Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers.

Messenger RNA vaccines lack specificity for dendritic cells (DCs)-the most effective cells at antigen presentation. Here we report the design and performance of a DC-targeting virus-like particle pseudotyped with an engineered Sindbis-virus glycoprotein that recognizes a surface protein on DCs, and packaging mRNA encoding for the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or for the glycoproteins B and D of herpes simplex virus 1. Injection of the DC-targeting SARS-CoV-2 mRNA vaccine in the footpad of mice led to substantially higher and durable antigen-specific immunoglobulin-G titres and cellular immune responses than untargeted virus-like particles and lipid-nanoparticle formulations. The vaccines also protected the mice from infection with SARS-CoV-2 or with herpes simplex virus 1. Virus-like particles with preferential uptake by DCs may facilitate the development of potent prophylactic and therapeutic vaccines.

Identification of restrictive molecules involved in oncolytic virotherapy using genome-wide CRISPR screening.

Oncolytic viruses (OVs) offer a novel approach to treat solid tumors; however, their efficacy is frequently suboptimal due to various limiting factors. To address this challenge, we engineered an OV containing targets for neuron-specific microRNA-124 and Granulocyte-macrophage colony-stimulating factor (GM-CSF), significantly enhancing its neuronal safety while minimally compromising its replication capacity. Moreover, we identified PARP1 as an HSV-1 replication restriction factor using genome-wide CRISPR screening. In models of glioblastoma (GBM) and triple-negative breast cancer (TNBC), we showed that the combination of OV and a PARP inhibitor (PARPi) exhibited superior efficacy compared to either monotherapy. Additionally, single-cell RNA sequencing (scRNA-seq) revealed that this combination therapy sensitized TNBC to immune checkpoint blockade, and the incorporation of an immune checkpoint inhibitor (ICI) further increased the survival rate of tumor-bearing mice. The combination of PARPi and ICI synergistically enhanced the ability of OV to establish durable tumor-specific immune responses. Our study effectively overcomes the inherent limitations of OV therapy, providing valuable insights for the clinical treatment of TNBC, GBM, and other malignancies.

PtPd Atomic Layer Shelled PdCu Hollow Nanoparticles on Partially Unzipped Carbon Nanotubes for Breaking the Activity-Stability Trade-Off toward the Hydrogen Oxidation Reaction in Alkaline Media.

Developing highly active yet stable catalysts for the hydrogen oxidation reaction (HOR) in alkaline media remains a significant challenge. Herein, we designed a novel catalyst of atomic PtPd-layer shelled ultrasmall PdCu hollow nanoparticles (HPdCu NPs) on partially unzipped carbon nanotubes (PtPd@HPdCu/W-CNTs), which can achieve a high mass activity, 5 times that of the benchmark Pt/C, and show exceptional stability with negligible decay after 20,000 cycles of accelerated degradation test. The atomically thin PtPd shell serves as the primary active site for the HOR and a protective layer that prevents Cu leaching. Additionally, the HPdCu substrate not only tunes the adsorption properties of the PtPd layer but also prevents corrosive Pt from reaching the interface between NPs and the carbon support, thereby mitigating carbon corrosion. This work introduces a new strategy that leverages the distinct advantages of multiple components to address the challenges associated with slow kinetics and poor durability toward the HOR.

The Simulation of Ester Lubricants and Their Application in Weak Gel Drilling Fluids.

