Porous NiMoO4 Nanosheet Films and a Device with Ultralarge Optical Modulation for Electrochromic Energy-Storage Applications.

Reducing building energy consumption, improving aesthetics, and improving occupant privacy as well as comfort by dynamically adjusting solar radiation are important application areas for electrochromic (EC) smart windows. However, the current transition metal oxides still cannot meet the requirements of neutral coloration and large optical modulation. We report NiMoO4 nanosheet films directly grown on fluorine-doped tin oxide glasses. The as-grown NiMoO4 film not only achieves neutral coloration from transparent to dark brown but also shows an ultralarge optical modulation (86.8% at 480 nm) and excellent cycling stability (99.4% retention of maximum optical modulation after 1500 cycles). Meanwhile, an EC device demonstrating good EC performance was constructed. These results will greatly promote the research and development of binary transition metal oxides for both EC and energy-storage applications, and NiMoO4 films may be an excellent candidate to replace NiO films as ion-storage layers in complementary EC devices with WO3 films as EC layers.

Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.

MicroRNA-98-5p Inhibits IFI44L-Mediated Differentiation of Dendritic Cells and Activation of Interferon Pathway in Systemic Lupus Erythematosus.

MicroRNA-98-5p (miR-98-5p) plays a protective role in the pathogenesis of autoimmune diseases through anti-inflammatory effects, but little is known about its role in Systemic lupus erythematosus (SLE). Our previous study suggested Interferon-inducible 44 like (IFI44L) overexpressed in monocytes which contributes to the pathogenesis of SLE by enhancing the maturation and functions of monocyte-derived dendritic cells (Mo-DCs), and miR-98-5p can regulate the expression of IFI44L. In this study, we identified miR-98-5p lowly expressed in both peripheral blood mononuclear cells (PBMCs) and monocytes of SLE patients along with high expression of IFI44L. IFI44L serves as target gene of miR-98-5p which inhibits differentiation of Mo-DCs and IFI44L-mediated activation of interferon pathway. We further showed that miR-98-5p promotes methylation of the IFI44L promoter to down-regulate its expression in SLE. Our results reveal an important role for miR-98-5p in the IFI44L-mediated immune imbalance of SLE and suggest a potential therapeutic target for SLE in the future.

A Dual-Signal Sensing for the Visual and Luminescent Detection of p-Phenylenediamine Based on Cerium-Nitrogen-Co-Doped Carbon Dots.

Herein, a visual and luminescent dual-mode (colorimetric and fluorometric) method for the detection of P-phenylenediamine (PPD) in hair dye was successfully established based on cerium-nitrogen co-doped carbon dots (Ce, N-CDs) that displayed remarkable luminescence and peroxidase activity. Ce, N-CDs catalyzed H2O2 to produce superoxide anion, which then oxidized the colorless 3,3,5,5-tetramethylbenzidine (TMB) into blue oxidized TMB (oxTMB), capable of quenching the fluorescence through fluorescence resonance energy transfer (FRET) between Ce, N-CDs and oxTMB. The reducing properties of PPD could reduce oxTMB back to TMB, leading to a decrease in the absorption intensity of oxTMB and a fluorescence recovery of Ce, N-CDs. As a result, the quantitative detection of PPD could be achieved by measuring the absorption values of oxTMB and the fluorescence signal of Ce, N-CDs. The detection limits for PPD were calculated as 0.36 µM and 0.10 µM for colorimetry and fluorimetry, respectively. Furthermore, smartphone application (ColorPicker) capable of measuring the RGB value of the color was utilized in the detection system, facilitating on-site quantitative detection. This approach effectively shortens the detection time and simplifies the operation, offering a powerful and convenient tool for real-time monitoring of PPD.

Environmental forcing and policy synergy: A multidimensional approach in the governance of air pollution and carbon emission.

