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Triple-negative breast cancer (TNBC) is highly heterogeneous, lacks accessible therapeutic targets, and features an immunosuppressive tumor microenvironment (TME). Anthracycline-based chemotherapy remains the primary treatment method for TNBC, while the current popular immune checkpoint inhibitors persistently encounter therapeutic resistance. Therefore, there is an urgent need to explore combined therapeutic strategies to remodel the TME and improve the treatment response. Considering the highly specific homing ability of tumor cell-derived vesicles and the key role of the signal transduction and activation of the transcription factor 3 (STAT3) pathway in TNBC, we propose a synergistic therapeutic strategy that integrates gene therapy, chemotherapy, and immunotherapy based on STAT3 short interfering RNA (siSTAT3) and doxorubicin (DOX)-functionalized tumor-derived extracellular vesicles (TEVs) (siSTAT3-DOX@TEV). The in vitro and in vivo results demonstrate that siSTAT3-DOX@TEV target tumor tissues precisely, downregulate STAT3 expression, and synergistically and efficiently induce immunogenic death, thereby reversing the immunosuppressive TME. Moreover, mass cytometry and immunohistochemistry reveal the local immune activation effect of siSTAT3-DOX@TEV, with a significant increase in M1 macrophages, CD4+T cells, and CD8+T cells in tumor tissues. These results provide strong hints for the development of TEV-based chemo-gene therapeutic agents for TNBC treatment at the clinical level.

This first multicenter real-world study demonstrated that olaparib combined with abiraterone improved survival outcomes in patients with DNA damage repair–deficient metastatic castration-resistant prostate cancer progressing after abiraterone, in comparison to olaparib monotherapy. Our results provide direct evidence of a synergistic effect of olaparib and abiraterone in this setting.

Diagnostic and monitoring for drug-induced liver injury (DILI) predominantly rely on serum aminotransferases. However, owing to their widespread expression across multiple organs, a significant challenge emerges from the absence of reliable biomarkers for DILI diagnosis. Herein, we introduce a concept for DILI detection, circumventing the nonspecific elevation and delayed release of aminotransferases and then straightforwardly focusing on the core feature of DILI, abnormal gene expression caused by drug overdose. The developed full-scale platform integrates the properties of spherical nucleic acids with elaborately designed fluorescence in situhybridization sequences, enabling the sensitive and specific profiling of drug-overdosed miR-122 expression alterations across molecular, cellular, organismal, and clinical scales and effectively bypassing the phenotypic features of disease. Furthermore, the diagnostic efficacies of serum and total RNA extracted from both mouse and human blood samples for DILI diagnosis were analyzed using the receiver operating characteristic curve and principal component analysis. We anticipate that this universal platform holds potential in facilitating DILI diagnosis, therapeutic evaluation, and prognosis.

Concerns over toxic nitrogenous disinfection byproducts (N-DBPs) necessitate identifying their precursors in source water. Natural organic amino compounds are known precursors to N-DBPs. Three Suwannee River (SR) standard reference materials (SRMs), humic acids (HA), fulvic acids (FA), and natural organic matter (NOM), are commonly used to study DBP formation, but the chemical makeup of amino compounds in SRSRMs remains largely unknown. To address this, we combined stable hydrogen/deuterium isotope labeling, HDPairFinder bioinformatics, and nontargeted high-performance liquid chromatography–high-resolution mass spectrometry (HPLC-HRMS) to characterize these compounds in SRSRMs. This method classifies reactive amines, provides accurate masses and MS/MS spectra, and quantifies intensities. We identified 2707 high-quality features with primary and/or secondary amines in SRSRMs and 75% of them having an m/z< 300. Across all three SRSRMs, 327 amino features were detected, while 856, 794, and 200 unique features were found in SRNOM, SRHA, and SRFA, respectively. In North Saskatchewan River (NSR) samples, a total of 6449 amino features were detected, 818 of them matched those in SRSRMs, and 87% of them were different between the two rivers. Using chemical standards, we confirmed 10 compounds and tentatively identified 5 more. This study highlights similarities and differences in reactive N-precursors in SRSRMs and local river water, enhancing the understanding of geo-differences in reactive N-precursors in different source waters.

