Spatiotemporal single-cell RNA sequencing reveals the role of steroid hormone pathway during chicken primordial follicle formation.

The size of the initial primordial follicle pool in the ovary depends on primordial follicle formation, which determines the female reproductive lifespan. However, the molecular regulation of primordial follicle formation in chickens remains unclear. In this study, the left ovaries of chickens were collected at 2 d posthatch (dph), 5.5 dph, and 10.5 dph to examine the formation of primordial follicles. Single-cell mRNA sequencing (scRNA-seq) and spatial transcriptomic analysis were performed to explore the ovarian microenvironment and identify regulatory pathways involved in the formation of primordial follicles in chickens. Histomorphological analysis of chicken ovary tissues revealed the presence of germ cell cysts at 1 dph, which began to disintegrate at 2 dph. Primordial follicles appeared at 5.5 dph and continued to develop into larger-diameter follicles. scRNA-seq and spatial transcriptomic analysis revealed 24 cellular clusters involved in chicken primordial follicle formation. The metabolic pathway of steroid hormone synthesis was found in pregranulosa and pretheca cells. Histological analysis showed that chicken ovaries did not form primordial follicles after the inhibition of the steroid hormone synthesis pathway by simvastatin or tamoxifen. In addition, mRNA transcriptomic and bioinformatics analyses revealed that GREB1 was a downstream gene of the steroid hormone synthesis pathway during the formation of chicken primordial follicles. This study provides a valuable foundation for investigating primordial follicle formation in avian species and optimizing their reproductive performance.

Endogenous Hormone Levels and Transcriptomic Analysis Reveal the Mechanisms of Bulbil Initiation in Pinellia ternata.

Pinellia ternata is a medicinal plant that has important pharmacological value, and the bulbils serve as the primary reproductive organ; however, the mechanisms underlying bulbil initiation remain unclear. Here, we characterized bulbil development via histological, transcriptomic, and targeted metabolomic analyses to unearth the intricate relationship between hormones, genes, and bulbil development. The results show that the bulbils initiate growth from the leaf axillary meristem (AM). In this stage, jasmonic acid (JA), abscisic acid (ABA), isopentenyl adenosine (IPA), and salicylic acid (SA) were highly enriched, while indole-3-acetic acid (IAA), zeatin, methyl jasmonate (MeJA), and 5-dexoxystrigol (5-DS) were notably decreased. Through OPLS-DA analysis, SA has emerged as the most crucial factor in initiating and positively regulating bulbil formation. Furthermore, a strong association between IPA and SA was observed during bulbil initiation. The transcriptional changes in IPT (Isopentenyltransferase), CRE1 (Cytokinin Response 1), A-ARR (Type-A Arabidopsis Response Regulator), B-ARR (Type-B Arabidopsis Response Regulator), AUX1 (Auxin Resistant 1), ARF (Auxin Response Factor), AUX/IAA (Auxin/Indole-3-acetic acid), GH3 (Gretchen Hagen 3), SAUR (Small Auxin Up RNA), GA2ox (Gibberellin 2-oxidase), GA20ox (Gibberellin 20-oxidase), AOS (Allene oxide synthase), AOC (Allene oxide cyclase), OPR (Oxophytodienoate Reductase), JMT (JA carboxy l Methyltransferase), COI1 (Coronatine Insensitive 1), JAZ (Jasmonate ZIM-domain), MYC2 (Myelocytomatosis 2), D27 (DWARF27), SMAX (Suppressor of MAX2), PAL (Phenylalanine Ammonia-Lyase), ICS (Isochorismate Synthase), NPR1 (Non-expressor of Pathogenesis-related Genes1), TGA (TGACG Sequence-specific Binding), PR-1 (Pathogenesis-related), MCSU (Molybdenium Cofactor Sulfurase), PP2C (Protein Phosphatase 2C), and SnRK (Sucrose Non-fermenting-related Protein Kinase 2) were highly correlated with hormone concentrations, indicating that bulbil initiation is coordinately controlled by multiple phytohormones. Notably, eight TFs (transcription factors) that regulate AM initiation have been identified as pivotal regulators of bulbil formation. Among these, WUS (WUSCHEL), CLV (CLAVATA), ATH1 (Arabidopsis Thaliana Homeobox Gene 1), and RAX (Regulator of Axillary meristems) have been observed to exhibit elevated expression levels. Conversely, LEAFY demonstrated contrasting expression patterns. The intricate expression profiles of these TFs are closely associated with the upregulated expression of KNOX(KNOTTED-like homeobox), suggesting a intricate regulatory network underlying the complex process of bulbil initiation. This study offers a profound understanding of the bulbil initiation process and could potentially aid in refining molecular breeding techniques specific to P. ternata.

