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Objectives: To evaluate the safety and effectiveness of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC), and open radical cystectomy (ORC) in bladder cancer., Methods: A literature search for network meta-analysis was conducted using international databases up to February 29, 2024. Outcomes of interest included baseline characteristics, perioperative outcomes and oncological outcomes., Results: Forty articles were finally selected for inclusion in the network meta-analysis. Both LRC and RARC were associated with longer operative time, smaller amount of estimated blood loss, lower transfusion rate, shorter time to regular diet, fewer incidences of complications, and fewer positive surgical margin compared to ORC. LRC had a shorter time to flatus than ORC, while no difference between RARC and ORC was observed. Considering lymph node yield, there were no differences among LRC, RARC and ORC. In addition, there were statistically significant lower transfusion rates (OR=-0.15, 95% CI=-0.47 to 0.17), fewer overall complication rates (OR=-0.39, 95% CI=-0.79 to 0.00), fewer minor complication rates (OR=-0.23, 95% CI=-0.48 to 0.02), fewer major complication rates (OR=-0.23, 95% CI=-0.68 to 0.21), fewer positive surgical margin rates (OR=0.22, 95% CI=-0.27 to 0.68) in RARC group compared with LRC group., Conclusion: LRC and RARC could be considered as a feasible and safe alternative to ORC for bladder cancer. Notably, compared with LRC, RARC may benefit from significantly lower transfusion rates, fewer complications and lower positive surgical margin rates. These data thus showed that RARC might improve the management of patients with muscle invasive or high-risk non-muscle invasive bladder cancer., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Two complementary patient cases are presented to highlight the importance of estrogen receptor (ER)-targeting imaging in treatment planning and selection for endocrine therapy in breast cancer patients. This article will discuss the radiopharmaceuticals and biology, imaging interpretation, and current clinical applications of ER-targeting imaging using fluorine 18 fluoroestradiol PET., (© RSNA, 2024.)

It has been validated that enhancing crystallinity and passivating the deep-level defect are critical for improving the device performance of kesterite Cu 2 ZnSn(S,Se) 4 (CZTSSe) solar cells. Coordination chemistry interactions within the Cu-Zn-Sn-S precursor solution play a crucial role in the management of structural defects and the crystallization kinetics of CZTSSe thin films. Therefore, regulating the coordination environment of anion and cation in the precursor solution to control the formation process of precursor films is a major challenge at present. Herein, a synergetic crystallization modulation and defect passivation method is developed using P 2 S 5 as an additive in the CZTS precursor solution to optimize the coordination structure and improve the crystallization process. The alignment of theoretical assessments with experimental observations confirms the ability of the P 2 S 5 molecule to coordinate with the metal cation sites of CZTS precursor films, especially more liable to the Zn 2+ , effectively passivating the Zn-related defects, thereby significantly reducing the defect density in CZTSSe absorbers. As a result, the device with a power conversion efficiency of 14.36% has been achieved. This work provides an unprecedented strategy for fabricating high-quality thin films by anion-coordinate regulation and a novel route for realizing efficient CZTSSe solar cells., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Purpose: To characterize the response and survival outcomes of yttrium-90 transarterial radioembolization (90Y-TARE) for unresectable, liver-dominant metastases from primary neoplasms other than colorectal carcinoma., Materials and Methods: This study included 1474 patients enrolled in the RESiN registry who received resin 90Y-TARE as part of their oncologic management for unresectable primary or secondary liver tumors (NCT02685631). 33% (481/1474) were treated for liver metastases of non-colorectal origin (m-nonCRC), compared to 34% (497/1474) treated for colorectal liver metastases (mCRC) and 34% (496/1474) treated for hepatocellular carcinoma (HCC). Treatment response and cancer survival probabilities were computed and compared for each primary cancer type. The Kaplan-Meier method and log-rank test were used to compare survival outcomes., Results: Radiological responses were observed in 12 unique cancer types, mostly heavily pre-treated malignancies refractory to multiple lines of systemic therapies. The overall use of resin 90Y-TARE in m-nonCRC resulted in better treatment outcomes in terms of duration of response, progression free survival, time to progression and overall survival (P = 0.04, P = 0.02, P = 0.01, P = 0.04). Analyses of cancer cell types revealed that metastatic neuroendocrine tumor, sarcoma, and ovarian, renal, prostate, and breast cancers were associated with superior treatment outcomes, whereas worse treatment outcomes were observed in metastatic lung, gastric, pancreatic and esophageal cancers., Conclusion: Real-world data demonstrate the use of resin 90Y-TARE in m-nonCRC refractory to standard chemotherapy. For some cell types, this expanded use achieved superior treatment outcomes relative to the reference standard of mCRC, suggesting the need for inquiry into broadened indications for 90Y-TARE., (Copyright © 2024. Published by Elsevier Inc.)

Polycyclic aromatic hydrocarbons (PAHs) are a type of organic pollution that can accumulate in crops and hazard human health. This study used phenanthrene (PHE) as a model PAH and employed hydroponic experiments to illustrate the role of indole-3-acetic acid (IAA) in the regulation of PHE accumulation in wheat roots. At optimal concentrations, wheat roots treated with PHE + IAA showed a 46.9% increase in PHE concentration, whereas treatment with PHE + P-chlorophenoxyisobutyric acid resulted in a 38.77% reduction. Transcriptome analysis identified TaSAUR80-5A as the crucial gene for IAA-enhancing PHE uptake. IAA increases plasma membrane H + -ATPase activity, promoting active transport of PHE via the PHE/H + cotransport mechanism. These results provide not only the theoretical basis necessary to better understand the function of IAA in PAHs uptake and transport by staple crops, but also a strategy for controlling PAHs accumulation in staple crops and enhancing phytoremediation of PAH-contaminated environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: This retrospective cohort study aims to investigate whether high-normal fasting blood glucose (FBG) affects assisted reproductive technology (ART) outcomes undergoing single blastocyst frozen-thawed embryo transfer (FET) cycles in women with normal body mass index (BMI)., Methods: 944 women with normal BMI and FBG levels undergoing single blastocyst FET cycles were enrolled. Based on the median of FBG (4.97 mmol/L, 1 mmol/L = 18 mg/dL), the subjects were categorized into the low-normal group (3.90 ≤ FBG ≤ 4.97 mmol/L, n = 472) and the high-normal group (4.97 < FBG < 6.10 mmol/L, n = 472). Multivariable logistic regression and receiver operating characteristic (ROC) were used to analyze the relationship between high-normal FBG and ART outcomes., Primary Outcome: live birth rate (LBR)., Results: LBR was significantly lower in the high-normal group than in the low-normal group (36.8% vs. 45.1%, p = 0.010), and the miscarriage rate was considerably higher than that in the low-normal group (23.9% vs. 16.5%, p = 0.041). High-normal FBG of female was an independent predictor of live birth (adjusted OR:0.747, 95% CI: 0.541-0.963, p = 0.027) and miscarriage (adjusted OR:1.610, 95% CI: 1.018-2.547, p = 0.042). ROC analyses showed that the cut-off values of FBG (endpoints: live birth and miscarriage) were 5.07 mmol/L, and 5.01 mmol/L, respectively., Conclusions: In women with normal BMI, high-normal FBG is an independent risk factor for lower LBR and higher miscarriage rate in single blastocyst FET cycles. Attention to preconception FBG monitoring in this particular population may allow early intervention to improve ART outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Previous research has primarily employed deep learning models such as Convolutional Neural Networks (CNNs), and Recurrent Neural Networks (RNNs) for decoding imagined character signals. These approaches have treated the temporal and spatial features of the signals in a sequential, parallel, or single-feature manner. However, there has been limited research on the cross-relationships between temporal and spatial features, despite the inherent association between channels and sampling points in Brain-Computer Interface (BCI) signal acquisition, which holds significant information about brain activity. To address the limited research on the relationships between temporal and spatial features, we proposed a Temporal-Spatial Cross-Attention Network model, named TSCA-Net. The TSCA-Net is comprised of four modules: the Temporal Feature (TF), the Spatial Feature (SF), the Temporal-Spatial Cross (TSCross), and the Classifier. The TF combines LSTM and Transformer to extract temporal features from BCI signals, while the SF captures spatial features. The TSCross is introduced to learn the correlations between the temporal and spatial features. The Classifier predicts the label of BCI data based on its characteristics. We validated the TSCA-Net model using publicly available datasets of handwritten characters, which recorded the spiking activity from two micro-electrode arrays (MEAs). The results showed that our proposed TSCA-Net outperformed other comparison models (EEG-Net, EEG-TCNet, S3T, GRU, LSTM, R-Transformer, and ViT) in terms of accuracy, precision, recall, and F1 score, achieving 92.66 % , 92.77 % , 92.70 % , and 92.58 % , respectively. The TSCA-Net model demonstrated a 3.65 % to 7.49 % improvement in accuracy over the comparison models., (© 2024. The Author(s).)

