Time-varying contributions of FeII and FeIII to AsV immobilization under anoxic/oxic conditions: The impacts of biochar and dissolved organic carbon.

Engineering black carbon (e.g. biochar) has been widely found in natural environments due to natural processes and extensive applications in engineering systems, and could influence the geochemical processes of coexisting arsenic (AsV) and FeII, especially when they are exposed to oxic conditions. Here, we studied time-varying kinetics and efficiencies of AsV immobilization by solid-phase FeII (FeIIsolid) and FeIII (FeIIIsolid) in FeII-AsV-biochar systems under both anoxic and oxic conditions at pH 7.0, with focuses on the effects of biochar surface and biochar-derived dissolved organic carbon (DOC). Under anoxic conditions, FeII could rapidly immobilize AsV via co-adsorption onto biochar surfaces, which also serves as the dominant pathway of AsV immobilization at the initial stage of reaction (0-5 min) under oxic conditions at high biochar concentrations. Subsequently, with increasing biochar concentrations, FeIIIsolid precipitation from aqueous FeII (FeIIaq) oxidation (5-60 min) starts to play an important role in AsV immobilization but in decreased efficiencies of AsV immobilization per unit iron. In the following stage (60-300 min), FeIIsolid oxidation is suppressed and leads to AsV release into solutions at >1.0 g·L-1 biochar. The decreasing efficiency of AsV immobilization over time is attributed to the gradual release of DOC into solution from biochar particles, which significantly inhibit AsV immobilization when FeIIIsolid is generated from FeIIsolid oxidation in the vicinity of biochar surfaces. Specifically, 4.06 mg·L of biochar-derived DOC can completely inhibit the immobilization of AsV in the 100 µM FeII system under oxic conditions. The findings are crucial to comprehensively understand and predict the behavior of FeII and AsV with coexisting engineering black carbon in natural environments.

LX1 Targets Androgen Receptor Variants and AKR1C3 to overcome Therapy Resistance in Advanced Prostate Cancer.

The development of resistance to current standard-of-care treatments, such as androgen receptor (AR) targeting therapies, remains a major challenge in the management of advanced prostate cancer. There is an urgent need for therapeutic strategies targeting key resistance drivers, such as AR variants like AR-V7 and steroidogenic enzymes like AKR1C3, to improve outcomes for patients with advanced prostate cancer. Here, we designed, synthesized, and characterized a class of LX compounds targeting both AR/AR variants and AKR1C3. Molecular docking indicated that LX compounds bound to the AKR1C3 active sites. LX1 blocked AKR1C3 enzymatic activity, suppressing the conversion of androstenedione into testosterone. LX compounds also reduced AR/AR-V7 expression and downregulated their target genes. In vitro, LX1 inhibited the growth of prostate cancer cells resistant to antiandrogens, including enzalutamide, abiraterone, apalutamide, and darolutamide. Treatment with LX1 in vivo significantly decreased tumor growth, lowered serum PSA levels, and reduced intratumoral testosterone levels, without affecting mouse body weight. Furthermore, LX1 overcame resistance to enzalutamide treatment, and the combination of LX1 with enzalutamide further suppressed tumor growth. Collectively, the dual effect of LX1 in reducing intratumoral testosterone and AR signaling, along with its synergy with standard therapies in resistant models, underscores its potential as a valuable treatment option for advanced prostate cancer.

Effects of ionic strength and bentonite ratio on the migration of Cr(VI) in clayey soil-bentonite engineered barrier.

Soil-bentonite (S-B) barriers have been widely used for heavy metal pollution containment. This study conducted batch adsorption tests and diffusion-through tests to evaluate how ionic strength and bentonite ratio influence the migration of Cr(VI) in natural clay-bentonite mixtures. The test results indicated that the adsorption of Cr(VI) exhibited an obvious anion adsorption effect, the pH of the soil mixture increased with the addition of bentonite, resulting in a decrease in the positive surface charge. This change led to a decrease in Cr(VI) adsorption capacity, from 775.19 mg/kg for pure clay to 378 mg/kg for mixture samples with excessive bentonite. Furthermore, as the ionic strength increases from 0 to 0.1 M, the Cr(VI) adsorption capacity increases slightly due to the weakening of electrostatic repulsion on the clay particle surface, but the effective diffusion coefficient (De) increases by 21.97%. The compression of the diffusion double layer (DDL) under high ionic strength conditions enlarges the diffusion path and enhances the migration of Cr(VI) through the pore flow paths. Moreover, hydrated bentonite effectively fills the interaggregate pores of natural clay, thus creating narrower and more tortuous flow paths. However, excessive bentonite increases the pH value and pore volume, resulting in changes to the soil microstructure and disrupting the continuous skeleton of natural clay, which is unfavorable for Cr(VI) containment. Based on the study of the Cr(VI) contaminated site, a bentonite ratio of 2:10 is recommended for optimal natural performance of the natural clay-bentonite barrier.

Selenium-Mediated Shaping of Citrus Rhizobiome for Promotion in Root Growth and Soil Phosphorus Activation.

