Anti-Solvent-Free Fabrication of Stable FA0.9Cs0.1PbI3 Perovskite Solar Cells with Efficiency Exceeding 24.0% through a Naphthalene-Based Passivator.

The anti-solvent-free fabrication of high-efficiency perovskite solar cells (PSCs) holds immense significance for the transition from laboratory-scale to large-scale commercial applications. However, the device performance is severely hindered by the increased occurrence of surface defects resulting from the lack of control over nucleation and crystallization of perovskite using anti-solvent methods. In this study, 2-(naphthalen-2-yl)ethylamine hydriodide (NEAI) is employed as the surface passivator for perovskite films without using any anti-solvent. Naphthalene demonstrates strong π-π conjugation, which aids in the efficient extraction of charge carriers. Additionally, the naphthalene-ring moieties form a tight attachment to the perovskite surface. After NEAI treatment, FA and I vacancies are selectively occupied by NEA+ and I- in NEAI respectively, thus effectively passivating the surface defects and isolating the surface from moisture. Ultimately, the optimized NEAI-treated device achieves a promising power conversion efficiency (PCE) of 24.19% (with a certified efficiency of 23.94%), featuring a high fill factor of 83.53%. It stands out as one of the reported high PCEs achieved for PSCs using the spin-coating technique without the need for any anti-solvent so far. Furthermore, the NEAI-treated device can maintain ≈87% of its initial PCE after 2000 h in ambient air with a relative humidity of 30% ± 5%.

Clinicopathologic and Molecular Characterization of Xanthomatous Giant Cell Renal Cell Carcinomas: Further Support for a Close Morphologic Spectrum to Eosinophilic Solid and Cystic Renal Cell Carcinomas.

A recent study described a rare subtype of tuberous sclerosis complex (TSC)-mutated renal cell carcinoma primarily characterized by Xanthomatous giant cell morphology. Only 2 cases in young individuals have been reported so far, making the correct diagnosis challenging from a pathological perspective. It remains unknown whether this tumor represents an independent subtype or belongs to other TSC-mutated tumors. We conducted a clinicopathologic evaluation and immunohistochemical profiling of 5 cases of Xanthomatous Giant Cell Renal Cell Carcinoma (XGC RCC) with confirmed TSC2 mutations through targeted DNA sequencing. In addition, we analyzed transcriptomic profiles using RNA-seq for the following samples: XGC RCC, Low-grade Oncocytic tumors (LOT), High-grade Oncocytic tumors/Eosinophilic Vacuolar Tumors (HOT/EVT), Eosinophilic Solid and Cystic Renal Cell Carcinomas (ESC RCC), Chromophobe cell Renal Cell Carcinomas (ChRCC), Renal Oncocytomas (RO), clear cell Renal Cell Carcinomas (ccRCC), and normal renal tissues. There were 2 female and 3 male patients, aged 22 to 58 years, who underwent radical nephrectomy for tumor removal. The tumor sizes ranged from 4.7 to 9.5 cm in diameter. These tumors exhibited ill-defined boundaries, showed an expansive growth pattern, and featured distinctive tumor giant cells with abundant eosinophilic to Xanthomatous cytoplasm and prominent nucleoli. All tumors had low Ki-67 proliferation indices (<1%) and demonstrated immune reactivity for CD10, PAX8, CK20, CathepsinK, and GPNMB. Next-generation sequencing confirmed TSC2 mutations in all cases. RNA sequencing-based clustering indicated a close similarity between the tumor and ESC RCC. One patient (1/5) died of an accident 63 months later, while the remaining patients (4/5) were alive without tumor recurrences or metastases at the time of analysis, with a mean follow-up duration of 43.4 months. Our research supports the concept that Xanthomatous giant cell renal cell carcinoma (XGC RCC) shares clinicopathological and molecular characteristics with ESC RCC and shows a relatively positive prognosis, providing further support for a close morphologic spectrum between the two. We propose considering XGC RCC as a distinct subtype of ESC RCC.

