Trends and predictors of changes in renal function after radical nephrectomy for renal tumours.

BACKGROUND: Chronic kidney disease (CKD) is a common postoperative complication in patients who undergo radical nephrectomy for renal tumours. However, the factors influencing long-term renal function require further investigation. OBJECTIVE: This study was designed to investigate the trends in renal function changes and risk factors for renal function deterioration in renal tumour patients after radical nephrectomy. METHODS: We monitored changes in renal function before and after surgery for 3 years. The progression of renal function was determined by the progression and degradation of CKD stages. Univariate and multivariate logistic regression analyses were used to analyse the causes of renal function progression. RESULTS: We analysed the data of 329 patients with renal tumours who underwent radical nephrectomies between January 2013 and December 2018. In this study, 43.7% of patients had postoperative acute kidney injury (AKI), and 48.3% had CKD at advanced stages. Further research revealed that patients' renal function stabilized 3 months after surgery. Additionally, renal function changes during these 3 months have a substantial impact on the progression of long-term renal function changes in patients. CONCLUSION: AKI may be an indicator of short-term postoperative changes in renal function. Renal function tests should be performed in patients with AKI after radical nephrectomy to monitor the progression of functional impairment, particularly within the first 3 months after radical nephrectomy.

Predictive model of positive surgical margins after radical prostatectomy based on Bayesian network analysis.

Objective: This study aimed to analyze the independent risk factors for marginal positivity after radical prostatectomy and to evaluate the clinical value of the predictive model based on Bayesian network analysis. Methods: We retrospectively analyzed the clinical data from 238 patients who had undergone radical prostatectomy, between June 2018 and May 2022. The general clinical data, prostate specific antigen (PSA)-derived indicators, puncture factors, and magnetic resonance imaging (MRI) characteristics were included as predictive variables, and univariate and multivariate analyses were conducted. We established a nomogram model based on the independent predictors and adopted BayesiaLab software to generate tree-augmented naive (TAN) and naive Bayesian models based on 15 predictor variables. Results: Of the 238 patients included in the study, 103 exhibited positive surgical margins. Univariate analysis revealed that PSA density (PSAD) (P = 0.02), Gleason scores for biopsied tissue (P = 0.002) and the ratio of positive biopsy cores (P < 0.001), preoperative T staging (P < 0.001), and location of abnormal signals (P = 0.002) and the side of the abnormal signal (P = 0.009) were all statistically significant. The area under curve (AUC) of the established nomogram model based on independent predictors was 73.80%, the AUC of the naive Bayesian model based on 15 predictors was 82.71%, and the AUC of the TAN Bayesian model was 80.80%. Conclusion: The predictive model of positive resection margin after radical prostatectomy based on Bayesian network demonstrated high accuracy and usefulness.

A general platform for targeting MHC-II antigens via a single loop.

Class-II major histocompatibility complexes (MHC-IIs) are central to the communications between CD4+ T cells and antigen presenting cells (APCs), but intrinsic structural features associated with MHC-II make it difficult to develop a general targeting system with high affinity and antigen specificity. Here, we introduce a protein platform, Targeted Recognition of Antigen-MHC Complex Reporter for MHC-II (TRACeR-II), to enable the rapid development of peptide-specific MHC-II binders. TRACeR-II has a small helical bundle scaffold and uses an unconventional mechanism to recognize antigens via a single loop. This unique antigen-recognition mechanism renders this platform highly versatile and amenable to direct structural modeling of the interactions with the antigen. We demonstrate that TRACeR-II binders can be rapidly evolved across multiple alleles, while computational protein design can produce specific binding sequences for a SARS-CoV-2 peptide of unknown complex structure. TRACeR-II sheds light on a simple and straightforward approach to address the MHC peptide targeting challenge, without relying on combinatorial selection on complementarity determining region (CDR) loops. It presents a promising basis for further exploration in immune response modulation as well as a broad range of theragnostic applications.