Selenium (Se) has been widely reported to affect plant growth, nutrient cycling, and the rhizobiome. However, how Se shapes the rhizobiome and interacts with plants remains largely elusive. Pot and hydroponic experiments were employed to elucidate the regulatory mechanism of Se in the citrus rhizobiome. Compared to the control, soil Se application significantly increased the root biomass (34.7%) and markedly reduced rhizosphere HCl-P, H2O-P, NaHCO3-IP, and residual-P of citrus, which were related to the variation of citrus rhizobiome. Se primarily enriched Proteobacteria and Actinobacteria as well as the phosphorus (P) functional genes phod and pqqc. Further study revealed that Se altered the metabolite profile of root exudate, particularly enhancing the abundance of l-cyclopentylglycine, cycloleucine, l-proline, l-pipecolic acid, and inositol, which played a key role in reshaping the citrus rhizobiome. These metabolites could serve as both nutrient sources and signaling molecules, thus supporting the growth or chemotaxis of the functional microbes. These bacterial taxa have the potential to solubilize P or stimulate plant growth. These findings provide a novel mechanistic understanding of the intriguing interactions between Se, root exudate, and rhizosphere microbiomes, and demonstrate the potential for utilizing Se to regulate rhizobiome function and enhance soil P utilization in citrus cultivation.

Roles of the SOM and clay minerals in alleviating the leaching of Pb, Zn, and Cd from the Pb/Zn smelter soil: Multi-surface model and DFT study.

Soil organic matter (SOM) and clay minerals are important sinks for reactive heavy metals (HMs) and exogenous hydrogen ions (H+). Therefore, HMs are likely to be released into soil porewater under acid rainfall conditions due to the competitive adsorption of H+. However, negligible Lead, Zinc, and Cadmium (<6 ‰) in the Pb/Zn smelter soil were leached, and the effects of SOM and clay minerals on HMs leaching were unclear. Herein, the H+ consumption and HMs redistribution on SOM and clay minerals were quantitated by the multi-surface model and density functional theory calculations to reveal the roles of SOM and clay minerals in alleviating HMs' leaching. Clay minerals consumed 43.2 %-52.0 % of the exogenous H+, serving as the dominant sink for the exogenous H+ due to its high content and hindering H+ competitive adsorption on SOM. Protonation of the functional groups constituted >90 % of the total H+ captured by clay minerals. Meanwhile, some H+ also competed with HMs for adsorption sites on clay minerals due to its 0.497-fold to 1.54-fold higher binding energies than HMs, resulting in the release of HMs. On the contrary, SOM served as an accommodator for taking over the released HMs from clay minerals. The HMs complexation on the low-affinity sites (R-L-) of SOM was responsible for the recapture of HMs. In Ca-enriched soil, the released HMs were also recaptured by SOM via ion exchange on the R-L-Ca+ and the high-affinity sites (R-H-Ca+) sites due to the 30.8 %-178 % higher binding energies of HMs on these sites than those of Ca. As a result, >63.4 % of the released HMs from clay minerals were transferred to the SOM. Thus, the synergy of SOM and clay minerals in alleviating the leaching of HMs in Pb/Zn smelter soils cannot be ignored in risk assessment and soil remediation.

Structure Embedded Nucleus Classification for Histopathology Images.

Nuclei classification provides valuable information for histopathology image analysis. However, the large variations in the appearance of different nuclei types cause difficulties in identifying nuclei. Most neural network based methods are affected by the local receptive field of convolutions, and pay less attention to the spatial distribution of nuclei or the irregular contour shape of a nucleus. In this paper, we first propose a novel polygon-structure feature learning mechanism that transforms a nucleus contour into a sequence of points sampled in order, and employ a recurrent neural network that aggregates the sequential change in distance between key points to obtain learnable shape features. Next, we convert a histopathology image into a graph structure with nuclei as nodes, and build a graph neural network to embed the spatial distribution of nuclei into their representations. To capture the correlations between the categories of nuclei and their surrounding tissue patterns, we further introduce edge features that are defined as the background textures between adjacent nuclei. Lastly, we integrate both polygon and graph structure learning mechanisms into a whole framework that can extract intra and inter-nucleus structural characteristics for nuclei classification. Experimental results show that the proposed framework achieves significant improvements compared to the previous methods. Code and data are made available via https://github.com/lhaof/SENC.

[Real-time traking and virtual reality technology-assisted trauma orthopaedic surgery robot for femoral neck fractures].