Protective effect of resveratrol on nickel-refining fumes-induced inflammatory damage.

Nickel (Ni), a ductile and hard silver-white transition metal, is commonly found in occupational environments and can harm the human body. Since it is a toxic compound, long-term Ni exposure can cause pneumonia, rhinitis, and other types of respiratory inflammatory diseases. Resveratrol (Res) is a plant antitoxin polyphenol, which also has anti-cancer and anti-inflammatory properties. In this report, the toxicity of Ni-refining fumes on the human lung bronchial epithelial (BEAS-2B) cells, as well as the protective effects of Res were investigated in vitro, and the specific mechanism of its anti-inflammatory effect was explained. The experimental observations of this study revealed that Ni-refining fumes induce BEAS-2B cell damage, increase reactive oxygen species (ROS) content, activate NLRP3 (LRR-, NOD-, and pyrin domain-containing 3) inflammasome, and promote the secretion of the cytokine Interleukin (IL)-1ß, leading to cellular inflammation and reducing cell activity. Resveratrol (20 µmol/L) activated sirtuin 1 (SIRT1) in BEAS-2B cells to increase protein and mRNA expression. SIRT1 was observed to inhibit the transcriptional activity of nuclear factor-kappaB (NF-κB), reduced the expression of NLRP3 protein and mRNA, and inhibited NLRP3 inflammation. The level of inflammasome activation and IL-1ß overexpression could reduce the inflammatory damage caused by the Ni-refining fume particles on the BEAS-2B cells and exert anti-inflammatory protective effects. In vivo experiments further confirmed that resveratrol could effectively alleviate the acute inflammatory injuries caused due to exposure to the Ni-refining fume particles in the lung tissues of the Wistar rats, and verified that resveratrol could exert its anti-inflammatory impact through the SIRT1-NF-κB-NLRP3 pathway. These results provide an important theoretical basis for developing novel protective drugs and investigating the mechanism of action for inflammatory injury in occupational populations caused by exposure to nickel and other heavy metals.

Adipocyte-targeted delivery of rosiglitazone with localized photothermal therapy for the treatment of diet-induced obesity in mice.

Obesity represents a growing public health concern and is closely associated with metabolic complications such as diabetes and fatty liver disease. Anti-obesity medications currently available have limited efficacy in weight loss and are often accompanied by adverse effects. This study proposes a localized photothermal therapy (PTT) combined with adipocyte-targeted delivery of rosiglitazone (RSG) to address obesity. Specifically, cationic albumin nanoparticles (cNPs) were synthesized to deliver RSG precisely to white adipocytes, stimulating the browning process. An IR780-loaded thermosensitive hydrogel was injected and allowed to gel in situ to afford a subcutaneous reservoir that enables localized PTT and controlled release of RSG cNPs. Notably, cNPs significantly enhanced the internalization efficiency in adipocytes in vitro and prolonged the therapeutic retention in the adipose tissue in vivo. Co-administration of RSG cNPs and PTT substantially reduced fat content, induced browning in white adipose tissue in diet-induced obese mice, and mitigated complications such as insulin resistance, fatty liver, and hyperlipidemia. The increased expression of uncoupling protein 1 contributes to enhancing energy expenditure and facilitating adipose metabolism, thereby effectively combating obesity. This therapeutic approach integrates localized PTT with adipocyte-targeted delivery to combat the global obesity epidemic thus offering a promising solution with reduced systemic toxicity and enhanced efficacy. STATEMENT OF SIGNIFICANCE.

Prediction of false-positive PI-RADS 5 lesions on prostate multiparametric MRI: development and internal validation of a clinical-radiological characteristics based nomogram.