Simulation Study of Coal Seam Gas Extraction Characteristics Based on Coal Permeability Evolution Model under Thermal Effect.

The permeability evolution law of high temperature and high stress coal seam is determined by the influence of multiphase coexistence and multifield coupling. In an environment greatly affected by disturbance and high temperature, the coal permeability model under the coupling of thermal and mechanical creep is not only a vital framework from which to examine gas migration law in multiphase and multifield coal seams but also an important theoretical foundation for gas control in coal seams. The influence of high-temperature environment on creep deformation and permeability is analyzed by several creep seepage tests under different temperature conditions.A mathematical model for the evolution of coal permeability considering the influence of temperature is established through the theory of matrix-crack interaction based on gas adsorption and desorption and thermal expansion deformation. Based on the permeability model under the coupling of thermal and mechanical creep, the numerical model of gas migration, seepage field, diffusion field, stress field, and temperature field is constructed, and the law of gas migration in coal seam under multifield coupling is explored. The influence law of thermal effect on gas extraction characteristics is analyzed, in which the time-varying mechanism of temperature field, the relationship between creep deformation and temperature and pressure, the influence of creep deformation on permeability, the dynamic distribution of gas pressure, and the change of gas extraction quantity are described in detail. It is concluded that the influence of temperature on permeability is much greater than that of creep deformation and that a high initial coal seam temperature is beneficial to gas extraction. It provides theoretical basis and technical guidance for the study of multifield coupled gas migration and coal seam gas treatment.

SlPHL1 positively modulates acid phosphatase in response to phosphate starvation by directly activating the genes SlPAP10b and SlPAP15 in tomato.

Increased acid phosphatase (APase) activity is a prominent feature of tomato (Solanum lycopersicum) responses to inorganic phosphate (Pi) restriction. SlPHL1, a phosphate starvation response (PHR) transcription factor, has been identified as a positive regulator of low Pi (LP)-induced APase activity in tomato. However, the molecular mechanism underlying this regulation remains to be elucidated. Here, SlPHL1 was found to positively regulate the LP-induced expression of five potential purple acid phosphatase (PAP) genes, namely SlPAP7, SlPAP10b, SlPAP12, SlPAP15, and SlPAP17b. Furthermore, we provide evidence that SlPHL1 can stimulate transcription of these five genes by binding directly to the PHR1 binding sequence (P1BS) located on their promoters. The P1BS mutation notably weakened SlPHL1 binding to the promoters of SlPAP7, SlPAP12, and SlPAP17b but almost completely abolished SlPHL1 binding to the promoters of SlPAP10b and SlPAP15. As a result, the transcriptional activation of SlPHL1 on SlPAP10b and SlPAP15 was substantially diminished. In addition, not only did transient overexpression of either SlPAP10b or SlPAP15 in tobacco leaves increase APase activity, but overexpression of SlPAP15 in Arabidopsis and tomato also increased APase activity and promoted plant growth. Subsequently, two SPX proteins, SlSPX1 and SlSPX4, were shown to physically interact with SlPHL1. Moreover, SlSPX1 inhibited the transcriptional activation of SlPHL1 on SlPAP10b and SlPAP15 and negatively regulated the activity of APase. Taken together, these results demonstrate that SlPHL1-mediated LP signaling promotes APase activity by activating the transcription of SlPAP10b and SlPAP15, which may provide valuable insights into the mechanisms of tomato response to Pi-limited stress.

Waterlogging increases greenhouse gas release and decreases yield in winter rapeseed (Brassica napus L.) seedlings.

