Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

Enantioselective [2π + 2σ] Cycloadditions of Bicyclo[1.1.0]butanes with Vinylazaarenes through Asymmetric Photoredox Catalysis.

Here we present a highly enantioselective [2π + 2σ] photocycloaddition of bicyclo[1.1.0]butanes (BCBs). The reaction uses a variety of vinylazaarenes as partners and is catalyzed by a polycyclic aromatic hydrocarbon (PAH)-containing chiral phosphoric acid as a bifunctional chiral photosensitizer. A wide array of pharmaceutically important bicyclo[2.1.1]hexane (BCH) derivatives have been synthesized with high yields, enantioselectivity, and diastereoselectivity. In addition to the diverse 1-ketocarbonyl-3-substituted BCBs, α/ß-substituted vinylazaarenes are compatible with such an unprecedented photoredox catalytic pathway, resulting in the successful assembly of an all-carbon quaternary stereocenter or two adjacent tertiary stereocenters on the product.

Hydroxylation of Aryl Sulfonium Salts for Phenol Synthesis under Mild Reaction Conditions.

Hydroxylation of aryl sulfonium salts could be realized by utilizing acetohydroxamic acid and oxime as hydroxylative agents in the presence of cesium carbonate as a base, leading to a variety of structurally diverse hydroxylated arenes in 47-95% yields. In addition, the reaction exhibited broad functionality tolerance, and a range of important functional groups (e.g., cyano, nitro, sulfonyl, formyl, keto, and ester) could be well amenable to the mild reaction conditions.

Plasmonic Multi-Layered Built-in Hotspots Nanogaps for Effectively Activating Analytes.

Multi-layered plasmonic nanostructures are able to highly promote the near-field confinement and effectively activate analytes, which are of predominate significance but are extremely challenging. Herein, the semi-open Au core@carved AuAg multi-shell superstructure nanoparticles (multi-Au@Ag-Au NPs, multi = mono, bi, tri, tetra, and penta) are reported with a high designability on electromagnetic field and capability of effectively capturing analytes. By controlling synthetic parameters such as the number of galvanic exchange and Ag growth, multi-Au@Ag-Au NPs are successfully obtained, with tunable layer numbers and asymmetric nanoholes. Due to collective plasmon oscillations of multi-layered built-in nanogaps, the electromagnetic field strength of a single penta-Au@Ag-Au entity reach 48841. More importantly, the penta-Au@Ag-Au NPs show a remarkable light-harvesting capability, which is adaptive to different Raman lasers, supporting high-diversity detection. Additionally, the structural specificity allows analytes to be sufficiently captured into interior hotspots, and further achieve highly sensitive detection with limit of detection down to 3.22 × 10-12  M. This study not only provides an effective pathway for integrating abundant hotspots and activating target molecules in single plasmonic superstructure, but stimulates advancements in SERS substrates for various applications.

Rich-grain-boundary Ni-Co-Se nanowire arrays for fast charge storage in alkaline electrolyte.

In this work, the one-dimensional (1D) Ni-Co-Se nanowire arrays with rich grain-boundaries were prepared through the solvothermal method and gas-phase selenizaiton. The results showed that the structure and crystallization of the Ni-Co-Se nanowire arrays could be modulated through the optimization of selenizaiton time. The optimal Ni-Co-Se electrode sample displayed an area specific capacitance of 242.6µAh cm-2at 30 mA cm-2with a current retention rate of 68.34%. The assembled Ni-Co-Se/Active carbon (AC) electrode-based asymmetric supercapacitor (ASC) showed the area specific capacitances of 329.2µAh cm-2and 225.8µAh cm-2at 3 mA cm-2and 30 mA cm-2, respectively. A 73.33% retention rate of capacitance was observed after 8000 charge/discharge cycles. Besides, the further fabricated all-solid ASC delivered the power densities of 342.94 W kg-1and 3441.33 W kg-1at the energy densities of 37.62 Wh kg-1and 25.81 Wh kg-1, respectively. Those results suggested the potentials of the obtained Ni-Co-Se nanowire arrays as electrode material for the high-performance pseudocapacitors.