Prediction model of gleason score upgrading after radical prostatectomy based on a bayesian network.

OBJECTIVE: To explore the clinical value of the Gleason score upgrading (GSU) prediction model after radical prostatectomy (RP) based on a Bayesian network. METHODS: The data of 356 patients who underwent prostate biopsy and RP in our hospital from January 2018 to May 2021 were retrospectively analysed. Fourteen risk factors, including age, body mass index (BMI), total prostate-specific antigen (tPSA), prostate volume, total prostate-specific antigen density (PSAD), the number and proportion of positive biopsy cores, PI-RADS score, clinical stage and postoperative pathological characteristics, were included in the analysis. Data were used to establish a prediction model for Gleason score elevation based on the tree augmented naive (TAN) Bayesian algorithm. Moreover, the Bayesia Lab validation function was used to calculate the importance of polymorphic Birnbaum according to the results of the posterior analysis and to obtain the importance of each risk factor. RESULTS: In the overall cohort, 110 patients (30.89%) had GSU. Based on all of the risk factors that were included in this study, the AUC of the model was 81.06%, and the accuracy was 76.64%. The importance ranking results showed that lymphatic metastasis, the number of positive biopsy cores, ISUP stage and PI-RADS score were the top four influencing factors for GSU after RP. CONCLUSIONS: The prediction model of GSU after RP based on a Bayesian network has high accuracy and can more accurately evaluate the Gleason score of prostate biopsy specimens and guide treatment decisions.

Multifunctional Photoelectrochemical Biosensor Based on ZnIn2S4/ZnS QDs@Au-Ag-Reversed Photocurrent of Cu-Metal-Organic Framework Coupled with CRISPR/Cas-12a-Shearing for Assay of Dual Targets.

False positives and negatives in bioanalytical assays remain a persistent problem. Herein, a multifunctional photoelectrochemical (PEC) biosensor based on ZnIn2S4 (ZIS)/ZnS quantum dots (QDs)@Au-Ag-reversed photocurrent of Cu-metal-organic framework (MOF) coupled with CRISPR/Cas-12a-shearing was innovatively developed for assay of dual targets. First, Cu-MOF as a good PEC material shows cathodic photocurrent. Then, numerous ZIS/ZnS QDs were assembled to the Au-Ag nanoparticles (NPs) to prepare a stable and highly amplified signal probe, which can just match the energy level of Cu-MOFs and realized the polarity-reversed photocurrent of Cu-MOF for the first time. As the empty-core nanostructure of Au-Ag NPs has a high specific surface area and low material density, the bimetallic nanocrystal can much increase the reaction rate and improve the redox efficiency. When target CEA-produced cDNA opened the hairpin DNA (HP1 DNA) on the electrode, the ZIS/ZnS QDs@Au-Ag signal probe was conjugated to the electrode via DNA hybridization, achieving a significantly reversed PEC current for CEA detection. Moreover, the specific binding of kanamycin/aptamer generated the acDNA (activator), which can activate the trans-cleavage activity of the CRISPR-CAS12a system on ssDNA, so the signal probe was sheared and caused the obvious decrease of PEC signal for kanamycin detection. The newly developed ZIS/ZnS QDs@Au-Ag NPs displayed excellent PEC properties and reversed photocurrent to MOF and were combined with the unique CRISPR-Cas12a system to achieve sensitive detection of dual targets, which can open a new polarity-reversed PEC sensing platform for rapid and accurate analysis of multiple targets and can effectively avoid false positives results in clinical testing.

Dual-wavelength electrochemiluminescence biosensor based on a multifunctional Zr MOFs@PEI@AuAg nanocomposite with intramolecular self-enhancing effect for simultaneous detection of dual microRNAs.