To enhance the performance and reduce the amount of ester-based lubricants used in weak gel drilling fluids, a shear dynamics simulation under extreme pressure conditions was employed to refine the formulation of the base oil and pressure additives. The simulation results were validated using fatty acid methyl, ethyl, and butyl esters. Fatty acid methyl ester demonstrated the lowest temperature increase and the highest load-bearing capacity post-shear. The four-ball friction test revealed that methyl oleate had a coefficient of friction of 0.0018, approximately a third of that for butyl oleate, confirming the simulation's accuracy. By using methyl oleate as the base oil and oleamide as the pressure-resistant component, the optimal shear stress was achieved with a 10% addition of oleamide. A lubricant composed of 90% methyl oleate and 10% oleamide was tested and showed a coefficient of friction of 0.03 when 0.5% was added to bentonite slurry, indicating a strong lubricating film. Adding 1% of this lubricant to a low gel drilling fluid system did not affect its rheological properties, and the gel structure remained stable after seven days of aging. Field tests at the Fu86-3 well in the Jiangsu Oilfield of Sinopec confirmed that adding 1% of the ester-based lubricant to the drilling fluid significantly improved drilling efficiency, reduced drag by an average of 33%, and increased the drilling rate to 22.12 m/h. This innovation effectively prevents drilling complications and successfully achieves the objectives of enhancing efficiency.

Enhancing Ultraviolet Stability and Performance of Wide Bandgap Perovskite Solar Cells Through Ultraviolet Light-Absorbing Passivator.

Ultraviolet light (UV) has caused tremendous damage to perovskite solar cells (PSCs), degrading the perovskite and shortening their lifetime. Defects act as non-radiative recombination sites, accelerate the degradation process, reduce the efficiency of the device and weaken the stability of solar cell. In this work, to realize efficient and stable p-i-n wide bandgap solar cells under UV, a synergetic strategy utilizing UV light-absorbing passivator, (Trifluoroacetyl) benzotriazole (TFABI), enhance UV photostability and regulate the defect passivation is proposed. By using TFABI, the degradation of the perovskite absorption layer under UV light is suppressed, spectral response is enhanced and the Pb vacancy defects are passivated. As a result, the target device achieves an efficiency of 21.54%, exhibiting excellent long-term stability under 365 nm UV irradiation. After 60 h of irradiation, it retains 85% of its initial value (60 mW cm-2 , RH 25-30%, 25 °C).

Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism.

BACKGROUND: Liver fibrosis is a formidable global medical challenge, with no effective clinical treatment currently available. Yinhuang granule (YHG) is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos. It is frequently used for upper respiratory tract infections, pharyngitis, as well as acute and chronic tonsillitis. AIM: To investigate the potential of YHG in alleviating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. METHODS: To induce a hepatic fibrosis model in mice, this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk. Meanwhile, liver fibrosis mice in the low dose of YHG (0.4 g/kg) and high dose of YHG (0.8 g/kg) groups were orally administered YHG once a day for 4 wk. Serum alanine/aspartate aminotransferase (ALT/AST) activity and liver hydroxyproline content were detected. Sirius red and Masson's trichrome staining assay were conducted. Real-time polymerase chain reaction, western-blot and enzyme-linked immunosorbent assay were conducted. Liver glutathione content, superoxide dismutase activity level, reactive oxygen species and protein carbonylation amount were detected. RESULTS: The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice, as reflected by decreased serum ALT/AST activity and improved liver histological evaluation. YHG also attenuated liver fibrosis, evident through reduced liver hydroxyproline content, improvements in Sirius red and Masson's trichrome staining, and lowered serum hyaluronic acid levels. Furthermore, YHG hindered the activation of hepatic stellate cells (HSCs) and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice. YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-dependent downstream antioxidant genes. In addition, YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice, as demonstrated by increased liver adenosine triphosphate content, mitochondrial DNA levels, and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1. CONCLUSION: YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs, reducing inflammation, alleviating liver oxidative stress damage through Nrf2 activation, and promoting liver mitochondrial biogenesis.

[Tetramethylpyrazine regulates angiogenesis of endothelial cells in cerebral ischemic stroke injury via SIRT1/VEGFA signaling pathway].