Policy synergies effectively contribute to the integrated management of air pollution and carbon emissions, which is crucial for safeguarding ecosystem stability and public health. This study uses the causal network model of Gaussian process regression to analyze the combined impacts of dynamic and static carbon emission reduction and air quality policies on carbon emissions and air quality. The causal effects of policy measures and their synergistic effects are also examined. The study results indicate: (1) There is significant geographical heterogeneity in the implementation of environmental policies and regional economic development, with the economically developed eastern coastal regions adopting more stringent carbon emission and air pollution control measures, while the western provinces adopt relatively lax environmental policies. (2) The synergistic effect of carbon emission reduction policies and air quality policies exists, and the two types of static policies are substitutable for managing carbon dioxide emissions and air pollution. (3) Policies' forced effect exists, where the exacerbation of environmental problems leads to the formation and implementation of policies. (4) The value added by the secondary industry is a key motivation for forming carbon emission reduction policies and air quality control policies. Additionally, the value added by the secondary industry directly impacts the incidence of respiratory diseases (e.g., tuberculosis). Finally, dynamic and synergistic policy recommendations are proposed based on the study's findings.

Identification of shared gene signatures in major depressive disorder and triple-negative breast cancer.

BACKGROUND: Patients with major depressive disorder (MDD) have an increased risk of breast cancer (BC), implying that these two diseases share similar pathological mechanisms. This study aimed to identify the key pathogenic genes that lead to the occurrence of both triple-negative breast cancer (TNBC) and MDD. METHODS: Public datasets GSE65194 and GSE98793 were analyzed to identify differentially expressed genes (DEGs) shared by both datasets. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape to identify key PPI genes using cytoHubba. Hub DEGs were obtained from the intersection of hub genes from a PPI network with genes in the disease associated modules of the Weighed Gene Co-expression Network Analysis (WGCNA). Independent datasets (TCGA and GSE76826) and RT-qPCR validated hub gene expression. RESULTS: A total of 113 overlapping DEGs were identified between TNBC and MDD. The PPI network was constructed, and 35 hub DEGs were identified. Through WGCNA, the blue, brown, and turquoise modules were recognized as highly correlated with TNBC, while the brown, turquoise, and yellow modules were similarly correlated with MDD. Notably, G3BP1, MAF, NCEH1, and TMEM45A emerged as hub DEGs as they appeared both in modules and PPI hub DEGs. Within the GSE65194 and GSE98793 datasets, G3BP1 and MAF exhibited a significant downregulation in TNBC and MDD groups compared to the control, whereas NCEH1 and TMEM45A demonstrated a significant upregulation. These findings were further substantiated by TCGA and GSE76826, as well as through RT-qPCR validation. CONCLUSIONS: This study identified G3BP1, MAF, NCEH1 and TMEM45A as key pathological genes in both TNBC and MDD.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Multi-omics and tumor immune microenvironment characterization of a prognostic model based on aging-related genes in melanoma.

Melanoma is a common and fatal cutaneous malignancy with strong invasiveness and high mortality rate. Clinically, elderly melanoma patients tend to exhibit stronger invasion ability and poorer prognosis. Given the heterogeneity of tumors, we analyzed the prognosis and risk assessment of melanoma through aging-related genes rather than age stratification. FOXM1 and CCL4 were identified to be closely associated with melanoma prognosis. Single-cell transcriptome analysis showed that FOXM1 was significantly up-regulated in tumor cells, while CCL4 was markedly elevated in immune cells. A melanoma prognostic model was constructed based on the two independent prognostic factors. This model showed a high accuracy in predicting the mortality of melanoma patients over several years. The patients in low-risk group appeared to have more immune cell infiltration and better immune therapy efficacy. Cellular experiments showed that CCL4 could promote apoptosis of melanoma cells through immune cells, and apoptosis could regulate the expression of FOXM1. In addition, the results of the spatial transcriptome and immunohistochemistry suggested that CCL4 was highly expressed in macrophages and the expression of FOXM1 in melanoma cell was negatively correlated with immune cell infiltration, especially macrophages. Here, we established a novel prognostic model for melanoma, which showed promising predictive performance and may serve as a biomarker for the efficacy of immune checkpoint inhibition therapy in melanoma patients. In addition, we explored the function of two genes in the model in melanoma.

Dissociable functional responses along the posterior-anterior gradient of the frontal and parietal cortices revealed by parametric working memory and training.

