Prevention of supercritical carbon dioxide fluid extract from Chrysanthemum indicum Linnén on cutaneous squamous cell carcinomas progression following UV irradiation in mice.

Chrysanthemum indicum Linnén (C. indicum), a medicinal and food herb with various bioactive components, may be of beneficial use in cosmetics and the treatment of skin-related diseases. However, to date, few studies have been reported on its potential preventive and therapeutic effects on skin cancer. Therefore, the present study aimed to investigate the effect and potential mechanism of action of supercritical carbon dioxide extract from C. indicum (CISCFE) on UV-induced skin cancer in a mouse model. Kunming mice were allocated randomly to five treatment groups: Sham, model, low concentration CISCFE, high concentration CISCFE and positive control nicotinamide groups. The dorsal skin of mice was irradiated with UV light for 31 weeks. Histopathological changes, ELISA assays, immunohistochemical analysis and western blotting were performed to investigate the potential therapeutic effects of CISCFE. The results showed that CISCFE alleviated skin oxidative and inflammatory damage in a UV-induced mouse model of skin cancer. Moreover, CISCFE suppressed abnormal activation of proto-oncogene c-Myc and the overexpression of Ki-67 and VEGF, and increased expression of the anti-oncogene PTEN, thereby reducing abnormal proliferation of the epidermis and blood vessels. Additionally, CISCFE increased the protein expression levels of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), Kelch-like ECH associated protein 1 (Keap1) and inhibited the expression of nuclear factor 2 erythroid 2-related factor 2 (Nrf2), phosphorylated (p)-p62 (Ser 349), p-p65 and acetyl-p65 proteins in a UV-induced skin cancer mouse model. In summary, CISCFE exhibited potent anti-skin cancer activity, which may be attributed its potential effects on the p62/Keap1-Nrf2 and SIRT1/NF-κB pathways.

ErbB4 deficiency exacerbates olfactory dysfunction in an early-stage Alzheimer's disease mouse model.

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aß and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aß, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aß: ß-amyloid, GABA: gamma-aminobutyric acid.

Sediment subduction in Hadean revealed by machine learning.

Due to the scarcity of rock samples, the Hadean Era predating 4 billion years ago (Ga) poses challenges in understanding geological processes like subaerial weathering and plate tectonics that are critical for the evolution of life. The Jack Hills zircon from Western Australia, the primary Hadean samples available, offer valuable insights into magma sources and tectonic genesis through trace element signatures. However, a consensus on these signatures has not been reached. To address this, we developed a machine learning classifier capable of deciphering the geochemical fingerprints of zircon. This allowed us to identify the oldest detrital zircon originating from sedimentary-derived "S-type" granites. Our results indicate the presence of S-type granites as early as 4.24 Ga, persisting throughout the Hadean into the Archean. Examining global detrital zircon across Earth's history reveals consistent supercontinent-like cycles from the present back to the Hadean. These findings suggest that a significant amount of Hadean continental crust was exposed, weathered into sediments, and incorporated into the magma sources of Jack Hills zircon. Only the early operation of both subaerial weathering and plate subduction can account for the prevalence of S-type granites we observe. Additionally, the periodic evolution of S-type granite proportions implies that subduction-driven tectonic cycles were active during the Hadean, at least around 4.2 Ga. The evidence thus points toward an early Earth resembling the modern Earth in terms of active tectonics and habitable surface conditions. This suggests the potential for life to originate in environments like warm ponds rather than extreme hydrothermal settings.

Experimental study on the biomechanical stability of complex acetabular fractures in the quadrilateral area: application of a dynamic anterior titanium-plate screw system.

