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1.
BMC Med Genomics ; 17(1): 175, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956616

ABSTRACT

This research analyzes the clinical data, whole-exome sequencing results, and in vitro minigene functional experiments of a child with developmental delay and intellectual disability. The male patient, aged 4, began experiencing epileptic seizures at 3 months post-birth and has shown developmental delay. Rehabilitation training was administered between the ages of one and two. There were no other significant family medical histories. Through comprehensive family exome genetic testing, a hemizygous variant in the 11th exon of the OPHN1 gene was identified in the affected child: c.1025 + 1G > A. Family segregation analysis confirmed the presence of this variant in the patient's mother, which had not been previously reported. According to the ACMG guidelines, this variant was classified as a likely pathogenic variant. In response to this variant, an in vitro minigene functional experiment was designed and conducted, confirming that the mutation affects the normal splicing of the gene's mRNA, resulting in a 56 bp retention on the left side of Intron 11. It was confirmed that OPHN1: c.1025 + 1G > A is the pathogenic cause of X-linked intellectual disabilities in the child, with clinical phenotypes including developmental delay and seizures.


Subject(s)
Intellectual Disability , Nuclear Proteins , RNA Splicing , Humans , Male , Child, Preschool , Intellectual Disability/genetics , Nuclear Proteins/genetics , Cytoskeletal Proteins/genetics , GTPase-Activating Proteins/genetics , Developmental Disabilities/genetics , Pedigree , Mutation , Exome Sequencing
2.
Int J Hyg Environ Health ; 261: 114410, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38925082

ABSTRACT

The gut microbiota is closely related to infant health. However, the impact of environmental factors on the gut microbiota has not been widely investigated, particularly in vulnerable populations such as infants admitted to the neonatal intensive care unit (NICU). This study investigated the association between exposure to 12 metals and the composition of the gut microbiota in infants admitted to the NICU. Metal concentrations were determined in serum samples obtained from 107 infants admitted to the NICU at Hunan Children's hospital, China. Gut microbiota data were derived from 16S rRNA sequencing using stool samples. Generalized linear regression (GLR) models and Bayesian kernel machine regression (BKMR) analyses were used to estimate the associations between metals and both alpha-diversity indices and bacterial taxa. The GLR models showed that tin correlated negatively with the Shannon index (ß = -0.55, 95% conficence interval [CI]: -0.79, -0.30, PFDR< 0.001) and positively with the Simpson index (ß = 0.26, 95% CI: 0.13, 0.39, PFDR< 0.001). The BKMR analysis yielded similar results, showing that tin had the largest posterior inclusion probability for both the Shannon (0.986) and the Simpson (0.796) indices. Tin, cadmium, mercury, lead, and thallium were associated with changes in one or more taxa at the genus level. The BKMR analysis also revealed a negative correlation between metal mixtures and Clostridium_sensu_stricto, and tin contibuted mostly to the negative correlation. Early postnatal exposure to metals were associated with differences in the microbiome among infants admitted to the NICU. However, as the study was cross-sectional, these relationships must be confirmed in further studies.

3.
iScience ; 27(6): 110128, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38939105

ABSTRACT

The hemoglobinless Antarctic icefish develop large hearts to compensate for reduced oxygen-carrying capacity, which serves as a naturally occurred model to explore the factors regulating cardiogenesis. Through miRNAome and microRNAome comparisons between an icefish (Chionodraco hamatus) and two red-blooded notothenioids, we discovered significant upregulation of factors in the BMP signaling pathways and altered expression of many miRNAs, including downregulation of 14 miRNAs in the icefish heart. Through knocking down of these miRNAs, we identified two of them, miR-458-3p and miR-144-5p, involved in enlarged heart development. The two miRNAs were found to regulate cardiomyocyte proliferation by targeting bone morphogenetic protein-2 (bmp2). We further validated that activation of the miRNA-bmp2 signaling in the fish heart could be triggered by hypoxic exposure. Our study suggested that a few miRNAs play important roles in the hypoxia-induced cardiac remodeling of the icefish which shed new light on the mechanisms regulating cardiomyocyte proliferation in heart.