While the storage capacity is limited, accumulating studies have indicated that working memory (WM) can be improved by cognitive training. However, understanding how exactly the brain copes with limited WM capacity and how cognitive training optimizes the brain remains inconclusive. Given the hierarchical functional organization of WM, we hypothesized that the activation profiles along the posterior-anterior gradient of the frontal and parietal cortices characterize WM load and training effects. To test this hypothesis, we recruited 51 healthy volunteers and adopted a parametric WM paradigm and training method. In contrast to exclusively strengthening the activation of posterior areas, a broader range of activation concurrently occurred in the anterior areas to cope with increased memory load for all subjects at baseline. Moreover, there was an imbalance in the responses of the posterior and anterior areas to the same increment of 1 item at different load levels. Although a general decrease in activation after adaptive training, the changes in the posterior and anterior areas were distinct at different memory loads. Particularly, we found that the activation gradient between the posterior and anterior areas was significantly increased at load 4-back after adaptive training, and the changes were correlated with improvement in WM performance. Together, our results demonstrate a shift in the predominant role of posterior and anterior areas in the frontal and parietal cortices when approaching WM capacity limits. Additionally, the training-induced performance improvement likely benefits from the elevated neural efficiency reflected in the increased activation gradient between the posterior and anterior areas.

Different baseline functional patterns of the frontal cortex in amyotrophic lateral sclerosis patients with Corticospinal tract hyperintensity.

Nearly half of the amyotrophic lateral sclerosis (ALS) patients showed hyperintensity of the corticospinal tract (CST+), yet whether brain functional pattern differs between CST+and CST- patients remains obscure. In the current study, 19 ALS CST+, 41 ALS CST- patients and 37 healthy controls (HC) underwent resting state fMRI scans. We estimated local activity and connectivity patterns via the Amplitude of Low Frequency Fluctuations (ALFF) and the Network-Based Statistic (NBS) approaches respectively. The ALS CST+patients did not differ from the CST- patients in amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R) score and disease duration. ALFF of the superior frontal gyrus (SFG) and the inferior frontal gyrus pars opercularis (OIFG) were highest in the HC and lowest in the ALS CST- patients, resulting in significant group differences (PFWE<0.05). NBS analysis revealed a frontal network consisting of connections between SFG, OIFG, orbital frontal gyrus, middle cingulate cortex and the basal ganglia, which exhibited HC>ALS CST+ > ALS CST- group differences (PFWE=0.037) as well. The ALFF of the OIFG was significantly correlated with ALSFRS-R (R=0.34, P=0.028) and mean connectivity of the frontal network was trend-wise significantly correlated with disease duration (R=-0.31, P=0.052) in the ALS CST- patients. However, these correlations were insignificant in ALS CST+patients (P values > 0.8). In conclusion, The ALS CST+patients exhibited different patterns of baseline functional activity and connectivity in the frontal cortex which may indicate a functional compensatory effect.

Predicting in vivo therapeutic efficacy of CelTrac1000-labeled hair follicle epidermal neural crest stem cells in models of repairing rat facial nerve defects via second near-infrared fluorescence imaging.

AIMS: To detect the therapeutic efficacy of CelTrac1000-labeled hair follicle epidermal neural crest stem cells (EPI-NCSCs) on repairing facial nerve defects by second near-infrared (NIR-II) fluorescence imaging. MATERIALS AND METHODS: Firstly, CelTrac1000-labeled EPI-NCSCs were microinjected into the acellular nerve allografts (ANAs) to bridge a 10-mm-long gap in the buccal branch of facial nerve in adult rats. Then, Celtrac1000-labeled EPI-NCSCs were detected by NIR-II fluorescence imaging system to visualize the behavior of the transplanted cells in vivo. Additionally, the effect of the transplanted EPI-NCSCs on repairing facial nerve defect was examined. KEY FINDINGS: Through 14 weeks of dynamic observation, the transplanted EPI-NCSCs survived in the ANAs in vivo after surgery. Meanwhile, the region of the NIR-II fluorescence signals was gradually limited to be consistent with the direction of the regenerative nerve segment. Furthermore, the results of functional and morphological analysis showed that the transplanted EPI-NCSCs could promote the recovery of facial paralysis and neural regeneration after injury. SIGNIFICANCE: Our research provides a novel way to track the transplanted cells in preclinical studies of cell therapy for facial paralysis, and demonstrates the therapeutic potential of EPI-NCSCs combined with ANAs in bridging rat facial nerve defects.

A label-free activatable biosensor for in situ detection of exosomal microRNAs based on DNA-AgNCs and hairpin type nucleic acid probes.