Rapid parallel detection of multi-targets has always been an exploration aim in electrochemiluminescence (ECL) assays. Herein, a multifunctional nanocomposite of Zr metal-organic frameworks (MOFs) @PEI@AuAg nanoclusters (NCs) with intense and stable dual-wavelength ECL was synthesized for the first time, and used to construct a new ECL biosensor for rapid simultaneous detection of dual targets. Notably, the novel ECL emitter Zr MOFs with high-performance was not only integrated with a co-reactant polyethyleneimine (PEI) to form a unique intramolecular self-enhancing structure, but also loaded a large number of another ECL emitter AuAg NCs, furthermore, AuAg NCs with superior electron transfer property can much enhance the electrical conductivity of the composites, thus achieving the goal of "killing three birds with one stone". Moreover, a unique stable and rigid three-dimensional DNA tetrahedron (TDN) structure was connected with two quenching probes BHQ1 and BHQ3 and immobilized on the composites-modified electrode, so ECL emission of the nanocomposites at two wavelengths of 535 nm and 644 nm were both quenched by resonance energy transfer (RET). In the presence of target miRNAs, the efficient DNA cycling double-amplification processes were performed by using exonuclease (T7 Exo) combined with DNA Walker, thus both quenching groups were separated to restore the ECL at two wavelengths, achieving simultaneous and rapid ECL detection of two miRNAs. Therefore, this present work not only opens a unique nanocomplex with dual wavelength ECL and self-enhancing performance, but also develops a highly sensitive ECL biosensor with promising value for rapid multi-target analysis in clinical fields.

ß-Cyclodextrin-functionalized graphene and metal-organic framework composites for ultrasensitive electrochemical detection of chloramphenicol.

Novel ß-cyclodextrin (ß-CD)@functionalized graphene (G)/Cu-1,3,5-benzenetricarboxylic acid (BTC) composites were in situ prepared using ß-CD functionalized graphene and Cu-BTC, and a new electrochemical sensor for sensitive detection of chloramphenicol (CAP) was developed based on the composites. A series of investigations on the ß-CD@G/Cu-BTC composite material were conducted. The ß-CD functionalized graphene solution has an excellent and stable dispersion effect. The composite was further combined with metal-organic frameworks (MOFs) to overcome the disadvantages of a single material, displaying excellent conductivity and a synergistic catalytic effect on the detection of chloramphenicol; so an electrochemical sensor for CAP detection is developed. An actual sample was also detected using the proposed sensor.

Electrospun Elastic Films Containing AgNW-Bridged MXene Networks as Capacitive Electronic Skins.

Electronic skins (e-skins) are increasingly investigated and applied in wearable devices, but the robustness and convenient production of traditional e-skins are restricted. In this work, electrospun sandwich-structured elastic films (ESEFs) are developed and utilized as capacitive e-skins. The ESEFs consist of two nanocomposite mats as the electrode layers and a sandwiched thermoplastic polyurethane (TPU) mat as the dielectric layer. The nanocomposite mats are composed of thermoplastic polyurethane (TPU) and AgNW-bridged MXene (AgNW, silver nanowire; MXene, Ti3C2Tx) conductive network. The resulting ESEFs achieve a tensile strength of 14.80 MPa, an elongation at break of 270%, and an outstanding antifatigue property. E-skins of such ESEFs have the ability to respond to both strain and pressure with a high gauge factor (GF) (strain: GF = 1.21; pressure: GF = 0.029 kPa-1), wide response range (strain: 0-150%; pressure: 0-70 kPa), low response time, and outstanding stability (2000 cycles). On the basis of integrated sensing performances, such e-skins are further applied in monitoring various mechanical stimuli in daily life, including bending of a plastic plate, joint bending, and swallowing.

Detection of Cu2+ and S2- with fluorescent polymer nanoparticles and bioimaging in HeLa cells.