Prostate-specific membrane antigen (PSMA) is frequently overexpressed in nonprostate malignancies. This preclinical study investigated the molecular basis of the application of PMSA-targeting radiopharmaceuticals in breast cancer subtypes. Methods: The somatic copy number status and the transcriptomic and protein expressions of FOLH1 (gene name of PSMA) were analyzed across breast cancer subtypes in 998 patients from The Cancer Genome Atlas dataset. Results: FOLH1 was frequently amplified in basallike breast cancer (BLBC) (32%) compared with luminal and human epidermal growth factor receptor 2-positive subtypes (16% and 17%, respectively; P < 0.01). FOLH1 expression was higher in BLBC ( P < 0.001) and was negatively correlated with estrogen-receptor and progesterone-receptor expressions. Consistently, the PSMA protein level was higher in BLBC ( P < 0.05). Interestingly, FOLH1 expression was associated with relapse-free and distant metastasis-free survival in patients with BLBC. Conclusion: The BLBC subtype exhibited frequent amplification and overexpression of PSMA, supporting the exploration of PSMA-targeting radiopharmaceuticals in this aggressive breast cancer subtype., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Human fertility is impacted by changes in lifestyle and environmental deterioration. To increase human fertility, assisted reproductive technology (ART) has been extensively used around the globe. As early as 2009, the Endocrine Society released its first scientific statement on the potential adverse effects of environmental endocrine-disrupting chemicals (EDCs) on human health and disease development. Chemicals known as phthalates, frequently employed as plasticizers and additives, are common EDCs. Numerous studies have shown that phthalate metabolites in vivo exert estrogen-like or anti-androgenic effects in both humans and animals. They are associated with the progression of a range of diseases, most notably interference with the reproductive process, damage to the placenta, and the initiation of chronic diseases in adulthood. Phthalates are ingested by infertile couples in a variety of ways, including household products, diet, medical treatment, etc. Exposure to phthalates may exacerbate their infertility or poor ART outcomes, however, the available data on phthalate exposure and ART pregnancy outcomes are sparse and contradictory. Therefore, this review conducted a systematic evaluation of 16 papers related to phthalate exposure and ART pregnancy outcomes, to provide more aggregated results, and deepen our understanding of reproductive outcomes in infertile populations with phthalate exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Methyl-CpG-binding protein 2 ( Mecp2 ) is an epigenetic modulator and numerous studies have explored its impact on the central nervous system manifestations. However, little attention has been given to its potential contributions to the peripheral nervous system (PNS). To investigate the regulation of Mecp2 in the PNS on specific central regions, we generated Mecp2 fl/fl Advillin cre mice with the sensory-neuron-specific deletion of the Mecp2 gene and found the mutant mice had a heightened sensitivity to temperature, which, however, did not affect the sense of motion, social behaviors, and anxiety-like behavior. Notably, in comparison to Mecp2 fl/fl mice, Mecp2 fl/fl Advillin cre mice exhibited improved learning and memory abilities. The levels of hippocampal synaptophysin and PSD95 proteins were higher in Mecp2 fl/fl Advillin cre mice than in Mecp2 fl/fl mice. Golgi staining revealed a significant increase in total spine density, and dendritic arborization in the hippocampal pyramidal neurons of Mecp2 fl/fl Advillin cre mice compared to Mecp2 fl/fl mice. In addition, the activation of the BDNF-TrkB-CREB1 pathway was observed in the hippocampus and spinal cord of Mecp2 fl/fl Advillin cre mice. Intriguingly, the hippocampal BDNF/CREB1 signaling pathway in mutant mice was initiated within 5 days after birth. Our findings suggest a potential therapeutic strategy targeting the BDNF-TrkB-CREB1 signaling pathway and peripheral somasensory neurons to treat learning and cognitive deficits associated with Mecp2 disorders.