This study aims to investigate whether tetramethylpyrazine(TMP) can stimulate angiogenesis in cerebral microvascular endothelial cells and alleviate cerebral ischemic stroke(CIS) and to explore the underlying mechanisms. In the animal study, adult Sprague-Dawley rats(n=15) were assigned into sham surgery(sham), middle cerebral artery occlusion/reperfusion(MCAO/R), and MCAO/R+TMP(intraperitoneal injection of 20 mg·kg~(-1)) groups. The neurological function was evaluated by the Z-Longa method. The cerebral infarction volume was detected by TTC staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression of vascular endothelial growth factor(VEGF), angiopoietin(Ang), and platelet-derived growth factor(PDGF). Immunofluorescence staining was employed to detect Ki67 and the expression of vascular endothelial growth factor A(VEGFA) and slient information regulator 1(SIRT1). Western blot was employed to determine the expression levels of VEGFA, SIRT1, angiopoietin-2(Ang-2), and platelet-derived growth factor B(PDGFB). In the cell study, mouse brain-derived endothelial cells(Bend.3) were cultured, and the optimal concentration of TMP was determined. Then, VEGF, Ang, and PDGF were detected by ELISA after the addition of cabozantinib. Western blot was employed to measure the expression of VEGFA, Ang-2, and PDGFB. Immunofluorescence staining was used to detect CD31, CD34, and Ki67, and the proliferation, migration, and tube formation ability of Bend.3 cells were observed in vitro. Western blot and immunofluorescence staining were performed to measure the expression of SIRT1 and VEGFA after addition of the SIRT1-specific inhibitor selisistat(EX-527). The results showed that compared with the sham group, the MCAO/R group had severe neurological function damage, increased infarction volume, up-regulated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, and PDGFB, and down-regulated expression of Ki67 and SIRT1(P<0.01). Compared with the MCAO/R group, the MCAO/R+TMP group presented alleviated neurological function damage, reduced infarction volume, and activated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, Ki67, and SIRT1(P<0.01). The cell experiments showed that compared with the normal group, Bend.3 cells were activated by oxygen glucose deprivation/reoxygenation(OGD/R) treatment(P<0.05, P<0.01). Compared with the OGD/R group, the OGD/R+TMP group upregulated the expression levels of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, SIRT1, Ki67, CD31, and CD34, enhanced the angiogenic ability of Bend.3 cells without being inhibited by BMS or EX-527(P<0.05, P<0.01, P<0.001). The results suggest that TMP can activate the SIRT1/VEGFA signaling pathway to stimulate angiogenesis and alleviate CIS injury.

Associating Peritoneal Metastasis With T2-Weighted MRI Images in Epithelial Ovarian Cancer Using Deep Learning and Radiomics: A Multicenter Study.

BACKGROUND: The preoperative diagnosis of peritoneal metastasis (PM) in epithelial ovarian cancer (EOC) is challenging and can impact clinical decision-making. PURPOSE: To investigate the performance of T2 -weighted (T2W) MRI-based deep learning (DL) and radiomics methods for PM evaluation in EOC patients. STUDY TYPE: Retrospective. POPULATION: Four hundred seventy-nine patients from five centers, including one training set (N = 297 [mean, 54.87 years]), one internal validation set (N = 75 [mean, 56.67 years]), and two external validation sets (N = 53 [mean, 55.58 years] and N = 54 [mean, 58.22 years]). FIELD STRENGTH/SEQUENCE: 1.5 or 3 T/fat-suppression T2W fast or turbo spin-echo sequence. ASSESSMENT: ResNet-50 was used as the architecture of DL. The largest orthogonal slices of the tumor area, radiomics features, and clinical characteristics were used to construct the DL, radiomics, and clinical models, respectively. The three models were combined using decision-level fusion to create an ensemble model. Diagnostic performances of radiologists and radiology residents with and without model assistance were evaluated. STATISTICAL TESTS: Receiver operating characteristic analysis was used to assess the performances of models. The McNemar test was used to compare sensitivity and specificity. A two-tailed P < 0.05 was considered significant. RESULTS: The ensemble model had the best AUCs, outperforming the DL model (0.844 vs. 0.743, internal validation set; 0.859 vs. 0.737, external validation set I) and clinical model (0.872 vs. 0.730, external validation set II). After model assistance, all readers had significantly improved sensitivity, especially for those with less experience (junior radiologist1, from 0.639 to 0.820; junior radiologist2, from 0.689 to 0.803; resident1, from 0.623 to 0.803; resident2, from 0.541 to 0.738). One resident also had significantly improved specificity (from 0.633 to 0.789). DATA CONCLUSIONS: T2W MRI-based DL and radiomics approaches have the potential to preoperatively predict PM in EOC patients and assist in clinical decision-making. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Apparent diffusion coefficient measurements of bone marrow infiltration patterns in multiple myeloma for the assessment of tumor burden - a feasibility study.

