DDX58 deficiency leads to triple negative breast cancer chemotherapy resistance by inhibiting Type I IFN-mediated signalling apoptosis.

Introduction: Triple-negative breast cancer (TNBC) is characterized by its aggressive nature and absence of specific therapeutic targets, necessitating the reliance on chemotherapy as the primary treatment modality. However, the drug resistance poses a significant challenge in the management of TNBC. In this study, we investigated the role of DDX58 (DExD/H-box helicase 58), also known as RIG-I, in TNBC chemoresistance. Methods: The relationship between DDX58 expression and breast cancer prognosis was investigated by online clinical databases and confirmed by immunohistochemistry analysis. DDX58 was knockout by CRISPR-Cas9 system (DDX58-KO), knockdown by DDX58-siRNA (DDX58-KD), and stably over expressed (DDX58-OE) by lentivirus. Western blotting, immunofluorescence and qPCR were used for related molecules detection. Apoptosis was analyzed through flow cytometry (Annexin V/7AAD apoptosis assay) and Caspase 3/7 activity assay. Results: Patients with lower expression of DDX58 led to lower rate of pathological complete response (pCR) and worse prognosis by online databases and hospital clinical data. DDX58-KD cells showed multiple chemo-drugs resistance (paclitaxel, doxorubicin, 5-fluorouracil) in TNBC cell lines. Similarly, DDX58-KO cells also showed multiple chemo-drugs resistance in a dosage-dependent manner. In the CDX model, tumours in the DDX58-KO group had a 25% reduction in the tumour growth inhibition rate (IR) compared to wild-type (WT) group after doxorubicin (Dox) treatment. The depletion of DDX58 inhibited proliferation and promoted the migration and invasion in MDA-MB-231 cells. The findings of our research indicated that DDX58-KO cells exhibit a reduction in Dox-induced apoptosis both in vivo and in vitro. Mechanistically, Dox treatment leads to a significant increase in the expression of double-stranded RNAs (dsRNAs) and activates the DDX58-Type I interferon (IFN) signaling pathway, ultimately promoting apoptosis in TNBC cells. Discussion: In the process of TNBC chemotherapy, the deficiency of DDX58 can inhibit Dox-induced apoptosis, revealing a new pathway of chemotherapy resistance, and providing a possibility for developing personalized treatment strategies based on DDX58 expression levels.

Biomechanical analysis of the maxillary sinus floor membrane during internal sinus floor elevation with implants at different angles of the maxillary sinus angles.

OBJECTIVE: This study analyzed and compared the biomechanical properties of maxillary sinus floor mucosa with implants at three different maxillary sinus angles during a modified internal sinus floor elevation procedure. METHODS: 3D reconstruction of the implant, maxillary sinus bone, and membrane were performed. The maxillary sinus model was set at three different angles. Two internal maxillary sinus elevation models were established, and finite element analysis was used to simulate the modified maxillary sinus elevation process. The implant was elevated to 10 mm at three maxillary sinus angles when the maxillary sinus floor membrane was separated by 0 and 4 mm. The stress of the maxillary sinus floor membrane was analyzed and compared. RESULTS: When the maxillary sinus floor membrane was separated by 0 mm and elevated to 10 mm, the peak stress values of the implant on the maxillary sinus floor membrane at three different angles were as follows: maxillary sinus I: 5.14-78.32 MPa; maxillary sinus II: 2.81-73.89 MPa; and maxillary sinus III: 2.82-51.87 MPa. When the maxillary sinus floor membrane was separated by 4 mm and elevated to 10 mm, the corresponding values were as follows: maxillary sinus I: 0.50-7.25 MPa; maxillary sinus II: 0.81-16.55 MPa; and maxillary sinus III: 0.49-22.74 MPa. CONCLUSION: The risk of sinus floor membrane rupture is greatly reduced after adequate dissection of the maxillary sinus floor membrane when performing modified internal sinus elevation in a narrow maxillary sinus. In a wide maxillary sinus, the risk of rupture or perforation of the wider maxillary sinus floor is reduced, regardless of whether traditional or modified internal sinus elevation is performed at the same height.