Nanocatalytic therapy, an emerging approach in cancer treatment, utilizes nanomaterials to initiate enzyme-mimetic catalytic reactions within tumors, inducing tumor-suppressive effects. However, the targeted and selective catalysis within tumor cells is challenging yet critical for minimizing the adverse effects. The distinctive reliance of tumor cells on glycolysis generates abundant lactate, influencing the tumor's pH, which can be manipulated to selectively activate nanozymatic catalysis. Herein, small interfering ribonucleic acid (siRNA) targeting lactate transporter-mediated efflux is encapsulated within the iron-based metal-organic framework (FeMOF) and specifically delivered to tumor cells through cell membrane coating. This approach traps lactate within the cell, swiftly acidifying the tumor cytoplasm and creating an environment for boosting the catalysis of the FeMOF nanozyme. The nanozyme generates hydroxyl radical (·OH) in the reversed acidic environment, using endogenous hydrogen peroxide (H 2 O 2 ) produced by mitochondria as a substrate. The induced cytoplasmic acidification disrupts calcium homeostasis, leading to mitochondrial calcium overload, resulting in mitochondrial dysfunction and subsequent tumor cell death. Additionally, the tumor microenvironment is also remodeled, inhibiting migration and invasion, thus preventing metastasis. This groundbreaking strategy combines metabolic regulation with nanozyme catalysis in a toxic drug-free approach for tumor treatment, holding promise for future clinical applications., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two common subtypes of autoimmune bullous disease (AIBD). The key role of circulating autoreactive immune cells contributing to skin damage of AIBD has been widely recognized. Nevertheless, the immune characteristics in cutaneous lesions remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell VDJ sequencing (scRNA-seq) to generate transcriptional profiles for cells and T/B cell clonetype in skin lesions of BP and PV. We found that the proportions of NK&T, macrophages/ dendritic cells, B cells, and mast cells increased in BP and PV lesions. Then, BP and PV cells constituted over 75% of all myeloid cell subtypes, CD4 + T cell subtypes and CD8 + T cell subtypes. Strikingly, CD8 + Trm was identified to be expanded in PV, and located in the intermediate state of the pseudotime trajectory from CD8 + Tm to CD8 + Tem. Interestingly, CD8 + Tem and CD4 + Treg highly expressed exhaustion-related genes, especially in BP lesions. Moreover, the enhanced cell communication between stromal cells and immune cells like B cells and macrophages/ dendritic cells was also identified in BP and PV lesions. Finally, clone expansion was observed in T cells of BP and PV compared with HC, while CD8 + Trm represented the highest ratio of hyperexpanded TCR clones among all T cell subtypes. Our study generally depicts a large and comprehensive single-cell landscape of cutaneous lesions and highlights immune cell features in BP and PV. This offers potential research targets for further investigation., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Plant senescence is a highly regulated developmental program crucial for nutrient reallocation and stress adaptation in response to developmental and environmental cues. Stress-induced and age-dependent natural senescence share both overlapping and distinct molecular responses and regulatory schemes. Previously, we have utilized a carbon-deprivation (C-deprivation) senescence assay using Arabidopsis (Arabidopsis thaliana) seedlings to investigate senescence regulation. Here we conducted a comprehensive time-resolved transcriptomic analysis of Arabidopsis wild type seedlings subjected to C-deprivation treatment at multiple time points, unveiling substantial temporal changes and distinct gene expression patterns. Moreover, we identified ALTERED MERISTEM PROGRAM 1 (AMP1), encoding an endoplasmic reticulum protein, as a potential regulator of senescence based on its expression profile. By characterizing loss-of-function alleles and overexpression lines of AMP1, we confirmed its role as a negative regulator of plant senescence. Genetic analyses further revealed a synergistic interaction between AMP1 and the autophagy pathway in regulating senescence. Additionally, we discovered a functional association between AMP1 and the endosome-localized ABNORMAL SHOOT3 (ABS3)-mediated senescence pathway and positioned key senescence-promoting transcription factors downstream of AMP1. Overall, our findings shed light on the molecular intricacies of transcriptome reprogramming during C-deprivation-induced senescence and the functional interplay among endomembrane compartments in controlling plant senescence., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

High-crystalline-quality absorbers with fewer defects are crucial for further improvement of open-circuit voltage (V OC ) and efficiency of Cu 2 ZnSn(S,Se) 4 (CZTSSe) solar cells. However, the preparation of high-quality CZTSSe absorbers remains challenging due to the uncontrollability of the selenization reaction and the complexity of the required selenization environment for film growth. Herein, a novel segmented control strategy for the selenization environment, specifically targeting the evaporation area of Se, to regulate the selenization reactions and improve the absorber quality is proposed. The large evaporation area of Se in the initial stage of the selenization provides a great evaporation and diffusion flux for Se, which facilitates rapid phase transition reactions and enables the attainment of a single-layer thin film. The reduced evaporation area of Se in the later stage creates a soft-selenization environment for grain growth, effectively suppressing the loss of Sn and promoting element homogenization. Consequently, the mitigation of Sn-related deep-level defects on the surface and in the bulk induced by element imbalance is simultaneously achieved. This leads to a significant improvement in nonradiative recombination suppression and carrier collection enhancement, thereby enhancing the V OC . As a result, the CZTSSe device delivers an impressive efficiency of 13.77% with a low V OC deficit., (© 2024 Wiley‐VCH GmbH.)

Objectives: This study evaluated the expression and significance of SNHG3 in Rheumatoid arthritis (RA) aiming to explore a biomarker and regulator for RA., Methods: The expression of SNHG3 in serum and synovial tissue was compared between RA patients and healthy individuals using PCR. The RA animal models were induced by the porcine type II collagen with Wistar rats and validated by the foot volume and AI score. The human fibroblast-like synoviocytes (H-FLS) were treated with LPS to mimic the injury during RA onset and the cell growth was assessed by CCK8 assay., Results: SNHG3 was significantly downregulated in the serum and synovial tissue of RA patients compared with healthy individuals. Downregulated SNHG3 could discriminate RA patients from healthy individuals with high sensitivity (0.875) and specificity (0.844). Porcine type II collagen induced increasing foot volume and AI scores of rats and SNHG3 was downregulated in RA rats. In LPS-induced H-FLS, SNHG3 negatively regulated miR-128-3p, and the alleviated effect of SNHG3 overexpression on cellular inflammation and oxidative stress was reversed by miR-128-3p upregulation., Conclusions: Serum SNHG3 was considered a potential diagnostic biomarker for RA from healthy individuals. SNHG3 regulated inflammatory response and oxidative stress via negatively modulating miR-128-3p., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objectives: In several disorders, the monocyte to high-density lipoprotein ratio (MHR) has been considered a biomarker of systemic inflammation and oxidative stress. However, its role in Bell's palsy (BP) remains unclear. This study investigates the relationship between elevated MHR and poor recovery in BP patients., Methods: The clinical data of 729 BP patients were analyzed retrospectively. The House-Brackmann Facial Nerve Grading System (H-B) was utilized to assess the severity of facial motor dysfunction during admission and the follow-up period after discharge. According to the 6 months follow-up data, H-B grades 1-2 were classified as recovered (n = 557), and H-B grades 3-6 as unrecovered (n = 172). The patients were split into MHR ≤ 0.26 (n = 361) and MHR > 0.26 (n = 368) groups based on the median MHR to further analyze the connection between different MHRs and prognosis., Results: The level of MHR was substantially greater in the unrecovered group of BP patients than in the restored group (medians[interquartile range], 0.32[0.20, 0.49] vs 0.24[0.11, 0.39], P < 0.001). MHR was an independent risk factor for BP prognosis as indicated by the multivariate logistic regression analysis (OR = 4.467, 95% CI = 1.875-10.646, P = 0.001). The area under the curve (AUC) was 0.615 (95% CI = 0.566-0.664, P < 0.001). The initial H-B score did not differ significantly between MHR ≤ 0.26 (n = 361) and MHR > 0.26 (n = 368) groups. However, after 6 months of follow-up, the high-MHR group's H-B score was considerably greater than the low-MHR group's., Conclusions: MHR is expected to be an accessible and effective biomarker of BP. In BP patients, elevated MHR is related to an increased chance of poor recovery., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Metabolic factors are major and controllable risk factors for cardiovascular diseases (CVD), and few studies have described this burden. We aim to assess it from 1990 to 2019 and predict the trends through 2034. Global Burden of Disease (GBD) provides data on sex, age, and socio-demographic index (SDI) levels. Numbers, age-standardized death rates (ASDR) and estimated annual percentage change (EAPC) were used. Future trends were estimated by NORDPRED model. The deaths cases of metabolic-related CVD increased from 8.61 million (95% UI: 7.91-9.29) to 13.71 million (95% UI: 12.24-14.94) globally. The ASDR continued to decline globally (EAPC = -1.36). The burden was heavier in male and middle-aged people and elderly people. CVD-related ASDR caused by high systolic blood pressure (SBP) had a downward trend globally (EAPC = -1.45), while trends of high body mass index (BMI) (EAPC = 1.29, 1.97, 0.92) and fasting plasma glucose (FPG) (EAPC = 0.95, 1.08, 0.46) were increasing in the middle, low-middle, and low SDI regions, respectively. Compared to 2015-2019, cumulative deaths will increase by 27.85% from 2030 to 2034, while ASDR will decrease 10.47%. The metabolic-related CVD burden remained high globally and deaths will continue to rise in the future. Men, middle-aged and elderly people were focus of concern. High SBP was globally well-managed over the past 30 years, but the CVD burden due to high BMI and FPG remained high. Exceptional initiatives are needed to regarding interventions targeting high BMI and FPG in middle and lower SDI regions., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

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., (© 2024 European Academy of Dermatology and Venereology.)