Novel spherical polymer nanoparticles were synthesized by hyperbranched polyethylenimine (hPEI) and 6-hydroxy-2-naphthaldehyde (HNA) via Schiff base reaction (one-pot reaction), which had great advantages in water solubility and green synthesis. Meanwhile, probe PEI-HNA could quickly detect Cu2+ in the range of 0-60 µM in 30 s with the detection limit of 243 nM. The fluorescence of PEI-HNA-Cu2+ could be recovered by the addition of S2- in 50 s with the detection limit of 227 nM. Based on the excellent optical properties, PEI-HNA has been used in the bioimaging of living cells with excellent cell penetrability and low toxicity. More importantly, PEI-HNA has been doped into filter paper, hydrogel, and nanofibrous film to prepare solid-phase sensors, displaying rapid response and excellent sensitivity. Moreover, the low-cost and simple preparation of these sensors offers great potential and possibilities for industrialization, which could help accelerate the development of sensors in environmental and biological fields.

Capacitive Pressure Sensors Containing Reliefs on Solution-Processable Hydrogel Electrodes.

Highly sensitive capacitive-type pressure sensor has been achieved by fabricating reliefs on solution-processable hydrogel electrodes. Hybrid PVA/PANI hydrogels (PVA, poly(vinyl alcohol); PANI, polyaniline) with a fully physically cross-linked binary network are selected as the electrodes of the pressure sensors. On the basis of the solution processability, reliefs are fabricated on the surface of PVA/PANI hydrogel electrodes by a template method. The gauge factor (GF) is enhanced by introducing reliefs and regulated by controlling the composition and relief dimension of hydrogel electrodes. The optimized pressure sensor containing reliefs achieves the highest GF of 7.70 kPa-1 and a sensing range of 0-7.4 kPa. Furthermore, the freezing and drying problems of the hydrogel sensors are overcome by introducing a binary solvent of water/glycerol and the pressure sensing ability at -18 °C has been achieved. Finally, monitoring of various pressures in daily life, such as joint bending, blowing, and brush writing, is demonstrated using such pressure sensors.

Rapid and Large-Scale Quality Assessment of Two-Dimensional MoS2 Using Sulfur Particles with Optical Visualization.

The efficient nondestructive assessment of quality and homogeneity for two-dimensional (2D) MoS2 is critically important to advance their practical applications. Here, we presented a rapid and large-area assessment method for visually evaluating the quality and uniformity of chemical vapor deposition (CVD)-grown MoS2 monolayers simply with conventional optical microscopes. This was achieved through one-pot adsorbing abundant sulfur particles selectively onto as-grown poorer-quality MoS2 monolayers in a CVD system without any additional treatment. We further revealed that this favorable adsorption of sulfur particles on MoS2 originated from their intrinsic higher-density sulfur vacancies. Based on unadsorbed MoS2 monolayers, superior performance field effect transistors with a mobility of ∼49 cm2 V-1 s-1 were constructed. Importantly, the assessment approach was noninvasive due to the all-vapor-phase and moderate adsorption-desorption process. Our work offers a new route for the performance and yield optimization of devices by quality assessment of 2D semiconductors prior to device fabrication.

Molecular imaging in the second near-infrared window.

In the past decade, noticeable progress has been achieved regarding fluorescence imaging in the second near-infrared (NIR-II) window. Fluorescence imaging in the NIR-II window demonstrates superiorities of deep tissue penetration and high spatial and temporal resolution, which are beneficial for profiling physiological processes. Meanwhile, molecular imaging has emerged as an efficient tool to decipher biological activities on the molecular and cellular level. Extending molecular imaging into the NIR-II window would enhance the imaging performance, providing more detailed and accurate information of the biological system. In this progress report, selected achievements made in NIR-II molecular imaging are summarized. The organization of this report is based on strategies underlying rational designs of NIR-II imaging probes and their applications in molecular imaging are highlighted. This progress report may provide guidance and reference for further development of functional NIR-II probes designed for high-performance molecular imaging.

In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles.