BACKGROUND AND OBJECTIVE: Complex acetabular fractures involving quadrilateral areas are more challenging to treat during surgery. To date, there has been no ideal internal fixation for these acetabular fractures. The purpose of this study was to evaluate the biomechanical stability of complex acetabular fractures using a dynamic anterior titanium-plate screw system of the quadrilateral area (DAPSQ) by simulating the standing and sitting positions of pelvic specimens. MATERIALS AND METHODS: Eight formal in-preserved cadaveric pelvises aged 30-50 years were selected as the research objects. First, one hip of the normal pelvises was randomly used as the control model (group B) for measurement, and then one hip of the pelvises was randomly selected to make the fracture model in the 8 intact pelvises as the experimental model (group A) for measurement. In group A, acetabular both-column fractures in the quadrilateral area were established, and the fractures were fixed by DAPSQ. The biomechanical testing machine was used to load (simulated physiological load) from 400 N to 700 N at a 1 mm/min speed for 30 s in the vertical direction when the specimens were measured at random in simulated standing or sitting positions in groups. The horizontal displacement and longitudinal displacement of the acetabular fractures in the quadrilateral area were measured in both the standing and sitting simulations. RESULTS: As the load increased, no dislocation or internal fixation breakage occurred during the measurements. In the standing position, the horizontal displacement of the quadrilateral area fractures in group A and group B appeared to be less than 1 mm with loads ranging from 400 N to 700 N, and there was no significant difference between group A and group B (p > 0.05). The longitudinal displacement appeared to be greater than 1 mm with a load of 700 mm in group A (700 N, 2 cases), and the difference was significant between group A and group B (p < 0.05). In the sitting position, the horizontal and longitudinal displacements of the quadrilateral areas were within 0.5 mm in group A and group B, and there was no significant difference between group A and group B (p > 0.05). CONCLUSION: For complex acetabular fractures in the quadrilateral area, DAPSQ fixation may provide early sitting stability, but it is inappropriate for patients to stand too early.

Development of an Integrated Disposable Device for SARS-CoV-2 Nucleic Acid Extraction and Detection.

Objective: To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We designed, developed, and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection. The precision of the liquid transfer and temperature control was tested. A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). The entire process, from SARS-CoV-2 nucleic acid extraction to amplification, was evaluated. Results: The precision of the syringe transfer volume was 19.2 ± 1.9 µL (set value was 20), 32.2 ± 1.6 (set value was 30), and 57.2 ± 3.5 (set value was 60). Temperature control in the amplification tube was measured at 60.0 ± 0.0 °C (set value was 60) and 95.1 ± 0.2 °C (set value was 95) respectively. SARS-Cov-2 nucleic acid extraction yield through the device was 7.10 × 10 6 copies/mL, while a commercial kit yielded 2.98 × 10 6 copies/mL. The mean time to complete the entire assay, from SARS-CoV-2 nucleic acid extraction to amplification detection, was 36 min and 45 s. The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL. Conclusion: The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test (POCT).

The Efficacy of Active Fistulation in Duckett Procedure for Proximal Hypospadias in Children.

PURPOSE: To explore the efficacy of active fistulation in the treatment of proximal hypospadias in children by comparing one-stage and two-stage Duckett  procedure. MATERIALS AND METHODS:  A total of sixty-seven children who were diagnosed with proximal hypospadias and underwent Duckett operation at our hospital between January 2013 and January 2021 were selected for this study. These subjects were divided into two groups: the research group (n=36), using two-stage Duckett procedure with active fistulation, and the control group (n=31), using one-stage Duckett procedure. The incidence of postoperative complications and the score of pediatric penile perception Scale were compared between the two groups. RESULTS:  The research group exhibits significantly lower incidence rate of urethral fistula (8.3% Vs 16.1%) and urethral stricture (5.6% Vs 12.9%) in comparison to the control group (P<0.01). Furthermore, the analysis of Pediatric Penile Perception Scale scores indicates that the research group achieves significantly higher scores in terms of urethral shape, penile skin shape, and overall appearance than the control group (P<0.05).  Conclusion: In the treatment of proximal hypospadias in children, The active fistulation within the two-stage Duckett procedure significantly reduces the rate of stage 1 postoperative complications and improves parental satisfaction. The active fistulation may offer a more promising option for the treatment of proximal hypospadias in children.