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. Its etiology may be associated with genetic, environmental, and lifestyle factors. With the advancement of technology, the integration of genomics, transcriptomics, and imaging data related to AD allows simultaneous exploration of molecular information at different levels and their interaction within the organism. This paper proposes a hypergraph-regularized joint deep semi-non-negative matrix factorization (HR-JDSNMF) algorithm to integrate positron emission tomography (PET), single-nucleotide polymorphism (SNP), and gene expression data for AD. The method employs matrix factorization techniques to nonlinearly decompose the original data at multiple layers, extracting deep features from different omics data, and utilizes hypergraph mining to uncover high-order correlations among the three types of data. Experimental results demonstrate that this approach outperforms several matrix factorization-based algorithms and effectively identifies multi-omics biomarkers for AD. Additionally, single-cell RNA sequencing (scRNA-seq) data for AD were collected, and genes within significant modules were used to categorize different types of cell clusters into high and low-risk cell groups. Finally, the study extensively explores the differences in differentiation and communication between these two cell types. The multi-omics biomarkers unearthed in this study can serve as valuable references for the clinical diagnosis and drug target discovery for AD. The realization of the algorithm in this paper code is available at https://github.com/ShubingKong/HR-JDSNMF ., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Crop genomics has advanced rapidly during the past decade, which generated a great abundance of omics data from multi-omics studies. How to utilize the accumulating data becomes a critical and urgent demand in crop science. As an attempt to integrate multi-omics data, we developed a database, LettuceDB (https://db.cngb.org/lettuce/), aiming to assemble multidimensional data for cultivated and wild lettuce germplasm. The database includes genome, variome, phenome, microbiome and spatial transcriptome. By integrating user-friendly bioinformatics tools, LettuceDB will serve as a one-stop platform for lettuce research and breeding in the future. Database URL: https://db.cngb.org/lettuce/., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: This study aimed to develop and validate a mortality risk prediction model for older people based on the Chinese Longitudinal Healthy Longevity Survey using the stacking ensemble strategy., Material and Methods: A total of 12,769 participants aged 65 or more at baseline were included. Ensemble machine learning models were applied to develop a mortality prediction model. We selected three base learners, including logistic regression, eXtreme Gradient Boosting, and Categorical + Boosting, and used logistic regression as the meta-learner. The primary outcome was five-year survival. Variable importance was evaluated by the SHapley Additive exPlanations method., Results: The mean age at baseline was 88, and 57.8 % of participants were women. The CatBoost model performed the best among the three base learners, the area under the receiver operating characteristics curve (AUC) reached 0.8469 (95%CI: 0.8345-0.8593), and the stacking ensemble model further improved the discrimination ability (AUC = 0.8486, 95%CI: 0.8367-0.8612, P = 0.046). Conventional logistic regression had comparable performance (AUC = 0.8470, 95 % CI: 0.8346-0.8595). Older age, higher scores for self-care activities of daily living, being male, higher objective physical performance capacity scores, not undertaking housework, and lower scores on the Mini-Mental State Examination contributed to higher risk., Conclusions: We successfully constructed and validated a few death risk prediction models for a Chinese population of older adults. While the stacking ensemble approach had the best prediction performance, the improvement over conventional logistic regression was insubstantial., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the abnormal aggregation of α-synuclein (α-syn) and the loss of dopaminergic neurons. Although microbial infection has been implicated in the pathogenesis of PD, the associated virulence factors and the underlying molecular mechanisms require further elucidation. Here, we found that intestinal infection with Nocardia farcinica induced a series of PD-like symptoms in Caenorhabditis elegans, such as the accelerated degeneration of dopaminergic neurons, impaired locomotion capacity, and enhanced α-syn aggregation, through the disturbance of mitochondrial functions. To identify the potential virulence factors involved in these effects, we knocked out the nbtB/C and nbtS genes in N. farcinica, which are localized in the gene clusters responsible for nocobactin biosynthesis. The deletion of either gene partially rescued the degenerative effects of wild-type N. farcinica on dopaminergic neurons by attenuating mitochondrial dysfunction. LC-MS analysis further identified a decrease in the abundance of several siderophores in the two mutants, including nocobactin NA-a, nocobactin NA-b, and nocardimicin B. Collectively, our results demonstrated that intestinal N. farcinica infection in C. elegans facilitates PD-like pathogenesis and provides novel evidence for the involvement of pathogenic bacteria in neurodegenerative diseases via non-neuroinvasive mechanisms., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Grain boundaries (GBs)-triggered severe non-radiative recombination is recently recognized as the main culprits for carrier loss in polycrystalline kesterite photovoltaic devices. Accordingly, further optimization of kesterite-based thin film solar cells critically depends on passivating the grain interfaces of polycrystalline Cu 2 ZnSn(S,Se) 4 (CZTSSe) thin films. Herein, 2D material of graphene is first chosen as a passivator to improve the detrimental GBs. By adding graphene dispersion to the CZTSSe precursor solution, single-layer graphene is successfully introduced into the GBs of CZTSSe absorber. Due to the high carrier mobility and electrical conductivity of graphene, GBs in the CZTSSe films are transforming into electrically benign and do not act as high recombination sites for carrier. Consequently, benefitting from the significant passivation effect of GBs, the use of 0.05 wt% graphene additives increases the efficiency of CZTSSe solar cells from 10.40% to 12.90%, one of the highest for this type of cells. These results demonstrate a new route to further increase kesterite-based solar cell efficiency by additive engineering., (© 2023 Wiley-VCH GmbH.)

Answering text-related questions while reading is a questioning strategy which is called adjunct questions or embedded questions, the benefits of which have been established in first-language reading as to enhance comprehension. The present study aims to study the effects different adjunct questions exert on second-language (L2) readers' comprehension of texts of various types. One hundred and forty-four intermediate-level Chinese EFL learners participated in this study and were divided randomly into six groups. Each group was given either a narrative or an expository text with 'what or why' questions or no questions. A brief topic familiarity questionnaire was attached to the end of each text paper. The results showed that inserted adjunct questions improved the readers' reading comprehension both in expository and narrative texts, but only narrative texts inserted with why questions had significant effects on the L2 reading comprehension. The findings suggested that text types and question types modulate the effects of inserted adjunct questions on the English reading of intermediate learners. Pedagogical implications and suggestions for future studies are provided.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA., Methods: Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis., Results: NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p., Conclusions: There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA., (© 2024. The Author(s).)

