Neural Network Enables High Accuracy for Hepatitis B Surface Antigen Detection with a Plasmonic Platform.

The detection of hepatitis B surface antigen (HBsAg) is critical in diagnosing hepatitis B virus (HBV) infection. However, existing clinical detection technologies inevitably cause certain inaccuracies, leading to delayed or unwarranted treatment. Here, we introduce a label-free plasmonic biosensing method based on the thickness-sensitive plasmonic coupling, combined with supervised deep learning (DL) using neural networks. The strategy of utilizing neural networks to process output data can reduce the limit of detection (LOD) of the sensor and significantly improve the accuracy (from 93.1%-97.4% to 99%-99.6%). Compared with widely used emerging clinical technologies, our platform achieves accurate decisions with higher sensitivity in a short assay time (∼30 min). The integration of DL models considerably simplifies the readout procedure, resulting in a substantial decrease in processing time. Our findings offer a promising avenue for developing high-precision molecular detection tools for point-of-care (POC) applications.

Preferred Orientation and Phase Distribution of Quasi-2D Perovskite for Bifunctional Light-Emitting Photodetectors.

In traditional optical wireless communication (OWC) systems, the simultaneous use of multiple sets of light-emitting diodes (LEDs) and photodetectors (PDs) increases the system complexity and instability. Here we report bifunctional light-emitting photodetectors (LEPDs) fabricated with quasi-2D perovskite (F-PEA)2Cs4Pb5I11Br5 as light-emitting/detecting layers for efficient, miniaturized, and intelligent bidirectional OWC. By simply changing the solvent composition of the precursor solution and using antisolvent engineering, we manipulated the crystal orientation and phase distribution of (F-PEA)2Cs4Pb5I11Br5, realizing high irradiance (4.36 µW cm-2) and a -3 dB refresh rate (0.21 MHz) of electroluminescence in LED mode as well as low noise (below 1 pA Hz-1/2) and high responsivity (0.1 A W-1) in PD mode. The rapid and accurate OWC process was demonstrated through interaction of LEPDs. We also demonstrated the high-fidelity compression and digitization of high-resolution (256 × 256 pixels) color images using the four-step phase shift method to realize intelligent encrypted image OWC.

Solvent-Reconstructed Interface That Enhances Light Out-Coupling in Quasi-Two-Dimensional Perovskite Light-Emitting Diodes.

Light management is critical to maximizing the external quantum efficiency of perovskite light-emitting diodes (PeLEDs), but strategies for enhancing light out-coupling are typically complex and expensive. Here, using a facile solvent treatment strategy, we create a layer of lithium fluoride (LiF) nanoislands that serve as a template to reconstruct the light-extracting interfaces for PeLEDs. The nanoisland interface rearranges the near-field light distribution in order to maximize the efficiency of internal light extraction. With the proper adjustment of the nanoisland size and distribution, we have achieved an optimal balance between charge injection and light out-coupling, resulting in bright, pure-red quasi-two-dimensional PeLEDs with a 21.8% peak external quantum efficiency.

Structures of the ADGRG2-Gs complex in apo and ligand-bound forms.

Adhesion G protein-coupled receptors are elusive in terms of their structural information and ligands. Here, we solved the cryogenic-electron microscopy (cryo-EM) structure of apo-ADGRG2, an essential membrane receptor for maintaining male fertility, in complex with a Gs trimer. Whereas the formations of two kinks were determinants of the active state, identification of a potential ligand-binding pocket in ADGRG2 facilitated the screening and identification of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate and deoxycorticosterone as potential ligands of ADGRG2. The cryo-EM structures of DHEA-ADGRG2-Gs provided interaction details for DHEA within the seven transmembrane domains of ADGRG2. Collectively, our data provide a structural basis for the activation and signaling of ADGRG2, as well as characterization of steroid hormones as ADGRG2 ligands, which might be used as useful tools for further functional studies of the orphan ADGRG2.

Nanocomposite Hydrogel Bioinks for 3D Bioprinting of Tumor Models.