BACKGROUND: The purpose of our study was to explore and compare the tumor burden of different bone marrow infiltration patterns and evaluate the feasibility of apparent diffusion coefficient (ADC) value to identify patterns in multiple myeloma (MM). PATIENTS AND METHODS: Ninety-three patients with newly diagnosed multiple myeloma and 23 controls had undergone routine magnetic resonance imaging (MRI) and diffusion-weighted MRI (DWI) from January 2019 to November 2020. Five bone marrow (BM) infiltration patterns were allocated according to routine MRI. The laboratory data and ADC values of patterns were analyzed and compared. ROC analysis was used to establish the best diagnostic ADC threshold value for identifying these patterns and distinguishing normal pattern from controls. Besides, the correlation between the ADC values of diffuse pattern and the plasma cells ratio was assessed. RESULTS: The values of hemoglobin, beta-2 microglobulin (ß2-MG), plasma cell, M protein, the percentages of stage, high-risk fluorescence in situ hybridization, and ADC values showed significant difference among patterns. ADCmean at a specific value (368.5×10-6 mm2/s) yielded a maximum specificity (95.5%) and sensitivity (92.0%) in diagnosing MM. A specific value (335.5×10-6mm2/s) yielded a maximum specificity (84.7%) and sensitivity (88.0%) in discriminating visually normal pattern in MM from controls. There was a moderate positive correlation between the plasma cells ratio and ADCs of diffuse infiltration patterns (r = 0.648, P < 0.001). CONCLUSIONS: The bone marrow infiltration patterns in MM patients can indicate the tumor burden and ADC value has the ability to discriminate these patterns objectively.

Deep Learning Radiomics Nomogram Based on Magnetic Resonance Imaging for Differentiating Type I/II Epithelial Ovarian Cancer.

RATIONALE AND OBJECTIVES: To develop and validate a T2-weighted magnetic resonance imaging (MRI)-based deep learning radiomics nomogram (DLRN) to differentiate between type I and type II epithelial ovarian cancer (EOC). MATERIALS AND METHODS: This multicenter study incorporated 437 patients from five centers, divided into training (n = 271), internal validation (n = 68), and external validation (n = 98) sets. The deep learning (DL) model was constructed using the largest orthogonal slices of the tumor area. The extracted radiomics features were employed in building the radiomics model. The clinical model was developed based on clinical characteristics. A DLRN was built by integrating the DL signature, radiomics signature, and independent clinical predictors. Model performances were evaluated through receiver operating characteristic (ROC) analysis, Brier score, calibration curve, and decision curve analysis (DCA). The areas under the ROC curve (AUCs) were compared using the DeLong test. A two-tailed P < 0.05 was considered significantly different. RESULTS: The DLRN exhibited satisfactory discrimination between type I and type II EOC with the AUC of 0.888 (95% confidence interval [CI] 0.810, 0.966) and 0.866 (95% CI 0.786, 0.946) in the internal and external validation sets, respectively. These AUCs significantly exceeded those of the clinical model (P = 0.013 and 0.043, in the internal and external validation sets, respectively). The DLRN demonstrated optimal classification accuracy and clinical application value, according to Brier scores, calibration curves, and DCA. CONCLUSION: A T2-weighted MRI-based DLRN showed promising potential in differentiating between type I and type II EOC, which could offer assistance in clinical decision-making.