A sustainable future depends on increasing agricultural carbon (C) and nitrogen (N) sequestration. Winter rapeseeds are facing severe yield loss after waterlogging due to the effects of extreme rainfall, especially in the seedling stage, where rainfall is most sensitive. Uncertainty exists over the farming greenhouse gas (GHG) release of rapeseed seedlings following the onset of waterlogging. The effect of waterlogging on GHG release and leaf gas exchange in winter rapeseed was examined in a pot experiment. The experiment included waterlogging treatments lasting 7-day and 21-day and normal irrigation as a control treatment. According to our findings, (1) The ecosystem of rapeseed seedlings released methane (CH4) and nitrous oxide (N2O) in a clear up change that was impacted by ongoing waterlogging. Among them, N2O release had a transient rise during the early stages under the effect of seedling fertilizer. (2) The net photosynthetic rate, transpiration rate, stomatal conductance, plant height, soil moisture, and soil oxidation-reduction potential of rapeseed all significantly decreased due to the ongoing waterlogging. However, rapeseed leaves showed a significant increase in intercellular carbon dioxide (CO2) concentration and leaf chlorophyll content values after waterlogging. Additionally, the findings demonstrated an extremely significant increase in the sustained-flux global warming potential of the sum CO2-eq of CH4 and N2O throughout the entire waterlogging stress period. Therefore, continuous waterlogging can increase C and N release from rapeseed seedlings ecosystem and decrease yield. Therefore, we suggest increasing drainage techniques to decrease the release of agricultural GHGs and promote sustainable crop production.

Advancements in oral and maxillofacial surgery medical images segmentation techniques: An overview.

OBJECTIVES: This article reviews recent advances in computer-aided segmentation methods for oral and maxillofacial surgery and describes the advantages and limitations of these methods. The objective is to provide an invaluable resource for precise therapy and surgical planning in oral and maxillofacial surgery. Study selection, data and sources: This review includes full-text articles and conference proceedings reporting the application of segmentation methods in the field of oral and maxillofacial surgery. The research focuses on three aspects: tooth detection segmentation, mandibular canal segmentation and alveolar bone segmentation. The most commonly used imaging technique is CBCT, followed by conventional CT and Orthopantomography. A systematic electronic database search was performed up to July 2023 (Medline via PubMed, IEEE Xplore, ArXiv, Google Scholar were searched). RESULTS: These segmentation methods can be mainly divided into two categories: traditional image processing and machine learning (including deep learning). Performance testing on a dataset of images labeled by medical professionals shows that it performs similarly to dentists' annotations, confirming its effectiveness. However, no studies have evaluated its practical application value. CONCLUSION: Segmentation methods (particularly deep learning methods) have demonstrated unprecedented performance, while inherent challenges remain, including the scarcity and inconsistency of datasets, visible artifacts in images, unbalanced data distribution, and the "black box" nature. CLINICAL SIGNIFICANCE: Accurate image segmentation is critical for precise treatment and surgical planning in oral and maxillofacial surgery. This review aims to facilitate more accurate and effective surgical treatment planning among dental researchers.

The Accumulation of Toxic Elements (Pb, Hg, Cd, As, and Cu) in Red Swamp Crayfish (Procambarus clarkii) in Qianjiang and the Associated Risks to Human Health.

Due to rapidly expanding crayfish consumption worldwide, the food safety of red swamp crayfish (Procambarus clarkii) is of great concern. China is the largest consumer and producer of crayfish globally. As of yet, it is unknown whether the main crayfish production cities in China are within safe levels of toxic heavy metals and metalloids. For 16 consecutive years, Qianjiang city ranked first in China in processing export volumes of red swamp crayfish. This study presents a comprehensive analysis of the enrichment levels and associated health risks of the species in Qianjiang. In our research, samples of four crayfish tissues, including the head, hepatopancreas, gills, and muscles, were collected from 38 sampling sites distributed in Qianjiang to evaluate the concentration levels of five heavy metals (Pb, Hg, Cd, As, and Cu). The concentration levels of all five metals in muscle did not surpass the national standard. Furthermore, eight significant correlations have been found. For further in-depth assess risk of crayfish in Qianjiang, estimated daily intake (EDI), target hazard quotient (THQ), carcinogenic risk (CR), and estimated maximum allowable consumption rates (CRmm) were evaluated in the abdomen muscle and hepatopancreas. The THQ values for each metal were found to be less than 1, while the CR values were below 10-6. Additionally, the CRmm for adults was determined to be 17.2 meals per month. These findings, based on the analysis of five metallic elements included in this study, suggest that the consumption of crayfish abdomen muscle in Qianjiang does not pose any significant health risks. However, it is noteworthy that certain regions exhibit elevated levels of arsenic in the hepatopancreas, surpassing the national standard, thereby rendering them unsuitable for excessive consumption. In general, the findings can be used to provide guidance for safe dietary practices in China.