In vitro tumor models were successfully constructed by 3D bioprinting; however, bioinks with proper viscosity, good biocompatibility, and tunable biophysical and biochemical properties are highly desirable for tumor models that closely recapitulated the main features of native tumors. Here, we developed a nanocomposite hydrogel bioink that was used to construct ovarian and colon cancer models by 3D bioprinting. The nanocomposite bioink was composed of aldehyde-modified cellulose nanocrystals (aCNCs), aldehyde-modified hyaluronic acid (aHA), and gelatin. The hydrogels possessed tunable gelation time, mechanical properties, and printability by controlling the ratio between aCNCs and gelatin. In addition, ovarian and colorectal cancer cells embedded in hydrogels showed high survival rates and rapid growth. By the combination of 3D bioprinting, ovarian and colorectal tumor models were constructed in vitro and used for drug screening. The results showed that gemcitabine had therapeutic effects on ovarian tumor cells. However, the ovarian tumor model showed drug resistance for oxaliplatin treatment.

"All in one" nanoprobe Au-TTF-1 for target FL/CT bioimaging, machine learning technology and imaging-guided photothermal therapy against lung adenocarcinoma.

The accurate preoperative diagnosis and tracking of lung adenocarcinoma is hindered by non-targeting and diffusion of dyes used for marking tumors. Hence, there is an urgent need to develop a practical nanoprobe for tracing lung adenocarcinoma precisely even treating them noninvasively. Herein, Gold nanoclusters (AuNCs) conjugate with thyroid transcription factor-1 (TTF-1) antibody, then multifunctional nanoprobe Au-TTF-1 is designed and synthesized, which underscores the paramount importance of advancing the machine learning diagnosis and bioimaging-guided treatment of lung adenocarcinoma. Bright fluorescence (FL) and strong CT signal of Au-TTF-1 set the stage for tracking. Furthermore, the high specificity of TTF-1 antibody facilitates selective targeting of lung adenocarcinoma cells as compared to common lung epithelial cells, so machine learning software Lung adenocarcinoma auxiliary detection system was designed, which combined with Au-TTF-1 to assist the intelligent recognition of lung adenocarcinoma jointly. Besides, Au-TTF-1 not only contributes to intuitive and targeted visualization, but also guides the following noninvasive photothermal treatment. The boundaries of tumor are light up by Au-TTF-1 for navigation, it penetrates into tumor and implements noninvasive photothermal treatment, resulting in ablating tumors in vivo locally. Above all, Au-TTF-1 serves as a key platform for target bio-imaging navigation, machine learning diagnosis and synergistic PTT as a single nanoprobe, which demonstrates attractive performance on lung adenocarcinoma.

Efficacy of Daiwenjiu ointment on the treatment of cervical spondylosis with nerve root type caused by cold dampness obstruction.

OBJECTIVE: This study aimed to assess the clinical efficacy of Daiwenjiu ointment in the treatment of cervical spondylosis with cold dampness obstruction nerve root type. METHODS: A retrospective analysis was conducted on a cohort of 110 patients diagnosed with cervical spondylotic radiculopathy. Based on the treatment method, the patients were divided into two groups. The control group received electroacupuncture treatment, while the observation group received a combination of Daiwenjiu ointment and electroacupuncture treatment. The outcome measures included Japanese Orthopedic Association (JOA) scores for cervical spine function, Simplified McGill Pain Questionnaire (SF-MPQ) scores, and changes in serum inflammatory factors TNF-α and IL-1ß. RESULTS: Following treatment, the JOA score in the observation group increased from 9.45 ± 1.35 to 14.82 ± 1.29 after treatment, indicating better recovery of cervical spine function compared to the control group (p < 0.001). The SF-MPQ score in the observation group decreased to 18.25 ± 3.80 after treatment, while it remained at 30.20 ± 4.30 in the control group. This difference between the groups was statistically significant (p < 0.001). Furthermore, the observation group demonstrated a significant decrease in serum levels of TNF-α and IL-1ß after treatment compared to the control group (p < 0.001). CONCLUSION: Daiwenjiu ointment exhibits significant therapeutic effects in patients with cold dampness obstruction nerve root type cervical spondylosis. It effectively improves cervical function, reduces pain, and downregulates inflammatory cytokine levels.

