Assessment of the influence of levees along Yangtze River on Oncomelania hupensis, the intermediate host of Schistosoma japonicum.

BACKGROUND: Oncomelania hupensis is the exclusive intermediate host of Schistosoma japonicum in China. Snail control is an essential component of schistosomiasis elimination programme. With 70 years of continuous efforts, the range of O. hupensis had reduced significantly, but slowed down in last decades. A large number of levees against flooding were constructed along Yangtze River and its affiliated lakes in the middle and lower reaches, which influenced the hydrology and ecology in the alluvial plains. The purpose of this study was to assess the impact of levees on the distribution of O. hupensis in the middle and lower reaches of the Yangtze River. METHODS: The snail habitats were digitalised by hand-held GPS system. The years for discovery and elimination of snail habitats were extracted from historical records. The accumulated snail-infested range for each habitat was calculated on the basis of annual reports. The current distribution of O. hupensis was determined by systematic and environmental sampling. The geographical distribution of levees was obtained from satellite imagery. To assess the impact of levees, the data pertaining to O. hupensis were divided into two parts: inside and outside the Yangtze River. Joinpoint regression was utilised to divide the study time span and further characterise the regression in each period. The 5-year-period moving averages of eliminated area infested by snails were calculated for the habitats inside and outside Yangtze River. The moving routes of corresponding geographical median centres were simulated in ArcGIS. Hotspot analysis was used to determine the areas with statistical significance clustering of O. hupensis density. RESULTS: Three periods were identified according to Joinpoint regression both inside and outside Yangtze River. The area infested by O. hupensis increased in the first two periods. It decreased rapidly outside Yangtze River year over year after 1970, while that inside the Yangtze River did not change significantly. Furthermore, the latter was significantly higher than the former. It was observed that the present density of O. hupensis inside Yangtze River was lower than outside the Yangtze River. The median centre for eliminated ranges inside Yangtze River wavered between the east (lower reach) and the west (middle reach). In contrast, the median centre for eliminated ranges continuously moved from the east to the west. CONCLUSIONS: Our findings indicated that the levees had a considerable negative impact on the distribution of O. hupensis outside Yangtze River. Some hotspots observed in the irrigation areas need a sluice system at the inlet of branch for snail control. The major distribution of O. hupensis located in Hubei might be caused by severe waterlogging. The intensive surveillance should be implemented there. The biggest two freshwater lakes, the major endemic regions historically, were identified as cold spots. The long-term impact of Three Gorges Dam on the distribution of O. hupensis in the lakes should be monitored and evaluated.

Wetting State Transition of Laser Direct Writing Aluminum Surface Based on Coupling Effect of Micro/Nanoscale Characteristics.

Micro/nanostructured metal surfaces fabricated by laser direct writing (LDW) have been widely used in wettability-related fields. Previous studies focused on the effects of surface structural patterns or chemical composition on wettability, while the coupling mechanism and respective contributions of the two are not distinct. This paper reveals the coupling effect of micro/nanoscale characteristics on the wettability of LDW aluminum surfaces and elucidates the transition mechanism between wetting states on the surfaces with linear laser energy density. Through the contact angle experiments, a wetting state transition of the LDW surface is found from a more hydrophilic than pristine rose petal effect to lotus effect. Based on the bionic analysis method of the superhydrophobicity factors of lotus leaves, the contributions to the wettability of LDW surfaces are divided into the micro/nanoscale characteristics. The theoretical model for identifying the wetting state of a rough surface is proposed. Based on this model, the average Young's contact angle, θ̅Y, is calculated, which indicates the contribution of the nanoscale characteristics. During the transition process from rose petal effect to lotus effect, θ̅Y > 90° is a necessary condition for detachment from the rose petal effect, which is contributed by the high specific surface organic adsorption at the nanoscale. What is more, the wetting state determined by the microscale characteristics further enhances its hydrophobicity, leading to the lotus effect. Based on the wetting state identification model and the Cassie-Baxter equation, the change of micro/nanoscale characteristics on aluminum surfaces after LDW treatment is presented, and the influence of micro/nanoscale characteristics on the wetting state is decoupled and quantified. This research helps to coordinate the effects of surface structure and chemical composition on wettability in the design of specific wettability functional surfaces and can also be applied to other high heat density surface processing fields.