As wearable and skin-friendly electronic devices become more popular, there is an increasing demand for devices that can smoothly conform to curved surfaces. However, the fabrication of electronic devices that can stretch or compress to fit these curved surfaces without wrinkles is still a challenge to the traditional planar techniques. In this work, we investigate and compare the stretchability and conformability of the “island-bridge” configuration with three different types of interconnects. The serpentine design with appropriate thickness and spacing is found to significantly excel in stretchability and conformability based on both calculations and experimental results. We propose a complete process for fabricating a stretchable interdigital electrode (IDE) array with serpentine interconnects on a polyimide base. These electrodes can sustain their electrical functionality even under 40% strain. Finally, a piezoresistive sensor array is provided on a dome using this stretchable IDE array. The sensor array exhibits outstanding performance both at the individual sensor level and across the array, demonstrating the viability of stretchable serpentine interconnects for curved electronics.

Complex structures and devices, both natural and artificial, can often undergo assembly and disassembly. Assembly and disassembly allow multiple stimuli to initiate, for example, the assembly and disassembly of primary cilia under the control of E3 ubiquitin ligases and deubiquitinases. Although biology relies on such schemes, they are rarely available in materials science. Here, we demonstrate a DNA-functionalized colloidal Au response to endogenous biomarkers to trigger simultaneous assembly and disassembly techniques. Colloidal Au is initially inert because the starting DNA strands are paired and prehybridized. TK1 mRNA competes to bind one of the paired strands and release its complement. The released complement binds to the next colloidal Au to initiate assembly, and APE1 can shear the colloidal Au assembly binding site to initiate disassembly. Our strategy provides temporal and spatial logic control during colloidal Au assembly and disassembly, and this simultaneous assembly and disassembly process can be used for sequential detection and cellular imaging of two biomarkers, effectively reducing signal false-positive results and shortening detection time. This work highlights biomarker-controlled colloidal Au simultaneous assembly and disassembly in ways that are simple and versatile, with the potential to enrich the application scope of DNA nanotechnology and provide an idea for the application of precision medicine testing.

Bimetallic alloy nanoparticles have garnered substantial attention for diverse catalytic applications owing to their abundant active sites and tunable electronic structures, whereas the synthesis of ultrafine alloy nanoparticles with atomic-level homogeneity for bulk-state immiscible couples remains a formidable challenge. Herein, we present the synthesis of RuxCo1–xsolid-solution alloy nanoparticles (ca. 2 nm) across the entire composition range, for highly efficient, durable, and selective CO2hydrogenation to CH4under mild conditions. Notably, Ru0.88Co0.12/TiO2and Ru0.74Co0.26/TiO2catalysts, with 12 and 26 atom % of Ru being substituted by Co, exhibit enhanced catalytic activity compared with the monometallic Ru/TiO2counterparts both in dark and under light irradiation. The comprehensive experimental investigations and density functional theory calculations unveil that the electronic state of Ru is subtly modulated owing to the intimate interaction between Ru and Co in the alloy nanoparticles, and this effect results in the decline in the CO2conversion energy barrier, thus ultimately culminating in an elevated catalytic performance relative to monometallic Ru and Co catalysts. In the photopromoted thermocatalytic process, the photoinduced charge carriers and localized photothermal effect play a pivotal role in facilitating the chemical reaction process, which accounts for the further boosted CO2methanation performance.

Primary plasmacytoma of the stomach is very rare. We describe contrast-enhanced CT and 18F-FAPI-04 PET/CT findings in a patient with primary gastric plasmacytoma and Helicobacter pyloriinfection. The gastric tumor appeared as a large hypervascular polypoid mass on contrast-enhanced CT and showed intense 18F-FAPI-04 uptake with SUVmaxof 11.8 on 18F-FAPI-04 PET/CT.