Mechanism and effectiveness of enzymatically induced phosphate precipitation (EIPP) in stabilizing coexisting lead, zinc, and cadmium in tailings.

Lead-zinc (Pb-Zn) tailings ponds carry the risk of multiple heavy metals (HMs) contamination and pile destabilization. This poses requirements for in-situ applicable, low-distribution, and effective stabilization/solidification (S/S) methods. For this, the novel enzymatically induced phosphate precipitation (EIPP) method was implemented in this study. Its mechanism and performance on stabilization of composite Pb, Zn, and cadmium (Cd) in tailings were explored and evaluated under typical erosion conditions for the first time. Results show that the EIPP stabilized HMs by chemically transforming the unstable carbonate-bound HMs to stable phosphate precipitates and by physically encapsulating tailings particles with newberyite precipitates. The stabilization effect on the three HMs was ranked as Pb > Zn > Cd. Comparing magnesium resources for the EIPP reactants, the EIPP utilizing Mg(CH3COO)2 was more effective at decontamination than MgCl2 because its special pre-activation and re-precipitation function enhanced the chemical transformation function of EIPP. The EIPP stabilization was confirmed to reduce simulated acid rain-leachable and bio-extractive HMs by about 90% and 60%, respectively. Under the prolonged acid attack, treated HMs were ultimately leached through the dissolution mechanism. Zn exhibited significant instability in highly acidic conditions (pH = 2.5-3.5), where its cumulative leaching toxicity after long-term dissolution warrants attention. Overall, EIPP presents a novel and effective strategy for on-site mitigation of composite HMs pollution.

DNAJC12 causes breast cancer chemotherapy resistance by repressing doxorubicin-induced ferroptosis and apoptosis via activation of AKT.

BACKGROUND: Chemotherapy is a primary treatment for breast cancer (BC), yet many patients develop resistance over time. This study aims to identify critical factors contributing to chemoresistance and their underlying molecular mechanisms, with a focus on reversing this resistance. METHODS: We utilized samples from the Gene Expression Omnibus (GEO) and West China Hospital to identify and validate genes associated with chemoresistance. Functional studies were conducted using MDA-MB-231 and MCF-7 cell lines, involving gain-of-function and loss-of-function approaches. RNA sequencing (RNA-seq) identified potential mechanisms. We examined interactions between DNAJC12, HSP70, and AKT using co-immunoprecipitation (Co-IP) assays and established cell line-derived xenograft (CDX) models for in vivo validations. RESULTS: Boruta analysis of four GEO datasets identified DNAJC12 as highly significant. Patients with high DNAJC12 expression showed an 8 % pathological complete response (pCR) rate, compared to 38 % in the low expression group. DNAJC12 inhibited doxorubicin (DOX)-induced cell death through both ferroptosis and apoptosis. Combining apoptosis and ferroptosis inhibitors completely reversed DOX resistance caused by DNAJC12 overexpression. RNA-seq suggested that DNAJC12 overexpression activated the PI3K-AKT pathway. Inhibition of AKT reversed the DOX resistance induced by DNAJC12, including reduced apoptosis and ferroptosis, restoration of cleaved caspase 3, and decreased GPX4 and SLC7A11 levels. Additionally, DNAJC12 was found to increase AKT phosphorylation in an HSP70-dependent manner, and inhibiting HSP70 also reversed the DOX resistance. In vivo studies confirmed that AKT inhibition reversed DNAJC12-induced DOX resistance in the CDX model. CONCLUSION: DNAJC12 expression is closely linked to chemoresistance in BC. The DNAJC12-HSP70-AKT signaling axis is crucial in mediating resistance to chemotherapy by suppressing DOX-induced ferroptosis and apoptosis. Our findings suggest that targeting AKT and HSP70 activities may offer new therapeutic strategies to overcome chemoresistance in BC.

Arginine-methylated c-Myc affects mitochondrial mitophagy in mouse acute kidney injury via Slc25a24.