Modulating surface electron density of Ni(OH)2 nanosheets with longitudinal Ti3C2Tx MXenenanosheets by Schottky effect toward enhanced hydrogen evolution reaction.

Due to their low cost and excellent electrocatalytic performance, nickel-based hydroxides are widely used as hydrogen evolution catalysts for large-scale hydrogen production by water electrolysis. In this study, a heterostructured composite with improved electron transport and modulated electron surface density was prepared by combining Ni(OH)2 with two-dimensional layered Ti3C2Tx (Ti3C2Tx-MXene). Ni(OH)2 nanosheets were formed on nickel foam (NF) substrates using acid etching, followed by the longitudinal growth of negatively charged Ti3C2Tx-MXene on positively charged Ni(OH)2/NF via electrophoretic deposition. The resulting structure facilitates spontaneous electron transfer from Ti3C2Tx-MXene to Ni(OH)2/NF by means of the Mott-Schottky heterostructure effect and establishes a continuous electron transport path which effectively increases the concentration of active sites, improving hydrogen evolution during water electrolysis. The obtained electrode is characterized by an HER overpotential of 66 mV (vs. RHE) and a Tafel slope of +105 mV dec-1 at a current density of 10 mA cm-2, combined with good electrochemical stability.

Electroacupuncture Ameliorates Depression-Like Behaviors Comorbid to Chronic Neuropathic Pain via Tet1-Mediated Restoration of Adult Neurogenesis.

Although electroacupuncture (EA) stimulation is a widely used therapy for chronic pain and comorbid psychiatric disorders, its long-term effects on chronic neuropathic pain-induced depression and the underlying mechanisms remain elusive. In the present study, we found that EA stimulation was able to restore adult neurogenesis in the ventral dentate gyrus (DG), by both increasing neuronal differentiation and restoring the normal morphology of newborn dendrites, in mice with spared nerve injury surgery. By ablating the Nestin+ neural stem cells (NSCs) via diphtheria toxin fragment A expression, we further proved that neurogenesis in the ventral DG was crucial to the long-term, but not the immediate antidepressant effect of EA, nor was it associated with nociception. Furthermore, we found that the restoration of neurogenesis was dependent on Tet1-mediated epigenetic modification upon EA treatment. Tet1 could bind to the promoter of the Prox1 gene, thus catalyzing its demethylation and facilitating its expression, which finally contributed to the restoration of neurogenesis and amelioration of depression-like behaviors induced by chronic neuropathic pain. Thus, we conclude that EA stimulation restores inhibited Tet1 expression in hippocampal NSCs of mice with chronic neuropathic pain, and increased Tet1 expression ameliorates hypermethylation of Prox1 and restores normal adult neurogenesis in the ventral DG, which contributes to the long-term antidepressant effect of EA.

Interfacial Regulation of ZIF-67 on Bacteria to Generate Bifunctional Sensing Material on Chip for Qualifying Cell-Released Reactive Oxygen Species.

Cell's activities are highly dependent on signal molecules, of which reactive oxygen species of the superoxide anion (O2•-) and hydrogen peroxide (H2O2) are important ones that always work together to regulate biological processes such as apoptosis and oxidative stress. It is of significance to realize simultaneous qualification of O2•- and H2O2 but it still faces challenges particularly in live-cell assay with a complex environment. We report the design of a bifunctional sensing material by interfacially regulating ZIF-67 on bacteria Shewanella putrefaciens to generate cobalt nanoparticles/nitrogen-doped porous carbon nanorods (Co/N-doped CNRs) and its sensing chip for qualifying cell-released O2•- and H2O2. Co/N-doped CNRs exhibit unique properties including porous structure for significantly increased reaction surface area and coordinating Co nanoparticles for rich active sites. The bifunctional Co/N-doped CNRs is used to fabricate the electrochemical sensing chip, which achieves a fast response time (0.5 s for O2•-, 1.9 s for H2O2), a low detection limit (0.69 nM for O2•-, 2.25 µM for H2O2), and a remarkably high sensitivity (792.30 µA·µM-1·cm-2 for O2•-, 153.91 µA·mM-1·cm-2 for H2O2), among the best of reported bifunctional nanozymes.