Background: Prosthetic loosening and infection are still common complications after joint replacement. Over the past few years, single-photon emission computed tomography–computed tomography (SPECT/CT) was widely used and showed unique value based on the combination of anatomic and metabolic information of foci. However, its performance in differentiating between prosthetic loosening and periprosthetic infection after joint replacement is still the focus of clinicians and deserves further investigation. Purpose: This retrospective study was aimed to determine whether bone scintigraphy combined with SPECT/CT still can differentiate prosthetic infection from loosening in patients after joint replacement. The differential efficacy in hip and knee prosthesis was also analyzed. Blood biomarkers for the diagnosis of periprosthetic infection were also evaluated. Patients and methods: Data sets of 74 prosthetic joints (including knees and hips), with suspected prosthetic loosening or infection between 2015 and 2021, were evaluated. Besides the results of nuclear imaging, X-ray images and serum biomarker were also recorded. Telephone follow-up and revision surgery after SPECT/CT were used as a gold standard. The sensitivity and accuracy of different imaging modalities were calculated by Chi-square test. The diagnostic efficacy of imaging methods and serum biomarkers were then analyzed by the area under curve (receiver operating characteristic curves, ROC) in SPSS 26. Results: In all, 47 joints (14 knees and 33 hips) were confirmed as aseptic loosening, while 25 joints (18 knees and 7 hips) were confirmed as infection. The sensitivity and accuracy of SPECT combined with SPECT/CT imaging were the highest (92.86% and 87.84%, respectively). The differential efficacy of bone scintigraphy combined with SPECT/CT imaging was also better than any other single imaging modality. In the analysis of involved prosthesis, prosthetic loosening occurred more in hip prosthesis and knee prosthesis was easily infected (P&lt; 0.05). Finally, the sensitivity of ESR and CRP were 80% and 84%, respectively. Conclusions: Bone scintigraphy with hybrid SPECT/CT remains encouraging in differentiating prosthetic infection from loosening after joint replacement. The diagnostic efficacy of differentiation in hip prosthesis was better than knee. Serum biomarkers cannot be used alone to differentiate prosthetic infection from loosening.

The skin-like pressure and temperature sensing ability is essential for electronic skin, human–machine interactions and soft robotics. The previous studies have primarily addressed single-point detection of either pressure or temperature, whereas the simultaneous mapping of these parameters still remain challenging. This study introduces a sensor array based on an amorphous indium gallium zinc oxide (a-IGZO) thin film transistors (TFTs) that can detect pressure (5.29 kPa $^{-{1}}$ , 0.25 to 16 kPa) and temperature ( ${0}.{55}\times {10}{^{-{2}}}~{^{\circ }}\text {C}^{-1}$ , 20 to 70 °C) simultaneously and independently. Pressure detection is achieved by a temperature-insensitive piezoresistive film coupled with the gate of TFTs. The temperature is detected by a thermistor diode array in a parallel series, where the diode is formed by connecting the gate and drain of TFTs. The integration of TFTs significantly enhance the spatial resolution of pressure sensor array to 50 pixels per square centimeter (PPSC), surpassing that of human skin (approximately 30 PPSC). The development of this dual-parameter and high-density sensor array has profound significance in electronic skin application.

ABSTRACTHigh photocatalytic activity composites of TiO2/acid-activated kaolinite (T/AK) were optimally constructed utilizing a simple hydrothermal method for the high-performance photocatalytic degradation to sodium ethyl xanthate (SEX) in mineral processing wastewater in this work. The synthesized T/AK composites under different preparation conditions were characterized by SEM, TEM, XRD, XPS, and UV-vis DRS to determine their structure, morphology, elemental composition, and photochemical properties. Compared with pristine TiO2and kaolinite, the T/AK composites exhibited enhanced photocatalytic degradation performance to SEX due to their synergistic effects of adsorption and catalysis. The photocatalytic degradation efficiency of 0.4 g/L of 0.6T/AK composites to 30 mg/L of SEX reached 94% in 50 min under optimal preparation conditions, demonstrating that T/AK composites photocatalysts could effectively degrade toxic and corrosive SEX. The active radical studies revealed that the most significant active component in the photocatalytic system is h+ . The enhanced photocatalytic activity originated from its large specific surface area and suppressed the recombination rate of the photogenerated carriers of T/AK composites, which makes them great potential in wastewater treatment of mineral processing.