BACKGROUND: To develop a risk model including clinical and radiological characteristics to predict false-positive The Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. METHODS: Data of 612 biopsy-naïve patients who had undergone multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy were collected. Clinical variables and radiological variables on mpMRI were adopted. Lesions were divided into the training and validation cohort randomly. Stepwise multivariate logistic regression analysis with backward elimination was performed to screen out variables with significant difference. A diagnostic nomogram was developed in the training cohort and further validated in the validation cohort. Calibration curve and receiver operating characteristic (ROC) analysis were also performed. RESULTS: 296 PI-RADS 5 lesions in 294 patients were randomly divided into the training and validation cohort (208 : 88). 132 and 56 lesions were confirmed to be clinically significant prostate cancer in the training and validation cohort respectively. The diagnostic nomogram was developed based on prostate specific antigen density, the maximum diameter of lesion, zonality of lesion, apparent diffusion coefficient minimum value and apparent diffusion coefficient minimum value ratio. The C-index of the model was 0.821 in the training cohort and 0.871 in the validation cohort. The calibration curve showed good agreement between the estimation and observation in the two cohorts. When the optimal cutoff values of ROC were 0.288 in the validation cohort, the sensitivity, specificity, PPV, and NPV were 90.6%, 67.9%, 61.7%, and 92.7% in the validation cohort, potentially avoiding 9.7% unnecessary prostate biopsies. CONCLUSIONS: We developed and validated a diagnostic nomogram by including 5 factors. False positive PI-RADS 5 lesions could be distinguished from clinically significant ones, thus avoiding unnecessary prostate biopsy.

Modified Retzius-sparing robot-assisted radical prostatectomy for cases with anterior tumor: a propensity score-matched analysis.

OBJECTIVE: To compare the outcomes between a modified Retzius-sparing robot-assisted radical prostatectomy (mRS-RARP) technique and conventional robot-assisted radical prostatectomy (Con-RARP) technique for cases with anterior prostate cancer (PCa), especially positive surgical margin (PSM) rates and urinary continence (UC). PATIENTS AND METHODS: We retrospectively included 193 mRS-RARP and 473 Con-RARP consecutively performed by a single surgeon for anterior PCa. Perioperative complications, pathology, and continence were compared after propensity score matching using 9 variables. RESULTS: After matching (n = 193 per group), PSM were not significantly different in the two groups (16.1% in mRS-RARP group vs. 15.0% in Con-RARP group, p = 0.779). The UC at catheter removal and at 1-month was significantly higher in the mRS-RARP (24.9% vs. 9.8%, p < 0.001; 29.0% vs. 13.5%, p < 0.001, respectively), but not at 3-, 6-, and 12-month follow-ups (p = 0.261, 0.832, and 0.683, respectively). CONCLUSION: mRS-RARP seems to be an oncologically safe approach for patients with anterior PCa. Compared with the conventional approach, mRS-RARP approach shows benefits in the short-term postoperative UC recovery.

GCNGAT: Drug-disease association prediction based on graph convolution neural network and graph attention network.

Predicting drug-disease associations can contribute to discovering new therapeutic potentials of drugs, and providing important association information for new drug research and development. Many existing drug-disease association prediction methods have not distinguished relevant background information for the same drug targeted to different diseases. Therefore, this paper proposes a drug-disease association prediction model based on graph convolutional network and graph attention network (GCNGAT) to reposition marketed drugs under the distinguishment of background information. Firstly, in order to obtain initial drug-disease information, a drug-disease heterogeneous graph structure is constructed based on all known drug-disease associations. Secondly, based on the heterogeneous graph structure, the corresponding subgraphs of each group of drug-disease association pairs are extracted to distinguish different background information for the same drug from different diseases. Finally, a model combining Graph neural network with global Average pooling (GnnAp) is designed to predict potential drug-disease associations by learning drug-disease interaction feature representations. The experimental results show that adding subgraph extraction can effectively improve the prediction performance of the model, and the graph representation learning module can fully extract the deep features of drug-disease. Using the 5-fold cross-validation, the proposed model (GCNGAT) achieves AUC (Area Under the receiver operating characteristic Curve) values of 0.9182 and 0.9417 on the PREDICT dataset and CDataset dataset, respectively. Compared with other predictors on the same dataset (PREDICT dataset), GCNGAT outperforms the existing best-performing model (PSGCN), with a 1.58% increase in the AUC value. It is anticipated that this model can provide experimental reference for drug repositioning and further promote the drug research and development process.

