produces a multi-cellular organism by mitosis. Due to the complication of processes and mechanisms, research on embryo cell clusters in different ...early embryo developmental stages with significant phenotypic differences is still lacking. In this work, we identified some gene characters and expression rules to classify these individual cells using several advanced computational methods. The single cell expression profiles of embryo cells were analyzed by the Monte Carlo feature selection (MCFS) method, resulting in a feature list. Then, the incremental feature selection (IFS) method, incorporating support vector machine (SVM), applied on such list to extract key gene characters. These gene characters include KHDC1, HMGN1, DCP, GDF9, RNF11, DNMT3L, and CDX1. Furthermore, a rule learning algorithm, Repeated Incremental Pruning to Produce Error Reduction (RIPPER), was applied to the informative features yielded by MCFS method, producing a group of classification rules. These rules can clearly uncover different expression patterns on cells in different stages. This study provided a group of effective gene signatures and rules for embryo cell subtyping and presented an applicable computational tool to further dig into the regulatory mechanisms of embryo development.
Mupirocin, a polyketide antibiotic produced by
Pseudomonas fluorescens
, is used as a topical antimicrobial treatment to cure various skin infections. Quorum sensing system plays an important role in ...regulation of mupirocin biosynthesis in
P. fluorescens
NCIMB 10586. In
Pseudomonas
, the RpeA/RpeB two-component signal transduction (TCST) system regulates quorum sensing system. However, the influences of the RpeA/RpeB TCST system on mupirocin production or other cell activities have not been studied. In this work, the homologous genes of
rpeA
and
rpeB
in
P. fluorescens
NCIMB 10586 were identified and inactivated in the chromosome, respectively. The deletion of
rpeA
reduced the mupirocin production from 160 in the wild-type to 21.3 mg/L along with slightly decreased cell growth, while no significant effected on mupirocin production in the
rpeB
mutant. Next, it was found that the RpeA/RpeB TCST system regulated the biosynthesis of mupirocin by modulating the quorum sensing system. Furthermore, untargeted metabolomics analysis was employed to detect the influences of RpeA on other cell activities modulated by quorum sensing system. Combined with quantitative real-time PCR, the results demonstrated that RpeA also regulated other cell activities including central carbon, amino acids, fatty acids, and purine metabolism. Overall, this study expands the current understanding of the RpeA/RpeB TCST system and provides several targets for increasing yields of mupirocin.
Key points
• In
P. fluorescens
, the RpeA/RpeB TCST system regulates the biosynthesis of mupirocin.
• RpeA modulates the cell activities through effecting the central carbon metabolism.
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