Exosomal microRNA (miRNA) is a potential biomarker for cancer diagnosis, metastasis, and treatment. In situ detection of exosomal miRNA is an attractive option due to its simplicity and high accuracy. However, in situ exosomal miRNA detection has encountered challenges because of the low target abundance of targets and limited probe permeability. Herein, a label-free and activatable biosensor was developed for in situ exosomal miRNA assays by utilizing hairpin-shaped nucleic acid probes and DNA-hosted silver nanoclusters (DNA-AgNCs). The probe is directly internalized into the exosomes, and then hybridized with the target miRNA-21. Subsequently, the DNA-AgNCs are pulled closer to the G-rich sequence, ultimately leading to in situ red fluorescence activation. The biosensor not only can detect exosomal miRNA-21 but also distinguish cancer cells from normal cells. Under optimal reaction conditions, the detection limit (LOD) of exosomal miRNA-21 is 1.53 × 107 particles per mL. Furthermore, DNA-AgNCs are used as label-free signal elements for in situ detection of exosomal miRNAs for the first time, expanding the application of nanomaterials in this field. This strategy does not require tedious RNA extraction steps and expensive instruments, and may develop into a non-invasive diagnostic tool for ovarian cancer.

Dual-signal detection of tannic acid in red wines based on the peroxidase activity of carbon dots.

Herein, a novel type of phosphorus and iron-doped carbon dot (P,Fe-CD) with outstanding peroxidase activity and excellent fluorescence performance was hydrothermally synthesized to colorimetrically and fluorimetrically detect tannic acid (TA). In the presence of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2, the P,Fe-CDs could oxidize colorless TMB to a blue oxidation product (oxTMB) resulting in an increased value of absorbance. Simultaneously, the fluorescence intensity of P,Fe-CDs at 430 nm could be quenched owing to the fluorescence resonance energy transfer (FRET) between P,Fe-CDs and the generated oxTMB. Meanwhile, after adding the TA to the system containing TMB, H2O2 and P,Fe-CDs, the value of absorbance could be decreased and the fluorescence could be recovered because of the reduction reaction between TA and oxTMB. Therefore, fluorescence intensity and value of absorbance could be applied to quantitatively detect TA with good linearities between the concentration of TA and the fluorescence intensity/value of absorbance (0.997 and 0.997 for the colorimetric signal and fluorimetric one, respectively) and low limits of detection (0.093 µmol L-1 and 0.053 µmol L-1 for the colorimetry and the fluorimetry, respectively), which was successfully applied to the detection of TA in red wines. Moreover, we applied a smartphone-assisted method to the point-of-care detection of TA with accurate results, providing a new technique for TA detection and food quality monitoring.

Efficient Direct X-ray Detection and Imaging Based on a Lead-Free Electron Donor-Acceptor MOF.

Metal-organic frameworks (MOFs) have recently gained extensive attention as potential materials for direct radiation detection due to their strong radiation absorption, long-range order, and chemical tunability. However, it remains challenging to develop a practical MOF-based X-ray direct detector that possesses high X-ray detection efficiency, radiation stability, and environmental friendliness. The integration of donor-acceptor (D-A) pairs into crystalline MOFs is a powerful strategy for the precise fabrication of multifunctional materials with unique optoelectronic properties. Herein, a new lead-free MOF, Cu2I2(TPPA) (CuI-TPPA, TPPA = tris[4-(pyridine-4-yl)phenyl]amine), with a 6-fold interpenetrated structure is designed and synthesized based on the electron donor-acceptor strategy. CuI-TPPA has a large mobility-lifetime (µτ) product of 5.8 × 10-4 cm2 V-1 and a high detection sensitivity of 73.1 µC Gyair-1 cm-2, surpassing that of commercial α-Se detectors. Moreover, the detector remains fairly stable with only a 2% reduction in photocurrent under continuous bias irradiation conditions with a total dose of over 42.83 Gyair. The CuI-TPPA/poly(vinylidene fluoride) flexible composite X-ray detector films are successfully manufactured with different thicknesses. Through multifaceted assessments, the optimal thickness is found with a high detection sensitivity of up to 143.6 µC Gyair-1 cm-2. As proof-of-concept, 11 × 9 pixelated X-ray detectors are fabricated on the same composite film to realize X-ray direct imaging. This work opens up potential applications of MOFs in environmentally friendly and wearable devices for direct X-ray detection and imaging.