Mangrove degradation retarded microplastics weathering and affected metabolic activities of microplastics-associated microbes.

Currently, information on microplastics (MPs) weathering characteristics and ecological functions driven by MPs-associated microbes in mangrove ecosystems remains unclear, especially in the degraded areas. Herein, we compared the weathering characteristics of MPs in both undegraded and degraded mangrove sediments, and then explored the potential interactions between their weathering characteristics and microbially-driven functions. After 70 days of incubation, different MPs (including polyethylene PE, polystyrene PS, and polylactic acid PLA) were strongly weathered in mangrove sediments, with significant erosion features. Interestingly, more obvious weathering characteristics were found for MPs in the undegraded mangrove sediments. O/C ratio value of MPs in the undegraded sediments was 2.3-3.0 times greater than that in the degraded ones. Besides, mangrove degradation reduced network complexity among MPs-associated microorganisms and affected their metabolic activities. Bacteria involved in carbon cycle process enriched on nondegradable MPs, whereas abundant bacteria responsible for sulphur cycle were observed on PLA-MPs. Moreover, these relevant bacteria were more abundant on MPs in the undegraded mangrove sediments. Mangrove degradation could directly and indirectly affect MPs weathering process and microbially-driven functions through regulating sediment properties and MPs-associated microbes. During weathering, contact angle and roughness of MPs were key factors influencing the colonisation of hydrocarbon degradation bacteria on MPs.

Novel 2-Benzo[d]thiazolyl-4-quinolinylphenol Skeleton-Based Turn-on Fluorescent Probe for H2S Detection and its Multiple Applications in Water Environment, Foodstuffs, and Living Organisms.

Hydrogen sulfide (H2S) has comprehensive contributions to maintaining the normal operation and stability of organisms, and it also occurs in the wastewater environment and is related to the deterioration of foodstuffs. Therefore, developing high-sensitive detection techniques for tracing H2S is promising and meaningful. Inspired by this, a novel nopinone-based fluorescent probe NPS for the recognition of H2S was designed and synthesized with excellent sensitivity, low limit of detection (79 nM), good selectivity, and wide pH range (5-9). NPS could emit strong yellow fluorescence and its emission intensity showed a remarkable augmentation at 520 nm upon the supplement of H2S. Furthermore, the recognition mechanism of NPS for H2S was verified by the HRMS analysis, 1H NMR spectra titration, and DFT computation. What is more, NPS also had broad applications in the monitoring of real water samples, red wine, beer, and eggs samples, which showed its development prospect and value in environmental pollution, foodstuffs quality analysis fields. NPS also was applied to monitor trace exogenous H2S and bioimaging in living cells and zebrafish.

Signal-enhanced multi-core fiber-based WaveFlex biosensor for ultra-sensitive xanthine detection.