Organic-Inorganic Hybrid Interfaces Enable the Preparation of Nitrogen-Doped Hollow Carbon Nanospheres as High-Performance Anodes for Lithium and Potassium-Ion Batteries.

An abundant hollow nanostructure is crucial for fast Li+ and K+ diffusion paths and sufficient electrolyte penetration, which creates a highly conductive network for ionic and electronic transport. In this study, we successfully developed a molecular-bridge-linked, organic-inorganic hybrid interface that enables the preparation of in situ nitrogen-doped hollow carbon nanospheres. Moreover, the prepared HCNSs, with high nitrogen content of up to 10.4%, feature homogeneous and regular morphologies. The resulting HCNSs exhibit excellent lithium and potassium storage properties when used as electrode materials. Specifically, the HCNS-800 electrode demonstrates a stable reversible discharge capacity of 642 mA h g-1 at 1000 mA g-1 after 500 cycles for LIBs. Similarly, the electrode maintains a discharge capacity of 205 mA h g-1 at 100 mA g-1 after 500 cycles for KIBs. Moreover, when coupled with a high-mass-loading LiFePO4 cathode to design full cells, the HCNS-800‖LiFePO4 cells provide a specific discharge capacity of 139 mA h g-1 at 0.1 C. These results indicate that the HCNS electrode has promising potential for use in high-energy and environmentally sustainable lithium-based and potassium-based batteries.

Functional Interrogation of Ca2+ Signals in Human Cancer Cells In Vitro and Ex Vivo by Fluorescent Microscopy and Molecular Tools.

Genetically encoded calcium indicators (GECIs) and high-resolution confocal microscopy enable dynamic visualization of calcium signals in cells and tissues. Two-dimensional and 3D biocompatible materials mimic the mechanical microenvironments of tumor and healthy tissues in a programmable manner. Cancer xenograft models and ex vivo functional imaging of tumor slices reveal physiologically relevant functions of calcium dynamics in tumors at different progression stages. Integration of these powerful techniques allows us to quantify, diagnose, model, and understand cancer pathobiology. Here, we describe detailed materials and methods used to establish this integrated interrogation platform, from generating transduced cancer cell lines that stably express CaViar (GCaMP5G + QuasAr2) to in vitro and ex vivo calcium imaging of the cells in 2D/3D hydrogels and tumor tissues. These tools open the possibility for detailed explorations of mechano-electro-chemical network dynamics in living systems.

Dual-energy CT in assessment of thrombus perviousness and its application in predicting outcomes after intravenous thrombolysis in acute ischemic stroke.

PURPOSE: To evaluate the feasibility of using iodine overlay maps reconstructed from dual-energy CT (DECT) to assess thrombus perviousness and investigate its value in predicting outcomes after intravenous thrombolysis in patients with acute ischemic stroke. METHOD: 86 patients with proximal intracranial occlusions of the anterior circulation who underwent intravenous thrombolysis were included in this study. Thrombus iodine concentrations (ICthrombus) and normalized iodine concentrations (NICthrombus) were compared to conventional perviousness parameters (thrombus attenuation increase, TAI; void fraction, ε and CTA-index). The associations between perviousness parameters and outcomes were analyzed by Spearman's correlation and regression analysis. RESULTS: ICthrombus and NICthrombus were significantly correlated with conventional perviousness parameters (P < 0.001). The median ICthrombus was 6.81 (interquartile range [IQR], 4.76-8.73) mg/ml in the favorable functional outcome group, which was higher than 3.52 (IQR, 2.08-6.86) mg/ml in the unfavorable outcome group (P = 0.001). The median NICthrombus was 0.095 (IQR, 0.068-0.116) and 0.054 (IQR, 0.031-0.083) in the favorable and unfavorable outcome groups, respectively (P < 0.001). NICthrombus predicted favorable outcome with a higher area under the curve (AUC) of 0.755 than any conventional perviousness parameter (P < 0.05). In the multivariable regression model, ICthrombus was independently associated with favorable outcome (odds ratio [OR] = 1.472, 95 % CI: 1.154-1.877, P = 0.002) and successful recanalization (OR = 1.356, 95 % CI: 1.093-1.681, P = 0.006). ICthrombus was negatively correlated with the final infarct volume (FIV) (r = -0.262, P = 0.020). Results for NICthrombus were similar. CONCLUSIONS: DECT is of great value in assessing thrombus perviousness. NICthrombus is a meaningful predictor of stroke prognosis and recanalization after intravenous thrombolysis in acute ischemic stroke.