OBJECTIVE: To investigate the effectiveness of real-time tracking and virtual reality technology（RTVI） used to assist the intraoperative alignment of the trauma orthopaedic surgery robot for the treatment of femoral neck fractures and its impact on the treatment outcome. METHODS: A retrospective analysis was conducted on 60 patients with femoral neck fractures treated with trauma orthopedic robotic surgery from September 2020 to September 2022. Patients were divided into two groups according to whether RTVI technology was used during surgery to assist robotic surgery. There were 28 patients in the RTVI group （12 males and 16 females）, with an average age of （46.2±9.3） years old ranging from 28 to 60 years old. There were 32 patients in the simple Tianji surgical robot group, including 15 males and 17 females, aged （48.2±7.8） years old ranging from 32 to 58. The number of registered fluoroscopy, operation time, total number of intraoperative fluoroscopy, intraoperative blood loss, and hospitalization time of the two groups of patients were observed and recorded. All patients received regular follow-up after surgery, and hip X-rays were routinely reviewed to record Garden alignment index, fracture healing time, postoperative complications, and Harris score. RESULTS: All 60 patients were followed up. The RTVI group was followed up for 9 to 16 months with an average of （13.0±1.2） months, and the Tianji surgical robot group alone was followed up for 10 to 14 months with an average of （12.0±1.3） months. During the follow-up period, the femoral neck fractures of both groups of patients healed well, and no complications such as internal fixation loosening and incision infection occurred. The number of registered fluoroscopy, operation time, and number of intraoperative fluoroscopy of patients in the RTVI group were significantly better than those in the simple Tianji surgical robot group（P<0.01）. There was no statistically significant difference in intraoperative blood loss, hospital stay, Garden alignment index, fracture healing time, and hip Harris score between two groups（P>0.05）. CONCLUSION: Although RTVI technology assisted by the surgical robot for femoral neck fracture surgery has little impact on its postoperative outcome, it can effectively reduce the operating time, the number of intraoperative X-ray projections, and the risk of intraoperative radiation exposure to patients. It also shortened the learning curve of the operator and better reflected the precision and efficiency of the trauma orthopaedic surgery robot.

The multimodality cell segmentation challenge: toward universal solutions.

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyper-parameters in different experimental settings. Here, we present a multimodality cell segmentation benchmark, comprising more than 1,500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.

Improving Accuracy of In-The-Bag Intraocular Lens Power Calculation in Adult Eyes with Unilateral Subluxated Lenses by Using the Anterior Chamber Depth of the Unaffected Eye.

INTRODUCTION: This study aimed to determine the interchangeability of bilateral anterior chamber depth (ACD) in intraocular lens (IOL) power calculations for cataractous eyes and refractive outcomes using the unaffected fellow eye's ACD in subluxated crystalline lenses. METHODS: The predicted postoperative spherical equivalent (SE) calculated using the Kane formula with and without fellow eye's ACD in 202 cataract patients was compared. Refractive outcomes of the newer formulas (the Kane, Barrett Universal II [BUII], and Pearl-DGS formulas) with affected eye's ACD and with unaffected fellow eye's ACD were compared in 33 eyes with lens subluxation (the affected eye) undergoing in-the-bag IOL implantation. The SD of the prediction error (PE) was assessed using the heteroscedastic method. RESULTS: In 202 paired cataractous eyes, no marked ACD difference was found bilaterally; the predicted SE obtained without the fellow eye's ACD was comparable with that calculated with the fellow eye one (p = 0.90), with a mean absolute difference of 0.03 ± 0.03 D. With the affected eye AL, keratometry, and ACD, the median absolute error (MedAE) was 0.38-0.64 D, and the percentage of PE within ±0.50 D was 30.30-57.58%. The unaffected eye's ACD improved the results (MedAE, 0.35-0.49 D; the percentage of PE within ±0.50 D, 54.55-63.64%). The SDs of the BUII (0.82 D) and Pearl-DGS formulas (0.87 D) with the affected eye's ACD were significantly larger than those of the Kane and Pearl-DGS formulas (both 0.69 D) with the unaffected eye's ACD. CONCLUSION: Bilateral ACD was interchangeable in IOL power calculation for cataractous eyes when using the Kane formula. Unaffected eye's ACD in lieu of affected eye's ACD can enhance the accuracy of newer formulas in patients with unilateral subluxated lenses undergoing in-the-bag IOL implantation.

IGFBP3 promotes resistance to Olaparib via modulating EGFR signaling in advanced prostate cancer.

Olaparib is a pioneering PARP inhibitor (PARPi) approved for treating castration-resistant prostate cancer (CRPC) tumors harboring DNA repair defects, but clinical resistance has been documented. To study acquired resistance, we developed Olaparib-resistant (OlapR) cell lines through chronic Olaparib treatment of LNCaP and C4-2B cell lines. Here, we found that IGFBP3 is highly expressed in acquired (OlapR) and intrinsic (Rv1) models of Olaparib resistance. We show that IGFBP3 expression promotes Olaparib resistance by enhancing DNA repair capacity through activation of EGFR and DNA-PKcs. IGFBP3 depletion enhances efficacy of Olaparib by promoting DNA damage accumulation and subsequently, cell death in resistant models. Mechanistically, we show that silencing IGFBP3 or EGFR expression reduces cell viability and resensitizes OlapR cells to Olaparib treatment. Inhibition of EGFR by Gefitinib suppressed growth of OlapR cells and improved Olaparib sensitivity, thereby phenocopying IGFBP3 inhibition. Collectively, our results highlight IGFBP3 and EGFR as critical mediators of Olaparib resistance.