Integration of molecular breeding and multi-resistance screening for developing a promising restorer line Guihui5501 with heavy grain, good grain quality, and endurance to biotic and abiotic stresses.

Rice, a critical staple on a global scale, faces escalating challenges in yield preservation due to the rising prevalence of abiotic and biotic stressors, exacerbated by frequent climatic fluctuations in recent years. Moreover, the scorching climate prevalent in the rice-growing regions of South China poses obstacles to the cultivation of good-quality, heavy-grain varieties. Addressing this dilemma requires the development of resilient varieties capable of withstanding multiple stress factors. To achieve this objective, our study employed the broad-spectrum blast-resistant line Digu, the brown planthopper (BPH)-resistant line ASD7, and the heavy-grain backbone restorer lines Fuhui838 (FH838) and Shuhui527 (SH527) as parental materials for hybridization and multiple crossings. The incorporation of molecular markers facilitated the rapid pyramiding of six target genes (Pi5, Pita, Pid2, Pid3, Bph2, and Wxb ). Through a comprehensive evaluation encompassing blast resistance, BPH resistance, cold tolerance, grain appearance, and quality, alongside agronomic trait selection, a promising restorer line, Guihui5501 (GH5501), was successfully developed. It demonstrated broad-spectrum resistance to blast, exhibiting a resistance frequency of 77.33% against 75 artificially inoculated isolates, moderate resistance to BPH (3.78 grade), strong cold tolerance during the seedling stage (1.80 grade), and characteristics of heavy grains (1,000-grain weight reaching 35.64 g) with good grain quality. The primary rice quality parameters for GH5501, with the exception of alkali spreading value, either met or exceeded the second-grade national standard for premium edible rice varieties, signifying a significant advancement in the production of good-quality heavy-grain varieties in the southern rice-growing regions. Utilizing GH5501, a hybrid combination named Nayou5501, characterized by high yield, good quality, and resistance to multiple stresses, was bred and received approval as a rice variety in Guangxi in 2021. Furthermore, genomic analysis with gene chips revealed that GH5501 possessed an additional 20 exceptional alleles, such as NRT1.1B for efficient nitrogen utilization, SKC1 for salt tolerance, and STV11 for resistance to rice stripe virus. Consequently, the restorer line GH5501 could serve as a valuable resource for the subsequent breeding of high-yielding, good-quality, and stress-tolerant hybrid rice varieties.

Statistical optimal parameters obtained by using clinical human ocular aberrations for high-precision aberration measurement.

PURPOSE: Compared to Shack-Hartmann wavefront sensor (SHWS), the parameters of virtual SHWS (vSHWS) can be easily adjusted to obtain the optimal performance of aberration measurement. Its current optimal parameters are obtained with only a set of statistical aberrations and not statistically significant. Whether the above parameters are consistent with the statistical results of the optimal parameters corresponding to each set of aberrations, and which performance is better if not? The purpose of this study was to answer these questions. METHODS: The optimal parameters to reconstruct 624 sets of clinical ocular aberrations in the highest accuracy, including the numbers of sub-apertures (NSAs) and the expansion ratios (ERs) of electric field zero-padding, were determined sequentially in this work. By using wavefront-reconstruction accuracy as an evaluation index, the statistical optimal parameter configuration was selected from some possible configurations determined by the optimal NSAs and ERs. RESULTS: The statistical optimal parameters are consistent for normal and abnormal eyes. They are different from the optimal parameters obtained with a set of statistical aberrations from the same 624 sets of aberrations, and the performance using the former is better than that using the latter. The performance using a fixed set of statistical optimal parameters is even close to that using the respective optimal parameters corresponding to each set of aberrations. CONCLUSION: The vSHWS configured with a fixed set of statistical optimal parameters can be used for high-precision aberration measurement of both normal and abnormal eyes. The statistical optimal parameters are more suitable for vSHWS than the parameters obtained with a set of statistical aberrations. These conclusions are significant for the designs of vSHWS and also SHWS.

Deciphering the TCF19/miR-199a-5p/SP1/LOXL2 pathway: Implications for breast cancer metastasis and epithelial-mesenchymal transition.