In this work, we introduce a novel multimode fiber (MMF) - seven core fiber (SCF) - MMF (MCM) optical fiber biosensor, also known as the WaveFlex biosensor (plasma wave assisted fiber biosensor), based on localized surface plasmon resonance (LSPR) for qualitative detection of xanthine. Xanthine is a purine base widely distributed in human blood and tissues, and commonly used as an indicator for various disease detections. The MCM sensor incorporates a tapered optical fiber structure, fabricated using the combiner manufacturing system (CMS), and is designed with SCF and MMF. By effectively harnessing LSPR, the sensor boosts the attachment points of biomolecules on the probe surface through immobilized tungsten disulfide (WS2)-thin layers, gold nanoparticles (AuNPs), and carbon nitride quantum dots (C3N-QDs). The functionalization of xanthine oxidase (XO) on the sensing probe further enhances the sensor's specificity. The proposed WaveFlex biosensor exhibits a remarkable sensitivity of 3.2 nm/mM and a low detection limit of 96.75 µM within the linear detection range of 100 - 900 µM. Moreover, the sensor probe demonstrates excellent reusability, reproducibility, stability, and selectivity. With its sensitivity, biocompatibility, and immense potential for detecting human serum and fish products, this WaveFlex biosensor presents a promising platform for future applications.

Electrically responsive photonic crystals with bistable states for low-power electrophoretic color displays.

Electrically responsive photonic crystals are promising materials for electrophoretic color displays with better brightness and color saturation. However, electric field must always be applied to maintain the specific colors, which brings concerns about the power consumption and signal stability and reversibility. Here, we show an electrically responsive photonic crystal with two stable states at 0 V, which are the colored state or the colorless state with ordered or disordered particle arrangement. The color state can be reversibly switched by applying a short-time electrical field, just like in the case of commercial electrophoretic ink. With optimized recipe and electric field, the photonic crystals encapsulated in the prototype display panel are proved to have potentials in high resolution, multi-color, and greyscale display, which lays down a firm basis for reflective displays with low power consumption and good visibility.

Diagnosis of mediastinal cysts: the role and safety of EUS-FNA with 19-gauge needle: a retrospective cohort study.

Background: Mediastinal cysts are uncommon, and their diagnosis remains a clinical challenge, especially for patients with a solid mass on computed tomography (CT). Endoscopic ultrasound (EUS) is considered a valuable method to differentiate mediastinal cysts and EUS-fine needle aspiration (FNA) is a strategy for obtaining specimens from the cysts for cytological diagnosis. This study aims to evaluate the safety and utility of EUS-FNA for diagnosis of mediastinal cysts. Methods: This was a retrospective analysis of patients who underwent EUS-FNA with 19-gauge needle at Tianjin Medical University Cancer Institute and Hospital and were further diagnosed with mediastinal cysts confirmed by cytological and surgical pathological results between January 2016 and December 2020. Safety was estimated by the incidence of reported adverse events (AEs). Patients were followed for 48 hours and 1 week after the EUS-FNA procedure to evaluate AEs. Results: A total of 20 patients were diagnosed with mediastinal cysts using EUS-FNA, yet only 5 were diagnosed by CT. There were 15 patients diagnosed with bronchogenic cyst, 4 with enteric cyst, and 1 with pericardial cyst. The EUS appearance of cyst content varied, ranging from anechoic (4 cases) to hypoechoic (16 cases). AEs occurred in 2/20 (10%) patients after the EUS-FNA indicating an acceptable low rate of AEs. For all anechoic cysts that underwent complete FNA drainage, 3 patients had good prognosis, whereas 1 experienced recurrence. For 16 patients with hypoechoic cysts, adequate tissue was obtained for cytological examination. No patient developed an infection-related complication. Conclusions: For the diagnosis of mediastinal cysts, EUS-FNA was more accurate than CT. The EUS-FNA of mediastinal cysts is safe with an acceptable low rate of AEs when antibiotic prophylaxis is used postoperatively. Cysts containing free-flowing fluid can be achieved with complete needle drainage by a single pass with a 19-gauge needle.

Endoscopic ultrasound-guided fine needle aspiration for smooth benign appearing malignant esophageal stricture: a cross-sectional study.