[Prognostic Factors Affecting Recurrence in Peripheral T-Cell Lymphoma Patients with Different HDAC Levels].

OBJECTIVE: To analyze the distribution characteristics of prognostic factors affecting recurrence in peripheral T-cell lymphoma (PTCL) patients with different levels of histone deacetylase (HDAC) based on latent class analysis. METHODS: 112 PTCL patients who were treated in our hospital from September 2012 to September 2019 were selected and divided into recurrence group and non-recurrence group. The clinical data of the two groups of patients were compared. Multivariate logistic regression was used to analyze the risk factors for recurrence. Latent class analysis was used to compare the distribution characteristics of prognostic factors affecting recurrence between the high-risk group and the low-risk group. RESULTS: There were 87 patients (77.68%) in recurrence group and 25 patients (22.32%) in non-recurrence group. The result of multivariate logistic regression showed that ECOG score ≥2, Ann Arbor stage III-IV, IPI score >2, bone marrow involvement, elevated serum ß2-microglobulin (ß2-MG), short-term efficacy not reaching complete remission (CR) or partial remission (PR), and the high expression of HDAC were all independent risk factors for recurrence in patients with PTCL (P <0.05). The recurrence rate of patients with high HDAC levels was significantly higher than that of patiens with low HDAC levels (P <0.05). The results of cluster analysis showed that the risk of recurrence was obviously clustered, and the patients could be divided into high recurrence risk group (HDAC＞5 points) and low recurrence risk group (HDAC≤5 points). The results of latent class analysis showed that patients with multiple risk factors account for a higher proportion in the high recurrence risk group, compared with the low recurrence risk group (P <0.05). CONCLUSION: There are differences in recurrence rates among PTCL patients with different HDAC levels and in distribution characteristics of risk factors between high recurrence risk and low recurrence risk groups.

Evaluation of hair transplantation for improving unnatural hairlines after laser hair removal: A multicenter retrospective study.

CONTEXT: Laser hair removal treatment for hairlines with an unsatisfactory appearance often leads to an unnatural appearance; however, few studies have reported treatment outcomes. OBJECTIVE: To explore the satisfaction rate of laser hair removal involving the hairline. DESIGN: Retrospective analysis. SETTING: Data from 5 clinical institutions. PATIENTS: Patients (915; 630 female and 285 male) who underwent laser hair removal. INTERVENTIONS: Issues associated with hair removal were classified, and their proportions were calculated. Hair transplantation was performed to improve the appearance of different hairline issues. MAIN OUTCOME MEASURES: Relevant indicators of hair transplantation and postoperative effects. RESULTS: Overall, 82 patients were unsatisfied with their hairline appearance; of these patients, 58 underwent hair transplantation to improve the hairline. Additionally, demographic statistics showed that 68% and 32% of patients were in the 20 to 30 and 30 to 40 years age groups, respectively; there were no patients in the 40 to 50 years age group. Among female patients who underwent hair transplantation, 25% had a poor hairline position, 64% had a stiff hairline appearance, and 11% experienced both issues. Among male patients, 50% had a stiff hairline appearance, 28% had temporal absence, and 22% experienced both issues. Surgical treatment included moving the hairline forward and rebuilding the frontal curves. All patients were satisfied with hair transplantation outcomes. CONCLUSIONS: Laser hair removal can result in diverse types of unnatural hairlines. Hair transplantation has been proven to effectively improve the aesthetic appearance of the hairline.

Segmentation Guided Crossing Dual Decoding Generative Adversarial Network for Synthesizing Contrast-Enhanced Computed Tomography Images.