The near-infrared-IIb (NIR-IIb) (1,500-1,700 nm) window is ideal for deep-tissue optical imaging in mammals, but lacks bright and biocompatible probes. Here, we developed biocompatible cubic-phase (α-phase) erbium-based rare-earth nanoparticles (ErNPs) exhibiting bright downconversion luminescence at ~1,600 nm for dynamic imaging of cancer immunotherapy in mice. We used ErNPs functionalized with cross-linked hydrophilic polymer layers attached to anti-PD-L1 (programmed cell death-1 ligand-1) antibody for molecular imaging of PD-L1 in a mouse model of colon cancer and achieved tumor-to-normal tissue signal ratios of ~40. The long luminescence lifetime of ErNPs (~4.6 ms) enabled simultaneous imaging of ErNPs and lead sulfide quantum dots emitting in the same ~1,600 nm window. In vivo NIR-IIb molecular imaging of PD-L1 and CD8 revealed cytotoxic T lymphocytes in the tumor microenvironment in response to immunotherapy, and altered CD8 signals in tumor and spleen due to immune activation. The cross-linked functionalization layer facilitated 90% ErNP excretion within 2 weeks without detectable toxicity in mice.

Light-sheet microscopy in the near-infrared II window.

Non-invasive deep-tissue three-dimensional optical imaging of live mammals with high spatiotemporal resolution is challenging owing to light scattering. We developed near-infrared II (1,000-1,700 nm) light-sheet microscopy with excitation and emission of up to approximately 1,320 nm and 1,700 nm, respectively, for optical sectioning at a penetration depth of approximately 750 µm through live tissues without invasive surgery and at a depth of approximately 2 mm in glycerol-cleared brain tissues. Near-infrared II light-sheet microscopy in normal and oblique configurations enabled in vivo imaging of live mice through intact tissue, revealing abnormal blood flow and T-cell motion in tumor microcirculation and mapping out programmed-death ligand 1 and programmed cell death protein 1 in tumors with cellular resolution. Three-dimensional imaging through the intact mouse head resolved vascular channels between the skull and brain cortex, and allowed monitoring of recruitment of macrophages and microglia to the traumatic brain injury site.

The Latitudinal Patterns of Leaf and Soil C:N:P Stoichiometry in the Loess Plateau of China.

Understanding the spatial patterns and the driving factors of plant leaf and soil stoichiometry are critical for improving the parameterization of future ecological models and to predict the responses of ecosystems to environmental changes. This study aimed to determine how the latitudinal patterns of leaf and soil C:N:P stoichiometry are affected by climate and vegetation types in the dryland ecosystems. The concentrations of leaf C, N, and P in herb community as well as soil nutrient concentrations along a 500-km-long latitudinal gradient in Northern Shaanxi of the Loess Plateau, were measured. The results showed that the soil C, N, P and C:N:P ratios at all three depths (0-10, 10-20, and 20-40 cm) showed significant latitudinal trends (except for soil C:N ratios) (P < 0.01). In general, the soil C, N and C:N:P ratios decreased exponentially while soil P increased first and then decreased with the latitude. The soil C, N, C:P, and N:P ratios at all three depths (0-10, 10-20 and 20-40 cm) were positively correlated with MAT and MAP (P < 0.05), while soil P and C:N ratios at all three depths were weakly correlated with MAT and MAP (P > 0.05). In addition, leaf C:N:P stoichiometry was significantly correlated with the latitude, MAT, and MAP (except for N:P ratios) (P < 0.01), such that, leaf C, C:N, and C:P ratios decreased as the latitude increased and MAT and MAP decreased, and leaf N, P concentrations increased as the latitude increased and MAT and MAP decreased, while leaf N:P ratios were weakly correlated with the latitude, MAT, and MAP (P > 0.05). Furthermore, the leaf C:N:P stoichiometry of herbaceous communities was related to the soil properties (except for soil P), and we found that the C:P ratios between the soil and leaves were strongly correlated. Compared with the global scale, the relatively high N:P ratios indicated that the vegetation growth of the herb community in the dryland of the Loess Plateau was more susceptible to P limitation.