4.
Br J Hosp Med (Lond) ; 85(6): 1-10, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38941970

ABSTRACT

Aims/Background Coronary heart disease is a common disease in the elderly and has a complex pathogenesis, which complicates the clinical diagnostic process. Thus, enhancing the diagnostic efficiency for coronary heart disease is imperative to improve the life expectancy of the elderly. This study aimed to explore the diagnostic value of multimodal cardiovascular imaging technology coupled with biomarker detection in elderly patients with coronary heart disease. Methods The medical records of 421 patients with suspected coronary heart disease obtained from the geriatric department of the First Affiliated Hospital of Hebei North University from February 2020 to February 2023 were retrospectively analysed. After excluding 10 patients who did not meet the inclusion criteria, the remaining 411 patients were included in this study. The included subjects had undergone coronary computed tomography angiography and were divided into coronary heart disease group (n=208) and non-coronary heart disease group (n=203) according to the diagnostic results. Multimodal cardiovascular imaging (coronary computed tomography angiography and echocardiography) and detection of serum biomarkers such as small dense low-density lipoprotein, lipoprotein a, and gamma-glutamyl transferase were performed in both groups. The clinical indicators of the two groups were compared, and the combined diagnostic efficacy of multimodal cardiovascular imaging and biomarker detection was evaluated. Results Compared to the non-coronary heart disease group, the coronary heart disease group had significantly higher levels of maximum area stenosis, total plaque volume, total plaque burden and fibrotic plaque volume (p < ..001), and lower left ventricular ejection fraction level (p < ..001). Additionally, the coronary heart disease group exhibited higher levels of left ventricular end-diastolic volume, left ventricular end-systolic volume and stroke volume than the non-coronary heart disease group (p < ..001), and had higher levels of small dense low-density lipoprotein, lipoprotein a and gamma-glutamyl transferase (p < ..001). Our results demonstrated that combined diagnosis had better diagnostic efficacy than individual approaches, marked by higher area under the curve and sensitivity of the former (p < ..001). Conclusion Multimodal cardiovascular imaging technology combined with biomarker detection can distinctly improve the accuracy of coronary heart disease diagnosis in elderly patients.


Subject(s)
Biomarkers , Computed Tomography Angiography , Coronary Disease , Echocardiography , Multimodal Imaging , Humans , Male , Aged , Female , Biomarkers/blood , Retrospective Studies , Multimodal Imaging/methods , Computed Tomography Angiography/methods , Echocardiography/methods , Coronary Disease/diagnostic imaging , Coronary Disease/blood , Coronary Disease/diagnosis , Coronary Angiography , Aged, 80 and over , gamma-Glutamyltransferase/blood
5.
J Imaging ; 10(6)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38921612

ABSTRACT

The automatic segmentation of cardiac computed tomography (CT) and magnetic resonance imaging (MRI) plays a pivotal role in the prevention and treatment of cardiovascular diseases. In this study, we propose an efficient network based on the multi-scale, multi-head self-attention (MSMHSA) mechanism. The incorporation of this mechanism enables us to achieve larger receptive fields, facilitating the accurate segmentation of whole heart structures in both CT and MRI images. Within this network, features extracted from the shallow feature extraction network undergo a MHSA mechanism that closely aligns with human vision, resulting in the extraction of contextual semantic information more comprehensively and accurately. To improve the precision of cardiac substructure segmentation across varying sizes, our proposed method introduces three MHSA networks at distinct scales. This approach allows for fine-tuning the accuracy of micro-object segmentation by adapting the size of the segmented images. The efficacy of our method is rigorously validated on the Multi-Modality Whole Heart Segmentation (MM-WHS) Challenge 2017 dataset, demonstrating competitive results and the accurate segmentation of seven cardiac substructures in both cardiac CT and MRI images. Through comparative experiments with advanced transformer-based models, our study provides compelling evidence that despite the remarkable achievements of transformer-based models, the fusion of CNN models and self-attention remains a simple yet highly effective approach for dual-modality whole heart segmentation.