Although contrast-enhanced computed tomography (CE-CT) images significantly improve the accuracy of diagnosing focal liver lesions (FLLs), the administration of contrast agents imposes a considerable physical burden on patients. The utilization of generative models to synthesize CE-CT images from non-contrasted CT images offers a promising solution. However, existing image synthesis models tend to overlook the importance of critical regions, inevitably reducing their effectiveness in downstream tasks. To overcome this challenge, we propose an innovative CE-CT image synthesis model called Segmentation Guided Crossing Dual Decoding Generative Adversarial Network (SGCDD-GAN). Specifically, the SGCDD-GAN involves a crossing dual decoding generator including an attention decoder and an improved transformation decoder. The attention decoder is designed to highlight some critical regions within the abdominal cavity, while the improved transformation decoder is responsible for synthesizing CE-CT images. These two decoders are interconnected using a crossing technique to enhance each other's capabilities. Furthermore, we employ a multi-task learning strategy to guide the generator to focus more on the lesion area. To evaluate the performance of proposed SGCDD-GAN, we test it on an in-house CE-CT dataset. In both CE-CT image synthesis tasks-namely, synthesizing ART images and synthesizing PV images-the proposed SGCDD-GAN demonstrates superior performance metrics across the entire image and liver region, including SSIM, PSNR, MSE, and PCC scores. Furthermore, CE-CT images synthetized from our SGCDD-GAN achieve remarkable accuracy rates of 82.68%, 94.11%, and 94.11% in a deep learning-based FLLs classification task, along with a pilot assessment conducted by two radiologists.

Promotive effect of skin precursor-derived Schwann cells on brachial plexus neurotomy and motor neuron damage repair through milieu-regulating secretome.

Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP-SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.

Scalable Dual In Situ Synthesis of Polyester Nanocomposites for High-Energy Storage.

Incorporating ultralow loading of nanoparticles into polymers has realized increases in dielectric constant and breakdown strength for excellent energy storage. However, there are still a series of tough issues to be dealt with, such as organic solvent uses, which face enormous challenges in scalable preparation. Here, a new strategy of dual in situ synthesis is proposed, namely polymerization of polyethylene terephthalate (PET) synchronizes with growth of calcium borate nanoparticles, making polyester nanocomposites from monomers directly. Importantly, this route is free of organic solvents and surface modification of nanoparticles, which is readily accessible to scalable synthesis of polyester nanocomposites. Meanwhile, uniform dispersion of as ultralow as 0.1 wt% nanoparticles and intense bonding at interfaces have been observed. Furthermore, the PET-based nanocomposite displays obvious increases in both dielectric constant and breakdown strength as compared to the neat PET. Its maximum discharged energy density reaches 15 J cm-3 at 690 MV m-1 and power density attains 218 MW cm-3 under 150 Ω resistance at 300 MV m-1, which is far superior to the current dielectric polymers that can be produced at large scales. This work presents a scalable, safe, low-cost, and environment-friendly route toward polymer nanocomposites with superior capacitive performance.

Micronized acellular dermal matrix combined with platelet rich plasma in the treatment of atrophic acne scars: A self-controlled split face study.

BACKGROUND: Micronized acellular dermal matrix (mADM) can induce tissue regeneration and repair, and filling. OBJECTIVES: The efficacy and safety of (mADM) were evaluated in the treatment of atrophic acne scar. METHODS: In this single-blinded, self-controlled, split-face study, 16 patients (48 scar sites) were divided into treatment group (24 scar sites) and control group (24 scar sites). One side of the affected area was treated with mADM combined with platelet rich plasma (PRP) injection as the treatment group; the other side of the affected area was treated with PRP injection as the control group. The efficacy was evaluated by the Acne scar assessment scale (ASAS) and Acne Scar Weight Rating Scale (ECCA) 3 months after treatment. RESULTS: After 3-month treatment in 16 patients, the atrophic acne scars in both groups were all improved. The ASAS score and ECCA weight score in the treatment group was significantly lower than that in the control group (2.50 ± 0.51 vs. 3.62 ± 0.77 and 14.17 ± 10.18 vs. 31.88 ± 13.25; p < 0.001). LIMITATIONS: Short-term 3-month treatment period. Small sample size limits generalizability of results. CONCLUSION: The curative effect of mADM combined with PRP is significantly better than that of PRP alone.

