Effects of artificial management on culm properties of Dendrocalamus brandisii.

The artificial cultivation and management were extensively carried out in Dendrocalamus brandisii stands. However, the influences of artificial management on the anatomical and chemical characteristics of the bamboo culms were unknown. In this study, the fiber morphology, chemical composition and sugar accumulation of the D. brandisii culms with management and without management were compared in order to determine the influences of artificial management on bamboo culms. The results indicated that artificial management had a significant influence on the fiber morphology, resulting in shorter fiber length, larger L/T ratio, and smaller W/Lu value. However, the management not only increased the contents of moisture, ash, SiO2, and extractive, but also increased the holocellulose contents and decreased the lignin contents, as compared to those without management. Moreover, the management significantly increased the endogenous carbohydrates storage in the culms so as to improve the shoot production. The bamboos under management conditions could still be utilized as a raw material for papermaking. This provided a theoretical basis for the artificial management of D. brandisii stands.

Color-coded parametric imaging support display of vessel hemorrhage-an in vitro experiment and clinical validation study.

Background: Digital Subtraction Angiography (DSA) is currently the most effective diagnostic method for vascular diseases, but it is still subject to various factors, resulting in uncertain diagnosis. Therefore, a new technology is needed to help clinical doctors improve diagnostic accuracy and efficiency. Purpose: The objective of the study was to investigate the effect of utilizing color-coded parametric imaging techniques on the accuracy of identifying active bleeding through DSA, the widely accepted standard for diagnosing vascular disorders. Methods: Several variables can delay the diagnosis and treatment of active bleeding with DSA. To resolve this, we carried out an in vitro simulation experiment to simulate vascular hemorrhage and utilized five color-coded parameters (area under curve, time to peak, time-of-arrival, transit time, and flow rate of contrast agent) to determine the optimal color coding parameters. We then verified it in a clinical study. Results: Five different color-coded parametric imaging methods were compared and the time-of-arrival color coding was the most efficient technique for diagnosing active hemorrhage, with a statistically significant advantage (P < 0.001). In clinical study, 135 patients (101 with confirmed bleeding and 34 with confirmed no bleeding) were collected. For patients whose bleeding could not be determined using DSA alone (55/101) and whose no bleeding could not be diagnosed by DSA alone (35/55), the combination of time-of-arrival color parametric imaging was helpful for diagnosis, with a statistically significant difference (P < 0.01 and P = 0.01). Conclusions: The time-of-arrival color coding imaging method is a valuable tool for detecting active bleeding. When combined with DSA, it improves the visual representation of active hemorrhage and improves the efficiency of diagnosis.

Dynamic memristor for physical reservoir computing.

Reservoir computing (RC) has attracted considerable attention for its efficient handling of temporal signals and lower training costs. As a nonlinear dynamic system, RC can map low-dimensional inputs into high-dimensional spaces and implement classification using a simple linear readout layer. The memristor exhibits complex dynamic characteristics due to its internal physical processes, which renders them an ideal choice for the implementation of physical reservoir computing (PRC) systems. This review focuses on PRC systems based on memristors, explaining the resistive switching mechanism at the device level and emphasizing the tunability of their dynamic behavior. The development of memristor-based reservoir computing systems is highlighted, along with discussions on the challenges faced by this field and potential future research directions.

Prevalence of subthreshold depression and its related factors in Chinese college students: A cross-sectional study.

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

Activation of Piezo1 or TRPV2 channels inhibits human ureteral contractions via NO release from the mucosa.

We aimed to investigate the expression and motor modulatory roles of several mechano-sensitive channels (MSCs) in human ureter. Human proximal ureters were obtained from eighty patients subjected to nephrectomy. Expression of MSCs at mRNA, protein and functional levels were examined. Contractions of longitudinal ureter strips were recorded in organ bath. A fluorescent probe Diaminofluoresceins was used to measure nitric oxide (NO). RT-PCR analyses revealed predominant expression of Piezo1 and TRPV2 mRNA in intact ureter and mucosa. Immunofluorescence assays indicate proteins of MSCs (Piezo1/Piezo2, TRPV2 and TRPV4) were mainly distributed in the urothelium. Ca2+ imaging confirmed functional expression of TRPV2, TRPV4 and Piezo1 in cultured urothelial cells. Specific agonists of Piezo1 (Yoda1, 3-300 µM) and TRPV2 (cannabidiol, 3-300 µM) attenuated the frequency of ureteral contractions in a dose-dependent manner while the TRPV4 agonist GSK1016790A (100 nM-1 µM) exerted no effect. The inhibitory effects of Piezo1 and TRPV2 agonists were significantly blocked by the selective antagonists (Dooku 1 for Piezo1, Tranilast for TRPV2), removal of the mucosa, and pretreatment with NO synthase inhibitor L-NAME (10 µM). Yoda1 (30 µM) and cannabidiol (50 µM) increased production of NO in cultured urothelial cells. Our results suggest that activation of Piezo1 or TRPV2 evokes NO production and release from mucosa that may mediate mechanical stimulus-induced reduction of ureter contractions. Our findings support the idea that targeting Piezo1 and TRPV2 channels may be a promising pharmacological strategy for ureter stone passage or colic pain relief.