Carbon dioxide (CO2) hydrogenation to methane (CH4) is regarded as a promising approach for CO2utilization, whereas achieving desirable conversion efficiency under mild conditions remains a significant challenge. Herein, we have identified ultrasmall Ru nanoparticles (∼2.5 nm) anchored on MnCo2O4nanosheets as prospective photothermal catalysts for CO2methanation at ambient pressure with light irradiation. Our findings revealed that MnCo2O4nanosheets exhibit dual functionality as photothermal substrates for localized temperature enhancement and photocatalysts for electron donation. As such, the optimized Ru/MnCo2O4-2 gave a high CH4production rate of 66.3 mmol gcat–1h–1(corresponding to 5.1 mol gRu–1h–1) with 96% CH4selectivity at 230 °C under ambient pressure and light irradiation (420–780 nm, 1.25 W cm–2), outperforming most reported plasmonic metal-based catalysts. The mechanisms behind the intriguing photothermal catalytic performance improvement were substantiated through a comprehensive investigation involving experimental characterizations, numerical simulations and density functional theory (DFT) calculations, which unveiled the synergistic effects of enhanced charge separation efficiency, improved reaction kinetics, facilitated reactant adsorption/activation and accelerated intermediate conversion under light irradiation over Ru/MnCo2O4. A comparison study showed that, with identical external input energy during the reaction, Ru/MnCo2O4-2 had a much higher catalytic efficiency compared to Ru/TiO2and Ru/Al2O3. This study underscores the pivotal role played by photothermal supports and is believed to engender a heightened interest in plasmonic metal nanoparticles anchored on photothermal substrates for CO2methanation under mild conditions.

Most of the current bioinspired sensory neuron (BSN) focus on the single-mode sensory data, due to the problems of power supply and integration complexity when involving multimodal sensing signals. This work presents a bimodal BSN consisting of a piezoelectric nanogenerator and a photosynaptic transistor to implement the tactile-visual fusion. The PNG serving as a tactile sensor can effectively drive and modulate the photosynaptic transistor. Since there is no additional energy supply and moving parts, this bimodal BSN has low consumption but high integration level. The strengthened and modulated synaptic plasticity of the sensory neuron based on the synergistic effect of pressure and light stimuli are demonstrated. The pattern recognition results simulated by artificial neural networks confirm that multiple sense fusion with higher recognition accuracy outperforms the single sense.

Heparin-mimicking polymers (HMPs) are artificially synthesized alternatives to heparin with comparable regulatory effects on protein adsorption and cell behavior. By introducing two major structural elements of HMPs (sulfonate- and glyco-containing units) to different areas of material surfaces, heterogeneous surfaces patterned with different HMPs and homogeneous surfaces patterned with the same HMPs can be obtained. In this work, heterogeneous HMP-patterned poly(dimethylsiloxane) (PDMS) surfaces with sulfonate-containing polySS (pS) and glyco-containing polyMAG (pM) distributed in circular patterns (with a diameter of 300 μm) were prepared (S–M and M–S). Specifically, pS and pM were distributed inside and outside the circles on S–M, respectively, and exchanged their distribution on M–S. Homogeneous HMP-patterned silicone surfaces (SM–SM) where sulfonate- and glyco-containing poly(SS-co-MAG) (pSM) were distributed uniformly were prepared. Vascular cells showed interestingly different behaviors between chemically homogeneous and heterogeneous surfaces. They tended to grow in the sulfonate-modified area on S–M and M–S and were distributed uniformly on SM–SM. Compared with M–S, S–M showed a better promoting effect on the growth of vascular cells. Among all the samples, SM–SM exhibited the highest proliferation density and an optimum spreading state of vascular cells, as well as the highest human umbilical vein endothelial cell (HUVEC) viability (∼99%) and relatively low human umbilical vein smooth muscle cell (HUVSMC) viability (∼72%). By heterogeneous or homogeneous patterning with different structural elements of HMPs, the modified silicone surfaces spatially guided vascular cell distribution and functions. This strategy provides a new surface engineering approach to the study of cell–HMP interactions.