Background: Chronic knee pain after total knee arthroplasty (TKA) is a common complication that is difficult to treat. This report aims to highlight the benefit of combining embolotherapy and neurolysis intervention for symptomatic relief of post-TKA pain in a patient with long-standing pain refractory to conservative management., Case Presentation: A 77-year-old man who had previously undergone left knee arthroplasty has been grappling with worsening knee effusion and debilitating pain, resulting in limited mobility and progressive musculature deconditioning over a 20-year period. Diagnostic arteriography showed marked diffuse periarticular hyperemia around the medial and lateral joint spaces of the left knee, along with capsular distention. The patient initially underwent microsphere embolization to selectively target multiple branches of the genicular arteries, achieving a 50% reduction in pain at the one-month follow-up. Subsequently, the patient underwent image-guided genicular nerve neurolysis, targeting multiple branches of the genicular nerves, which led to further pain reduction (80% compared to the initial presentation or 60% compared to post-embolization) at the one-month follow-up. This improvement facilitated weight-bearing and enabled participation in physical therapy, with sustained pain relief over the 10-month follow-up period., Conclusion: The combination of genicular artery embolization and genicular nerve block may be a technically safe and effective option for alleviating chronic pain after total knee arthroplasty., (© 2023. The Author(s).)

Brain consumes nearly 20% supply of energy from glucose metabolism by oxidative phosphorylation and aerobic glycolysis. Less active state of glycolytic enzymes results in a limited capacity of glycolysis in the neurons of adult brain. Here we identified that Warburg effect is enhanced in hippocampal neurons during aging. As hippocampal neurons age, lactate levels progressively increase. Notably, we observed upregulated protein levels of PFKFB3 in the hippocampus of 20-month-old mice compared to young mice, and this higher PFKFB3 expression correlated with declining memory performance in aging mice. Remarkably, in aging mice, knocking down Pfkfb3 in hippocampal neurons rescued cognitive decline and synapse loss. Conversely, Pfkfb3 overexpression in hippocampal neurons led to cognitive impairment and synapse elimination, associated with heightened glycolysis. In vitro experiments with cultured primary neurons confirmed that Pfkfb3 overexpression increased glycolysis and that glycolytic inhibition could prevent apoptotic competency in neurons. These findings underscore that glycolysis in hippocampal neurons could potentially be targeted as a therapeutic avenue to mitigate cognitive decline and preserve synaptic integrity during aging., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The relationship of metabolic issues to pregnancy outcomes during assisted reproductive technology (ART) is gaining much attention. Fasting Plasma Glucose (FPG) is one of the most common metabolic indicators. Abnormal FPG not only affects the quality of life of human body, but also has a bearing on reproductive health. However, most attentions are paid on women's physical health and reproductive assessment, the health status of the male partner on pregnancy outcomes during ART treatment is often neglected. This study investigated whether male fasting hyperglycemia (FH, FPG > 6.1 mmol/L) can affect live birth rates (LBR) in singleton intrauterine clinical pregnancy women with cryo-thawed embryo transfer (CET) cycles., Material and Methods: A retrospective cohort study (370 CET cycles with first singleton clinical intrauterine pregnancy and grouped by male FPG) was conducted to analyze the relationship between male FH and clinical pregnancy outcomes using binary logistic regression; the odds ratios (ORs) and 95% confidence intervals (CIs) were calculated as a measure of relevancy. Live birth rate was the main outcome measure., Results: The live birth rate (LBR) was significantly lower [58.6% vs. 81.8%, P = 0.007, adjusted OR 0.635, 95% CI 0.456-0.884] and miscarriage rate (MR) was significantly higher [41.4% vs. 18.2%, P = 0.007, adjusted OR 1.575, 95% CI 1.131-2.195] in the FH group when compared with the Con group. There was no difference in healthy baby rate [88.2% vs. 89.6%, P = 0.058, adjusted OR 2.143, 95% CI 0.974-4.716] or abnormal birth weight rate (23.5% vs. 11.8%, P = 0.238, adjusted OR 2.859, 95% CI 0.777-10.460] between the FH and control group. No birth defects were observed in the present study., Conclusion: Male FH is an independent risk factor for lower LBR and higher MR in singleton intrauterine pregnancy women with CET cycles., (© 2023. The Author(s).)

The ability of the model organism, Caenorhabditis elegans , to distinguish and escape from pathogenic bacteria has been extensively studied; however, studies on the repulsive response of Meloidogyne incognita are still in their infancy. We have recently demonstrated that biocontrol bacteria induce a repulsive response in M. incognita via two classical signaling pathways. The present study aimed to identify the novel genes and signaling molecules of M. incognita that potentially contribute to its defense reaction. Analysis of the transcriptome data of M. incognita with and without a repulsive response against Bacillus nematocida B16 obtained 15 candidate genes, of which the novel genes Minc3s01748g26034 and Minc3s02548g30585 were found to regulate the aversive behavior of M. incognita , and their functions were further validated. To further confirm the neuronal localization of the two novel genes in M. incognita , in situ hybridization was conducted using the digoxin-labeled probes of ten tag genes, and preferentially profiled the localization of amphid sensory neurons of M. incognita . Analysis of the overviewed neuronal map suggested that Minc3s01748g26034 and Minc3s02548g30585 functioned in ASK/ASI and CEPD/V neurons, respectively. During their interactions, the volatile compounds 3-methyl-butyric acid and 2-methyl-butyric acid produced by the biocontrol bacteria were predicted as the primary signaling molecules that promoted the repulsive behavior of M. incognita against biocontrol bacteria. The findings provided novel insights into the mechanisms underlying the repulsive response of M. incognita that are different from the canonical molecular pathways previously found in C. elegans and can aid in developing novel strategies for controlling root-knot nematodes.

This retrospective study was performed to investigate the predictive power of the Ovarian Sensitivity Index (OSI) for IVF/ICSI outcomes in infertile patients who were of normal expected ovarian response. A total of 912 infertile patients who underwent GnRH antagonist protocol between January 2017 to August 2019 at the Medical Center for Human Reproduction, Beijing Chao-Yang Hospital were included. All patients completed the full oocyte retrieval cycle and either had a live birth or had no embryos left. OSI was significantly lower in patients with a live birth (196.0 ± 120.4 in the live birth group vs 276.4 ± 235.7 in the non-live birth group, p  < 0.001) while follicular output rate (FORT, defined as the ratio of pre-ovulatory follicle count on hCG day x 100/small antral follicle count at baseline) showed no significant difference. Patients were divided into low, average and high OSI groups and analysed in tertiles. From the low to the high OSI group, the cumulative live birth rate (CLBR) decreased dramatically (72.7 vs 67.2 vs 54.8%, p  < 0.001). Multivariate regression analysis showed that OSI was an independent factor affecting CLBR (OR: 0.996, 95%CI: 0.995-0.998, p  < 0.001) in our study population. In conclusion, OSI can be used as an independent indicator to distinguish fecundity in infertile patients with normal expected ovarian response and is probably more sensitive than FORT.