Globally, breast cancer (BC) is the predominant malignancy with a significant death rate due to metastasis. The epithelial-mesenchymal transition (EMT) is a fundamental initiator for metastatic progression. Through advanced computational strategies, TCF19 was identified as a critical EMT-associated gene with diagnostic and prognostic significance in BC, based on a novel EMT score. Molecular details and the pro-EMT impact of the TCF19/miR-199a-5p/SP1/LOXL2 axis were explored in BC cell lines through in vitro validations, and the oncogenic and metastatic potential of TCF19 and LOXL2 were investigated using subcutaneous and tail-vein models. Additionally, BC-specific enrichment of TCF19 and LOXL2 was measured using a distribution landscape driven by diverse genomic analysis techniques. Molecular pathways revealed that TCF19-induced LOXL2 amplification facilitated migratory, invasive, and EMT activities of BC cells in vitro, and promoted the growth and metastatic establishment of xenografts in vivo. TCF19 decreases the expression of miR-199a-5p and alters the nuclear dynamics of SP1, modulating SP1's affinity for the LOXL2 promoter, leading to increased LOXL2 expression and more malignant characteristics in BC cells. These findings unveil a novel EMT-inducing pathway, the TCF19/miR-199a-5P/SP1/LOXL2 axis, highlighting the pivotal role of TCF19 and suggesting potential for novel therapeutic approaches for more focused BC interventions.

Bacillus amyloliquefaciens LM-1 Affects Multiple Cell Biological Processes in Magnaporthe oryzae to Suppress Rice Blast.

Magnaporthe oryzae, one of the most destructive rice pathogens, causes significant losses during the rice harvest every year. Bacillus amyloliquefaciens has been explored in many crops as a potential biocontrol agent. However, the mechanisms of B. amyloliquefaciens controled rice blast are not fully understood. Here, a biocontrol strain LM-1, isolated from a contaminated medium, was identified as B. amyloliquefaciens using morphological observation, physiological and biochemical tests, and 16S rDNA sequencing. LM-1 inhibited the growth and pathogenicity of M. oryzae and Bipolaris oryzae (Breda de Haan) Shoem. The mycelia of M. oryzae co-cultured with LM-1 were enlarged and broken by fluorescence microscopy using calcofluor white. LM-1 inhibited the mycelia of M. oryzae from producing conidia. Genes itu, srf, and fenB were detected in LM-1. Furthermore, the supernatant of LM-1 interfered with the appressorium formation of M. oryzae, blocked conidial cell death, and reduced autophagy degradation but did not affect the normal germination of rice seeds and seeding growth. Additionally, we observed hypersensitivity reactions, reactive oxygen species, and iron accumulation reduction in rice cells inoculated with supernatant. Our study reveals that LM-1 has a control effect on rice blast and affects cell wall integrity, sporulation, appressorium formation, cell death, and autophagy.

Understanding music and aging through the lens of Bayesian inference.

Bayesian inference has recently gained momentum in explaining music perception and aging. A fundamental mechanism underlying Bayesian inference is the notion of prediction. This framework could explain how predictions pertaining to musical (melodic, rhythmic, harmonic) structures engender action, emotion, and learning, expanding related concepts of music research, such as musical expectancies, groove, pleasure, and tension. Moreover, a Bayesian perspective of music perception may shed new insights on the beneficial effects of music in aging. Aging could be framed as an optimization process of Bayesian inference. As predictive inferences refine over time, the reliance on consolidated priors increases, while the updating of prior models through Bayesian inference attenuates. This may affect the ability of older adults to estimate uncertainties in their environment, limiting their cognitive and behavioral repertoire. With Bayesian inference as an overarching framework, this review synthesizes the literature on predictive inferences in music and aging, and details how music could be a promising tool in preventive and rehabilitative interventions for older adults through the lens of Bayesian inference.

Causal relationship between T2DM microvascular complications and gut microbiota: a Mendelian randomization study.