Fine Tuning Ag(I)-Sb(III) Hybrid Iodides for Light Detection.

Lead-free hybrid double perovskite iodides (HDPIs) have piqued increasing research interest due to their environmental friendliness and high stability. However, such antimony-based HDPIs with strong photocurrent response are currently very limited. Here, we successfully design and construct five Ag(I)-Sb(III)-based HDPIs using two types of cyclic aliphatic amines as A-site templates. Interestingly, these Ag(I)-Sb(III) HDPIs exhibit relatively narrow band gaps, preferred orientation, and high stability after being processed into thin films on the indium tin oxide (ITO) substrate. Notably, under illuminations of a xenon lamp, all HDPIs exhibit considerable photocurrent responses, reaching a maximum difference of 17 µA·cm-2 for ASI 1, which is the highest among lead-free halogen-based organic-inorganic hybrid compounds to date. Combining the considerable photocurrents and the high stability, the optoelectronic applications of two-dimensional Ag(I)-Sb(III) HDPIs can be expected.

Huangqin decoction attenuates spared nerve injury (SNI)-induced neuropathic pain by modulating microglial M1/M2 polarization partially mediated by intestinal nicotinamide metabolism.

BACKGROUND: The incidence of neuropathic pain is progressively increasing over time. The activation of M1-type microglia plays a crucial role in the initiation and progression of neuropathic pain. Huangqin Decoction (HQD) is traditionally used to alleviate dysentery and abdominal pain. However, it remains unclear whether HQD can effectively mitigate neuropathic pain and the underlying mechanisms. PURPOSE: The present study aims to investigate the impact of HQD on neuropathic pain induced by spared nerve injury (SNI) in mice, and to elucidate whether the analgesic effect of HQD is associated with microglia polarization. METHODS: The analgesic effect of HQD on SNI mice was investigated through assessments of mechanical pain threshold, thermal pain threshold, cold pain threshold, and motor ability. We elucidated the molecular mechanisms of HQD in alleviating SNI-induced neuropathic pain by focusing on microglia polarization and intestinal metabolite abnormalities. The expression levels of markers associated with microglia polarization (Iba-1, CD68, CD206, iNOS) was detected by immunofluorescence and Western blot, and the levels of inflammatory factors (IL-4, IL-10, IL-6, TNF-α) were assessed by ELISA. UPLC-QTOF-MS metabolomics was utilized to identify differential metabolites in the intestines of SNI mice. We screened the differential metabolites related to microglial polarization by correlation analysis, subsequently nicotinamide was selected for validation in LPS-induced BV-2 cells. RESULTS: Our findings demonstrated that HQD (20 g/kg) significantly enhanced the mechanical pain threshold, thermal pain threshold, and cold pain threshold, and protected the injured DRG neurons of SNI mice. Moreover, HQD (20 g/kg) obviously suppressed the expression of microglia M1 polarization markers (Iba-1, CD68, iNOS, IL-6, TNF-α), and promoted the expression of microglia M2 polarization markers (CD206, IL-10, IL-4) in the spinal cord of SNI mice. Additionally, HQD (20 g/kg) prominently ameliorated intestinal barrier damage by upregulating Claudin 1 and Occludin expression in the colon of SNI mice. Furthermore, HQD (20 g/kg) rectified 19 metabolite abnormalities in the intestine. Notably, nicotinamide (100 µM), an amide derivative with anti-inflammatory property, effectively suppresses microglia activation and polarization in LPS-induced BV-2 cells by downregulating IL-6 level and CD68 expression while upregulating IL-4 level and CD206 expression. CONCLUSION: In summary, HQD alleviates neuropathic pain in SNI mice by regulating the activation and polarization of microglia, partially mediated through intestinal nicotinamide metabolism.

A Low-Complexity Beamformer for Ultrasound Imaging Based on Sub-Beamformer and Multi-Apodization With Cross-Correlation.