Integrative analysis identifies region- and sex-specific gene networks and Mef2c as a mediator of anxiety-like behavior.

The molecular mechanisms underlying multi-brain region origins and sexual dimorphism of anxiety remain unclear. Here, we leverage large-scale transcriptomics from seven brain regions in mouse models of anxiety and extensive experiments to dissect brain-region- and sex-specific gene networks. We identify 4,840 genes with sex-specific expression alterations across seven brain regions, organized into ten network modules with sex-biased expression patterns. Modular analysis prioritizes 86 sex-specific mediators of anxiety susceptibility, including myocyte-specific enhancer factor 2c (Mef2c) in the CA3 region of male mice. Mef2c expression is decreased in the pyramidal neurons (PyNs) of susceptible male mice. Up-regulating Mef2c in CA3 PyNs significantly alleviates anxiety-like behavior, whereas down-regulating Mef2c induces anxiety-like behavior in male mice. The anxiolytic effect of Mef2c up-regulation is associated with enhanced neuronal excitability and synaptic transmission. In summary, this study uncovers brain-region- and sex-specific networks and identifies Mef2c in CA3 PyNs as a critical mediator of anxiety in male mice.

Bacteroides fragilis alleviates necrotizing enterocolitis through restoring bile acid metabolism balance using bile salt hydrolase and inhibiting FXR-NLRP3 signaling pathway.

Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants with no specific treatments available. We aimed to identify the molecular mechanisms underlying NEC and investigate the therapeutic effects of Bacteroides fragilis on NEC. Clinical samples of infant feces, bile acid-targeted metabolomics, pathological staining, bioinformatics analysis, NEC rat model, and co-immunoprecipitation were used to explore the pathogenesis of NEC. Taxonomic characterization of the bile salt hydrolase (bsh) gene, enzyme activity assays, 16S rRNA sequencing, and organoids were used to explore the therapeutic effects of B. fragilis on NEC-related intestinal damage. Clinical samples, NEC rat models, and in vitro experiments revealed that total bile acid increased in the blood but decreased in feces. Moreover, the levels of FXR and other bile acid metabolism-related genes were abnormal, resulting in disordered bile acid metabolism in NEC. Taurochenodeoxycholic acid accelerated NEC pathogenesis and taurodeoxycholate alleviated NEC. B. fragilis displayed bsh genes and enzyme activity and alleviated intestinal damage by restoring gut microbiota dysbiosis and bile acid metabolism abnormalities by inhibiting the FXR-NLRP3 signaling pathway. Our results provide valuable insights into the therapeutic role of B. fragilis in NEC. Administering B. fragilis may substantially alleviate intestinal damage in NEC.

The regulation pathways of biochar and microorganism in soil-plant system by multiple statistical methods: the forms of carbon participation in coastal wetlands.

Coastal wetlands possess significant carbon storage capabilities. However, in coastal soil-plant systems augmented with biochar and microorganisms, the mechanisms of these amendments and carbon participation remain unclear. This study utilized pot experiments to explore how Enteromorpha prolifera biochar and Arbuscular mycorrhizal fungi (AMF) affect soil organic carbon (SOC), carbon-related microbes, photosynthetic and osmotic system of Suaeda salsa. The results showed biochar reduced exchangeable sodium percentage by 6.9% through adsorption and ion exchange, and increased SOC content by 34.4%. The abundance of carbon-related microorganisms (Bacteroidota and Chloroflexi) was increased and carbon metabolizing enzyme (cellulase and sucrase) activity in the soil was enhanced. AMF significantly improved plant growth compared with CK, as evidenced by the enhanced dry weight by 2.34 times. A partial least squares pathway model (PLS-PM) and correlation analysis suggested that the combined effect of biochar and AMF could be outlined as two pathways: soil and plant. Biochar increased SOC, improved the growth of soil carbon metabolizing microorganisms, and further promoted the activity of carbon-related enzymes. Additionally, AMF facilitated nutrient absorption by plants through root symbiosis, with biochar further enhancing this process by acting as a nutrient adsorber. These combined effects of biochar and AMF at soil and plant level enhanced the photosynthetic process of Suaeda salsa. The transport of photosynthetic products to the roots can increase the carbon storage in the soil. This study provides quantitative evidence supporting the increase of carbon storage in coastal wetland soil-plant systems through a combined application of biochar and AMF.