Background: Gowing number of studies have demonstrated the association between gut microbiome and T2DM microvascular complications, however the causal relationship remains unclear. Therefore, we using the Mendelian randomization (MR) approach to investigate this causal relation. Methods: Using gut microbiome data from the International MiBioGen Consortium genome-wide association study (GWAS) and T2DM microvascular complications data from the FinnGen Consortium GWAS to perform MR analyses. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs), the inverse variance weighting (IVW) method was used as the primary analysis method, and the results were tested for heterogeneity and horizontal pleiotropy. Results: Our research identified that there are 5 known microbial species and 2 unknown microbial species in the gut microbiome that were causally related to T2DM retinopathy. Besides, three and seven known microbial species causal relationships between the gut microbiome and T2DM neuropathy and T2DM nephropathy, respectively. Conclusions: Using MR methods, we demonstrated the causal relationship between gut microbiome and microvascular complications in T2DM, providing a new strategy for the prevention and treatment of it.

Genetic Diversity and Natural Selection of Plasmodium vivax Merozoite Surface Protein 8 in Global Populations.

Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) is a promising candidate target for the development of multi-component vaccines. Therefore, determining the genetic variation pattern of Pvmsp8 is essential in providing a reference for the rational design of the P. vivax malaria vaccines. This study delves into the genetic characteristics of the Pvmsp8 gene, specifically focusing on samples from the China-Myanmar border (CMB) region, and contrasts these findings with broader global patterns. The study uncovers that Pvmsp8 exhibits a notable level of conservation across different populations, with limited polymorphisms and relatively low nucleotide diversity (0.00023-0.00120). This conservation contrasts starkly with the high polymorphisms found in other P. vivax antigens such as Pvmsp1. A total of 25 haplotypes and 14 amino acid mutation sites were identified in the global populations, and all mutation sites were confined to non-functional regions. The study also notes that most CMB Pvmsp8 haplotypes are shared among Burmese, Cambodian, Thai, and Vietnamese populations, indicating less geographical variance, but differ notably from those found in Pacific island regions or the Panama. The findings underscore the importance of considering regional genetic diversity in P. vivax when developing targeted malaria vaccines. Non departure from neutral evolution were found by Tajima's D test, however, statistically significant differences were observed between the kn/ks rates. The study's findings are crucial in understanding the evolution and population structure of the Pvmsp8 gene, particularly during regional malaria elimination efforts. The highly conserved nature of Pvmsp8, combined with the lack of mutations in its functional domain, presents it as a promising candidate for developing a broad and effective P. vivax vaccine. This research thus lays a foundation for the rational development of multivalent malaria vaccines targeting this genetically stable antigen.

Improvement of Post-Surgery Constipation in Patients with Fractures by Lactobacillus rhamnosus JYLR-127: A Single-Blind Randomized Controlled Trial.

The high prevalence of constipation after fracture surgery brings intolerable discomfort to patients on the one hand, and affects post-surgery nutrient absorption on the other hand, resulting in poor prognosis. Given the acknowledged probiotic properties of Lactobacillus rhamnosus, 100 fracture patients with post-surgery constipation were centrally enrolled and administered orally with L. rhamnosus JYLR-127 to assess the efficacy of probiotic-adjuvant therapy in alleviating post-fracture constipation symptoms. The results showed that L. rhamnosus JYLR-127 improved fecal properties, promoted gastrointestinal recovery, and relieved constipation symptoms, which were mainly achieved by elevating Firmicutes (p < 0.01) and descending Bacteroidetes (p < 0.001), hence remodeling the disrupted intestinal microecology. In addition, blood routine presented a decrease in C-reactive protein levels (p < 0.05) and an increase in platelet counts (p < 0.05) after probiotic supplementation, prompting the feasibility of L. rhamnosus JYLR-127 in anti-inflammation, anti-infection and hemorrhagic tendency prevention after fracture surgery. Our study to apply probiotics in ameliorating constipation after fracture surgery is expected to bless the bothered patients, and provide broader application scenarios for L. rhamnosus preparations.

Prior COVID-19 vaccination and reduced risk of cerebrovascular diseases among COVID-19 survivors.