Dual-Locked DNAzyme Platform for In Vitro and In Vivo Discrimination of Cancer Cells.

Imaging of tumor-associated microRNAs (miRNAs) can provide abundant information for cancer diagnosis, whereas the occurrence of trace amounts of miRNAs in normal cells inevitably causes an undesired false-positive signal in the discrimination of cancer cells during miRNA imaging. In this study, we propose a dual-locked (D-locked) platform consisting of the enzyme/miRNA-D-locked DNAzyme sensor and the honeycomb MnO2 nanosponge (hMNS) nanocarrier for highly specific cancer cell imaging. For a proof-of-concept demonstration, apurinic/apyrimidinic endonuclease 1 (APE1) and miR-21 were chosen as key models. The hMNS nanocarrier can efficiently release the D-locked DNAzyme sensor in living cells due to the decomposition of hMNS by glutathione, which can also supply Mn2+ for DNAzyme cleavage. Ascribing to the smart design of the D-locked DNAzyme sensor, the fluorescence signal can only be generated by the synergistic response of APE1 and miR-21 that are overexpressed in cancer cells. Compared with the miRNA single-locked DNAzyme sensor and the small-molecule (ATP)/miRNA D-locked DNAzyme sensor, the proposed enzyme (APE1)/miRNA D-locked DNAzyme sensor exhibited 2.6-fold and 2.4-fold higher discrimination ratio (Fcancer/Fnormal) for cancer cell discrimination, respectively. Owing to the superior performance, the D-locked strategy can selectively generate a fluorescence signal in cancer cells, facilitating accurate discrimination of cancer both in vitro and in vivo. Furthermore, this D-locked platform is easily adaptable toward other target molecules by redesigning the DNA sequences. The outstanding performance and expansibility of this D-locked platform holds promising prospects for cancer diagnosis and related biomedical applications.

Toxicological, Behavioral, and Horizontal Transfer Effects of Cycloxaprid Against Formosan Subterranean Termites (Blattodea: Rhinotermitidae).

Cycloxaprid, 9-((6-chloropyrid-3-yl)methyl)-4-nitro-8-oxa-10,11-dihydroimidazo-[2,3-a]-bicyclo-[3,2,1]-oct-3-ene, is a cis-configuration neonicotinoid insecticide. In the present study, the lethal and sublethal effect of cycloxaprid against Formosan subterranean termites, Coptotermes formosanus Shiraki (Blattodea: Rhinotermitidae), was evaluated and compared with fipronil. Toxicity bioassays showed that cycloxaprid had slightly lower toxicity than fipronil. The minimum cycloxaprid concentration in sand and soil that causes 100% termite mortality was 100 ppm. Similar to fipronil, cycloxaprid significantly reduced wood consumption and tunneling activities of termites. In the tunneling-choice tests, termite tunneling activity measured in both length and area was significantly lower in sand treated with cycloxaprid (10 or 100 ppm) than that in untreated sand. In the aggregation-choice tests, cycloxaprid exhibited inhibition to termite aggregation starting from 100 ppm. In addition, cycloxaprid exhibited significant horizontal transfer effect at 10 ppm. In conclusion, our study showed that cycloxaprid is slightly less toxic than fipronil and more repellent to C. formosanus than fipronil. Future studies are needed to evaluate the effectiveness of cycloxaprid against subterranean termites in the field.

FoxO3a cooperates with RUNX1 to promote chondrogenesis and terminal hypertrophic of the chondrogenic progenitor cells.