OBJECTIVE: This paper proposes an ultrasound imaging algorithm based on sub-beamformer and multi-apodization with cross-correlation (SUB-MAX), aiming to achieve high resolution close to the minimum variance (MV) beamforming with low complexity and to enhance image contrast while maintaining background quality. METHODS: The output of two (N/2)-element DAS beamformers with asymmetric phase centers is subtracted, resulting in a large drop in the main-lobe amplitude, while the sidelobe maintains a relatively high amplitude level. Inspired by this characteristic, the coefficients with opposite trends compared with the subtracted output are obtained and fused with the normalized cross-correlation (NCC) weighting matrix acquired by using multi-pair received apodization, the proposed SUB-MAX obtains a new weighting matrix to weight the output of the DAS beamformer. RESULTS: For ats_wire point targets, the average full-width at half-maximum (FWHM) of SUB-MAX compared with DAS, DMAS, CF, and MAX decreases by 52.7%, 43.5%, 33.3%, and 52.7%, respectively. For geabr_0 cysts, the average contrast ratio (CR) of SUB-MAX compared with DAS, MV, DMAS, and CF increases by 57.7%, 86.8%, 2.5%, and 14.4%, respectively. Experiments on rat_tumor dataset also indicate that SUB-MAX has a superior comprehensive imaging performance. CONCLUSION: The experimental results indicate that the superior comprehensive imaging performance of the proposed SUB-MAX is expected to be suitable for real-time imaging systems due to its non-reliance on covariance matrix inversion.

Novel MIP gene mutation causes autosomal-dominant congenital cataract.

AIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family. Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis. The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis. Major intrinsic protein (MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos. Zebrafish embryonic lens phenotypes were screened using confocal microscopy. RESULTS: A novel heterozygous mutation (c.85G>A; p.G29R) in the MIP gene was identified in the proband of one family. A known heterozygous mutation (c.97C>T; p.R33C; rs864309693) in MIP was found in the proband of another family. In-silico prediction indicated that the novel mutation might affect the MIP protein function. Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP. CONCLUSION: Two missense mutations in the MIP gene in Chinese cataract families are identified, and one of which is novel. These findings expand the genetic spectrum of MIP mutations associated with cataracts. The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

Aptamer-aided plasmonic nano-urchins for reporter-free surface-enhanced Raman spectroscopy analysis of cortisol.

Cortisol is a vital glucocorticoid hormone reflecting stress levels and related disease processes. In this study, we report an aptamer-functionalized plasmonic nano-urchin (α-FeOOH@Au-aptamer)-aided cortisol-capturing and surface-enhanced Raman spectroscopy (SERS) analysis approach. The designed α-FeOOH@Au-aptamer exhibits a well-patterned plasma structure, which combines the good SERS enhancement ability of reduced nanogaps between the Au plasma and the hot spot-favored structure of anisotropic tips from α-FeOOH urchins, with the high affinity of the aptamer towards cortisol molecules. The α-FeOOH@Au-aptamer achieved reporter-free SERS quantification for cortisol with good sensitivity (limit of detection <0.28 µmol L-1), robust salt (1.0 mol per L NaCl) and protein (5.0 mg per mL bovine serum protein) tolerance, favorable reproducibility, as well as good reusability. We further demonstrated the good cortisol-capturing ability and SERS efficacy of the α-FeOOH@Au-aptamer profiling in the serum and urine samples. Our approach provides an alternative tool for cortisol analysis and a reference strategy for report-free SERS detection of small molecules.

Modulation of immune-responses by DSF/Cu enhances the anti-tumor effects of DTX for metastasis breast cancer.

Metastasis has been one of the most important causes of death from breast cancer, and chemotherapy remains the major option for metastatic breast cancer. However, drug resistance and higher toxicity from chemotherapy have been an obstacle for clinical practice, and the combination of chemotherapy with immunotherapy has emerged as a promising treatment strategy. Here, we describe a therapy based on the combination of disulfiram (DSF) and Cu2+ with widely used cytotoxic docetaxel (DTX). DSF/Cu-induced immunogenic cell death promoted the release of type I interferon and human monocyte-induced dendritic cell maturation, which established a foundation for the combination with chemotherapy. Consequently, the combination of DSF/Cu and DTX resulted in significantly more potent anti-tumor effects in 4T1-bearing mice than in single therapy. The present study has shed new light on combining DSF/Cu-induced immune responses with traditional chemotherapeutic agents to achieve greater benefits for patients with metastasis.