The purity of tandem mass spectrometry (MS/MS) is essential to MS/MS-based metabolite annotation and unknown exploration. This work presents a de novoapproach to cleaning chimeric MS/MS spectra generated in liquid chromatography–tandem mass spectrometry (LC-MS/MS)-based metabolomics. The assumption is that true fragments and their precursors are well correlated across the samples in a study, while false or contamination fragments are rather independent. Using data simulation, this work starts with an investigation of the negative effects of chimeric MS/MS spectra on spectral similarity analysis and molecular networking. Next, the characteristics of true and false fragments in chimeric MS/MS spectra were investigated using MS/MS of chemical standards. We recognized three fragment peak attributes indicative of whether a peak is a false fragment, including (1) intensity ratio fluctuation, (2) appearance rate, and (3) relative intensity. Using these attributes, we tested three machine learning models and identified XGBoost as the best model to achieve an area under the precision–recall curve of 0.98 for a clear separation between true and false fragments. Based on the trained model, we constructed an automated bioinformatic platform, DNMS2Purifier (short for de novo MS2Purifier), for metabolic features from metabolomics studies. DNMS2Purifier recognizes and processes chimeric MS/MS spectra without additional sample analysis or library confirmation. DNMS2Purifer was evaluated on a metabolomics data set generated with different MS/MS precursor isolation windows. It successfully captured the increase in the number of false fragments from the increased isolation window. DNMS2Purifier was also compared to MS2Purifier, an existing MS/MS spectral cleaning tool based on the addition of data-independent acquisition (DIA) analysis. Results indicated that DNMS2Purifier uniquely recognizes false fragments, which complements the previous DIA-based approach. Finally, DNMS2Purifier was demonstrated using a real experimental metabolomics study, showing improved MS/MS spectral quality and leading to an improved spectral match ratio and molecular networking outcome.

The extension of least-squares tensor hypercontracted second- and third-order Møller–Plesset perturbation theory (LS-THC-MP2 and LS-THC-MP3) to open-shell systems is an important development due to the scaling reduction afforded by THC and the ubiquity of molecular ions, radicals, and other open-shell reactive species. The complexity of wavefunction-based quantum-chemical methods such as Møller–Plesset and coupled cluster theory is reflected in the steep scaling of the computational costs with the molecular size. The least-squares tensor hypercontraction (LS-THC) method is an efficient, single-step factorization for the two-electron integral tensor but can also be used to factorize the double excitation amplitudes, leading to significant scaling reduction. Here we extend this promising method to open-shell variants of LS-THC-MP2 and -MP3 by using diagrammatic techniques and explicit spin summation. The accuracy of the resulting methods for open-shell species is benchmarked on standard test systems such as regular alkanes as well as realistic systems involving bond breaking, radical stabilization, and other effects. We find that open-shell LS-THC-MPnmethods exhibit errors highly comparable to those produced by closed-shell LS-THC-MPnand are highly insensitive to particular chemical interactions, geometries, or even moderate spin contamination.

Although diabetic nephropathy (DN) is the leading cause of the end-stage renal disease, the exact regulation mechanisms remain unknown. In this study, we integrated the transcriptomics and proteomics profiles of glomeruli isolated from 50 biopsy-proven DN patients and 25 controls to investigate the latest findings about DN pathogenesis. First, 1152 genes exhibited differential expression at the mRNA or protein level, and 364 showed significant association. These strong correlated genes were divided into four different functional modules. Moreover, a regulatory network of the transcription factors (TFs)–target genes (TGs) was constructed, with 30 TFs upregulated at the protein levels and 265 downstream TGs differentially expressed at the mRNA levels. These TFs are the integration centers of several signal transduction pathways and have tremendous therapeutic potential for regulating the aberrant production of TGs and the pathological process of DN. Furthermore, 29 new DN-specific splice-junction peptides were discovered with high confidence; these peptides may play novel functions in the pathological course of DN. So, our in-depth integrative transcriptomics-proteomics analysis provided deeper insights into the pathogenesis of DN and opened the potential avenue for finding new therapeutic interventions. MS raw files were deposited into the proteomeXchange with the dataset identifier PXD040617.

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Developing an endogenous stimuli-responsive and ultrasensitive DNA sensing platform that contains a logic gate biocomputation for precise cell subtype identification holds great potential for disease diagnosis and prognostic estimation. Herein, a fluorescence-enhanced “OR-AND” DNA logic platform dual-driven by intracellular apurinic/apyrimidinic endonuclease 1 (APE 1) or a DNA strand anchored on membrane protein Mucin 1 (MUC 1) for sensitive and accurate cell subtype identification was rationally designed. The recognition toehold of the traditional activated probe (TP) was restrained by introducing a blocking sequence containing an APE 1 cleavable site (AP-site) that can be either cleaved by APE 1 or replaced by Mk-apt, ensuring the “OR-AND” gated molecular imaging for cell subtype identification. It is worth noting that this “OR-AND” gated design can effectively avoid the missing logical computation caused by membrane protein heterogeneous spatial distribution as a single input. In addition, a benefit from the excellent plasmon-enhanced fluorescence (PEF) ability of Au NSTs is that the detection limit can be decreased by nearly 165 times. Based on this, not only different kinds of MCF-7, HepG2, and L02 cells, but also different breast cancer cell subtypes, including malignant MCF-7, metastatic MDA-MB-231, and nontumorigenic MCF-10A cells, can be accurately identified by the proposed “OR-AND” gated DNA logic platform, indicating the prospect of this simple and universal design in accurate cancer screening.