The effects of COVID-19 vaccination on short-term and long-term cerebrovascular risks among COVID-19 survivors remained unknown. We conducted a national multi-center retrospective cohort study with 151 597 vaccinated and 151 597 unvaccinated COVID-19 patients using the TriNetX database, from January 1, 2020 to December 31, 2023. Patients baseline characteristics were balanced with propensity score matching (PSM). The outcomes were incident cerebrovascular diseases occurred between 1st and 30th days (short-term) after COVID-19 diagnosis. Nine subgroup analyses were conducted to explore potential effect modifications. We performed six sensitivity analyses, including evaluation of outcomes between 1st to 180th days, accounting for competing risk, and incorporating different variant timeline to test the robustness of our results. Kaplan-Meier curves and Log-Rank tests were performed to evaluate survival difference. Cox proportional hazards regressions were adopted to estimate the PSM-adjusted hazard ratios (HR). The overall short-term cerebrovascular risks were lower in the vaccinated group compared to the unvaccinated group (HR: 0.66, 95% CI: 0.56-0.77), specifically cerebral infarction (HR: 0.62, 95% CI: 0.48-0.79), occlusion and stenosis of precerebral arteries (HR: 0.74, 95% CI: 0.53-0.98), other cerebrovascular diseases (HR: 0.57, 95% CI: 0.42-0.77), and sequelae of cerebrovascular disease (HR: 0.39, 95% CI:0.23-0.68). Similarly, the overall cerebrovascular risks were lower in those vaccinated among most subgroups. The long-term outcomes, though slightly attenuated, were consistent (HR: 0.80, 95% CI: 0.73-0.87). Full 2-dose vaccination was associated with a further reduced risk of cerebrovascular diseases (HR: 0.63, 95% CI: 0.50-0.80) compared to unvaccinated patients. Unvaccinated COVID-19 survivors have significantly higher cerebrovascular risks than their vaccinated counterparts. Thus, clinicians are recommended to monitor this population closely for stroke events during postinfection follow-up.

Identification and characterisation of functional Kir6.1-containing ATP-sensitive potassium channels in the cardiac ventricular sarcolemmal membrane.

BACKGROUND AND PURPOSE: The canonical Kir6.2/SUR2A ventricular KATP channel is highly ATP-sensitive and remains closed under normal physiological conditions. These channels activate only when prolonged metabolic compromise causes significant ATP depletion and then shortens the action potential to reduce contractile activity. Pharmacological activation of KATP channels is cardioprotective, but physiologically, it is difficult to understand how these channels protect the heart if they only open under extreme metabolic stress. The presence of a second KATP channel population could help explain this. Here, we characterise the biophysical and pharmacological behaviours of a constitutively active Kir6.1-containing KATP channel in ventricular cardiomyocytes. EXPERIMENTAL APPROACH: Patch-clamp recordings from rat ventricular myocytes in combination with well-defined pharmacological modulators was used to characterise these newly identified K+ channels. Action potential recording, calcium (Fluo-4) fluorescence measurements and video edge detection of contractile function were used to assess functional consequences of channel modulation. KEY RESULTS: Our data show a ventricular K+ conductance whose biophysical characteristics and response to pharmacological modulation were consistent with Kir6.1-containing channels. These Kir6.1-containing channels lack the ATP-sensitivity of the canonical channels and are constitutively active. CONCLUSION AND IMPLICATIONS: We conclude there are two functionally distinct populations of ventricular KATP channels: constitutively active Kir6.1-containing channels that play an important role in fine-tuning the action potential and Kir6.2/SUR2A channels that activate with prolonged ischaemia to impart late-stage protection against catastrophic ATP depletion. Further research is required to determine whether Kir6.1 is an overlooked target in Comprehensive in vitro Proarrhythmia Assay (CiPA) cardiac safety screens.

Association Between Liver Fibrosis Score and Diabetic Kidney Disease: A Retrospective Cross-Sectional Study of Hospitalized Patients.