Downregulation of IL-11 regulates the TGFß/ERK1/2 signaling pathway to inhibit articular capsule fibrosis and alleviate post-traumatic articular capsule contracture.

BACKGROUND: Post-traumatic capsular contracture is a common complication of joint injury and surgery. Post-traumatic capsular contracture is associated with fibrosis characterized by excessive differentiation and proliferation of myofibroblasts and abnormal secretion and accumulation of extracellular matrix. Previous studies have suggested that IL11 plays a role in myocardial fibrosis. We thus hypothesized that IL11 may play a fibrotic role during capsular contracture, in order to discover new targets for preventing joint capsule contracture METHODS: We constructed a post-traumatic contracture model by excessively extending the knee joint and fixing the joint in the flexion position, and a post-traumatic joint capsule contracture model was constructed in the wild-type, IL11-/-, IL11R -/-, α-SMA-cre-IL11fl/fl, α-SMA-cre-IL11Rfl/fl mouse strain, with wild-type mice without any treatment of the knee joint as the control group. Fibrotic markers and the expression of IL11 and IL11R in knee joint tissue were detected in each group of mice. The NIH3T3 cell line was used for in vitro analyses. The expression of fibrosis markers, IL11, TGFß and ERK1/2 were detected by western blot, ELISA and RT-qPCR. RESULTS: Inhibition of IL11 inhibited ERK1/2 phosphorylation, reduced the secretion of collagen in the joint capsule, and inhibited the excessive differentiation and proliferation of myofibroblasts in the post-traumatic joint capsule contracture, thus alleviating the joint capsule contracture and obtaining better joint mobility. CONCLUSION: Downregulation of IL11 in traumatic joint capsule contracture inhibits ERK1/2 phosphorylation, thus significantly relieving joint capsule contracture. Our findings indicate the TGFß/IL11/ERK1/2 axis is an important pathway for the differentiation of fibroblasts into myofibroblasts. Anti-IL11 treatment is an effective means to prevent traumatic joint capsule contracture.

Naked-Eye Readable Microarray for Rapid Profiling of Antibodies against Multiple SARS-CoV-2 Variants.

Novel high-throughput protein detection technologies are critically needed for population-based large-scale SARS-CoV-2 antibody detection as well as for monitoring quality and duration of immunity against virus variants. Current protein microarray techniques rely heavily on labeled transduction methods that require sophisticated instruments and complex operations, limiting their clinical potential, particularly for point-of-care (POC) applications. Here, we developed a label-free and naked-eye readable microarray (NRM) based on a thickness-sensing plasmon ruler, enabling antibody profiling within 30 min. The NRM chips provide 100% accuracy for neutralizing antibody detection by efficiently screening antigen types and experimental conditions and allow for the profiling of antibodies against multiple SARS-CoV-2 variants in clinical samples. We further established a flexible "barcode" NRM assay with a simple tape-based operation, enabling an effective smartphone-based readout and analysis. These results demonstrate new strategies for high-throughput protein detection and highlight the potential of novel protein microarray techniques for realistic clinical applications.

Three-Dimensional Histological Electrophoresis for High-Throughput Cancer Margin Detection in Multiple Types of Tumor Specimens.

Accurate identification of tumor margins during cancer surgeries relies on a rapid detection technique that can perform high-throughput detection of multiple suspected tumor lesions at the same time. Unfortunately, the conventional histopathological analysis of frozen tissue sections, which is considered the gold standard, often demonstrates considerable variability, especially in many regions without adequate access to trained pathologists. Therefore, there is a clinical need for a multitumor-suitable complementary tool that can accurately and high-throughput assess tumor margins in every direction within the surgically resected tissue. We herein describe a high-throughput three-dimensional (3D) histological electrophoresis device that uses tumor-specific proteins to identify and contour tumor margins intraoperatively. Testing on seven cell-line xenograft models and human cervical cancer models (representing five types of tissues) demonstrated the high-throughput detection utility of this approach. We anticipate that the 3D histological electrophoresis device will improve the accuracy and efficiency of diagnosing a wide range of cancers.

Enabling Carbonized Polymer Dots with Color-tunable Time-dependent Room Temperature Phosphorescence through Confining Carboxyl Dimer Association.