Background: Endoscopic biopsy is standard for the diagnosis of esophageal malignancy. However, few cases are difficult to diagnose as they present with smooth esophageal stricture with negative biopsy results. We aimed to evaluate the effectiveness and safety of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of biopsy-negative suspected malignant esophageal strictures. Methods: We retrospectively analyzed cases of esophageal stricture with negative biopsies. From September 2016 to November 2021, 50 patients were enrolled. All the patients accepted the EUS-FNA examination. And histological and cytological specimens were obtained from all patients. Clinical, endoscopic, imaging, cytological, and histopathological results were noted and analyzed. Results: A total of 50 patients (40 male and 10 female) were enrolled in this study. The 19G puncture needle was used in 6 cases and the 22G puncture needle was used in 44 cases; an average of 2.7 needles were used per case. Satisfactory specimens were obtained by EUS-FNA for all subjects. All patients were diagnosed as malignant tumor. The diagnosis was confirmed by EUS-FNA biopsies in 98% of patients. Based on the surgical pathology results, there were 16 cases of esophageal squamous cell carcinoma, 2 cases of esophageal metastatic carcinoma, 1 case of esophageal sarcoma, 22 cases of lung cancer, 6 cases of mediastinal lymph node metastasis, and 3 cases of mediastinal tumor. No obvious complications were observed. A total of 5 cases were treated with surgery, 28 with chemotherapy, 3 with chemotherapy + surgery, and 12 with radiotherapy; 2 patients ceased treatment. No obvious complications, such as bleeding and mediastinal infection, were observed. Conclusions: EUS-FNA is effective and safe for the diagnosis of malignant esophageal strictures with smooth overlying esophageal mucosa. EUS-FNA is effective and safe for patients with smooth esophagus stenosis for whom satisfactory cytological and histological specimens can be obtained, and the diagnosis can be confirmed by cytological, histological, and immunohistochemical examinations. It can be used as the first choice for diagnosis and treatment.

High-Precision Colorimetric Sensing by Dynamic Tracking of Solvent Diffusion in Hollow-Sphere Photonic Crystals.

Expensive instruments and complicated data processing are often required to discriminate solvents with similar structures and properties. Colorimetric sensors with high selectivity, low cost, and good portability are highly desirable to simplify such detection tasks. Herein, we report the fabrication of a photonic crystal sensor based on the self-assembled resorcinol formaldehyde (RF) hollow spheres to realize colorimetric sensing of polar solvents, including homologs and isomers based on the saturated diffusion time. The diffusion of solvent molecules through the photonic crystal film exhibits a unique three-step diffusion profile accompanied by a dynamic color change, as determined by the physicochemical properties of the solvent molecules and their interactions with the polymer shells, making it possible to accurately identify the solvent type based on the dynamic reflection spectra or visual perception. With its superior selectivity and sensitivity, this single-component colorimetric sensor represents a straightforward tool for convenient solvent detection and identification.

Ultrafast and Irreversibly Thermochromic SiO2 -PC/PEG Double Layer for Green Thermal Printing.

Traditional thermochromic photonic crystal (PC) usually has a slow and reversible thermal response, which limits its application in thermal printing. Here, the authors develop a thermochromic "SiO2 -PC/PEG" double layer structure with a responding time of milliseconds for fast thermal printing. Controlled by the print-head, the polyethylene glycol (PEG) melts, infiltrates, and solidifies within the interparticle voids, which instantly and irreversibly changes the refractive index and produces the PC pattern. Multicolor printing can be realized by tuning the size and type of colloidal particles. Resolution as high as 300 DPI is achieved to print the high-resolution patterns and then the grayscale patterns based on the control of pixel densities. Different from fiber thermal paper, the "SiO2 -PC/PEG" film has no toxic bisphenol A and possesses superior light stability for keeping the images longer. It is fully compatible with the commercial printer, which provides a mature solution for fast and convenient preparation of PC patterns.

Caregivers' mind-mindedness and rural left-behind young children's insecure attachment: The moderated mediation model of theory of mind and family status.