FoxO transcription factors (FoxOs) have recently been shown to protect against chondrocyte dysfunction and modulate cartilage homeostasis in osteoarthritis. The mechanism underlying of FoxOs regulate chondrocyte differentiation remains unknown. Runt related transcription factor 1 (RUNX1) mediated both chondrocyte and osteoblast differentiation. Our data showed that FoxO3a and RUNX1 are co-expressed in ATDC5 cells and undifferentiated mesenchyme cells and have similar high levels in chondrocytes undergoing transition from proliferation to hypertrophy. Overexpression of FoxO3a in ATDC5 cells or mouse mesenchymal cells resulted in a potent induction of the chondrocyte differentiation markers. Knockdown FoxO3a or RUNX1 potently inhibits the expressions of chondrocyte differentiation markers, including Sox9, Aggrecan, Col2, and hypertrophic chondrocyte markers including RUNX2, ColX, MMP13 and ADAMTs-5 in ATDC5 cells. Co-immunoprecipitation showed that FoxO3a binds the transcriptional regulator RUNX1. Immunohistochemistry showed that FoxO3a and RUNX1 are highly co-expressed in the proliferative chondrocytes of the growth plates in the hind limbs of newborn mice. Collectively, we revealed that FoxO3a cooperated with RUNX1 promoted chondrocyte differentiation through enhancing both early chondrogenesis and terminal hypertrophic of the chondrogenic progenitor cells, indicating FoxO3a interacting with RUNX1 may be a therapeutic target for the treatment of osteoarthritis and other bone diseases.

Effect of different types of smoking materials on the flavor, heterocyclic aromatic amines, and sensory property of smoked chicken drumsticks.

This study investigated the effect of different types of smoking materials on the flavor, heterocyclic aromatic amine (HAA) content, and sensory attributes of smoked chicken drumsticks. All smoked samples showed lower pH and L*-value and higher a*-value and b*-value than the control sample (P < 0.05), but no significant differences in water content and water activity (P > 0.05). The samples smoked with sucrose combined with pear-tree woodchips (SP) or green tea leaves (ST) had higher overall acceptability than other samples (P < 0.05). Smoking increased the total HAA content, and the ST sample exhibited the highest total HAA content (P < 0.05). A total of 54 volatile compounds was identified. Overall, SP and ST are suitable for smoked chicken considering the sensory properties, while S and SA are proper for smoked chicken considering the minimization of HAAs, which may provide a theory basis for the production of smoked chicken.

Site-Selective Photosynthesis of Ag-AgCl@Au Nanomushrooms for NIR-II Light-Driven O2- and O2•--Evolving Synergistic Photothermal Therapy against Deep Hypoxic Tumors.

Light-driven endogenous water oxidation has been considered as an attractive and desirable way to obtain O2 and reactive oxygen species (ROS) in the hypoxic tumor microenvironment. However, the use of a second near-infrared (NIR-II) light to achieve endogenous H2O oxidation to alleviate tumor hypoxia and realize deep hypoxic tumor phototherapy is still a challenge. Herein, novel plasmonic Ag-AgCl@Au core-shell nanomushrooms (NMs) were synthesized by the selective photodeposition of plasmonic Au at the bulge sites of the Ag-AgCl nanocubes (NCs) under visible light irradiation. Upon NIR-II light irradiation, the resulting Ag-AgCl@Au NMs could oxidize endogenous H2O to produce O2 to alleviate tumor hypoxia. Almost synchronously, O2 could react with electrons on the conduction band of the AgCl core to generate superoxide radicals (O2•-)for photodynamic therapy. Moreover, Ag-AgCl@Au NMs with an excellent photothermal performance could further promote the phototherapy effect. In vitro and in vivo experimental results show that the resulting Ag-AgCl@Au NMs could significantly improve tumor hypoxia and enhance phototherapy against a hypoxic tumor. The present study provides a new strategy to design H2O-activatable, O2- and ROS-evolving NIR II light-response nanoagents for the highly efficient and synergistic treatment of deep O2-deprived tumor tissue.

[Oral Mucosal Diffuse Large B-cell Lymphoma Caused by Long-term Oral Methotrexate:Report of One Case].