Ferric citrate enhanced bioreduction of Cr(VI) by Bacillus cereus RCr in aqueous solutions: reduction performance and mechanisms.

The bioreduction characteristics and mechanisms of Cr(VI) onto Bacillus cereus RCr enhanced by ferric citrate were investigated. The optimum conditions were initial pH 9, temperature 40 °C, inoculation amount 4%, and glucose 3 g/L, respectively. The addition of 1.5 g/L ferric citrate increased the average reduction rate from 120.43 to 220.61 mg/(L∙h) compared with the control (without ferric citrate). The binding capacity of Cr(III) on the cell surface increased to 21%, in which the precipitates were mainly CrO(OH), Cr2O3, and FeCr2O4. Cell membrane was the main site of reduction, related important functional groups: - COOH, C-H, - NH2, C = C, and P-O. Fe(III) increased the yield of NADH and cytochrome c by approximately 48.51% and 68.63%, which significantly facilitated the electron generation and electron transfer, thus increasing the amount of electrons in the bioreduction of heavy metals by an average of 110%. Among the electrons obtained by Cr(VI), the proportion of indirect reduction mediated by Fe(III)/Fe(II) shuttle was 62% on average, whereas direct reduction mediated by reductase was 38%. These results may provide insights into the bioreduction process by bacteria enhanced by Fe(III) for detoxification of heavy metals with multiple valences, as an important step towards improving microbial remediation.

MaMYBR30, a Novel 1R-MYB, Plays Important Roles in Plant Development and Abiotic Stress Resistance.

The V-myb myeloblastosis viral oncogene homolog (MYB) family participate in various bioprocesses including development and abiotic stress responses. In the present study, we first report a 1R SHAQKYF-class MYB, MaMYBR30, in mulberry. Subcellular localization and sequence analysis indicated MaMYBR30 is located in the nucleus and belongs to a CCA-like subgroup with a conserved SHAQKYF motif. Expression profile analysis showed that MaMYBR30 is expressed in leaves and can be induced by drought and salt stress. The down-regulation of MaMYBR30 using virus-induced gene silence (VIGS) in mulberry and the overexpression of MaMYBR30 in Arabidopsis were induced to explore the function of MaMYBR30. The functional characterization of MaMYBR30 in vivo indicated that MaMYBR30 can positively regulate the resistance of mulberry to drought while negatively regulating the resistance of mulberry to salt stress. In addition, MaMYBR30 also affects flower development and reproductive growth, especially after exposure to salt stress. Weighted gene co-expression network analysis (WGCNA) primarily revealed the possible genes and signal pathways that are regulated by MaMYBR30. Our results also imply that complex molecular mechanisms mediated by MaMYBR30, including crosstalk of ion toxicity, phytohormone signal transduction, flowering development, and epigenetic modification, need to be further explored in the future.

Generation of attosecond gigawatt soft x-ray pulses through coherent Thomson backscattering.

Collision between relativistic electron sheets and counterpropagating laser pulses is recognized as a promising way to produce intense attosecond x rays through coherent Thomson backscattering (TBS). In a double-layer scheme, the electrons in an ultrathin solid foil are first pushed out by an intense laser driver and then interact with the laser reflected off a second foil to form a high-density relativistic electron sheet with vanishing transverse momentum. However, the repulsion between these concentrated electrons can increase the thickness of the layer, reducing both its density and subsequently the coherent TBS. Here, we present a systematic study on the evolution of the flying electron layer and find that its resulting thickness is determined by the interplay between the intrinsic space-charge expansion and the velocity compression induced by the drive laser. How the laser driver, the target areal density, the reflector, and the collision laser intensity affect the properties of the produced x rays is explored. Multidimensional particle-in-cell simulations indicate that employing this scheme in the nonlinear regime has the potential to stably produce soft x rays with several gigawatt peak power in hundreds of terawatt ultrafast laser facilities. The pulse duration can be tuned to tens of attoseconds. This compact and intense attosecond x-ray source may have broad applications in attosecond science.