A qualitative study of the experiences of interdisciplinary nurses during the COVID-19 outbreak following the announcement of the "Ten new guidelines" in China.

BACKGROUND: On December 7, 2022, the Joint Prevention and Control Mechanism of China's State Council released the "Ten New Guidelines" to optimize the coronavirus disease 2019 (COVID-19) prevention policies further. This signaled a broader shift from "dynamic clearing" to "coexisting with the virus" nationwide. OBJECTIVE: This study aims to examine the experiences and perspectives of interdisciplinary nurses during the COVID-19 outbreak in China after the implementation of the "Ten New Guidelines". The goal is to understand the challenges faced by this unique nursing group and inform organizational support to bolster their well-being and resilience. METHODS: Two tertiary hospitals in southeastern Zhejiang Province were selected, with interdisciplinary nurses chosen as subjects. A constructivist qualitative research approach was employed, using semi-structured face-to-face interviews. Research data were collected through interviews and analyzed using content analysis. RESULTS: Fifteen interdisciplinary nurses were included in this study. The analysis revealed four main themes and nine sub-themes. The main themes were: (1) ineffective organizational support (inadequate organizational care, poor PPE, excessive workload), (2) physiological distress after contracting COVID-19 (extreme physical fatigue, leakage of urine due to severe coughing), (3) fear of being wrong (fear of being reprimanded in public, psychological anxiety), and (4) family responsibility anxiety (difficulty of loyalty and filial piety, obligations to their children). CONCLUSION: We provide new evidence that organizations must proactively address the support, training, and communication needs of staff, particularly interdisciplinary nurses, to supplement epidemic containment. This is also essential in helping mitigate the work-family conflicts such roles can create.

Three-stage niobium mineralization at Bayan Obo, China.

The Chinese Bayan Obo deposit is a world-class rare earth element (REE) deposit with considerable niobium (Nb) and iron (Fe) resources. A complete genetic understanding on all metals is fundamental for establishing genetic models at Bayan Obo. With extensive research being focused on REE enrichment, the timing and controls of Nb enrichment remain unresolved at Bayan Obo, which is mainly due to the challenges in dating, i.e. multistage thermal events, fine-grained minerals with complex textures and the rare occurrence of uranium-enriched minerals with mature dating methods. Based on robust geological and petrographic frameworks, here we conducted ion probe uranium-lead (U-Pb) dating of ferrocolumbite to unravel the timing, hence the genesis of Nb mineralization. Three types of hydrothermal ferrocolumbites-key Nb-bearing minerals-are identified based on their textures and mineral assemblages. They yield U-Pb ages of 1312 ± 47 Ma (n = 99), 438 ± 7 Ma (n = 93), and 268 ± 5 Ma (n = 19), respectively. In line with deposit geology, we tentatively link the first, second and third stage Nb mineralization to Mesoproterozoic carbonatite magmatism, ubiquitous early Paleozoic hydrothermal activity, and Permian granitic magmatism, respectively. While quantifying the contribution of metal endowment from each stage requires further investigation, our new dates highlight that multi-stage mineralization is critical for Nb enrichment at Bayan Obo, which may also have implications for the enrichment mechanism of Nb in REE deposits in general.

High-efficient separation of deoxyribonucleic acid from pathogenic bacteria by hedgehog-inspired magnetic nanoparticles microextraction.