OBJECTIVES: To investigate the association between liver fibrosis score and diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). METHODS: A total of 897 hospitalized patients with T2DM were included in this study. Each patient completed DKD screening. Logistic regression analysis was used to assess the predictive value of non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) for the occurrence of DKD and risk for DKD progression, respectively. RESULTS: The prevalence of DKD and risk for its progression significantly increased with increasing NAFLD-FS risk category. DKD prevalence also increased with increasing FIB-4 risk category. Multivariate logistic regression analysis showed that the "high-risk" NAFLD-FS had a significantly higher risk of DKD (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.16-3.08) and risk for DKD progression (OR: 2.88, 95% CI: 1.23-6.78), and the "intermediate-risk" FIB-4 had a significantly higher risk of DKD (OR: 1.41, 95% CI: 1.00-1.98). Subgroup analysis showed that the association between NAFLD-FS and FIB-4 and DKD was significant in the female subgroup, whereas the association between the "high-risk" NAFLD-FS and risk for DKD progression was significant in the male subgroup. CONCLUSIONS: NAFLD-FS and FIB-4 are strongly associated with DKD and risk for DKD progression in patients with T2DM. Additionally, sexual dimorphism exists in this association.

Effects of Supplemental Lighting on Flavonoid and Anthocyanin Biosynthesis in Strawberry Flesh Revealed via Metabolome and Transcriptome Co-Analysis.

The spectral composition of light influences the biosynthesis of flavonoids in many plants. However, the detailed composition of flavonoids and anthocyanins and the molecular basis for their biosynthesis in strawberry fruits under two light-quality treatments, red light supplemented with blue light (RB) and ultraviolet B (UVB) irradiation, remain unclear. In this study, the content of flavonoids and anthocyanins was significantly increased in strawberry fruits under RB light and UVB, respectively. The content of flavonoids and anthocyanins in strawberry fruits under UVB light was dramatically higher than that in strawberry fruits irradiated with RB light, and a total of 518 metabolites were detected by means of LC-MS/MS analysis. Among them, 18 phenolic acids, 23 flavonoids, and 8 anthocyanins were differentially accumulated in the strawberry fruits irradiated with red/blue (RB) light compared to 30 phenolic acids, 46 flavonoids, and 9 anthocyanins in fruits irradiated with UVB. The major genes associated with the biosynthesis of flavonoids and anthocyanins, including structural genes and transcription factors (TFs), were differentially expressed in the strawberry fruits under RB and UVB irradiation, as determined through RNA-seq data analysis. A correlation test of transcriptome and metabolite profiling showed that the expression patterns of most genes in the biosynthesis pathway of flavonoids and anthocyanins were closely correlated with the differential accumulation of flavonoids and anthocyanins. Two TFs, bZIP (FvH4_2g36400) and AP2 (FvH4_1g21210), induced by RB and UVB irradiation, respectively, exhibited similar expression patterns to most structural genes, which were closely correlated with six and eight flavonoids, respectively. These results indicated that these two TFs regulated the biosynthesis of flavonoids and anthocyanins in strawberry fruit under RB light and UVB, respectively. These results provide a systematic and comprehensive understanding of the accumulation of flavonoids and anthocyanins and the molecular basis for their biosynthesis in strawberry fruits under RB light and UVB.

Analysis of Ethylene Signal Regulating Sucrose Metabolism in Strawberry Fruits Based on RNA-seq.

Ethylene is a key hormone that regulates the maturation and quality formation of horticultural crops, but its effects on non-respiratory climacteric fruits such as strawberries are not yet clear. In this study, strawberry fruits were treated with exogenous ethephon (ETH) and 1-methylcyclopropene (1-MCP). It was found that ETH treatment increased the soluble solids and anthocyanin content of the fruits, reduced hardness, and decreased organic acid content, while 1-MCP treatment inhibited these processes. Transcriptome analysis revealed that differentially expressed genes (DEGs) were enriched in the starch-sucrose metabolism pathway. qRT-PCR results further showed significant changes in the expression levels of sucrose metabolism genes, confirming the influence of ethylene signals on soluble sugar accumulation during strawberry fruit development. This study elucidates the quality changes and molecular mechanisms of ethylene signal in the development of strawberry fruits, providing some key targets and theoretical support for guiding strawberry cultivation and variety improvement.

Influence of Two Hexose Transporters on Substrate Affinity and Pathogenicity in Magnaporthe oryzae.