ExosomePurity: tumour purity deconvolution in serum exosomes based on miRNA signatures.

Exosomes cargo tumour-characterized biomolecules secreted from cancer cells and play a pivotal role in tumorigenesis and cancer progression, thus providing their potential for non-invasive cancer monitoring. Since cancer cell-derived exosomes are often mixed with those from healthy cells in liquid biopsy of tumour patients, accurately measuring the purity of tumour cell-derived exosomes is not only critical for the early detection but also essential for unbiased identification of diagnosis biomarkers. Here, we propose 'ExosomePurity', a tumour purity deconvolution model to estimate tumour purity in serum exosomes of cancer patients based on microribonucleic acid (miRNA)-Seq data. We first identify the differently expressed miRNAs as signature to distinguish cancer cell- from healthy cell-derived exosomes. Then, the deconvolution model was developed to estimate the proportions of cancer exosomes and normal exosomes in serum. The purity predicted by the model shows high correlation with actual purity in simulated data and actual data. Moreover, the model is robust under the different levels of noise background. The tumour purity was also used to correct differential expressed gene analysis. ExosomePurity empowers the research community to study non-invasive early diagnosis and to track cancer progression in cancers more efficiently. It is implemented in R and is freely available from GitHub (https://github.com/WangHYLab/ExosomePurity).

Primary assessment of the diversity of Omicron sublineages and the epidemiologic features of autumn/winter 2022 COVID-19 wave in Chinese mainland.

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures, there have been widespread SARS-CoV-2 infections in Chinese mainland. Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai, identifying a large number of sublineages of the SARS-CoV-2 Omicron family. Phylogenetic analysis, coupled with contact history tracing, revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China (BA.5.2 mainly in Guangzhou and Shanghai, and BF.7 mainly in Beijing) and two highly infectious sublineages recently imported from abroad (XBB and BQ.1). Publicly available data from August 31 to November 29, 2022 indicated an overall severe/critical case rate of 0.035% nationwide, while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26, 2022 showed that 20 cases (0.35%) without comorbidities progressed into severe/critical conditions and 153 cases (2.68%) with COVID-19-exacerbated comorbidities progressed into severe/critical conditions. These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases. Furthermore, mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year, whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023, and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival (January 21, 2023). Altogether, these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population, especially in the rural areas, to ensure the country's smooth exit from the ongoing pandemic and accelerate socio-economic recovery.

Isolation and screening of phosphorus solubilizing bacteria from saline alkali soil and their potential for Pb pollution remediation.