The transcription factor methylated c-Myc heterodimerizes with MAX to modulate gene expression, and plays an important role in energy metabolism in kidney injury but the exact mechanism remains unclear. Mitochondrial solute transporter Slc25a24 imports ATP into mitochondria and is central to energy metabolism. Gene Expression Omnibus data analysis reveals Slc25a24 and c-Myc are consistently upregulated in all the acute kidney injury (AKI) cells. Pearson correlation analysis also shows that Slc25a24 and c-Myc are strongly correlated (⍴ > 0.9). Mutant arginine methylated c-Myc (R299A and R346A) reduced its combination with MAX when compared with the wild type of c-Myc. On the other hand, the Slc25a24 levels were also correspondingly reduced, which induced the downregulation of ATP production. The results promoted reactive oxygen species (ROS) production and mitophagy generation. The study revealed that the c-Myc overexpression manifested the most pronounced mitochondrial DNA depletion. Additionally, the varied levels of mitochondrial proteins like TIM23, TOM20, and PINK1 in each group, particularly the elevated levels of PINK1 in AKI model groups and lower levels of TIM23 and TOM20 in the c-Myc overexpression group, suggest potential disruptions in mitochondrial dynamics and homeostasis, indicating enhanced mitophagy or mitochondrial loss. Therefore, arginine-methylated c-Myc affects mouse kidney injury by regulating mitochondrial ATP and ROS, and mitophagy via Slc25a24.

Non-destructive prediction of isoflavone and starch by hyperspectral imaging and deep learning in Puerariae Thomsonii Radix.

Accurate assessment of isoflavone and starch content in Puerariae Thomsonii Radix (PTR) is crucial for ensuring its quality. However, conventional measurement methods often suffer from time-consuming and labor-intensive procedures. In this study, we propose an innovative and efficient approach that harnesses hyperspectral imaging (HSI) technology and deep learning (DL) to predict the content of isoflavones (puerarin, puerarin apioside, daidzin, daidzein) and starch in PTR. Specifically, we develop a one-dimensional convolutional neural network (1DCNN) model and compare its predictive performance with traditional methods, including partial least squares regression (PLSR), support vector regression (SVR), and CatBoost. To optimize the prediction process, we employ various spectral preprocessing techniques and wavelength selection algorithms. Experimental results unequivocally demonstrate the superior performance of the DL model, achieving exceptional performance with mean coefficient of determination (R2) values surpassing 0.9 for all components. This research underscores the potential of integrating HSI technology with DL methods, thereby establishing the feasibility of HSI as an efficient and non-destructive tool for predicting the content of isoflavones and starch in PTR. Moreover, this methodology holds great promise for enhancing efficiency in quality control within the food industry.

Construction of an OCP-ATR-FTIR Spectroscopy Device to In Situ Monitor the Interfacial Reaction of Contaminants: Competitive Adsorption of Cr(VI) and Oxalate on Hematite.

The comprehensive understanding of contaminant interfacial behavior strongly depends on the in situ characterization technique, which is still a great challenge. In this study, we constructed a device integrated with open-circuit potentialand attenuated total reflectance Fourier transform infrared (OCP-ATR-FTIR) spectroscopy to simultaneously monitor the electrochemical and infrared spectral information on the interfacial reaction for the process analysis, taking the competitive adsorption of hexavalent chromium (Cr(VI)) and oxalate on hematite nanocubes (HNC) as an example. The synchronous OCP and infrared results revealed that Cr(VI) interacted with HNC via bidentate binuclear inner-sphere coordination, accompanied by electron transfer from HNC to Cr(VI), while oxalate was adsorbed on HNC through bidentate mononuclear side-on inner-sphere coordination with electron transfer from HNC to oxalate, and also outer-sphere coordination with negative charge accumulation. When oxalate was added to HNC with preadsorbed Cr(VI), oxalate would occupy the inner-sphere adsorption sites and thus cause the detaching of preadsorbed Cr(VI) from HNC. This study provides a promising in situ characterization technique for real-time interfacial reaction monitoring and also sheds light on the competitive adsorption mechanism of oxalate and Cr(VI) on the mineral surface.