Hexose transporters (HXT) play a crucial role in the pathogenicity of Magnaporthe oryzae, serving not only as key facilitators for acquiring and transporting sugar nutrients to support pathogen development, but also as sugar sensors which receive transduction signals. The objective of this study is to investigate the impact of MoHXT1-3 on rice pathogenicity and hexose affinity. MoHXT1-3 deletion mutants were generated using CRISPR/Cas9 technology, and their affinity for hexose was evaluated through yeast complementation assays and electrophysiological experiments in Xenopus oocytes. The results suggest that MoHXT1 does not contribute to melanin formation or hexose transportation processes. Conversely, MoHXT2, despite displaying lower affinity towards the hexoses tested in comparison to MoHXT3, is likely to have a more substantial impact on pathogenicity. The analysis of the transcription profiles demonstrated that the deletion of MoHXT2 caused a decrease in the expression of MoHXT3, whereas the knockout of MoHXT3 resulted in an upregulation of MoHXT2 transcription. It is noteworthy that the MoHXT2M145K variant displayed an incapacity to transport hexoses. This investigation into the functional differences in hexose transporters in Magnaporthe oryzae provides insights into potential advances in new strategies to target hexose transporters to combat rice blast by blocking carbon nutrient supply.

Specific CpG sites methylation is associated with hematotoxicity in low-dose benzene-exposed workers.

Benzene is a broadly used industrial chemicals which causes various hematologic abnormalities in human. Altered DNA methylation has been proposed as epigenetic biomarkers in health risk evaluation of benzene exposure, yet the role of methylation at specific CpG sites in predicting hematological effects remains unclear. In this study, we recruited 120 low-level benzene-exposed and 101 control male workers from a petrochemical factory in Maoming City, Guangdong Province, China. Urinary S-phenylmercapturic acid (SPMA) in benzene-exposed workers was 3.40-fold higher than that in control workers (P < 0.001). Benzene-induced hematotoxicity was characterized by reduced white blood cells counts and nuclear division index (NDI), along with an increased DNA damage and urinary 8-hydroxy-2'-deoxyguanosine (all P < 0.05). Methylation levels of TRIM36, MGMT and RASSF1a genes in peripheral blood lymphocytes (PBLCs) were quantified by pyrosequencing. CpG site 6 of TRIM36, CpG site 2, 4, 6 of RASSF1a and CpG site 1, 3 of MGMT methylation were recognized as hot CpG sites due to a strong correlation with both internal exposure and hematological effects. Notably, integrating hot CpG sites methylation of multiple genes reveal a higher efficiency in prediction of integrative damage compared to individual genes at hot CpG sites. The negative dose-response relationship between the combined methylation of hot CpG sites in three genes and integrative damage enabled the classification of benzene-exposed individuals into high-risk or low-risk groups using the median cut-off value of the integrative index. Subsequently, a prediction model for integrative damage in benzene-exposed populations was built based on the methylation status of the identified hot CpG sites in the three genes. Taken together, these findings provide a novel insight into application prospect of specific CpG site methylation as epi-biomarkers for health risk assessment of environmental pollutants.

MyoD Over-Expression Rescues GST-bFGF Repressed Myogenesis.

During embryogenesis, basic fibroblast growth factor (bFGF) is released from neural tube and myotome to promote myogenic fate in the somite, and is routinely used for the culture of adult skeletal muscle (SKM) stem cells (MuSC, called satellite cells). However, the mechanism employed by bFGF to promote SKM lineage and MuSC proliferation has not been analyzed in detail. Furthermore, the question of if the post-translational modification (PTM) of bFGF is important to its stemness-promoting effect has not been answered. In this study, GST-bFGF was expressed and purified from E.coli, which lacks the PTM system in eukaryotes. We found that both GST-bFGF and commercially available bFGF activated the Akt-Erk pathway and had strong cell proliferation effect on C2C12 myoblasts and MuSC. GST-bFGF reversibly compromised the myogenesis of C2C12 myoblasts and MuSC, and it increased the expression of Myf5, Pax3/7, and Cyclin D1 but strongly repressed that of MyoD, suggesting the maintenance of myogenic stemness amid repressed MyoD expression. The proliferation effect of GST-bFGF was conserved in C2C12 over-expressed with MyoD (C2C12-tTA-MyoD), implying its independence of the down-regulation of MyoD. In addition, the repressive effect of GST-bFGF on myogenic differentiation was almost totally rescued by the over-expression of MyoD. Together, these evidences suggest that (1) GST-bFGF and bFGF have similar effects on myogenic cell proliferation and differentiation, and (2) GST-bFGF can promote MuSC stemness and proliferation by differentially regulating MRFs and Pax3/7, (3) MyoD repression by GST-bFGF is reversible and independent of the proliferation effect, and (4) GST-bFGF can be a good substitute for bFGF in sustaining MuSC stemness and proliferation.