A visible-light-induced difluoroalkylation of unactivated alkenes by fluoro-containing hypervalent iodine-based difluoroalkylation reagent was achieved for the first time under photo-catalyst-free conditions. Moreover, the same reaction conditions were applicable to the difluoroalkylation of alkynes to give the hydrodifluoroalkylation products in moderate to excellent yields. The readily available reagent, broad substrate scope, and photo-catalyst-free conditions make this protocol an efficient and environmental friendly method for the hydrodifluoroalkylation of alkenes and alkynes.

Highly enantioretentive alcoholysis of epoxides is an important way to synthesize enantiopure β-alkoxy alcohols, which are irreplaceable intermediates demanded by biomedicines, fine chemicals and other industries. In this report, we exploit a series of Zr-based metal–organic frameworks (Zr-MOFs) as the catalysts to achieve high activity and enantioretentivity in the alcoholysis of styrene oxide viamodulating their assembly fashions. It is explored that hcp-UiO-66not only exhibits a ∼10 fold improved catalytic activity than both hxl-CAU-26and fcc-UiO-66of varied assemblies but also maintains superior product enantioretentivity. Theoretic calculations together with experimental proof discloses the origin of distinct catalytic activity caused by different assembly fashions. This assembly modulation strategy offers a potential protocol for seeking high-performance catalysts among MOFs by virtue of their rich polymorphisms.

Nitric oxide (NO) is a crucial cell-signaling molecule utilized in numerous physiological and pathological processes. Monitoring cellular levels of NO requires a sensor with sufficient sensitivity, transient recording capability, and biocompatibility. Owing to the large surface area and high catalytic activity of the metal–organic framework, Fe–BTC was used for the modification of screen-printed electrodes (SPEs). This study investigates the electrochemical sensing of NO on modified SPEs. Additionally, the introduction of a cell-adhesive molecule, arginine–glycine–aspartate peptide (RGD), considerably improved the cytocompatibility, resulting in superior cell attachment and growth on the SPE. The Fe–BTC/RGD-modified SPE (Fe–BTC/RGD/SPE) exhibited electrocatalytic NO oxidation at 0.8 V, demonstrating a linear response with a detection limit of 11.88 nM over a wide concentration range (0.17–47.37 μM) and a response time of approximately 0.9 s. Subsequently, the as-obtained Fe–BTC/RGD/SPE was successfully utilized for the real-time detection of NO released from human endothelial cells cultured on the electrode. Therefore, the study undertaken shows remarkable potential of Fe–BTC/RGD/SPE for practical applications in biological processes and clinical diagnostics.

In this article, we investigated Ytterbium (Yb)-doped Indium-oxide (In2O3)-based thin-film transistor (TFT) prepared by the solution-processed. Indium-Yb-oxide (InYbO) films with different Yb-doping concentrations were prepared by the solution-processed to reveal the variation of physical properties of In2O3 films with the changing of Yb-doping concentration. The results show that Yb-doping can improve the microstructure and surface roughness of In2O3 films and suppress the oxygen vacancy defects. When the Yb-doping concentration reaches 1 mol%, the InYbO-TFT exhibits optimal electrical performance. In addition, the performance of InYbO-TFT under positive bias stability (PBS) test is also significantly improved. The device with 1 mol% Yb concentration shows a voltage shift of 1.27 V after 3600 s of +20 V bias test, which is about $5\times $ stable than the In2O3-TFT. Eventually, based on this InYbO-TFT, a common-source amplifier was designed. This amplifier has a 16.03 dB Gain and a cut-off frequency of 470 Hz with excellent response speed, which shows great application potential.