Developing a facile strategy to realize fine-tuning of phosphorescence color in time-dependent room temperature phosphorescence (RTP) materials is essential but both theoretically and practically rarely exploited. Through simultaneously confining carboxyl dimer association and isolated carboxyl into the particle via a simple hydrothermal treatment of polyacrylic acid, a dual-peak emission of red phosphorescence (645 nm) and green phosphorescence (550 nm) was observed from carbonized polymer dots (CPDs). The ratio of the two luminescent species can be well regulated by hydrochloric acid inhibiting the dissociation of carboxyl to promote hydrogen bond. Due to comparable but different lifetimes, color-tunable time-dependent RTP with color changing from yellow to green or orange to green were obtained. Based on the crosslinking enhanced emission effect, the phosphorescence visible time was even extended to 7 s through introducing polyethylenimide. This study not only proposes a novel and facile method for developing CPDs with color-tunable time-dependent RTP, but also provides a bran-new non-conjugated red phosphorescence unit and its definite structure.

The Formation Mechanism of Carbonized Polymer Dots: Crosslinking-Induced Nucleation and Carbonization.

Carbon dots (CDs), as a kind of zero-dimensional nanomaterials, have been widely synthesized by bottom-up methods from various precursors. However, the formation mechanism is still unclear and controversial, which also brings difficulty to the regulation of structures and properties. Only some tentative formation processes were postulated by analyzing the products obtained at different reaction times and temperatures. Here, the effect of crosslinking on the formation of carbonized polymer dots (CPDs) is explored. Crosslinking-induced nucleation and carbonization (CINC) is proposed as the driving force for the formation of CPDs. Under hydrothermal synthesis, the precursors are initiated to polymerize and crosslink. The crosslinking brings higher hydrophobicity to generate the hydrophilic/hydrophobic microphase separation, which promotes dehydration and carbonization resulting in the formation of CPDs. Based on the principle of CINC, the influence factors of size are also revealed. Moreover, the dissipative particle dynamics (DPD) simulation is employed to support this formation mechanism. This concept of CINC will bring light to the formation process of CPDs, as well as facilitate the regulation of CPDs' size and photoluminescence.

Crosslink-Enhanced Emission-Dominated Design Strategy for Constructing Self-Protective Carbonized Polymer Dots with Near-Infrared Room-Temperature Phosphorescence.

Self-protective carbonized polymer dots (CPDs) with advantageous crosslinked nano-structures have attracted considerable attention in metal-free room temperature phosphorescence (RTP) materials, whereas, their RTP emissions are still limited to short wavelength. Expanding their RTP emission to Near-Infrared (NIR) range is attractive but suffers from the difficulties in constructing narrow energy levels and inhibiting intense nonradiative decay. Herein, a crosslink-enhanced emission (CEE)-dominated construction strategy was proposed, achieving desired NIR RTP (710 nm) in self-protective CPDs for the first time. Structural factors, i.e.，crosslinking (covalent-bond CEE), conjugation (conjugated amine with bridging N-H and C=C group), and steric hindrance (confined-domain CEE), were confirmed indispensable for triggering NIR RTP emission in CPDs. Contrast experiments and theoretical calculations further revealed the rationality of the design strategy originating from CEE in terms of promoting the narrow energy level emission of triplet excitons and inhibiting the nonradiative quenching. This work not only firstly achieves NIR RTP in self-protective CPDs, but also helps understand the NIR RTP origin to further guide the synthesis of diverse CPDs with efficient long-wavelength RTP emission.

Carbonized Polymer Dots Assemble in Proton-Conducting Channels to Enhance the Conductivity and Selectivity Simultaneously for High-Performance Fuel Cells.