Chromatin accessibility and transcriptional landscape in PK-15 cells during early exposure to Aflatoxin B1.

Aflatoxin B1 (AFB1) not only causes significant losses in livestock production but also poses a serious threat to human health. It is the most carcinogenic among known chemicals. Pigs are more susceptible to AFB1 and experience a higher incidence. However, the molecular mechanism of the toxic effect of AFB1 remains unclear. In this study, we used assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA-seq to uncover chromatin accessibility and gene expression dynamics in PK-15 cells during early exposure to AFB1. We observed that the toxic effects of AFB1 involve signaling pathways such as p53, PI3K-AKT, Hippo, MAPK, TLRs, apoptosis, autophagy, and cancer pathways. Basic leucine zipper (bZIP) transcription factors (TFs), including AP-1, Fos, JunB, and Fra2, play a crucial role in regulating the biological processes involved in AFB1 challenge. Several new TFs, such as BORIS, HNF1b, Atf1, and KNRNPH2, represent potential targets for the toxic mechanism of AFB1. In addition, it is crucial to focus on the concentration of intracellular zinc ions. These findings will contribute to a better understanding of the mechanisms underlying AFB1-induced nephrotoxicity and offer new molecular targets.

Visible-Light-Mediated Activation of Remote C(sp3)-H Bonds by Carbon-Centered Biradical via Intramolecular 1,5- or 1,6-Hydrogen Atom Transfer.

In this study, we introduce a novel intramolecular hydrogen atom transfer (HAT) reaction that efficiently yields azetidine, oxetane, and indoline derivatives through a mechanism resembling the carbon analogue of the Norrish-Yang reaction. This process is facilitated by excited triplet-state carbon-centered biradicals, enabling the 1,5-HAT reaction by suppressing the critical 1,4-biradical intermediates from undergoing the Norrish Type II cleavage reaction, and pioneering unprecedented 1,6-HAT reactions initiated by excited triplet-state alkenes. We demonstrate the synthetic utility and compatibility of this method across various functional groups, validated through scope evaluation, large-scale synthesis, and derivatization. Our findings are supported by control experiments, deuterium labeling, kinetic studies, cyclic voltammetry, Stern-Volmer experiments, and density functional theory (DFT) calculations.

Carbon monoxide polyhemoglobin improves the therapeutic effect and relieves inflammation in the colon tissue of haemorrhagic shock/resuscitation rats.

OBJECTIVE: The objective of this study was to test the therapeutic effect of carbon monoxide polyhemoglobin (polyCOHb) in haemorrhagic shock/resuscitation and its underlying mechanisms. METHODS: 48 rats were divided into two experimental parts, and 36 rats in the first experiment and 12 rats in the second experiment. In the first experimental part, 36 animals were randomly assigned to the following groups: hydroxyethyl starch group (HES group, n = 12), polyhemoglobin group (polyHb group, n = 12), and carbon monoxide polyhemoglobin group (polyCOHb group, n = 12). In the second experimental part, 12 animals were randomly assigned to the following groups: polyHb group (n = 6), and polyCOHb group (n = 6). Then the anaesthetised rats were haemorrhaged by withdrawing 50% of the animal's blood volume (BV), and resuscitated to the same volume of the animal's withdrawing BV with HES, polyHb, polyCOHb. In the first experimental part, the 72h survival rates of each groups animals were measured. In the second experimental part, the rats' mean arterial pressure (MAP), heart rate (HR), blood gas levels and other indicators were dynamically monitored in baseline, haemorrhagic shock (HS), at 0point resuscitation (RS 0h) and after 1 h resuscitation (RS 1h). The concentrations of malondialdehyde (MDA), superoxide dismutase (SOD), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by ELISA kits in both groups of rats at RS 1h. Changes in pathological sections were examined by haematoxylin-eosin (HE) staining. Nuclear factor erythroid 2-related factor 2 (Nrf2) and haem oxygenase-1 (HO-1) levels were detected by immunohistochemical analysis, while myeloperoxidase (MPO) levels were detected by immunofluorescence. DHE staining was used to determine reactive oxygen species (ROS) levels. RESULTS: The 72h survival rates of the polyHb and polyCOHb groups were 50.00% (6/12) and 58.33% (7/12) respectively, which were significantly higher than that of the 8.33% (1/12) in the HES group (p < 0.05). At RS 0h and RS 1h, the HbCO content of rats in the polyCOHb group (1.90 ± 0.21, 0.80 ± 0.21) g/L were higher than those in the polyHb group (0.40 ± 0.09, 0.50 ± 0.12)g/L (p < 0.05); At RS 1h, the MDA (41.47 ± 3.89 vs 34.17 ± 3.87 nmol/ml) in the plasma, Nrf2 and HO-1 content in the colon of rats in the polyCOHb group were lower than the polyHb group. And the SOD in the plasma (605.01 ± 24.46 vs 678.64 ± 36.37) U/mg and colon (115.72 ± 21.17 vs 156.70 ± 21.34) U/mg and the MPO content in the colon in the polyCOHb group were higher than the polyHb group (p < 0.05). CONCLUSIONS: In these haemorrhagic shock/resuscitation models, both polyCOHb and polyHb show similar therapeutic effects, and polyCOHb has more effective effects in maintaining MAP, correcting acidosis, reducing inflammatory responses than that in polyHb.