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disease characterized by multiple organ damage accompanied by the over-production of autoantibodies. Decreased intestinal flora diversity and disruption of homeostasis have been proven to be associated with pathogenesis of SLE. In previous study, a clinical trial was conducted to verify the safety and effectiveness of fecal microbiota transplantation (FMT) in the treatment of SLE. To explore the mechanism of FMT in the treatment of SLE, we included 14 SLE patients participating in clinical trials, including 8 in responders group (Rs) and 6 in non-responders group (NRs), and collected peripheral blood DNA and serum. We found that the serum of S-adenosylmethionine (SAM), methylation group donor, was upregulated after FMT, accompanied by an increase in genome-wide DNA methylation level in Rs. We further showed that the methylation levels in promoter regions of Interferon-γ (IFN-γ), induced Helicase C Domain Containing Protein 1 (IFIH1), endoplasmic reticulum membrane protein complex 8 (EMC8), and Tripartite motif-containing protein 58 (TRIM58) increased after FMT treatment. On the contrary, there was no significant change in the methylation of IFIH1 promoter region in the NRs after FMT, and the methylation level of IFIH1 in the Rs was significantly higher than that in the NRs at week 0. We included 850 K methylation chip sequencing, combining previous data of metagenomic sequencing, and metabolomic sequencing for multi-omics analysis to discuss the relationship between flora-metabolite-methylation in FMT. Finally, we found that hexanoic acid treatment can up-regulate the global methylation of peripheral blood mononuclear cells in SLE patients. Overall, our results delineate changes in methylation level after FMT treatment of SLE and reveal possible mechanisms of FMT treatment in terms of the recovery of abnormal hypomethylation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Systemic lupus erythematosus (SLE) is an autoimmune disease with the characterized presence of autoantibodies and resulting in multiple organ damage, which is incurable and can be lethal. The current treatments are limited and less progress has been made in drug discovery for the last few decades. Researches imply that gut dysbiosis exists in both patients and murine models with SLE, taking part in the pathogenesis of SLE through multiple mechanisms such as microbiota translocation and molecular mimicry. Intestinal interventions on the gut microbiome by fecal transplantations to reconstitute the gut-immunity homeostasis serve as a novel therapeutic option for SLE patients. Fecal microbiota transplantation (FMT), which is usually used in intestinal diseases, has been firstly demonstrated to be safe and efficient in recovering gut microbiota structure of SLE patients and reducing lupus activity in our recent clinical trial, which is the first trial testing FMT therapy in SLE treatment. In this paper, we reviewed the results of the single-arm clinical trial and made recommendations on FMT practice in SLE treatment including therapeutic indications, screening items and dosage regimen, trying to provide references for future study and clinical practice. We also came up with the unanswered questions that need to be solved by the ongoing randomized controlled trial as well as the future expectations for the intestinal intervention strategies of SLE patients., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Thinning of the sclera happens in myopia eyes owing to extracellular matrix (ECM) remodeling, but the initiators of the ECM remodeling in myopia are mainly unknown. The matrix metalloproteinase (MMPs) and tissue inhibitors of matrix metalloproteinase (TIMPs) regulate the homeostasis of the ECM. However, genetic studies of the MMPs and TIMPs in the occurrence of myopia are poor and limited. This study systematically investigated the association between twenty-nine genes of the TIMPs and MMPs families and early-onset high myopia (eoHM) based on whole exome sequencing data. Two TIMP4 heterozygous loss-of-function (LoF) variants, c.528C>A in six patients and c.234&#95;235insAA in one patient, were statistically enriched in 928 eoHM probands compared to that in 5469 non-high myopia control ( p = 3.7 × 10 -5 ) and that in the general population ( p = 2.78 × 10 -9 ). Consequently, the Timp4 gene editing rat was further evaluated to explore the possible role of Timp4 on ocular and myopia development. A series of ocular morphology abnormalities in a dose-dependent manner ( Timp4 -/- < Timp4 +/- < Timp4 +/+ ) were observed in a rat model, including the decline in the retinal thickness, the elongation in the axial length, more vulnerable to the form deprivation model, morphology changes in sclera collagen bundles, and the decrease in collagen contents of the sclera and retina. Electroretinogram revealed that the b-wave amplitudes of Timp4 defect rats were significantly reduced, consistent with the shorter length of the bipolar axons detected by HE and IF staining. Heterozygous LoF variants in the TIMP4 are associated with early onset high myopia, and the Timp4 defect disturbs ocular development by influencing the morphology and function of the ocular tissue.

The etiology of Bell's palsy (BP) is currently unknown, and the findings from previous studies examining the association between seasonal or meteorological factors and BP have been inconsistent. This research aims to clarify this relationship by analyzing a larger dataset and employing appropriate statistical methods. Data from 5387 patients with BP treated at Zhejiang Provincial Hospital of Traditional Chinese Medicine in Hangzhou, Zhejiang Province, from May 1, 2018, to June 30, 2023, was gathered. We assessed the temporal distribution of meteorological factors and the incidence of BP across seasons and months. A distributed lag non-linear model was used to further investigate the lagged and overall effects of temperature and air pressure on the onset of BP. The temporal distribution of BP incidence revealed the highest average number of cases occurring in December and the lowest in June. A correlation existed between BP episodes and temperature or air pressure. The model revealed a higher relative risk during periods of low temperature and high air pressure, characterized by a time lag effect. This correlation was notably more pronounced in female patients and individuals in the young and middle-aged groups. Our findings suggest that exposure to low temperatures and high air pressure constitute risk factors for BP development., (© 2023. The Author(s).)

Objective: To evaluate the impact of the COVID-19 pandemic on the occurrence of Peripheral Facial Nerve Paralysis (PFNP) in Chinese patients, identify contributing factors, and explore the relationship between COVID-19 and PFNP., Methods: We conducted a retrospective study covering the years 2020 to 2023, categorizing patients into three groups based on their visit dates: Group 1 (December 8, 2020 to February 28, 2021), Group 2 (December 8, 2021 to February 28, 2022), and Group 3 (December 8, 2022 to February 28, 2023). We collected and compared data on disease onset and patient characteristics among these groups., Results: In Group 3, following the widespread COVID-19 outbreak, there was a significant increase of 22.4 and 12.1% in PFNP cases compared to the same periods in the preceding 2 years ( p  < 0.001). Group 3 patients were more likely to be aged between 30 and 60 years, experience onset within 7 days, present with Hunter syndrome, and have a higher H-B score of VI compared to the previous 2 years ( p  < 0.017). Logistic regression analysis revealed a strong association between the COVID-19 pandemic and the incidence of Hunter syndrome in PFNP (OR = 3.30, 95% CI 1.81-6.03, p  < 0.001)., Conclusion: The incidence of PFNP increased in China after the COVID-19 pandemic, particularly in patients with Hunter syndrome, indicating that COVID-19 infection can trigger and worsen PFNP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Jin, Zhou, Chen, Cai, Hu and Xuan.)