The high pH and salinity of saline alkali soil not only seriously restrict the growth of crops, but also aggravate the pollution of heavy metals. The fixation of heavy metals and the regulation of pH by phosphorus solubilizing microorganisms may become a new way to repair heavy mental and improve saline alkali soil. In this study, a saline-alkali resistant bacteria (CZ-B1, CGMCC No: 1.19458) was screened from saline-alkali soil, and its tolerance to salt/alkali/lead stress was investigated by shaking flask experiment. The strain was identified as Bacillus amyloliquefaciens by morphology and 16S rRNA gene sequence analysis. The optimum growth temperature of CZ-B1 is about 35°C-40℃. The maximum salt stress and pH that it can tolerance are 100 g/L and 9 respectively, and its tolerance to Pb2+ can reach 2000 mg/L. The phosphorus release amount of CZ-B1 to Ca3(PO4)2 within 72 h is 91.00-102.73 mg/L. The phosphate solubilizing index in PVK agar medium and NBRIP agar medium are more than 2, which can be defined as phosphate solubilizing bacteria. Moreover, the dissolution of CZ-B1 to phosphorus is mainly attributed to tartaric acid, citric acid and succinic acid in inorganic medium. In addition, the removal rate of Pb2+ by CZ-B1 can reach 90.38% for 500 mg/L. This study found that CZ-B1 can immobilize Pb through three biological mechanisms (organic acid, extracellular polymers and mineralization reaction). The release of succinic acid (10.97 g/L) and citric acid (5.26 g/L) may be the main mechanism to promote the mineralization reaction of CZ-B1 (phosphate and oxalate) and resistance to Pb stress. In addition, the high enrichment of Pb2+ by EPS can increase the rate of extracellular electron transfer and accelerate the mineralization of CZ-B1. The screening and domestication of saline-tolerant phosphorus-solubilizing bacteria not only help to remediate Pb contamination in saline soils, but also can provide P element for plant growth in saline soil.

Access to information on sustainable intensification practices for new agricultural business entities in China.

The adoption of sustainable intensification practices (SIPs) is generally lagging in China, as disseminating new technology to millions of farmers on heterogeneous smallholdings is challenging. Agricultural development strategies emphasise the role of new agricultural business entities (NABEs) in driving smallholder farmers' development. This study used a sustainable intensive apple culture system as an example of an SIP. To understand the effects of different information dissemination channels, extension service attributes, social networking structures, and socioeconomic factors on the efficiency of acquiring information on SIPs by NABEs, we used the censored least absolute deviation to analyse the data obtained from face-to-face interview surveys of 218 NABEs in the Loess Plateau. This study found that direct connections between NABEs and research institutions had the strongest facilitating effect on information acquisition, farm shops had the second strongest effect, agricultural extension agencies had the weakest effect, and field agricultural material promotion workers showed a significant adverse effect. Improving the quality of extension services has a far greater effect on facilitating the acquisition of information on SIPs than does increasing extension intensity. Relying primarily on weak ties to manage plantations significantly facilitated information acquisition, whereas relying on strong ties to manage plantations significantly inhibited acquisition. The study results show that implementing the "research institute + NABEs + smallholder farmers" technology extension model can significantly improve the adoption efficiency of SIPs.

Targeting mTOR Complex 2 in Castration-Resistant Prostate Cancer with Acquired Docetaxel Resistance.

Purpose: Mammalian Target of rapamycin (mTOR) plays a central role in regulating cell growth, proliferation, and cell cycle. The key component of mTORC2 is highly expressed in docetaxel-resistant prostate cells. However, the underlying molecular effects on prostate cells remain unclear. Methods: A docetaxel-resistant human prostate cell line (PC-3/DTX) was constructed to investigate the role of mTORC2 in docetaxel resistance. The lentivirus was transfected into cells to knock down the expression of Rictor, and cell viability was measured by Cell Counting Kit 8 (CCK-8). Flow cytometry was used to analyze the cell cycle, and the changes in related signal cascades were assessed by immunohistochemistry (IHC) staining and Western blot. Results: Docetaxel showed the lowest IC50 (50% inhibitory concentration) in PC-3/DTX cells with sh-RNA. Decreased Rictor expression resulted in a larger proportion of arrested cells in the G0/G1 phase in PC-3/DTX cells. The IC50 values of the AZD8055 group were lower than in the Rapamycin group when treated with docetaxel again. Furthermore, a larger proportion of PC-3/DTX cells were arrested in the G0/G1 phase in the AZD8055 group compared to the Rapamycin group. The IHC results of the prostate cancer tissues from a CRPC patient revealed the over expression of Rictor only, while Raptor expression was unaffected. Conclusion: We investigated the role of mTORC2 signaling on the acquired docetaxel -resistant PC-3 cells to identify potential methods for clinical treatment. MTORC2 expression is essential for docetaxel drug resistance of PC-3 cells. The mTORC1/2 inhibitor AZD8055 caused more significant disruption of mTORC2 kinase activity than the mTORC1 inhibitor Rapamycin, which lead to decreased docetaxel-mediated resistance. Therefore, reversing docetaxel resistance, may become a therapeutic option in the treatment of mCRPC patients.