Triangle Cl-Ag1 -Cl Sites for Superior Photocatalytic Molecular Oxygen Activation and NO Oxidation of BiOCl.

BiOCl photocatalysis shows great promise for molecular oxygen activation and NO oxidation, but its selective transformation of NO to immobilized nitrate without toxic NO2 emission is still a great challenge, because of uncontrollable reaction intermediates and pathways. In this study, we demonstrate that the introduction of triangle Cl-Ag1 -Cl sites on a Cl-terminated, (001) facet-exposed BiOCl can selectively promote one-electron activation of reactant molecular oxygen to intermediate superoxide radicals (⋅O2 - ), and also shift the adsorption configuration of product NO3 - from the weak monodentate binding mode to a strong bidentate mode to avoid unfavorable photolysis. By simultaneously tuning intermediates and products, the Cl-Ag1 -Cl-landen BiOCl achieved >90 % NO conversion to favorable NO3 - of high selectivity (>97 %) in 10 min under visible light, with the undesired NO2 concentration below 20 ppb. Both the activity and the selectivity of Cl-Ag1 -Cl sites surpass those of BiOCl surface sites (38 % NO conversion, 67 % NO3 - selectivity) or control O-Ag1 -O sites on a benchmark photocatalyst P25 (67 % NO conversion and 87 % NO3 - selectivity). This study develops new single-atom sites for the performance enhancement of semiconductor photocatalysts, and also provides a facile pathway to manipulate the reactive oxygen species production for efficient pollutant removal.

Preparation of Li3V2(PO4)3 as cathode material for aqueous zinc ion batteries by a hydrothermal assisted sol-gel method and its properties.

To alleviate the depletion of lithium resources and improve battery capacity and rate capacity, the development of aqueous zinc-ion batteries (AZIBs) is crucial. The open channels monoclinic structure Li3V2(PO4)3 is conducive to the transfer and diffusion of guest ions, making it a promising cathode material for AZIBs. Therefore, in this study, nanoneedles and particles Li3V2(PO4)3 cathode materials for AZIBs were prepared by a hydrothermal assisted sol-gel method, and the effect of synthesized pH values was studied. XRD results show that all samples had the monoclinic structure, and the Li3V2(PO4)3 sample prepared at pH = 7 exhibits (LVP-pH7) the highest peak tips and narrowest peak widths. SEM images demonstrate that all samples have the morphology character of randomly oriented needles and irregular particles, with the LVP-pH7 sample having more needle-like particles that contribute to ion diffusion. EDS results show uniform distribution of P, V, and O elements in the LVP-pH7 sample, and no obvious aggregation phenomenon is observed. Electrochemical tests have shown that the LVP-pH7 sample exhibits excellent cycling performance (97.37% after 50 cycles at 200 mA g-1) and rate ability compared to other samples. The CV test results showed that compared with other samples, the LVP-pH7 sample had the most excellent ionic diffusion coefficient (2.44 × 10-12 cm2 s-1). Additionally, the Rct of LVP-pH7 is the lowest (319.83 Ω) according to the findings of EIS and Nyquist plot fitting, showing a decreased charge transfer resistance and raising the kinetics of the reaction.

Ionic Conductivity and Cycling Performance in PEO Polymer Electrolyte Enhanced by Non-Milled In Situ Nano-LLZO Powders.

High Li+ conductivity, good interfacial compatibility, and nano-scale particle size have always been essential conditions for selecting inorganic fillers in high-performance composite solid electrolytes. In this study, non-milled in situ LLZO fillers with nanosize was synthesized via the sol-gel method by rapid heating sintering, which resulted in more surface defects and fewer impurities in LLZO. Compared with milled LLZO fillers, these non-milled LLZO fillers with more surface defects and fewer impurities can effectively reduce the crystallinity of PEO and agglomeration in PEO, which can form composite electrolytes with high Li+ conductivity. Most importantly, the discharge capacity of the 7.5% non-milled LLZO-PEO-based LiFePO4/Li battery is about 135.5 mA h g-1 at 1C and 60 °C. After 100 cycles, the discharge specific capacity remains at 99%. It is worth noting that nano-sized non-milled LLZO will improve the discharge capacity of LiFePO4/Li batteries to 122.1 mA h g-1 at 0.2C and 30 °C.