Pharmacometrics-Enabled DOse OPtimization (PEDOOP) for seamless phase I-II trials in oncology.

We consider a dose-optimization design for a first-in-human oncology trial that aims to identify a suitable dose for late-phase drug development. The proposed approach, called the Pharmacometrics-Enabled DOse OPtimization (PEDOOP) design, incorporates observed patient-level pharmacokinetics (PK) measurements and latent pharmacodynamics (PD) information for trial decision-making and dose optimization. PEDOOP consists of two seamless phases. In phase I, patient-level time-course drug concentrations, derived PD effects, and the toxicity outcomes from patients are integrated into a statistical model to estimate the dose-toxicity response. A simple dose-finding design guides dose escalation in phase I. At the end of the phase I dose finding, a graduation rule is used to assess the safety and efficacy of all the doses and select those with promising efficacy and acceptable safety for a randomized comparison against a control arm in phase II. In phase II, patients are randomized to the selected doses based on a fixed or adaptive randomization ratio. At the end of phase II, an optimal biological dose (OBD) is selected for late-phase development. We conduct simulation studies to assess the PEDOOP design in comparison to an existing seamless design that also combines phases I and II in a single trial.

Advancements in enzymatic biotransformation and bioactivities of rare ginsenosides: A review.

Ginsenoside, the principal active constituent of ginseng, exhibits enhanced bioavailability and medicinal efficacy in rare ginsenosides compared to major ginsenosides. Current research is focused on efficiently and selectively removing sugar groups attached to the major ginsenoside sugar chains to convert them into rare ginsenosides that meet the demands of medical industry and functional foods. The methods for preparing rare ginsenosides encompass chemical, microbial, and enzymatic approaches. Among these, the enzyme conversion method is highly favored by researchers due to its exceptional specificity and robust efficiency. This review summarizes the biological activities of different rare ginsenosides, explores the various glycosidases used in the biotransformation of different major ginsenosides as substrates, and elucidates their respective corresponding biotransformation pathways. These findings will provide valuable references for the development, utilization, and industrial production of ginsenosides.

Polydopamine modified multifunctional carboxymethyl chitosan/pectin hydrogel loaded with recombinant human epidermal growth factor for diabetic wound healing.

The development of a multifunctional wound dressing that can adapt to the shape of wounds and provide controlled drug release is crucial for diabetic patients. This study developed a carboxymethyl chitosan-based hydrogel dressing with enhanced mechanical properties and tissue adherence that were achieved by incorporating pectin (PE) and polydopamine (PDA) and loading the hydrogel with recombinant human epidermal growth factor (rhEGF). This EGF@PDA-CMCS-PE hydrogel demonstrated robust tissue adhesion, enhanced mechanical properties, and superior water retention and vapor permeability. It also exhibited significant antioxidant capacity. The results showed that EGF@PDA-CMCS-PE could effectively scavenge 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate)， (1,1-diphenyl-2-picrylhydrazyl), and superoxide anions and increase superoxide dismutase and catalase levels in vivo. In vitro cytotoxicity and antibacterial assays showed good biocompatibility and antimicrobial properties. The sustained release of EGF by the hydrogel was confirmed, with a gradual release profile over 120 h. In vivo studies in diabetic mice showed that the hydrogel significantly accelerated wound healing, with a wound contraction rate of 97.84% by day 14. Histopathological analysis revealed that the hydrogel promoted fibroblast proliferation, neovascularization, and orderly connective tissue formation, leading to a more uniform and compact wound-healing process. Thus, EGF@PDA-CMCS-PE hydrogel presents a promising tool for managing chronic diabetic wounds, offering a valuable strategy for future clinical applications.