T2-weighted MRI-based radiomics for discriminating between benign and borderline epithelial ovarian tumors: a multicenter study.

BACKGROUND: Preoperative differentiation between benign and borderline epithelial ovarian tumors (EOTs) is challenging and can significantly impact clinical decision making. The purpose was to investigate whether radiomics based on T2-weighted MRI can discriminate between benign and borderline EOTs preoperatively. METHODS: A total of 417 patients (309, 78, and 30 samples in the training and internal and external validation sets) with pathologically proven benign and borderline EOTs were included in this multicenter study. In total, 1130 radiomics features were extracted from manually delineated tumor volumes of interest on images. The following three different models were constructed and evaluated: radiomics features only (radiomics model); clinical and radiological characteristics only (clinic-radiological model); and a combination of them all (combined model). The diagnostic performances of models were assessed using receiver operating characteristic (ROC) analysis, and area under the ROC curves (AUCs) were compared using the DeLong test. RESULTS: The best machine learning algorithm to distinguish borderline from benign EOTs was the logistic regression. The combined model achieved the best performance in discriminating between benign and borderline EOTs, with an AUC of 0.86 ± 0.07. The radiomics model showed a moderate AUC of 0.82 ± 0.07, outperforming the clinic-radiological model (AUC of 0.79 ± 0.06). In the external validation set, the combined model performed significantly better than the clinic-radiological model (AUCs of 0.86 vs. 0.63, p = 0.021 [DeLong test]). CONCLUSIONS: Radiomics, based on T2-weighted MRI, can provide critical diagnostic information for discriminating between benign and borderline EOTs, thus having the potential to aid personalized treatment options.

The construction of preclinical evidence for the treatment of liver fibrosis with quercetin: A systematic review and meta-analysis.

Quercetin (3,3',4',5,7-pentahydroxyflavone), a flavonoid, is widely found in fruits and vegetables and exerts broad-spectrum pharmacological effects in the liver. Many studies have explored the bioactivity of quercetin in the treatment of liver fibrosis. Hence, through a systematic review and biological mechanism evaluation, this study aimed to construct a body of preclinical evidence for the treatment of liver fibrosis using quercetin. The literature used in this study was mainly obtained from four databases, and the SYRCLE list (10 items) was used to evaluate the quality of the included literature. A meta-analysis of HA, LN, and other indicators was performed via STATA 15.0 software. Subgroup analyses based on animal species and model protocol were performed to further obtain detailed results. Moreover, the therapeutic mechanism of quercetin was summarized in a directed network form based on a comprehensive search of the literature. After screening, a total of 14 articles (comprising 15 studies) involving 254 animals were included. The results from the analysis showed that the corresponding liver function indexes, such as the levels of HA and LN, were significantly improved in the quercetin group compared with the model group, and liver function, such as the levels of AST and ALT, were also improved in the quercetin group. The species- and model-based subgroup analyses of AST and ALT revealed that quercetin exerts a significant effect. The therapeutic mechanism of quercetin was shown to be related to multiple pathways involving anti-inflammatory and antioxidant activities and lipid accumulation, including regulation of the TGF-ß, α-SMA, ROS, and P-AMPK pathways. The results showed that quercetin exerts an obvious effect on liver fibrosis, and more prominent improvement effects on liver function and liver fibrosis indicators were obtained with a dose of 5-200 mg during a treatment course ranging from 4 to 8 weeks. Quercetin might be a promising therapeutic for liver fibrosis.