A case of primary oral mucosal diffuse large B-cell lymphoma(DLBCL)due to long-term use of methotrexate(MTX)for the treatment of rheumatoid arthritis(RA)was admitted to the Department of Hematology,Fujian Medical University Union Hospital.We analyzed and discussed the clinical features,diagnosis and treatment,and prognosis of specific malignant lymphoma induced by MTX in this RA patient.Our purpose is to improve the awareness and knowledge of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of clinicians and pathologists.This study provides a new reference for the clinical diagnosis and treatment of MTX-associated DLBCL.

Generation of Knockout and Transgenic Zebrafish to Characterize Abcc4 Functions in Detoxification and Efflux of Lead.

Lead (Pb) is one of the major heavy metals that are toxic to vertebrates and usually considered as environmental pollutants. ABCC4/MRP4 is an organic anion transporter that mediates cellular efflux of a wide range of exogenous and endogenous compounds such as cyclic nucleotides and anti-cancer drugs; however, it remains unclear whether ABCC4 and its orthologs function in the detoxification and excretion of toxic lead. In this study, we found that the transcriptional and translational expression of zebrafish abcc4 was significantly induced under lead exposure in developing zebrafish embryos and adult tissues. Overexpression of zebrafish Abcc4 markedly decreased the cytotoxicity and accumulation of lead in pig renal proximal tubule cell line (LLC-PK1 cells). To further understand the functions of zebrafish Abcc4 in lead detoxification, the clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system was used to create an abcc4-/- mutant zebrafish line. In comparison with the wild-type (WT) zebrafish, the abcc4-/- mutants showed a higher death rate and lead accumulation upon exposure to lead. Furthermore, a stable abcc4-transgenic zebrafish line was successfully generated, which exerted stronger ability to detoxify and excrete lead than WT zebrafish. These findings indicate that zebrafish Abcc4 plays a crucial role in lead detoxification and cellular efflux and could be used as a potential biomarker to monitor lead contamination in a water environment.

Construction and Validation of a Clinical Predictive Nomogram for Improving the Cancer Detection of Prostate Naive Biopsy Based on Chinese Multicenter Clinical Data.

OBJECTIVES: Prostate biopsy is a common approach for the diagnosis of prostate cancer (PCa) in patients with suspicious PCa. In order to increase the detection rate of prostate naive biopsy, we constructed two effective nomograms for predicting the diagnosis of PCa and clinically significant PCa (csPCa) prior to biopsy. MATERIALS AND METHODS: The data of 1,428 patients who underwent prostate biopsy in three Chinese medical centers from January 2018 to June 2021 were used to conduct this retrospective study. The KD cohort, which consisted of 701 patients, was used for model construction and internal validation; the DF cohort, which consisted of 385 patients, and the ZD cohort, which consisted of 342 patients, were used for external validation. Independent predictors were selected by univariate and multivariate binary logistic regression analysis and adopted for establishing the predictive nomogram. The apparent performance of the model was evaluated via internal validation and geographically external validation. For assessing the clinical utility of our model, decision curve analysis was also performed. RESULTS: The results of univariate and multivariate logistic regression analysis showed prostate-specific antigen density (PSAD) (P<0.001, OR:2.102, 95%CI:1.687-2.620) and prostate imaging-reporting and data system (PI-RADS) grade (P<0.001, OR:4.528, 95%CI:2.752-7.453) were independent predictors of PCa before biopsy. Therefore, a nomogram composed of PSAD and PI-RADS grade was constructed. Internal validation in the developed cohort showed that the nomogram had good discrimination (AUC=0.804), and the calibration curve indicated that the predicted incidence was consistent with the observed incidence of PCa; the brier score was 0.172. External validation was performed in the DF and ZD cohorts. The AUC values were 0.884 and 0.882, in the DF and ZD cohorts, respectively. Calibration curves elucidated greatly predicted the accuracy of PCa in the two validation cohorts; the brier scores were 0.129 in the DF cohort and 0.131 in the ZD cohort. Decision curve analysis showed that our model can add net benefits for patients. A separated predicted model for csPCa was also established and validated. The apparent performance of our nomogram for PCa was also assessed in three different PSA groups, and the results were as good as we expected. CONCLUSIONS: In this study, we put forward two simple and convenient clinical predictive models comprised of PSAD and PI-RADS grade with excellent reproducibility and generalizability. They provide a novel calculator for the prediction of the diagnosis of an individual patient with suspicious PCa.