Dual-Coordination-Induced Poly(vinylidene fluoride)/Li6.4Ga0.2La3Zr2O12/Succinonitrile Composite Solid Electrolytes Toward Enhanced Rate Performance in All-Solid-State Lithium Batteries.

Pursuing high energy and power density in all-solid-state lithium batteries (ASSLBs) has been the focus of attention. However, due to their inferior ion transport, their rate performance is limited compared to traditional lithium-ion batteries. Herein, a dual-coordination mechanism is first proposed to construct a high-performance poly(vinylidene fluoride)/Li6.4Ga0.2La3Zr2O12/succinonitrile (PVDF/LLZO/SN) composite solid electrolyte. The dual-coordination interactions of SN with both LLZO and Li+ in lithium salts allow SN to act like a branched chain of PVDF, realizing an increase in the free volume of the composite electrolyte. Meanwhile, SN molecules are immobilized within the electrolyte membrane by coordinating with LLZO, ensuring good interfacial stability. Profiting from the dual-coordination mechanism, the PVDF/LLZO/SN composite solid electrolyte combines enhanced electrochemical performance and interfacial compatibility. When applied to ASSLBs, the composite solid electrolyte enables the battery to operate at rates up to 6 C. The LiFePO4/Li batteries operated at 4 C can still deliver a high capacity retention rate of 96.4% after 50 cycles. Notably, these batteries also exhibit good long-cycle stability. After 500 cycles at 0.5 C, the discharge capacity was maintained at 145.9 mAh g-1.

Predicting the prognosis of HER2-positive breast cancer patients by fusing pathological whole slide images and clinical features using multiple instance learning.

In 2022, breast cancer will become an important factor affecting women's public health and HER2 positivity for approximately 15-20$ \% $ invasive breast cancer cases. Follow-up data for HER2-positive patients are rare, and research on prognosis and auxiliary diagnosis is still limited. In light of the findings obtained from the analysis of clinical features, we have developed a novel multiple instance learning (MIL) fusion model that integrates hematoxylin-eosin (HE) pathological images and clinical features to accurately predict the prognostic risk of patients. Specifically, we segmented the HE pathology images of patients into patches, clustered them by K-means, aggregated them into a bag feature-level representation through graph attention networks (GATs) and multihead attention networks, and fused them with clinical features to predict the prognosis of patients. We divided West China Hospital (WCH) patients (n = 1069) into a training cohort and internal validation cohort and used The Cancer Genome Atlas (TCGA) patients (n = 160) as an external test cohort. The 3-fold average C-index of the proposed OS-based model was 0.668, the C-index of the WCH test set was 0.765, and the C-index of the TCGA independent test set was 0.726. By plotting the Kaplan-Meier curve, the fusion feature (P = 0.034) model distinguished high- and low-risk groups more accurately than clinical features (P = 0.19). The MIL model can directly analyze a large number of unlabeled pathological images, and the multimodal model is more accurate than the unimodal models in predicting Her2-positive breast cancer prognosis based on large amounts of data.

Electrochemical generation of hydrogen peroxide from a zinc gallium oxide anode with dual active sites.

Electrochemical water oxidation enables the conversion of H2O to H2O2. It holds distinct advantages to the O2 reduction reaction, which is restricted by the inefficient mass transfer and limited solubility of O2 in aqueous media. Nonetheless, most reported anodes suffer from high overpotentials (usually >1000 mV) and low selectivity. Electrolysis at high overpotentials often causes serious decomposition of peroxides and leads to declined selectivity. Herein, we report a ZnGa2O4 anode with dual active sites to improve the selectivity and resist the decomposition of peroxides. Its faradaic efficiency reaches 82% at 2.3 V versus RHE for H2O2 generation through both direct (via OH-) and indirect (via HCO3-) pathways. The percarbonate is the critical species generated through the conversion of bicarbonate at Ga-Ga dual sites. The peroxy bond is stable on the surface of the ZnGa2O4 anode, significantly improving faradaic efficiency.