Atomic Evolution Mechanism and Suppression of Edge Threading Dislocations in Nitride Remote Heteroepitaxy.

The majority of dislocations in nitride epilayers are edge threading dislocations (TDs), which diminish the performance of nitride devices. However, it is extremely difficult to reduce the edge TDs due to the lack of available slip systems. Here, we systematically investigate the formation mechanism of edge TDs and find that besides originating at the coalescence boundaries, these dislocations are also closely related to geometrical misfit dislocations at the interface. Based on this understanding, we propose a novel strategy to reduce the edge TD density of the GaN epilayer by nearly 1 order of magnitude via graphene-assisted remote heteroepitaxy. The first-principles calculations confirm that the insertion of graphene dramatically reduces the energy barrier required for interfacial sliding, which promotes a new strain release channel. This work provides a unique approach to directly suppress the formation of edge TDs at the source, thereby facilitating the enhanced performance of photoelectronic and electronic devices.

An oncogenic enhancer promotes melanoma progression via regulating ETV4 expression.

BACKGROUND: Enhancers are important gene regulatory elements that promote the expression of critical genes in development and disease. Aberrant enhancer can modulate cancer risk and activate oncogenes that lead to the occurrence of various cancers. However, the underlying mechanism of most enhancers in cancer remains unclear. Here, we aim to explore the function and mechanism of a crucial enhancer in melanoma. METHODS: Multi-omics data were applied to identify an enhancer (enh17) involved in melanoma progression. To evaluate the function of enh17, CRISPR/Cas9 technology were applied to knockout enh17 in melanoma cell line A375. RNA-seq, ChIP-seq and Hi-C data analysis integrated with luciferase reporter assay were performed to identify the potential target gene of enh17. Functional experiments were conducted to further validate the function of the target gene ETV4. Multi-omics data integrated with CUT&Tag sequencing were performed to validate the binding profile of the inferred transcription factor STAT3. RESULTS: An enhancer, named enh17 here, was found to be aberrantly activated and involved in melanoma progression. CRISPR/Cas9-mediated deletion of enh17 inhibited cell proliferation, migration, and tumor growth of melanoma both in vitro and in vivo. Mechanistically, we identified ETV4 as a target gene regulated by enh17, and functional experiments further support ETV4 as a target gene that is involved in cancer-associated phenotypes. In addition, STAT3 acts as a transcription factor binding with enh17 to regulate the transcription of ETV4. CONCLUSIONS: Our findings revealed that enh17 plays an oncogenic role and promotes tumor progression in melanoma, and its transcriptional regulatory mechanisms were fully elucidated, which may open a promising window for melanoma prevention and treatment.

Prediction of the short-term efficacy and recurrence of photodynamic therapy in the treatment of oral leukoplakia based on deep learning.

BACKGROUND: The treatment of oral leukoplakia (OLK) with aminolaevulinic acid photodynamic therapy (ALA-PDT) is widespread. Nonetheless, there is variation in efficacy. Therefore, this study constructed a model for predicting the short-term efficacy and recurrence of OLK after ALA-PDT. METHODS: The short-term efficacy and recurrence of ALA-PDT were calculated by statistical analysis, and the relevant influencing factors were analyzed by Logistic regression and COX regression model. Finally, prediction models for total response (TR) rate, complete response (CR) rate and recurrence in OLK patients after ALA-PDT treatment were established. Features from pathology sections were extracted using deep learning autoencoder and combined with clinical variables to improve prediction performance of the model. RESULTS: The logistic regression analysis showed that the non-homogeneous (OR: 4.911, P: 0.023) OLK and lesions with moderate to severe epithelial dysplasia (OR: 4.288, P: 0.042) had better short-term efficacy. The area under receiver operating characteristic curve (AUC) of CR, TR and recurrence predict models after the ALA-PDT treatment of OLK patients is 0.872, 0.718, and 0.564, respectively. Feature extraction revealed an association between inflammatory cell infiltration in the lamina propria and recurrence after PDT. Combining clinical variables and deep learning improved the performance of recurrence model by more than 30 %. CONCLUSIONS: ALA-PDT has excellent short-term efficacy in the management of OLK but the recurrence rate was high. Prediction model based on clinicopathological characteristics has excellent predictive effect for short-term efficacy but limited effect for recurrence. The use of deep learning and pathology images greatly improves predictive value of the models.