Background: As an important vegetable crop, cultivated lettuce is grown worldwide and a great variety of agronomic traits have been preserved within germplasm collections. The mechanisms underlying these phenotypic variations remain to be elucidated in association with sequence variations. Compared with single nucleotide polymorphisms, structural variations (SVs) that have more impacts on gene functions remain largely uncharacterized in the lettuce genome., Results: Here, we produced a comprehensive SV set for 333 wild and cultivated lettuce accessions. Comparison of SV frequencies showed that the SVs prevalent in L. sativa affected the genes enriched in carbohydrate derivative catabolic and secondary metabolic processes. Genome-wide association analysis of seven agronomic traits uncovered potentially causal SVs associated with seed coat color and leaf anthocyanin content., Conclusion: Our work characterized a great abundance of SVs in the lettuce genome, and provides a valuable genomic resource for future lettuce breeding., (© 2023. The Author(s).)

Although learning-based light field disparity estimation has achieved great progress in the most recent years, the performance of unsupervised light field learning is still hindered by occlusions and noises. By analyzing the overall strategy underlying the unsupervised methodology and the light field geometry implied in epipolar plane images (EPIs), we look beyond the photometric consistency assumption, and design an occlusion-aware unsupervised framework to deal with the situations of photometric consistency conflict. Specifically, we present a geometry-based light field occlusion modeling, which predicts a group of visibility masks and occlusion maps, respectively, by forward warping and backward EPI-line tracing. In order to learn better the noise-and occlusion-invariant representations of the light field, we propose two occlusion-aware unsupervised losses: occlusion-aware SSIM and statistics-based EPI loss. Experiment results demonstrate that our method can improve the estimation accuracy of light field depth over the occluded and noisy regions, and preserve the occlusion boundaries better.

Glioblastoma (GBM) is a highly aggressive cancer that currently lacks effective treatments. Pyroptosis has emerged as a promising therapeutic approach for cancer, but there is still a need for new pyroptosis boosters to target cancer cells. In this study, it is reported that Aloe-emodin (AE), a natural compound derived from plants, can inhibit GBM cells by inducing pyroptosis, making it a potential booster for pyroptosis-mediated GBM therapy. However, administering AE is challenging due to the blood-brain barrier (BBB) and its non-selectivity. To overcome this obstacle, AE@ZIF-8 NPs are developed, a biomineralized nanocarrier that releases AE in response to the tumor's acidic microenvironment (TAM). Further modification of the nanocarrier with transferrin (Tf) and polyethylene glycol-poly (lactic-co-glycolic acid) (PEG-PLGA) improves its penetration through the BBB and tumor targeting, respectively. The results show that AE-NPs (Tf-PEG-PLGA modified AE@ZIF-8 NPs) significantly increase the intracranial distribution and tumor tissue accumulation, enhancing GBM pyroptosis. Additionally, AE-NPs activate antitumor immunity and reduce AE-related toxicity. Overall, this study provides a new approach for GBM therapy and offers a nanocarrier that is capable of penetrating the BBB, targeting tumors, and attenuating toxicity., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Background: Few studies examined the associations of household fuel combustion with incident diabetes. The current study emphasizes the association of domestic fuel combustion with diabetes among middle- and older- Chinese., Methods: The data was extracted from a national and prospective cohort, the China Health and Retirement Longitudinal Study (CHARLS), which enrolled adults ≥ 45 years. A total of 4610 and 5570 participants were involved in heating and cooking-related analyses. Multivariable logistic models were conducted to assess the association of domestic fuel combustion for heating and cooking with diabetes. Furthermore, we also examined whether it differed from switching fuel types. Subgroup and interaction analyses were performed based on covariates to examine the robustness and find potential effect modifiers., Results: After about 5-year follow-up, 592 and 716 diabetes were diagnosed in heating and cooking-related analyses. Compared to cleaner fuel users, those who used solid fuel for heating [OR (95 % CI):1.32 (1.05-1.66)] maintained higher risks of incident diabetes. In addition, participants who were exposed to solid fuel for both heating and cooking [OR (95 % CI):1.55 (1.17-2.06)] might have further elevated diabetic risk. Those risks are likely to be attenuated if people switched cooking fuel from solid to cleaner [OR (95 % CI): 0.68 (0.53-0.89)]., Conclusions: Home solid fuel use for heating is associated with an increased risk of incident diabetes. If solid fuel was concurrently used for both cooking and heating, those risks might be further elevated. Interestingly, as compared to solid fuel users, the participants switching cooking fuel types from solid to cleaner presented reduced diabetic risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Situated against the backdrop of a politically fueled ethnic hate between the Northern Region and the rest, this study exposes the relationship between the students' regions of origin and their academic performance in Malawian higher education to contribute to appropriate student support and healthy study habits. Spearman's rHO indicated weak but statistically significant correlations between one's home region and academic performance. Kruskal Wallis Test (N = 20,263) revealed that no single region outperforms others. Thematic analysis of interview data (N = 15) through NVivo revealed that students believe effort matters more in academic performance irrespective of one's region of origin. Implications for education policy that harness healthy study habits to enhance student achievement, retention, and self-efficacy about success are discussed., Competing Interests: The authors declare no conflict of interest., (© 2023 Published by Elsevier Ltd.)

Solar cells based on emerging kesterite Cu 2 ZnSn(S,Se) 4 (CZTSSe) materials have reached certified power conversion efficiency (PCE) as high as 13.6%, showing great potential in the next generation of photovoltaic technologies because of their earth-abundant, tunable direct bandgap, high optical absorption coefficient, environment-friendly, and low-cost properties. The predecessor of CZTSSe is Cu(In,Ga) Se 2 (CIGS), and the highest PCE of CIGS fabricated by the vacuum method is 23.35%. However, the recorded PCE of CZTSSe devices are fabricated by a low-cost solution method. The characteristics of the solvent play a key role in determining the crystallization kinetics, crystal growth quality, and optoelectronic properties of the CZTSSe thin films in the solution method. It is still challenging to improve the efficiency of CZTSSe solar cells for future commercialization and applications. This review describes the current status of CZTSSe solar cell absorbers fabricated by protic solvents with NH (hydrazine), protic solvents with SH (amine-thiol), aprotic solvents (DMSO and DMF), ethylene glycol methyl ether-based precursor solution method (EGME), and thioglycolic acid (TGA)-ammonia solution (NH 3 H 2 O) deposition methods. Furthermore, the performances of vacuum-deposited devices and solution-based processed devices are compared. Finally, the challenges and outlooks of CZTSSe solar cells are discussed for further performance improvement.