Risk assessment of combined exposure to lead, cadmium, and total mercury among the elderly in Shanghai, China.

Lead (Pb), cadmium (Cd) and total mercury (THg) are toxic heavy metals (THMs) that are widely present in the environment and can cause substantial health problems. However, previous risk assessment studies have rarely focused on the elderly population and have usually targeted a single heavy metal, which might underestimate the long-term accumulative and synergistic effects of THMs in humans. Based on the food frequency questionnaire and inductively coupled plasma mass spectrometry, this study assessed external and internal exposures to Pb, Cd and THg in 1747 elderly people in Shanghai. Probabilistic risk assessment with the relative potential factor (RPF) model was used to assess the neurotoxicity and nephrotoxicity risks of combined THMs exposures. The mean external exposures of Pb, Cd and THg in Shanghai elderly were 46.8, 27.2 and 4.9 µg/day, respectively. Plant-based foods are the main source of Pb and THg exposure, while Cd is mainly from animal-based foods. The mean concentrations of Pb, Cd and THg were 23.3, 1.1 and 2.3 µg/L in the whole blood, and 6.2, 1.0 and 2.0 µg/L in the morning urine, respectively. Combined exposure to THMs leading to 10.0 % and 7.1 % of Shanghai elderly at risk of neurotoxicity and nephrotoxicity. The results of this study have important implications for understanding the profiles of Pb, Cd and THg exposure in the elderly living in Shanghai and provide data support for risk assessment and control of nephrotoxicity and neurotoxicity from combined THMs exposure in the elderly.

Raman spectroscopic and microscopic monitoring of on-site and in-situ remediation dynamics in petroleum contaminated soil and groundwater.

The mechanistic study of soil and groundwater remediation in petroleum contaminated lands significantly demands rapid qualitative and quantitative identification of petroleum substances. However, most traditional detection methods cannot provide the on-site or in-situ information of petroleum compositions and contents simultaneously even with multi-spot sampling and complex sample preparation. In this work, we developed a strategy for the on-site detection of petroleum compositions and in-situ monitoring of petroleum contents in soil and groundwater using dual-excitation Raman spectroscopy and microscopy. The detection time was 0.5 h for the Extraction-Raman spectroscopy method and one minute for the Fiber-Raman spectroscopy method. The limit of detection was 94 ppm for the soil samples and 0.46 ppm for the groundwater samples. Meanwhile, the petroleum changes at the soil-groundwater interface were successfully observed by Raman microscopy during the in-situ chemical oxidation remediation processes. The results revealed that hydrogen peroxide oxidation released petroleum from the interior to the surface of soil particles and then to groundwater during the remediation process, while persulfate oxidation only degraded petroleum on the soil surface and in groundwater. This Raman spectroscopic and microscopic method can shed light on the petroleum degradation mechanism in contaminated lands, and facilitate the selection of suitable soil and groundwater remediation plans.

Projection of Premature Cancer Mortality in Hunan, China, Through 2030: Modeling Study.