Fabricating polymer electrolyte membranes (PEMs) simultaneously with high ion conductivity and selectivity has always been an ultimate goal in many membrane-integrated systems for energy conversion and storage. Constructing broader ion-conducting channels usually enables high-efficient ion conductivity while often bringing increased crossover of other ions or molecules simultaneously, resulting in decreased selectivity. Here, the ultra-small carbon dots (CDs) with the selective barriers are self-assembled within proton-conducting channels of PEMs through electrostatic interaction to enhance the proton conductivity and selectivity simultaneously. The functional CDs regulate the nanophase separation of PEMs and optimize the hydration proton network enabling higher-efficient proton transport. Meanwhile, the CDs within proton-conducting channels prevent fuel from permeating selectively due to their repelling and spatial hindrance against fuel molecules, resulting in highly enhanced selectivity. Benefiting from the improved conductivity and selectivity, the open-circuit voltage and maximum power density of the direct methanol fuel cell (DMFC) equipped with the hybrid membranes raised by 23% and 93%, respectively. This work brings new insight to optimize polymer membranes for efficient and selective transport of ions or small molecules, solving the trade-off of conductivity and selectivity.

Molecular Structure and Properties of Sulfur-Containing High Refractive Index Polymer Optical Materials.

High refractive index polymers (HRIPs) are widely used in lenses, waveguide, antireflective layer and encapsulators, especially the advanced fields of augmented/virtual reality (AR / VR) holographic technology and photoresist for chip manufacturing. In order to meet the needs of different applications, the development of HRIPs focuses not only on the increase in refractive index but also on the balance of other properties. Sulfur-containing high refractive index polymers have received extensive attention from researchers due to their excellent properties. In recent years, not only ultrahigh refractive index sulfur-containing polymers have been continuously developed, but also low dispersion, low birefringence, high transparency, good mechanical properties, and machinability have been studied. The design of HRIPs is generally based on formulas and existing experience. In fact, molecular structure and properties are closely related. Mastering the structure-property relationship helps researchers to develop high refractive index polymer materials with balanced properties. This review briefly introduces the preparation methods of sulfur-containing high refractive index polymers, and summarizes the structure-property relationship between the sulfur-containing molecular structure and optical properties, mechanical properties, thermal properties, etc. Finally, the important role of synergistic effect in the synthesis of HRIPs and the prospect of future research on HRIPs are proposed.

Fe-doped carbon dots: a novel biocompatible nanoplatform for multi-level cancer therapy.

BACKGROUND: Tumor treatment still remains a clinical challenge, requiring the development of biocompatible and efficient anti-tumor nanodrugs. Carbon dots (CDs) has become promising nanomedicines for cancer therapy due to its low cytotoxicity and easy customization. RESULTS: Herein, we introduced a novel type of "green" nanodrug for multi-level cancer therapy utilizing Fe-doped carbon dots (Fe-CDs) derived from iron nutrient supplement. With no requirement for target moieties or external stimuli, the sole intravenous administration of Fe-CDs demonstrated unexpected anti-tumor activity, completely suppressing tumor growth in mice. Continuous administration of Fe-CDs for several weeks showed no toxic effects in vivo, highlighting its exceptional biocompatibility. The as-synthesized Fe-CDs could selectively induce tumor cells apoptosis by BAX/Caspase 9/Caspase 3/PARP signal pathways and activate antitumoral macrophages by inhibiting the IL-10/Arg-1 axis, contributing to its significant tumor immunotherapy effect. Additionally, the epithelial-mesenchymal transition (EMT) process was inhibited under the treatment of Fe-CDs by MAPK/Snail pathways, indicating the capacity of Fe-CDs to inhibit tumor recurrence and metastasis. CONCLUSIONS: A three-level tumor treatment strategy from direct killing to activating immunity to inhibiting metastasis was achieved based on "green" Fe-CDs. Our findings reveal the broad clinical potential of Fe-CDs as a novel candidate for anti-tumor nanodrugs and nanoplatform.

Carbon nanodots constructed by ginsenosides and their high inhibitory effect on neuroblastoma.