The Value of 68Ga-PSMA PET/MRI for Classifying Patients with PI-RADS 3 Lesions on Multiparametric MRI: A Prospective Single-Center Study.

Prostate Imaging Reporting and Data System (PI-RADS) category 3 lesions remain a diagnostic challenge for detecting clinically significant prostate cancer (csPCa). This article evaluates the added value of 68Ga-labeled prostate-specific membrane antigen-11 (68Ga-PSMA) PET/MRI in classifying PI-RADS 3 lesions to avoid unnecessary biopsies. Methods: Sixty biopsy-naïve men with PI-RADS 3 lesions on multiparametric MRI were prospectively enrolled between February 2020 and October 2022. In all, 56 participants underwent 68Ga-PSMA PET/MRI and prostate systematic biopsy. 68Ga-PSMA PET/MRI was independently evaluated and reported by the 5-level PRIMARY score developed within the PRIMARY trial. Receiver-operating-characteristic curve analysis was used to estimate the diagnostic performance. Results: csPCa was detected in 8 of 56 patients (14.3%). The proportion of patients with csPCa and a PRIMARY score of 1, 2, 3, 4, and 5 was 0% (0/12), 0% (0/13), 6.3% (1/16), 38.5% (5/13), and 100% (2/2), respectively. The estimated area under the curve of the PRIMARY score was 0.91 (95% CI, 0.817-0.999). For a PRIMARY score of 4-5 versus a PRIMARY score of 1-3, the sensitivity, specificity, positive predictive value, and negative predictive value were 87.5%, 83.3%, 46.7%, and 97.5%, respectively. With a PRIMARY score of at least 4 to make a biopsy decision in men with PI-RADS 3 lesions, 40 of 48 patients (83.3%) could avoid unnecessary biopsies, at the expense of missing 1 of 8 (12.5%) csPCa cases. Conclusion: 68Ga-PSMA PET/MRI has great potential to classify patients with PI-RADS 3 lesions and help avoid unnecessary biopsies.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.

Zein-Based Triple-Drug Nanoparticles to Promote Anti-Inflammatory Responses for Nerve Regeneration after Spinal Cord Injury.

Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem is developed to deliver autophagy-promoting, anti-inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor are combined into the zein-based nanoparticles, aiming to solubilize the drugs and prolong their circulation. The nanoparticles are internalized by BV2 microglia and SH-SY5Y neuron-like cells in culture; they inhibit the secretion of inflammatory factors by BV2 cells after insult with lipopolysaccharide, and they protect SH-SY5Y cells from the toxicity of H2O2. In a rat model of spinal cord injury, the nanoparticles mitigate inflammation and promote spinal cord repair. In the in vitro and in vivo experiments, the complete nanoparticles function better than the free drugs or nanoparticles containing only one or two drugs. These results suggest that the triple-drug nanoparticles show promise for treating spinal cord injury.

Microstructures and Corrosion Properties of Wire Arc Additive Manufactured Copper-Nickel Alloys.

The 70/30 copper-nickel alloy is used mainly in critical parts with more demanding conditions in marine settings. There is a need for innovative methods that offer fast production and cost-effectiveness in order to supplement current copper-nickel alloy manufacturing processes. In this study, we employ wire arc additive manufacturing (WAAM) to fabricate the 70/30 copper-nickel alloy. The as-built microstructure is characterized by columnar grains with prominent dendrites and chemical segregation in the inter-dendritic area. The aspect ratio of the columnar grain increases with increasing travel speed (TS) at the same wire feed speed (WFS). This is in contrast with the equiaxed grain structure, with a more random orientation, of the conventional sample. The sample built with a WFS of 8 m/min, TS of 1000 mm/min, and a track distance of 3.85 mm exhibits superior corrosion properties in the 3.5 wt% NaCl solution when compared with the conventional sample, as evidenced by a higher film resistance and breakdown potential, along with a lower passive current density of the WAAM sample. The corrosion morphology reveals the critical roles played by the nickel element that is unevenly distributed between the dendrite core and inter-dendritic area.