BACKGROUND: The United Nations Sustainable Development Goals for 2030 include reducing premature mortality from noncommunicable diseases by one-third. Although previous modeling studies have predicted premature mortality from noncommunicable diseases, the predictions for cancer and its subcategories are less well understood in China. OBJECTIVE: The aim of this study was to project premature cancer mortality of 10 leading cancers in Hunan Province, China, based on various scenarios of risk factor control so as to establish the priority for future interventions. METHODS: We used data collected between 2009 and 2017 from the Hunan cancer registry annual report as empirical data for projections. The population-attributable fraction was used to disaggregate cancer deaths into parts attributable and unattributable to 10 risk factors: smoking, alcohol use, high BMI, diabetes, physical inactivity, low vegetable and fruit intake, high red meat intake, high salt intake, and high ambient fine particulate matter (PM2.5) levels. The unattributable deaths and the risk factors in the baseline scenario were projected using the proportional change model, assuming constant annual change rates through 2030. The comparative risk assessment theory was used in simulated scenarios to reflect how premature mortality would be affected if the targets for risk factor control were achieved by 2030. RESULTS: The cancer burden in Hunan significantly increased during 2009-2017. If current trends for each risk factor continued to 2030, the total premature deaths from cancers in 2030 would increase to 97,787 in Hunan Province, and the premature mortality (9.74%) would be 44.47% higher than that in 2013 (6.74%). In the combined scenario where all risk factor control targets were achieved, 14.41% of premature cancer mortality among those aged 30-70 years would be avoided compared with the business-as-usual scenario in 2030. Reductions in the prevalence of diabetes, high BMI, ambient PM2.5 levels, and insufficient fruit intake played relatively important roles in decreasing cancer premature mortality. However, the one-third reduction goal would not be achieved for most cancers except gastric cancer. CONCLUSIONS: Existing targets on cancer-related risk factors may have important roles in cancer prevention and control. However, they are not sufficient to achieve the one-third reduction goal in premature cancer mortality in Hunan Province. More aggressive risk control targets should be adopted based on local conditions.

Silencing of adipocyte enhancer-binding protein 1 (AEBP1) alleviates renal fibrosis in vivo and in vitro via inhibition of the ß-catenin signaling pathway.

Renal fibrosis is the common final pathway in many renal diseases regardless of the underlying etiology. Adipocyte enhancer-binding protein 1 (AEBP1) was reported to play a vital role in the development of organ fibrosis, but its role in renal fibrosis has not been reported. Thus, the aim of this study was to investigate the possible function of AEBP1 in renal fibrosis and the mechanism associated with the ß-catenin signaling pathway. A total of 83 genes upregulated after unilateral ureteral obstruction (UUO) were screened from two Gene Expression Omnibus (GEO) datasets and subjected to Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Among them, AEBP1 was enriched in collagen binding and the regulation of collagen fibril organization and was confirmed to be upregulated in UUO kidneys and TGF-ß1-induced cells. Knockdown of AEBP1 ameliorated renal fibrosis via reducing collagen accumulation, inhibiting epithelial-mesenchymal transition and fibroblast transformation, as evidenced by decreases in the expression of collagen I and III, Col1a1, Col3a1, fibronectin, Snail, α-SMA, as well as collagen-specific staining of kidney tissues, whereas the E-cadherin was increased. Besides, AEBP1 silencing inhibited the expression of ß-catenin in nucleus and ß-catenin downstream proteins (Axin2, Myc, and Ccnd1). Continuously active ß-catenin-S33Y further restored the inhibitory effect of AEBP1 silencing on renal fibrosis. These findings indicate that knockdown of AEBP1 could potentially slow down renal fibrosis by blocking the ß-catenin signaling pathway, highlighting the potential of AEBP1 as a therapeutic target for renal fibrosis.

One-off low-dose CT screening of positive nodules in lung cancer: A prospective community-based cohort study.

BACKGROUND: To improve the early stage diagnosis and reduce the lung cancer (LC) mortality for positive nodule (PN) population, data on effectiveness of PN detection using one-off low-dose spiral computed tomography (LDCT) screening are needed to improve the PN management protocol. We evaluate the effectiveness of PN detection and developed a nomogram to predict LC risk for PNs. METHODS: A prospective, community-based cohort study was conducted. We recruited 292,531 eligible candidates during 2012-2018. Individuals at high risk of LC based on risk assessment underwent LDCT screening and were divided into PN and non-PN groups. The effectiveness of PN detection was evaluated in LC incidence, mortality, and all-cause mortality. We performed subgroup analysis of characteristic variables for the association between PN and LC risk. A competing risk model was used to develop the nomogram. RESULTS: Participants (n = 14901) underwent LDCT screening; PNs were detected in 1193 cases (8·0%). After a median follow-up of 6·1 years, 193 were diagnosed with LC (1·3%). Of these, 94 were in the PN group (8·0%). LC incidence, mortality, and all-cause mortality were significantly higher in the PN group (adjusted hazard ratios: 10.60 (7.91-14.20), 7.97 (5.20-12.20), and 1.94 (1.51-2.50), respectively). Additionally, various PN characteristics were associated with an increased probability of developing LC. The C-index value of the nomogram for predicting LC risk of PN individuals was 0·847. CONCLUSIONS: The protocol of PNs management for improvement could focus on specific characteristic population and high-risk PN individuals by nomogram assessment.