BACKGROUND: Neuroblastoma is one of the common extracranial tumors in children (infants to 2 years), accounting for 8 ~ 10% of all malignant tumors. Few special drugs have been used for clinical treatment currently. RESULTS: In this work, herbal extract ginsenosides were used to synthesize fluorescent ginsenosides carbon nanodots via a one-step hydrothermal method. At a low cocultured concentration (50 µg·mL- 1) of ginsenosides carbon nanodots, the inhibition rate and apoptosis rate of SH-SY5Y cells reached ~ 45.00% and ~ 59.66%. The in vivo experiments showed tumor volume and weight of mice in ginsenosides carbon nanodots group were ~ 49.81% and ~ 34.14% to mice in model group. Since ginsenosides were used as sole reactant, ginsenosides carbon nanodots showed low toxicity and good animal response. CONCLUSION: Low-cost ginsenosides carbon nanodots as a new type of nanomedicine with good curative effect and little toxicity show application prospects for clinical treatment of neuroblastoma. It is proposed a new design for nanomedicine based on bioactive carbon nanodots, which used natural bioactive molecules as sole source.

Comparative analysis of the genetic diversity of the neutral microsatellite loci and second exon of the goat MHC-DQB1 gene.

This study compared and analyzed the genetic diversity and population structure of exon 2 of the DQB1 gene and 13 autosomal neutral microsatellite markers from 14 Chinese goat breeds to explore the potential evolutionary mechanism of the major histocompatibility complex (MHC). A total of 287 haplotypes were constructed from MHC-DQB1 exon 2 from 14 populations, and 82 nucleotide polymorphic sites (SNPs, 31.78%) and 172 heterozygous individuals (79.12%) were identified. The FST values of the microsatellites and MHC-DQB ranged between 0.01831-0.26907 and 0.00892-0.38871, respectively. Furthermore, 14 goat populations showed rich genetic diversity in the microsatellite loci and MHC-DQB1 exon 2. However, the population structure and phylogenetic relationship represented by the two markers were different. Positive selection and Tajima's D test results showed the occurrence of a diversified selection mechanism, which was primarily based on a positive and balancing selection in goat DQB. This study also found that the DQB sequences of bovines exhibited trans-species polymorphism (TSP) among species and families. In brief, this study indicated that positive and balancing selection played a major role in maintaining the genetic diversity of DQB, and TSP of MHC in bovines was common, which enhanced the understanding of the MHC evolution.

Organic Amine-Bridged Quasi-2D Perovskite/PbS Colloidal Quantum Dots Composites for High-Gain Near-Infrared Photodetectors.

Near-infrared (NIR) II detection at weak flux intensity is required in medical imaging and is especially urgent in light of the low quantum efficiency of NIR-II dyes. The low responsivity of traditional photodetectors in this region limits image quality. Here, we report a NIR-II photodetector with high gain based on perovskite coupled PbS colloidal quantum dots (CQDs). Tailoring the trap density of CQDs by designing surface ligands with dual functionality contributed to control over trap-induced charge-injection upon light illumination. As a result, a detector with high gain is realized, showing external quantum efficiency of 1260% at 1200 nm and achieving the lowest detectable light intensity, that is, as low as 0.67 pW cm-2 with a linear dynamic range of 200 dB. Devices maintain over 90% of responsivity after 150 days of storage. We acquired images of a butterfly wing, showing the skeleton texture with a maximum spatial resolution of 3.9 lp/mm.

Thickness-Sensing Sandwiched Plasmonic Biosensors Enable Label-Free Naked-Eye Antibody Quantification.

Clinical serology assays for detecting the antibodies of the virus are time-consuming, are less sensitive/selective, or rely on sophisticated detection instruments. Here, we develop a sandwiched plasmonic biosensor (SPB) for supersensitive thickness-sensing via utilizing the distance-dependent electromagnetic coupling in sandwiched plasmonic nanostructures. SPBs quantitatively amplify the thickness changes on the nanoscale range (sensitivity: ∼2% nm-1) into macroscopically visible signals, thereby enabling the rapid, label-free, and naked-eye detection of targeted biomolecular species (via the thickness change caused by immunobinding events). As a proof of concept, this assay affords a broad dynamic range (7 orders of magnitude) and a low LOD (∼0.3 pM), allowing for the extremely accurate SARS-CoV-2 antibody quantification (sensitivity/specificity: 100%/∼99%, with a portable optical fiber device). This strategy is suitable for high-throughput multiplexed detection and smartphone-based sensing at the point-of-care, which can be expanded for various sensing applications beyond the fields of viral infections and vaccination.