Transcriptional response of zebrafish larvae exposed to lindane reveals two detoxification genes of ABC transporter family (abcg5 and abcg8).

Lindane is a highly toxic organochlorine pesticide and widely exist in water with harmful effects on fish. Although some genes have been found to be regulated by lindane in fish, the transcriptional response of fish exposed to lindane is still unknown. In this research, the transcriptional changes of zebrafish larvae exposed to 0.2 mg/L lindane from 96 to 120 hpf were studied by RNA sequencing. Our transcriptome identified 554 up-regulated and 118 down-regulated genes and the differentially expressed genes were closely related to the neuromast development, RNA silencing genes, ion transport, and response to estrogen. In addition, we characterized two sensitive and novel lindane-induced ABCG (ATP binding cassette G subfamily) transporter genes- abcg5 and abcg8. Abcg5 and abcg8 genes are located on chromosome 13 of zebrafish and contain 1956/2024 bp open reading frame. The polypeptide deduced by CDS amplification contains 652/676 amino acids and has most of the functional domains and key residues defined in human and mouse ABCG5/Abcg5 or ABCG8/Abcg8. Only when the co-expression of Abcg5 and Abcg8 enable them to transport to the cell membrane surface in 293T cells. In addition, lindane can induce the transcriptional expression of abcg5 and abcg8 genes, and overexpression of Abcg5 and Abcg8 significantly reduced the toxicity of lindane to zebrafish larvae, which means that zebrafish Abcg5 and Abcg8 are potential efflux transporters of lindane. Therefore, these findings provide useful insights for further understanding the zebrafish larvae's transcriptional response and detoxification ability after acute exposure to lindane.

Downregulation of vdac2 inhibits spermatogenesis via JNK and P53 signalling in mice exposed to cadmium.

Previous studies have reported the reproductive toxicity of cadmium (Cd); however, the effect of Cd on spermatogenesis and the underlying mechanism remain to be elucidated. In this study, mouse Leydig TM3 cells were treated with CdCl2 (0, 5, 10 and 50 µM) for 24 h to evaluate cytotoxicity, and C57BL/6 mice were treated intragastrically with 0.4 mL CdCl2 (0, 0.01, 0.05 and 0.1 g/L) for 2 months to investigate changes in spermatogenesis. The results showed that Cd aggravated apoptosis and proliferation in a dose-dependent manner, concomitant with deteriorated spermatogenesis and testosterone synthesis. For mechanism exploration, RNA-seq was used to profile alterations in gene expression in response to Cd, and the results indicated focus on P53/JNK signalling pathways and membrane proteins. We found that P53/JNK signalling pathways were activated upon Cd treatment, with the Cd-triggered downregulation of the vdac2 gene. P53/JNK pathway blockade ameliorated the Cd-induced inhibition of steroidogenic acute regulatory protein (STAR) expression and testosterone synthesis. Additionally, vdac2 knockdown in TM3 cells contributed to the phosphorylation of JNK/P53 and reduced the testosterone content. Vdac2 overexpression rescued the aforementioned Cd-induced events. Collectively, our study identified an innovative biomarker of Cd exposure in mice. The results demonstrated that vdac2 downregulation inhibits spermatogenesis via the JNK/P53 cascade. This finding may contribute to our understanding of the regulatory mechanism of Cd reproductive toxicity and provide a candidate list for sperm abnormality factors and pathways.

Enhanced functional DNA biosensor for distance-based read-by-eye quantification of various analytes based on starch-hydrolysis-adjusted wettability change in paper devices.

Low-cost, equipment-free and quantitative detection of a wide range of analytes of interest at home and in the field holds the potential to revolutionize disease diagnosis, environmental pollution monitoring, and food safety analysis. Herein, we describe a functional DNA biosensor for the first time that integrates analyte-directed assembly of enzyme-coated microbead probes for robust yet efficient signal amplification with a simple quantitative detection motif of distance measurement on portable paper devices based on starch-hydrolysis-adjusted wettability change of paper. Its utility is well demonstrated with highly sensitive and specific detection of model analytes ranging from adenosine (an important small biomolecule; 1.6 µM detection limit) to interferon-γ (a protein marker; 0.3 nM detection limit) and Pb2+ (a highly toxic metal ion; 0.5 nM detection limit) by simply using an inexpensive, ubiquitous ruler. The developed general method with the distance-measuring readout should be easily tailored for the portable, read-by-eye, quantitative detection of many other types of analytical targets by taking advantage of their specific functional DNA partners like aptamers and DNAzymes.