Development and validation of tumor-size-stratified prognostic nomograms for patients with uterine sarcoma: A SEER database analysis.

BACKGROUND: Tumor-size-stratified analysis on the prognosis of uterine sarcoma is insufficient. This study aimed to establish the tumor-size-stratified nomograms to predict the 3- and 5-year overall survival (OS) of patients with uterine sarcoma. METHODS: The data analyzed in this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. We collected data from patients with uterine sarcoma diagnosed between 2004 and 2015. According to the median tumor size of 7.8 cm, the enrolled patients were divided into two tumor size (TS) groups: TS <7.8 cm and TS ≥7.8 cm. Patients in each group were randomly divided into the training and validation cohorts with a ratio of 7:3. Chi-square test was used to compare differences between categorical variables. Multivariate Cox regression models were used to identify significant predictors. We calculated the concordance index (C-index) and the area under the receiver operating characteristics curve (AUC) to validate the nomograms. RESULTS: Compared with TS <7.8 cm group, TS ≥7.8 cm group had more patients of 45-64 years group, higher black race prevalence, higher proportion of myometrium tumor, higher stage, and higher grade; In the TS <7.8 cm training cohort, six variables (age, race, marital status, tumor primary site, stage, and grade) were identified as significantly associated with OS in multivariate analysis. However in the TS ≥7.8 cm training cohort, only four variables (surgery on primary site, tumor size, stage, and grade) were significantly identified; The C-index of two nomograms were 0.80 and 0.73 in training cohorts, respectively, and the AUC values for 3- and 5-year OS predictions in training cohorts were all above 0.80. Similar results were observed in validation cohorts. CONCLUSIONS: This study found that the significant prognostic factors were different between two tumor size groups of uterine sarcoma patients. The tumor-size-stratified nomograms, which we constructed and validated, might be useful to predict the probability of survival for patients with uterine sarcoma.

Pyrolysis temperature-switchable Fe-N sites in pharmaceutical sludge biochar toward peroxymonosulfate activation for efficient pollutants degradation.

Pyrolysis of pharmaceutical sludge (PS) is a promising way of safe disposal and to recover energy and resources from waste. The resulting PS biochar (PSBC) is often used as adsorbent, but has seldom been explored as catalyst. Herein we demonstrate that PSBC (0.4 g/L) could efficiently activate peroxymonosulfate (PMS) to 100% degrade 4-chlorophenol (4-CP) with rate constants of 0.42-1.70 min-1, outperforming other reported catalysts. Interestingly, the PMS activation pathway highly depended on PSBC pyrolysis temperature, which produced dominantly high-valent iron species (e.g., FeIVO2+) at low temperature but more sulfate radical (SO4·-) and hydroxyl radical (·OH) at higher temperature, e.g., 0.17, 0.23, 0.12 mmol/L of FeIVO2+ and 0.009, 0.038, 0.102 mmol/L of SO4·-/·OH were produced within 10 min by PSBC-600/PMS, PSBC-800/PMS, and PSBC-1000/PMS, respectively. Characterization, density functional theory (DFT) simulation and Pearson correlation analysis revealed that along with the increase of pyrolysis temperatures, the active sites of PSBC gradually shifted from atomically dispersed N-coordinated Fe moieties (FeNx) to iron nitrides (FexN), which activated PMS to produce FeIVO2+ and SO4·-/·OH, respectively. This study clarifies the structure-activity relationships of PSBC for PMS activation, and opens a new avenue for the treatment and utilization of PS as high value-added resources.