6.
RSC Adv ; 14(26): 18161-18170, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38854822

ABSTRACT

Ultra-high molecular weight polyethylene/graphene oxide (PE-UHMW/GO) composites have demonstrated potential in artificial joint applications. The tribological behavior of irradiated PE-UHMW/GO composites under water lubrication remained unclear, which limited their application range. In this study, the PE-UHMW/GO composites were gamma irradiated at 100 KGy in a vacuum and subsequently aged at 80 °C for 21 days in air. We assessed their water absorption, and mechanical and tribological properties post-treatment. Notably, gamma irradiation markedly enhanced the mechanical and tribological performance of PE-UHMW/GO composites. Irradiated composites had a 6.11% increase in compressive strength and a 25.72% increase in yield strength compared to unirradiated composites. Additionally, under water lubrication, the irradiated composites showed improved wear resistance and a reduced friction coefficient. The irradiation enhancement can be attributed to the irradiation-induced strengthening of the interface bonding between GO and PE-UHMW. Conversely, accelerated aging led to oxidative degradation, negatively impacting these properties. Aged composites exhibited lower compressive and yield strengths, higher friction coefficients, and diminished anti-wear properties compared to the irradiated composites. The wear mechanism evolved from predominantly fatigue wear in irradiated PE-UHMW/GO to a mix of abrasive and fatigue wear post-aging. While GO and aging influenced water absorption, irradiation had a minimal effect. These insights significantly contribute to the application potential of irradiated PE-UHMW/GO composites in artificial joints.

7.
RSC Med Chem ; 15(6): 1828-1848, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38911148

ABSTRACT

Endometrial cancer (EC) is a common malignancy among women worldwide, and its recurrence makes it a common cause of cancer-related death. Surgery and external radiation, chemotherapy, or a combination of strategies are the cornerstone of therapy for EC patients. However, adjuvant treatment strategies face certain drawbacks, such as resistance to chemotherapeutic drugs; therefore, it is imperative to explore innovative therapeutic strategies to improve the prognosis of EC. With the development of pathology and pathophysiology, several biological targets associated with EC have been identified, including PI3K/Akt/mTOR, PARP, GSK-3ß, STAT-3, and VEGF. In this review, we summarize the progress of small molecule targeted therapies in terms of both basic research and clinical trials and provide cases of small molecules combined with fluorescence properties in the clinical applications of integrated diagnosis and treatment. We hope that this review will facilitate the further understanding of the regulatory mechanism governing the dysregulation of oncogenic signaling in EC and provide insights into the possible future directions of targeted therapeutic regimens for EC treatment by developing new agents with fluorescence properties for the clinical applications of integrated diagnosis and treatment.

8.
Sci Total Environ ; 943: 173814, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38848915

ABSTRACT

The mattic layer is a main ecological function bearer of alpine meadow soils in the Qinghai-Tibet Plateau. It has high soil organic carbon (SOC) content with a variety of SOC fractions, which are thought to have different sensitivities to climate change. The effects of soil properties and climate on the SOC fractions in the mattic layer are not well understood. To address this, we analyzed the effects of environmental factors on two SOC fractions: particulate organic carbon (POC) and mineral-associated organic carbon (MAOC). A random forest model (RFM), partial correlation analysis, and structural equation model (SEM) were used to quantify the relative effects of soil and climatic factors on SOC fractions. We found that SOC and its fractions are primarily regulated by soil properties rather than climate. Partial correlation analysis and SEM revealed that climate indirectly affects SOC by influencing soil properties. Silt+Clay and exchangeable calcium (Caex) were found to be the strongest contributing factors of MAOC and POC, respectively. A distinct shift occurs in the mechanism underlying SOC stabilization with varying soil pH. In acidic and neutral environments, amorphous Al/Fe-(hydr) oxides contribute to the stability of MAOC, whereas free Al/Fe-(hydr) oxides promote SOC mineralization. Conversely, Caex positively influences the stabilization of both POC and MAOC throughout the pH range. These results can be extrapolated to predict SOC dynamics in future soil conditions affected by environmental change, especially for use in Earth system models.

9.
Sensors (Basel) ; 24(11)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38894419

ABSTRACT

The Giant Steerable Science Mirror prototype is being developed to assess the tertiary mirror system of the Thirty Meter Telescope. In this study, a new semi-kinematic coupling design is proposed for the prototype based on three pairs of V-grooves and canoe-like components to allow for high repeatability accuracy under heavy loads. A mathematical model was constructed to estimate the repeatability accuracy using the corresponding measurement results and machining errors. The proposed design was verified by an experiment, and the results were consistent with the mathematical model. Furthermore, the results indicate that the repeatability of the semi-kinematic coupling is sufficient for the requirement.