Efficient separation of deoxyribonucleic acid (DNA) through magnetic nanoparticles (MN) is a widely used biotechnology. Hedgehog-inspired MNs (HMN) possess a high-surface-area due to the distinct burr-like structure of hedgehog, but there is no report about the usage of HMN for DNA extraction. Herein, to improve the selection of MN and illustrate the performance of HMN for DNA separation, HMN and silica-coated Fe3O4 nanoparticles (Fe3O4@SiO2) were fabricated and compared for the high-efficient separation of pathogenic bacteria of DNA. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are typical Gram-negative and Gram-positive bacteria and are selected as model pathogenic bacteria. To enhance the extraction efficiency of two kinds of MNs, various parameters, including pretreatment, lysis, binding and elution conditions, have been optimized in detail. In most separation experiments, the DNA yield of HMN was higher than that of Fe3O4@SiO2. Therefore, a HMN-based magnetic solid-phase microextraction (MSPE) and quantitative real-time PCR (qPCR) were integrated and used to detect pathogenic bacteria in real samples. Interestingly, the HMN-based MSPE combined qPCR strategy exhibited high sensitivity with a limit of detection of 2.0 × 101 CFU mL-1 for E. coli and 4.0 × 101 CFU mL-1 for S. aureus in orange juice, and 2.8 × 102 CFU mL-1 for E. coli and 1.1 × 102 CFU mL-1 for S. aureus in milk, respectively. The performance of the proposed strategy was significantly better than that of commercial kit. This work could prove that the novel HMN could be applicable for the efficient separation of DNA from complex biological samples.

[Effect of L-Type Amino Acid Transporter 1 Expression on Clinicopathological Features and Prognosis of Non-Hodgkin's Lymphoma].

OBJECTIVE: To detect the expression of L-type amino acid transporter 1 (LAT1) in non-Hodgkin's lymphoma (NHL) tissues, and analyze its effect on clinicopathological characteristics and prognosis of patients. METHODS: A total of 92 NHL patients who were treated in our hospital from January 2017 to April 2019 were collected. The expression of LAT1 in NHL tissue was detected by immunohistochemistry and compared between patients with different pathological features (including sex, Ann Arbor stage, extranodal infiltration, Ki-67). The risk factors affecting mortality were analyzed using univariate and multivariate Cox proportional hazards regression. Receiver operating characteristic (ROC) curve was used to detect the predictive value of percentage of LAT1-positive cells in NHL tissue for patient mortality, and analyzing the effect of percentage of LAT1-positive cells on survival rate. RESULTS: LAT1 was positively expressed in NHL tissue. The high expression rate of LAT1 in Ann Arbor stage III and IV groups were higher than that in Ann Arbor stage I group, that in extranodal infiltration group was higher than non-extranodal infiltration group, and that in Ki-67 positive expression group was higher than Ki-67 negative expression group (all P < 0.05). The remission rate after 3 courses of treatment in high-LAT1 expression group was 70.7%, which was lower than 91.2% in low-LAT1 expression group (P < 0.05). Ann Arbor stage III and IV, extranodal invasion, Ki-67 positive expression and increased expression of LAT1 (LAT1-positive cell percentage score ≥2) were risk factors for mortality. The cut-off value of percentage of LAT1-positive cells for predicting NHL death was 45.6%, and the area under the ROC curve was 0.905 (95%CI: 0.897-0.924). The 3-year survival rate of high-LAT1 level group (the percentage of LAT1-positive cells≥45.6%) was 50.00%, which was lower than 78.26% of low-LAT1 level group (P < 0.05). CONCLUSION: The expression level of LAT1 in NHL tissue increases, which affects Ann Arbor stage and extranodal infiltration of patients. LAT1 is a risk factor for death.

Construction and analysis of a joint diagnostic model of machine learning for cryptorchidism based on single-cell sequencing.