Photodynamic therapy (PDT) induces immunogenic cell death (ICD) by producing reactive oxygen species (ROS), making it an ideal method for cancer treatment. However, the extremely lower level of oxygen, short half-life of produced ROS, and limited photosensitizers accumulating in the tumor site via intravenous administration are the main reasons that limit the further application of PDT. To address these issues, we loaded the photosensitizer porphine (THPP) into biomimetic gold nanorod-mesoporous silica core-shell nanoparticles (Au-MSN NPs) to prepare Au@MSN/THPP@CM NPs. We then seeded the NPs together with catalase (CAT) into a gelatin methacryloyl (GelMA) microgel matrix to form Au@MSN-Ter/THPP@CM@GelMA/CAT microspheres consisting of biomimetic nano@microgel. The NPs and biomimetic nano@microgel exhibited enhanced photodynamic (PD) reaction and excellent photothermal conversion ability. Moreover, we further conjugated an endoplasmic reticulum (ER) targeting ligand Tosyl Ethylenediamine (Ter) on the surface of Au-MSN NPs. The results showed that both Au@MSN-Ter/THPP@CM NPs and the finally formed Au@MSN-Ter/THPP@CM@GelMA/CAT biomimetic nano@microgel induced precise and prolonged ER stress through photodynamic reactions, which stimulated the exposure of the proapoptotic calreticulin (CRT) on the cell membrane and increased the release of high mobility group box 1 (HMGB1) form the nucleus in SKOV3 cells under near-infrared (NIR) laser irradiation. Additionally, a single dose of the nano@microgel delivered through minimally invasive injection generated a significant anti-tumor effect in the SKOV3 cell line-derived orthotopic ovarian cancer mouse model through a PD and PT combination therapy. This study offers a new strategy for enhanced PDT and provides a PD/PT synergistic treatment method for ovarian cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: As an interdisciplinary field, drug delivery relies on the developments of modern science and technology. Correspondingly, how to upgrade the traditional dosage forms for a more efficacious, safer, and convenient drug delivery poses a continuous challenge to researchers. Methods, results and discussion: In this study, a proof-of-concept demonstration was conducted to convert a popular traditional liquid dosage form (a commercial oral compound solution prepared from an intermediate licorice fluidextract) into a solid dosage form. The oral commercial solution was successfully encapsulated into the core-shell nanohybrids, and the ethanol in the oral solution was removed. The SEM and TEM evaluations showed that the prepared nanofibers had linear morphologies without any discerned spindles or beads and an obvious core-shell nanostructure. The FTIR and XRD results verified that the active ingredients in the commercial solution were compatible with the polymeric matrices and were presented in the core section in an amorphous state. Three different types of methods were developed, and the fast dissolution of the electrospun core-shell nanofibers was verified. Conclusion: Coaxial electrospinning can act as a nano pharmaceutical technique to upgrade the traditional oral solution into fast-dissolving solid drug delivery films to retain the advantages of the liquid dosage forms and the solid dosage forms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Dai, Li, Liu, Zhou, Yu and Ge.)

Systemic lupus erythematosus (SLE) is characterized by loss of self-tolerance and persistent self-aggression, sustained chronic inflammation, production of autoantibodies and multi-system damage, and is largely incurable to date. The gut microbiota and its metabolites, now recognized as crucial environmental triggers of local/systemic immune reactions, have been implicated in the development and progression of SLE. Fecal microbiota transplantation (FMT) is restoration of disturbed microbiota by transplanting foreign gut microbiota from healthy individuals into the gastrointestinal tract of diseased individuals. Our previous clinical trial suggests that FMT is a potentially safe and effective treatment for SLE. In order to elucidate the potential effect of FMT on peripheral immune cells of patients with SLE, we collected PBMCs (n = 30) of 13 SLE patients who participated in the clinical trial before and after the FMT-treatment, and performed single-cell RNA sequencing. The results first revealed that peripheral T lymphocytes of SLE patients decreased and NK cells increased after the FMT treatment. Then, sub-clustering analysis discovered that total CD4 + T cells highly expressed genes of IL7R, CD28, and CD8 + T cells highly expressed genes of GZMH and NKG7 after FMT treatment. Moreover, FMT treatment reduced the expression of interferon-related genes (IRGs) in CD4 + T, CD8 + T, DP, NK, and B cells of SLE patients. More importantly, interferon-related pathways were more enriched in cells of the FMT non-responder group, and further the interferon genes expression of lymphocytes and myeloid cells was negatively correlated with the efficiency of FMT treatment. Collectively, our data identified various immunophenotypic and associated gene set changes following FMT treatment, illustrating the heterogeneity of response to FMT treatment in SLE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor and is characterized by high mortality and morbidity rates and unpredictable clinical behavior. The disappointing prognosis for patients with GBM even after surgery and postoperative radiation and chemotherapy has fueled the search for specific targets to provide new insights into the development of modern therapies. MicroRNAs (miRNAs/miRs) act as oncomirs and tumor suppressors to posttranscriptionally regulate the expression of various genes and silence many target genes involved in cell proliferation, the cell cycle, apoptosis, invasion, stem cell behavior, angiogenesis, the microenvironment and chemo- and radiotherapy resistance, which makes them attractive candidates as prognostic biomarkers and therapeutic targets or agents to advance GBM therapeutics. However, one of the major challenges of successful miRNA-based therapy is the need for an effective and safe system to deliver therapeutic compounds to specific tumor cells or tissues in vivo, particularly systems that can cross the blood-brain barrier (BBB). This challenge has shifted gradually as progress has been achieved in identifying novel tumor-related miRNAs and their targets, as well as the development of nanoparticles (NPs) as new carriers to deliver therapeutic compounds. Here, we provide an up-to-date summary (in recent 5 years) of the current knowledge of GBM-related oncomirs, tumor suppressors and microenvironmental miRNAs, with a focus on their potential applications as prognostic biomarkers and therapeutic targets, as well as recent advances in the development of carriers for nontoxic miRNA-based therapy delivery systems and how they can be adapted for therapy., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Discoid lupus erythematosus (DLE) and systemic lupus erythematosus (SLE) are both types of lupus, yet the characteristics, and differences between them are not fully understood. Here we show single-cell RNA sequencing data of cutaneous lesions from DLE and SLE patients and skin tissues from healthy controls (HCs). We find significantly higher proportions of T cells, B cells and NK cells in DLE than in SLE. Expanded CCL20 + keratinocyte, CXCL1 + fibroblast, ISG hi CD4/CD8 T cell, ISG hi plasma cell, pDC, and NK subclusters are identified in DLE and SLE compared to HC. In addition, we observe higher cell communication scores between cell types such as fibroblasts and macrophage/dendritic cells in cutaneous lesions of DLE and SLE compared to HC. In summary, we clarify the heterogeneous characteristics in cutaneous lesions between DLE and SLE, and discover some specific cell subtypes and ligand-receptor pairs that indicate possible therapeutic targets of lupus erythematosus., (© 2022. The Author(s).)

Subacute cutaneous lupus erythematosus (SCLE) is a clinical subtype of cutaneous lupus erythematosus with psoriatic-like or annular papules with scaly erythemas, the pathological mechanism of which is poorly understood. To investigate the immune pathogenesis of SCLE, we performed single-cell RNA sequencing (scRNA-seq) of SCLE skin lesions and integrated the scRNA-seq data from skin tissues of healthy controls (HCs). Our results identified expanded fibroblasts and keratinocytes subtypes, abnormally activated lymphocyte and inflammatory M1 macrophages in SCLE. In SCLE, stromal cells, such as keratinocytes and fibroblasts, showed enhanced chemotactic functions for recruiting immune cells. Importantly, interferon-related genes were identified as key intermediate genes in the potential trajectory of fibroblasts, keratinocytes, and B cells from HCs to SCLE. Our investigation provides a comprehensive description of cell composition in SCLE and highlights several important clues for understanding the pathogenesis of SCLE., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)