10.
Gene ; 927: 148668, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38852695

ABSTRACT

Evidence has indicated that Enterococcus plays a vital role in non-alcoholic fatty liver disease (NAFLD) development. However, the microbial genetic basis and metabolic potential in the disease are yet unknown. We previously isolated a bacteria Enterococcus faecium B6 (E. faecium B6) from children with NAFLD for the first time. Here, we aim to systematically investigate the potential of strain B6 in lipogenic effects. The lipogenic effects of strain B6 were explored in vitro and in vivo. The genomic and functional characterizations were investigated by whole-genome sequencing and comparative genomic analysis. Moreover, the metabolite profiles were unraveled by an untargeted metabolomic analysis. We demonstrated that strain B6 could effectively induce lipogenic effects in the liver of mice. Strain B6 contained a circular chromosome and two circular plasmids and posed various functions. Compared to the other two probiotic strains of E. faecium, strain B6 exhibited unique functions in pathways of ABC transporters, phosphotransferase system, and amino sugar and nucleotide sugar metabolism. Moreover, strain B6 produced several metabolites, mainly enriched in the protein digestion and absorption pathway. The unique potential of strain B6 in lipogenic effects was probably associated with glycolysis, fatty acid synthesis, and glutamine and choline transport. This study pioneeringly revealed the metabolic characteristics and specific detrimental traits of strain B6. The findings provided new insights into the underlying mechanisms of E. faecium in lipogenic effects, and laid essential foundations for further understanding of E. faecium-related disease.

11.
Mikrochim Acta ; 191(7): 378, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853206

ABSTRACT

Porphyrin-based porous organic polymer (POP) with uniformly immobilized platinum nanoparticles (Pt NPs) were designed and synthesized, and it was demonstrated that such nanocomposites (Pt/POP) have oxidase-like activity. Surprisingly, Hg2+ significantly enhanced the oxidase-like activity of Pt/POP. The enhancement was attributed to the capture of Hg2+ by the thioether group in Pt/POP and the subsequent redox reaction of Hg2+ with Pt NPs, accelerating the electron transfer. In the presence of Hg2+, Pt/POP catalyzed the colorless 3,3',5,5'-tetramethylbenzidine (TMB) to turn blue rapidly and changed its absorbance at 652 nm. Based on this, a fast-response colorimetric sensor was constructed for the sensitive detection of Hg2+ with a linear range of 0.2-50 µM and a detection limit of 36.5 nM. Importantly, Pt/POP can be used as an adsorbent for the efficient removal of Hg2+ with a removal efficiency as high as 99.4%. This work provides a valuable strategy for colorimetric detection and efficient removal of Hg2+.

12.
Sci Rep ; 14(1): 13479, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867075

ABSTRACT

Surface coal development activities include mining and ecological restoration, which significantly impact regional carbon sinks. Quantifying the dynamic impacts on carbon sequestration in vegetation (VCS) during coal development activities has been challenging. Here, we provided a novel approach to assess the dynamics of VCS affected by large-scale surface coal mining and subsequent restoration. This approach effectively overcomes the limitations imposed by the lack of finer scale and long-time series data through scale transformation. We found that mining activities directly decreased VCS by 384.63 Gg CO2, while restoration activities directly increased 192.51 Gg CO2 between 2001 and 2022. As of 2022, the deficit in VCS at the mining areas still had 1966.7 Gg CO2. The study highlights that complete restoration requires compensating not only for the loss in the year of destruction but also for the ongoing accumulation of losses throughout the mining lifecycle. The findings deepen insights into the intricate relationship between coal resource development and ecological environmental protection.

13.
bioRxiv ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38826432

ABSTRACT

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain and, more importantly, preventing its transition to a chronic state. In a mouse model of post-surgical pain, local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. Importantly, preemptive drug treatment also inhibited the transition of post-surgical pain to a prolonged state. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways, and indirect pain relief by attenuating immune cell recruitment. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain and unravel the underlying mechanisms.