In-situ growth of MOF-derived Co3S4@MoS2 heterostructured electrocatalyst for the detection of furazolidone.

The over-exploitation of antibiotics in food and farming industries ruined the environmental and human health. Consequently, electrochemical sensors offer significant advantages in monitoring these compounds with high accuracy. Herein, MOF-derived hollow Co3S4@MoS2 (CS@MS) heterostructure has been prepared hydrothermally and applied to fabricate an electrochemical sensor to monitor nitrofuran class antibiotic drug. Various spectroscopic methodologies have been employed to elucidate the structural and morphological information. Our prepared electrocatalyst has better electrocatalytic performance than bare and other modified glassy carbon electrodes (GCE). Our CS@MS/GCE sensor exhibited a highly sensitive detection by offering a low limit of detection, good sensitivity, repeatability, reproducibility, and stability results. In addition, our sensor has shown a good selectivity towards the target analyte among other potential interferons. The practical reliability of the sensor was measured by analyzing various real-time environmental and biological samples and obtaining good recovery values. From the results, our fabricated CS@MS could be an active electrocatalyst material for an efficient electrochemical sensing application.

Single-cell transcriptomics reveal metastatic CLDN4+ cancer cells underlying the recurrence of malignant pleural effusion in patients with advanced non-small-cell lung cancer.

BACKGROUND: Recurrent malignant pleural effusion (MPE) resulting from non-small-cell lung cancer (NSCLC) is easily refractory to conventional therapeutics and lacks predictive markers. The cellular or genetic signatures of recurrent MPE still remain largely uncertain. METHODS: 16 NSCLC patients with pleural effusions were recruited, followed by corresponding treatments based on primary tumours. Non-recurrent or recurrent MPE was determined after 3-6 weeks of treatments. The status of MPE was verified by computer tomography (CT) and cytopathology, and the baseline pleural fluids were collected for single-cell RNA sequencing (scRNA-seq). Samples were then integrated and profiled. Cellular communications and trajectories were inferred by bioinformatic algorithms. Comparative analysis was conducted and the results were further validated by quantitative polymerase chain reaction (qPCR) in a larger MPE cohort from the authors' centre (n = 64). RESULTS: The scRNA-seq revealed that 33 590 cells were annotated as 7 major cell types and further characterized into 14 cell clusters precisely. The cell cluster C1, classified as Epithelial Cell Adhesion Molecule (EpCAM)+ metastatic cancer cell and correlated with activation of tight junction and adherence junction, was significantly enriched in the recurrent MPE group, in which Claudin-4 (CLDN4) was identified. The subset cell cluster C3 of C1, which was enriched in recurrent MPE and demonstrated a phenotype of ameboidal-type cell migration, also showed a markedly higher expression of CLDN4. Meanwhile, the expression of CLDN4 was positively correlated with E74 Like ETS Transcription Factor 3 (ELF3), EpCAM and Tumour Associated Calcium Signal Transducer 2 (TACSTD2), independent of driver-gene status. CLDN4 was also found to be associated with the expression of Hypoxia Inducible Factor 1 Subunit Alpha (HIF1A) and Vascular Endothelial Growth Factor A (VEGFA), and the cell cluster C1 was the major mediator in cellular communication of VEGFA signalling. In the extensive MPE cohort, a notably increased expression of CLDN4 in cells from pleural effusion among patients diagnosed with recurrent MPE was observed, compared with the non-recurrent group, which was also associated with a trend towards worse overall survival (OS). CONCLUSIONS: CLDN4 could be considered as a predictive marker of recurrent MPE among patients with advanced NSCLC. Further validation for its clinical value in cohorts with larger sample size and in-depth mechanism studies on its biological function are warranted. TRIAL REGISTRATION: Not applicable.