BACKGROUND: Cryptorchidism is a condition in which one or both of a baby's testicles do not fully descend into the bottom of the scrotum. Newborns with cryptorchidism are at increased risk of developing infertility later in life. The aim of this study was to develop a novel diagnostic model for cryptorchidism and to identify new biomarkers associated with cryptorchidism. METHODS: The study data were obtained from RNA sequencing data of cryptorchid patients from Nantong University Hospital and the Gene Expression Omnibus (GEO) database. Differential expression analysis was used to obtain differentially expressed genes (DEGs) between the control and cryptorchid groups. These DEGs were analyzed for their functions by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment using GSEA software. Random Forest algorithm was used to screen central genes based on these DEGs. Neuralnet software package was used to develop artificial neural network models. Based on clinical data, receiver operating characteristic (ROC) was used to validate the models. Single-cell sequencing analysis was used for the pathogenesis of cryptorchidism. RESULTS: We obtained a total of 525 important DEGs related to cryptorchidism, which are mainly associated with biological functions such as supramolecular complexes and microtubule cytoskeleton. Random forest approach screening obtained eight hub genes. A neural network based on the hub genes showed a 100% success rate of the model. Finally, single-cell sequencing analysis validated the hub genes. CONCLUSION: We developed a novel diagnostic model for cryptorchidism using artificial neural networks and validated its utility as an effective diagnostic tool.

Immobilisation remediation of arsenic-contaminated soils with promising CaAl-layered double hydroxide and bioavailability, bioaccessibility, and speciation-based health risk assessment.

Arsenic (As)-contaminated soil poses great health risk to human mostly through inadvertent oral exposure. We investigated CaAl-layered double hydroxide (CaAl-LDH), a promising immobilising agent, for the remediation of As-contaminated Chinese soils. The effects on specific soil properties and As fractionation were analyzed, and changes in the health risk of soil As were accurately assessed by means of advanced in vivo mice model and in vitro PBET-SHIME model. Results showed that the application of CaAl-LDH significantly increased soil pH and concentration of Fe and Al oxides, and effectively converted active As fractions into the most stable residual fraction, guaranteeing long-term remediation stability. Based on in vivo test, As relative bioavailability was significantly reduced by 37.75%. Based on in vitro test, As bioaccessibility in small intestinal and colon phases was significantly reduced by 25.65% and 28.57%, respectively. Furthermore, As metabolism (reduction and methylation) by the gut microbiota inhabiting colon was clearly observed. After immobilisation with CaAl-LDH, the concentration of bioaccessible As(Ⅴ) in the colon fluid was significantly reduced by 61.91%, and organic As (least toxic MMA(V) and DMA(V)) became the main species, which further reduced the health risk of soil As. In summary, CaAl-LDH proved to be a feasible option for immobilisation remediation of As-contaminated soils, and considerable progress was made in relevant health risk assessment.

Rapid evaluation of PHD2 inhibitory activity of natural products based on capillary electrophoresis online stacking strategy.

Prolyl hydroxylase domain 2 (PHD2) is an important enzyme in the human body that perceives changes in oxygen concentration and regulates response in hypoxic environments. Evaluation of PHD2 inhibitory activity of natural products is crucial for drug development of hypoxia related diseases. At present, the detection of low concentration of α-ketoglutaric acid (the substrate of PHD2 enzymatic reaction) requires derivatization reactions or sample pretreatment, which undoubtedly increases the workload of PHD2 inhibitory activity evaluation. In this paper, a direct detection approach of α-ketoglutaric acid was established by using the online stacking strategy of capillary electrophoresis to evaluate the PHD2 inhibitory activity of natural products. Under optimized conditions, detection of a single sample can be achieved within 2 min. By calculation, the intraday precision RSD of the apparent electrophoretic mobility and peak areas of α-ketoglutaric acid are 0.92 % and 0.79 %, respectively, and the interday RSD were 1.27 % and 0.96 % respectively. The recoveries of the present approach were 97.9-105.2 %, and the LOQ and LOD were 2.0 µM and 5.0 µM, respectively. Furthermore, this approach was applied for the evaluation of inhibitory activity of PHD2 for 13 natural products, and PHD2 inhibitory activity of salvianolic acid A was firstly reported. The present work not only realizes evaluation of PHD2 inhibitory activity through direct detection of α-ketoglutaric acid, but also provides technical support for the discovery of potential drug molecules in hypoxia related diseases.