Multi-cohort validation of Ascore: an anoikis-based prognostic signature for predicting disease progression and immunotherapy response in bladder cancer.

Bladder cancer ranks as the 10th most common cancer worldwide, with deteriorating prognosis as the disease advances. While immune checkpoint inhibitors (ICIs) have shown promise in clinical therapy in both operable and advanced bladder cancer, identifying patients who will respond is challenging. Anoikis, a specialized form of cell death that occurs when cells detach from the extracellular matrix, is closely linked to tumor progression. Here, we aimed to explore the anoikis-based biomarkers for bladder cancer prognosis and immunotherapeutic decisions. Through consensus clustering, we categorized patients from the TCGA-BLCA cohort into two clusters based on anoikis-related genes (ARGs). Significant differences in survival outcome, clinical features, tumor immune environment (TIME), and potential ICIs response were observed between clusters. We then formulated a four-gene signature, termed "Ascore", to encapsulate this gene expression pattern. The Ascore was found to be closely associated with survival outcome and served as an independent prognosticator in both the TCGA-BLCA cohort and the IMvigor210 cohort. It also demonstrated superior predictive capacity (AUC = 0.717) for bladder cancer immunotherapy response compared to biomarkers like TMB and PD-L1. Finally, we evaluated Ascore's independent prognostic performance as a non-invasive biomarker in our clinical cohort (Gulou-Cohort1) using circulating tumor cells detection, achieving an AUC of 0.803. Another clinical cohort (Gulou-Cohort2) consisted of 40 patients undergoing neoadjuvant anti-PD-1 treatment was also examined. Immunohistochemistry of Ascore in these patients revealed its correlation with the pathological response to bladder cancer immunotherapy (P = 0.004). Impressively, Ascore (AUC = 0.913) surpassed PD-L1 (AUC = 0.662) in forecasting immunotherapy response and indicated better net benefit. In conclusion, our study introduces Ascore as a novel, robust prognostic biomarker for bladder cancer, offering a new tool for enhancing immunotherapy decisions and contributing to the tailored treatment approaches in this field.

Dynamic DNA Assembly by Programmable Hybridization Chain Reaction Mimicking Tubulin.

Dynamic biological structures involve the continual turnover of molecules within supramolecular assemblies such as tubulin. Inspired by dynamic biology self-organizing systems, we build an artificial dynamic structure based on DNA nanotechnology through a nonequilibrium chemical system. Herein, a metastable domain (MD), essentially a stem-loop structure, was introduced into DNA hairpins within hybridization chain reaction (HCR), thereby imparting dynamic activity to the DNA polymers. Hairpins with MD thermodynamically assemble to a high-energy polymer in the presence of trigger strands. The polymer can relax back to the stable unassembled state once the invader is added and finally relax to the activated hairpin by an anti-invader. Reversible assembly/disassembly of the HCR is achieved through invader/anti-invader cycles. We accomplished kinetic modulation, reversible conformational switching, cascading regulation, and enzyme activity control through the MD-HCR. We believe that the design of the MD-HCR could inspire the development of autonomous biological functions within artificial systems.

Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application.

T-cell lymphoma is a highly invasive tumor with significant heterogeneity. Invasive tissue biopsy is the gold standard for acquiring molecular data and categorizing lymphoma patients into genetic subtypes. However, surgical intervention is unfeasible for patients who are critically ill, have unresectable tumors, or demonstrate low compliance, making tissue biopsies inaccessible to these patients. A critical need for a minimally invasive approach in T-cell lymphoma is evident, particularly in the areas of early diagnosis, prognostic monitoring, treatment response, and drug resistance. Therefore, the clinical application of liquid biopsy techniques has gained significant attention in T-cell lymphoma. Moreover, liquid biopsy requires fewer samples, exhibits good reproducibility, and enables real-time monitoring at molecular levels, thereby facilitating personalized health care. In this review, we provide a comprehensive overview of the current liquid biopsy biomarkers used for T-cell lymphoma, focusing on circulating cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), Epstein-Barr virus (EBV) DNA, antibodies, and cytokines. Additionally, we discuss their clinical application, detection methodologies, ongoing clinical trials, and the challenges faced in the field of liquid biopsy.