Spatiotemporally controlled O2 and singlet oxygen self-sufficient nanophotosensitizers enable the in vivo high-yield synthesis of drugs and efficient hypoxic tumor therapy.

Carrying out the in vivo syntheses of drugs toxic to tumors based on the specific features of the tumor microenvironment is critical for ensuring specific antitumor efficacy. However, achieving in situ high-yield synthetic toxic drugs from non-toxic agents and reducing their drug resistance in hypoxic tumors remain challenges. Herein we created a tumor-microenvironment-responsive porous Pt/Pt(iv) methylene blue coordination polymer nanoshuttle (Pt/PtMBCPNS) photosensitizer with spatiotemporally controlled O2 and singlet oxygen (1O2) self-sufficient for the in vivo high-yield synthesis of drugs and efficient hypoxic tumor therapy. After being endocytosed, the nanophotosensitizer as a cascade catalyst was observed to effectively catalyze the conversion of endogenous H2O2 to O2, and was hence found to play a dual role in the enhanced tumor therapy. PtMBCPNSs, upon being irradiated with red light, efficiently converted O2 into 1O2. Subsequently, 1O2 oxidized non-toxic 1,5-dihydroxynaphthalene to form the anticancer agent juglone with a high yield. In addition, O2 was found to be able to improve the hypoxic microenvironment without light irradiation, thus enhancing the antitumor efficacy of the produced drugs and reducing drug resistance. As a result, by enhancing the synergistic effect of the treatment, this nanophotosensitizer significantly inhibited the growth of tumors and avoided damage to normal tissues/organs. Collectively, this work highlights a robust nanoplatform with the spatiotemporally controlled in vivo high-yield synthesis of drugs and generation of O2 to help overcome the current limitations of chemical-based therapies against hypoxic tumors.

Diagnostic value of magnetic resonance and computed tomography colonography for the diagnosis of colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Surgical resection is the recommended procedure for colorectal cancer (CRC), but majority of the patients were diagnosed with advanced or metastatic CRC. Currently, there were inconsistent results about the diagnostic value of magnetic resonance colonography (MRC) and computed tomography colonography (CTC) in early CRC diagnosis. Our study conducted this meta-analysis to investigate the diagnostic value of MRC and CTC for CRC surveillance. METHODS: A comprehensive literature search was conducted in PubMed, Embase, and the Cochrane library to select relevant studies. The summary sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curves (AUC) were calculated to evaluate the diagnostic value of MRC and CTC, respectively. RESULT: Twenty-five studies including 2985 individuals were selected in the final analysis. Eight studies evaluated the diagnostic value of MRC, and 17 studies assessed CTC. The summary sensitivity, specificity, PLR, NLR, DOR, and AUC in MRC for early detection of CRC were 0.98 (95% confidence interval, CI: 0.80-1.00), 0.94 (95% CI: 0.85-0.97), 15.48 (95% CI: 6.30-38.04), 0.02 (95% CI: 0.00-0.25), 115.09 (95% CI: 15.37-862.01), and 0.98 (95% CI: 0.97-0.99), respectively. In addition, the sensitivity, specificity, PLR, NLR, DOR, and AUC of CTC for diagnosing CRC were 0.97 (95% CI: 0.88-0.99), 0.99 (95% CI: 0.99-1.00), 154.11 (95% CI: 67.81-350.22), 0.03 (95% CI: 0.01-0.13), 642.51 (95% CI: 145.05-2846.02), and 1.00 (95% CI: 0.99-1.00). No significant differences were found between MRC and CTC for DOR in all the subsets. CONCLUSION: The findings of meta-analysis indicated that MRC and CTC have higher diagnostic values for early CRC diagnosis. However, the DOR for diagnosing CRC between MRC and CTC showed no significance.