14.
Orthop Surg ; 16(7): 1732-1743, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38828840

ABSTRACT

OBJECTIVE: Numerous surgical techniques for addressing ulnar coronoid process fractures are available; however, a consensus on the optimal approach remains elusive. This study aimed to use the anterior neurovascular interval approach for the surgical management of ulnar coronoid process fractures and to evaluate its clinical outcomes over short- to mid-term follow-up. METHODS: This retrospective clinical study included 20 patients with ulnar coronoid process fractures who were treated using the anterior neurovascular interval approach between January 2018 and December 2022. Participants comprised 16 males and four females, aged between 20 and 64 years (mean, 34.3 ± 12.44 years). Clinical and radiological evaluations were based on elbow joint range of motion (ROM), Visual analogue scale (VAS), and Mayo elbow performance score (MEPS). A paired t-test was used to compare the pre-operative and final follow-up VAS and MEPS scores. RESULTS: The follow-up duration for all patients was at least 12 months (average, 12.65 ± 1.60 months). At the final follow-up, measurements of elbow ROM included a mean extension of 2.85 ± 3.17°, mean flexion of 135 ± 7.25°, mean pronation of 86.4 ± 4.56°, and mean supination of 84.85 ± 5.54°. All participants reached their target MEPS, with an average score of 97.25 ± 4.72 points, and the final mean VAS score was 0.2 ± 0.52 points. The VAS score was significantly lower and MEPS score was higher at the final follow-up than those before surgery (p < 0.05). Throughout the follow-up period, all the fractures united, and the stability of the affected elbows was satisfactory. CONCLUSION: Employing the anterior neurovascular interval approach for open reduction and internal fixation to manage coronoid process fractures effectively facilitates anatomical restoration and robust fixation of ulnar coronoid process fractures.


Subject(s)
Fracture Fixation, Internal , Ulna Fractures , Humans , Male , Female , Retrospective Studies , Adult , Middle Aged , Ulna Fractures/surgery , Follow-Up Studies , Young Adult , Fracture Fixation, Internal/methods , Range of Motion, Articular , Elbow Joint/surgery , Elbow Joint/physiopathology , Pain Measurement
15.
Shock ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38888497

ABSTRACT

ABSTRACT: Sepsis causes dysfunction in different organs, but the pathophysiological mechanisms behind it are similar and mainly involve complex haemodynamic and cellular dysfunction. The importance of microcirculatory dysfunction in sepsis is becoming increasingly evident, in which endothelial dysfunction and glycocalyx degradation play a major role. This study aimed to investigate the effects of hydrogen-rich saline (HRS) on renal microcirculation in septic renal failure, and whether Sirt1 was involved in the renoprotective effects of HRS. Rats model of sepsis was established by cecal ligation and puncture, and septic rats were intraperitoneal injected with HRS (10 ml/kg). We found that in sepsis, the degree of glycocalyx shedding was directly proportional to the severity of sepsis. The seven-day survival rate of rats in the HRS + CLP group (70%) was higher than that of the CLP group (30%). HRS improved acidosis and renal function and reduced the release of inflammatory factors (TNF, IL-1ßand IL-6). The endothelial glycocalyx of capillaries in the HRS + CLP group (115 nm) was observed to be significantly thicker than that in the CLP group (44 nm) and EX527 (67.2 nm) groups by electron microscopy, and fewer glycocalyx metabolites (SDC-1, HS, HA, and MMP9) were found in the blood. Compared with the CLP group, HRS reduced renal apoptosis and upregulated Sirt1 expression, and inhibited the NF-κB/MMP9 signalling pathway. In addition, HRS did not damage immune function in septic rats as well. Generally speaking, our results suggest that HRS can alleviate the inflammatory response, inhibit glycocalyx shedding, improve septic kidney injury, and enhance survival rate.