BACKGROUND: China's rapid development and urbanization since the early 1980s have compelled many rural residents to move from rural to urban areas for work, leaving thousands of children at home. OBJECTIVE: This study tested the mediating effect of children's theory of mind on the relationship between caregivers' mind-mindedness and their children's insecure attachment differently depending on the different family status (the moderator) of left-behind and non-left-behind. PARTICIPANTS: The participants were 3 to 6 years old 74 left-behind children (LBHC) and 89 non-left-behind children (NLBHC). SETTINGS: Participants were from rural counties of central China in Henan province that has experienced a large labor migration. METHODS: A cross-sectional moderated mediation model linked mind-mindedness (independent variable) and insecure attachment (dependent variable) through the theory of mind (mediator) and family status (moderator: left-behind/non-left-behind), controlling for age, gender, and siblings. RESULTS: First, LBHC scored higher on insecure-disorganized attachment than NLBHC. Second, the early childhood theory of mind mediated the relationship between the caregiver's mind-mindedness and young children's insecure attachment. Third, family status moderated the effects of the theory of mind on insecure attachment. The mediating role was established only for the left-behind family, and the lower theory of mind ability was associated with the greater insecure attachment of LBHC. CONCLUSIONS: Our findings highlight the critical role of mind-mindedness, theory of mind, and family status in the attachment theory and clarify the association between different levels of young children's theory of mind and insecure attachment based on family status.

A study on the efficacy of microwave ablation for benign thyroid nodules and related influencing factors.

OBJECTIVES: To explore the efficacy of microwave ablation (MWA) in the treatment of benign thyroid nodules, and analyze related influencing factors. METHODS: The clinical and ultrasound data of 115 patients with 115 benign thyroid nodules treated with MWA were retrospectively analyzed. The volume of nodules at 1, 3, 6, and 12 months after the procedure was obtained, and the volume reduction rate (VRR) at each time point was calculated. With VRR > 90% as the criterion for nodule cure, binary logistic regression was employed to screen the factors that affect the efficacy. RESULTS: ① At 1, 3, 6, and 12 months after the procedure, the volume of nodules continued to decrease, the VRR gradually increased, and the differences at each time point were statistically significant (p < 0.05). A total of 29 (25.21%) nodules disappeared completely at 12 months after the procedure; ② Multivariate stepwise logistic regression showed that there was a statistically significant difference for the internal component of nodules, enhancement mode, and immediate volume after the procedure in determining the ablation efficacy (p < 0.05); ③ The ROC curve was plotted for predicting the efficacy of MWA, with the results showing that the AUC, sensitivity, specificity, and accuracy were 0.82, 67.50, 88.00, 79.10%, respectively; ④ 11 cases (9.56%) had side effects, 10 cases (8.70%) had minor complications, and three cases (2.61%) had major complications. CONCLUSION: MWA is safe and effective in the treatment of benign thyroid nodules. The internal component of nodules, enhancement mode, and immediate volume after the procedure are independent factors that affect the efficacy of ablation.

Metal-Organic Framework-Coated Photonic Crystals for High-Performance Thin-Layer Chromatography.

Traditional SiO2 gel-based thin-layer chromatography (TLC) is unable to separate substances with close structures, and its detection requires dyeing when the sample has neither fluorescence nor ultraviolet (UV) absorption signals. Here, high-performance TLC was developed based on metal-organic framework-coated photonic crystal (MOF/PC) films. Using the MIL-100/PC as the TLC plate, the cresol isomers can now be separated in a 2 cm development distance due to the enhanced adsorption-desorption and the good selectivity from the micropores. Meanwhile, the cresol changes the refractive index of MOF/PC, which produces color changes for sample recognition. Compared to the traditional TLC, the MOF/PC TLC shows much higher selectivity toward the analytes, which fully compensates its limited plate numbers and ensures a high-resolution separation. It also provides a convenient solution for chemical analysis as the detection based on structural color change does not require UV irradiation or dyeing treatment.