Catalytic conversion of mixed polyolefins under mild atmospheric pressure.

The chemical recycling of polyolefin presents a considerable challenge, especially as upcycling methods struggle with the reality that plastic wastes typically consist of mixtures of polyethylene (PE), polystyrene (PS), and polypropylene (PP). We report a catalytic aerobic oxidative approach for polyolefins upcycling with the corresponding carboxylic acids as the product. This method encompasses three key innovations. First, it operates under atmospheric pressure and mild conditions, using O2 or air as the oxidant. Second, it is compatible with high-density polyethylene, low-density polyethylene, PS, PP, and their blends. Third, it uses an economical and recoverable metal catalyst. It has been demonstrated that this approach can efficiently degrade mixed wastes of plastic bags, bottles, masks, and foam boxes.

Massively parallel reporter assay confirms regulatory potential of hQTLs and reveals important variants in lupus and other autoimmune diseases.

We designed a massively parallel reporter assay (MPRA) in an Epstein-Barr virus transformed B cell line to directly characterize the potential for histone post-translational modifications, i.e., histone quantitative trait loci (hQTLs), expression QTLs (eQTLs), and variants on systemic lupus erythematosus (SLE) and autoimmune (AI) disease risk haplotypes to modulate regulatory activity in an allele-dependent manner. Our study demonstrates that hQTLs, as a group, are more likely to modulate regulatory activity in an MPRA compared with other variant classes tested, including a set of eQTLs previously shown to interact with hQTLs and tested AI risk variants. In addition, we nominate 17 variants (including 11 previously unreported) as putative causal variants for SLE and another 14 for various other AI diseases, prioritizing these variants for future functional studies in primary and immortalized B cells. Thus, we uncover important insights into the mechanistic relationships among genotype, epigenetics, and gene expression in SLE and AI disease phenotypes.

Systemic platelet inhibition with localized chemotherapy by an injectable ROS-scavenging gel against postsurgical breast cancer recurrence and metastasis.

Early solid tumors benefit from surgical resection, but residual stubborn microtumors, pro-inflammatory microenvironment and activated platelets at the postoperative wound site are prone to recurrence and metastasis, resulting in poor prognosis. Here, we developed a dual-pronged strategy consisting of (i) in-situ forming ROS-scavenging gels loaded with anticancer drugs at the postoperative wound site to improve the tumor microenvironment and inhibit the recurrence of residual microtumors after orthotopic surgery, and (ii) systemic administration of clopidegrol via albumin nanoparticles for inhibiting activated platelets in the circulation thus inhibiting tumor remote migration. In a mouse model of postoperative recurrence and metastasis of orthotopic 4T1 breast cancer, the dual-pronged strategy greatly inhibited postoperative orthotopic tumor recurrence and reduced lung metastasis. This work provides an effective strategy for the postoperative intervention and treatment of solid tumors to inhibit postoperative tumor recurrence and metastasis, which has the potential to improve the prognosis and survival of patients with postoperative solid tumors. STATEMENT OF SIGNIFICANCE: Early-stage solid tumors benefit from surgical resection. However, the presence of residual microtumors, pro-inflammatory tumor microenvironment, and activated platelets at the postoperative wound site lead to recurrence and metastasis, ultimately resulting in poor prognosis. Here, we have devised a dual-pronged approach that includes (i) in-situ forming ROS-scavenging gels loaded with anticancer drugs (TM@Gel) at the wound site after surgery to enhance the tumor microenvironment (TME) and hinder the reappearance of residual microtumors, and (ii) systemic administration of clopidegrol through albumin nanoparticles (HHP) for inhibiting activated platelets in the circulation thus impeding tumor distant migration. This work provides a viable option for postoperative intervention and treatment of solid tumors to suppress postoperative tumor recurrence and metastasis.