16.
Front Public Health ; 12: 1382217, 2024.
Article in English | MEDLINE | ID: mdl-38846615

ABSTRACT

Introduction: The mental health of unverisity students is influenced by diverse factorsis multifaceted, requiring further investigation to evaluate its current status and determinants. The present study aims to address this gap by targeting Chinese university students and employing the Psychological Resilience Dynamic System model. Through a questionnaire survey, this research endeavors to explore the mental health status and influencing factors. Ultimately, the findings of this study aim to provide a theoretical basis and tailored practical guidance for the development of mental health intervention strategies for university students. Methods: Based on the Psychological Resilience Dynamic System Model, the mental health status of 3,390 Chinese university students from 15 universities was empirically investigated with the principle of stratified sampling and the geographical distribution and disciplinary diversity of universities. The questionnaires used included Kessler psychological distress scale, psychological resilience scale,positive psychological capital scale, family hardiness index and social support scale. Among the participants, 47.85% were male and 52.15% were female. Regarding the origin, 42.89% of the students were from rural areas, while 57.11% were from urban areas. Results: Key findings unveil: (1) A prevalence of 24.54% in students has suboptimal mental health, with 18.70 and 5.84%, respectively, representing those with poor and relatively poor mental health conditions; (2) A noteworthy negative correlation (p < 0.01) between mental health scores of university students and nine pivotal factors, including psychological resilience, self-efficacy, optimism, hope, resilience, family resilience, objective support, subjective support, and support utilization; (3) Eight factors, including grade, family economic status, psychological resilience, self-efficacy, optimism, family resilience, objective support, and support utilization, emerge as significant predictors of university students' mental health (p <0.001), collectively elucidating 57.9% of the total variance in mental health. Discussion: The aforementioned research results, indicate that the influencing factors on the mental health of university students encompass four main aspects. These include individual demographic factors such as grade and family economic status, positive psychological capital factors such as psychological resilience, self-efficacy, optimism, hope, and resilience, family resilience factors including responsibility, control, and challenge, and societal support factors including objective support, subjective support, and support utilization. Based on this, this paper focuses on four recommendations: giving full play to the leading role of universities in mental health education and stress intervention, strengthening the educational power of positive family ideals and role modeling, building a support system for positive social atmosphere and psychological counseling, and improving the self-shaping ability of university students' psychological resilience and positive psychological capital. These recommendations aspire to better promote the mental health of university students and provide a strength reserve for psychological problem intervention.


Subject(s)
Mental Health , Resilience, Psychological , Students , Humans , Female , Students/psychology , Male , Universities , China , Surveys and Questionnaires , Young Adult , Social Support , Adult , Models, Psychological , Adolescent
17.
Br J Cancer ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760444

ABSTRACT

BACKGROUND: Risk of recurrence and progression of ductal carcinoma in situ (DCIS) to invasive cancer remains uncertain, emphasizing the need for developing predictive biomarkers of aggressive DCIS. METHODS: Human cell lines and mouse models of disease progression were analyzed for candidate risk predictive biomarkers identified and validated in two independent DCIS cohorts. RESULTS: RNA profiling of normal mammary and DCIS tissues (n = 48) revealed that elevated SOX11 expression correlates with MKI67, EZH2, and DCIS recurrence score. The 21T human cell line model of DCIS progression to invasive cancer and two mouse models developing mammary intraepithelial neoplasia confirmed the findings. AKT activation correlated with chromatin accessibility and EZH2 enrichment upregulating SOX11 expression. AKT and HER2 inhibitors decreased SOX11 expression along with diminished mammosphere formation. SOX11 was upregulated in HER2+ and basal-like subtypes (P < 0.001). Longitudinal DCIS cohort (n = 194) revealed shorter recurrence-free survival in SOX11+ than SOX11- patients (P = 0.0056 in all DCIS; P < 0.0001 in HER2+ subtype) associated with increased risk of ipsilateral breast event/IBE (HR = 1.9, 95%CI = 1.2-2.9; P = 0.003). DISCUSSION: Epigenetic activation of SOX11 drives recurrence of DCIS and progression to invasive cancer, suggesting SOX11 as a predictive biomarker of IBE.

18.
Chemosphere ; 361: 142416, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38797218

ABSTRACT

Although the promotive effect of direct interspecies electron transfer (DIET) on methane production has been well-documented, the practical applicability of DIET in different scenarios have not yet been systematically studied. This study compared the effects of magnetite-mediated DIET with conventional biogas mixing-driven interspecies hydrogen transfer (IHT) on anaerobic digestion (AD) of swine manure (SM). Compared with control, magnetite supplementation, biogas circulation, and their integration enhanced the CH4 yield by 19.3%, 25.9%, and 26.2%, respectively. Magnetite mainly enriched DIET-related syntrophic bacteria (Anaerolineae and Synergistia) and methanogens (Methanosarcina) to accelerate acidification and establish DIET, while biogas circulation mainly enriched hydrolytic bacteria (Clostridia) and hydrogenotrophic methanogens (Methanolinea and Methanobacterium) to promote hydrolysis and accelerate IHT. Coupling magnetite addition with biogas circulation led to the enrichment of the above six microorganisms to different extents. The effectiveness of the strategies for lowering the H2 pressure followed: magnetite + biogas circulation ≈ biogas circulation > magnetite. Under stress-free environment, the enhancement effect of magnetite-induced DIET was not even as pronounced as biogas circulation-a simple and common mixing strategy in commercial AD plants, and the promotion effect of magnetite was insignificant in the well-mixed digesters. In short, the magnetite-mediated DIET is not always effective in improving AD of SM.


Subject(s)
Biofuels , Ferrosoferric Oxide , Hydrogen , Manure , Methane , Anaerobiosis , Hydrogen/metabolism , Ferrosoferric Oxide/chemistry , Animals , Methane/metabolism , Electron Transport , Swine , Bacteria/metabolism , Bioreactors/microbiology
19.
Chemosphere ; 361: 142470, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38810802

ABSTRACT

Effective nitrate removal is a key challenge when treating low carbon-to-nitrogen ratio wastewater. How to select an effective inorganic electron donor to improve the autotrophic denitrification of nitrate nitrogen has become an area of intense research. In this study, the nitrate removal mechanism of three iron-based materials in the presence and absence of microorganisms was investigated with Fe2+/Fe0 as an electron donor and nitrate as an electron acceptor, and the relationship between the iron materials and denitrifying microorganisms was explored. The results indicated that the nitrogen removal efficiency of each iron-based material coupled sludge systems was higher than that of iron-based material. Furthermore, compared with the sponge iron coupled sludge system (60.6%-70.4%) and magnetite coupled sludge (56.1%-65.3%), the pyrite coupled sludge system had the highest removal efficiency of TN, and the removal efficiency increased from 62.5% to 82.1% with time. The test results of scanning electron microscope, X-ray photoelectron spectroscopy and X-ray diffraction indicated that iron-based materials promoted the attachment of microorganisms and the chemical reduction of nitrate in three iron-based material coupled sludge systems. Furthermore, the pyrite coupled sludge system had the highest nitrite reductase activity and can induce microorganisms to secrete more extracellular polymer substances. Combined with high-throughput sequencing and PICRUSt2 functional predictive analysis software, the total relative abundance of the dominant bacterial in pyrite coupled sludge system was the highest (72.06%) compared with the other iron-based material systems, and the abundance of Blastocatellaceae was relatively high. Overall, these results suggest that the pyrite coupled sludge system was more conducive to long-term stable nitrate removal.


Subject(s)
Autotrophic Processes , Carbon , Denitrification , Iron , Nitrates , Nitrogen , Waste Disposal, Fluid , Wastewater , Wastewater/chemistry , Nitrates/metabolism , Iron/chemistry , Iron/metabolism , Nitrogen/metabolism , Carbon/metabolism , Carbon/chemistry , Waste Disposal, Fluid/methods , Sewage/microbiology , Sewage/chemistry , Water Pollutants, Chemical/metabolism , Oxidation-Reduction , Sulfides/chemistry , Sulfides/metabolism
20.
Talanta ; 276: 126307, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38788381

ABSTRACT

Tungsten is an emerging environmental pollutant. However, a proved robust method for preserving and determining the concentrations of tungsten in environmental media is still lacking. This study examined and compared the suitability of classic methods and previously reported tungsten-oriented methods on preserving dissolved tungsten and recovering tungsten from soil/sediment matrix. Tungsten concentrations in the water samples and digestates were then determined by inductively coupled plasma mass spectrometry. Our data showed that the tungsten-oriented HF and alkaline preservatives indeed successfully maintained the stability of dissolved tungsten. Even when preserved using HNO3 or HCl, dissolved tungsten concentrations did not notably change in most of our water samples over the course of ∼4 months. Using glass containers for storing water samples also did not produce much difference from using high-density polyethylene containers. Our data further suggested that the addition of HF in digestion was important for tungsten solubilization from soil/sediment matrix. The digestion methods with HNO3/HCl/HF and HNO3/HF/NH4OH/EDTA both yielded quantitative recoveries of tungsten from certified reference materials and known synthetic samples, while the other tested methods had limited recoveries. The methods validated by this study could be used to accurately determine tungsten concentrations in environmental media and thereby to assess the fate and potential risks of tungsten.

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