Neuroprotective effects of probiotics on anxiety- and depression-like disorders in stressed mice by modulating tryptophan metabolism and the gut microbiota.

Anxiety- and depression-like behaviors are commonly observed clinical features of depression and many other mental disorders. Recent evidence has revealed the crucial role of the microbiota-gut-brain axis in the bidirectional communication between the gastrointestinal tract and the central nervous system. Supplementation with psychobiotics may provide a novel approach for the adjunctive treatment of mental disorders by regulating the intestinal microecology. We isolated and identified a novel probiotic, Lactiplantibacillus plantarum D-9 (D-9), from traditional Chinese fermented foods in our previous work, which exhibited a high yield of gamma-aminobutyric acid (GABA). Herein, it was proved that the oral administration of D-9 could alleviate the depression- and anxiety-like behaviors of Chronic Unpredicted Mild Stress (CUMS) mice, and show non-toxicity or side-effects in the mice. Physiological and biochemical analyses demonstrated that D-9 regulated tryptophan metabolism, the HPA-axis and inflammation in CUMS mice. Moreover, D-9 modulated the structure and composition of the gut microbiota, leading to an increase in the relative abundance of Ligilactobacillus murinus and Lactobacillus johnsonii, and a decrease in the levels of Kineothrix alysoides and Helicobacter bilis compared to those in CUMS mice. Our work demonstrates that D-9 alleviated anxiety- and depression-like disorders in CUMS mice by modulating tryptophan metabolism and the gut microbiota. These findings provide an innovative strategy for the intervention and treatment of depressive disorders.

PbS/CsPbBr3 Heterojunction for Broadband Neuromorphic Vision Sensing.

Neuromorphic light sensors with analogue-domain image processing capability hold promise for overcoming the energy efficiency limitations and latency of von Neumann architecture-based vision chips. Recently, metal halide perovskites, with strong light-matter interaction, long carrier diffusion length, and exceptional photoelectric conversion efficiencies, exhibit reconfigurable photoresponsivity due to their intrinsic ion migration effect, which is expected to advance the development of visual sensors. However, suffering from a large bandgap, it is challenging to achieve highly tunable responsivity simultaneously with a wide-spectrum response in perovskites, which will significantly enhance the image recognition accuracy through the machine learning algorithm. Herein, we demonstrate a broadband neuromorphic visual sensor from visible (Vis) to near-infrared (NIR) by coupling all-inorganic metal halide perovskites (CsPbBr3) with narrow-bandgap lead sulfide (PbS). The PbS/CsPbBr3 heterostructure is composed of high-quality single crystals of PbS and CsPbBr3. Interestingly, the ion migration of CsPbBr3 with the implementation of an electric field induces the energy band dynamic bending at the interface of the PbS/CsPbBr3 heterojunction, leading to reversible, multilevel, and linearly tunable photoresponsivity. Furthermore, the reconfigurable and broadband photoresponse in the PbS/CsPbBr3 heterojunction allows convolutional neuronal network processing for pattern recognition and edge enhancements from the Vis to the NIR waveband, suggesting the great potential of the PbS/CsPbBr3 heterostructure in artificial intelligent vision sensing.

KIF26B and CREB3L1 Derived from Immunoscore Could Inhibit the Progression of Ovarian Cancer.

Background: Ovarian cancer (OV) is characteristic of high incidence rate and fatality rate in the malignant tumors of female reproductive system. Researches on pathogenesis and therapeutic targets for OV need to be continued. This study mainly analyzed the immune-related pathogenesis and discovered the key immunotherapy targets for OV. Methods: WGCNA was used for excavating hub gene modules and hub genes related to the immunity of OV. Enrichment analysis was aimed to analyze the related pathways of hub gene modules. Biological experiments were used for exploring the effect of hub genes on SKOV3 cells. Results: We identified two hub gene modules related to the immunoscore of OV and found that these genes in the modules were related to the extracellular matrix and viral infections. At the same time, we also discovered six hub genes related to the immunity of OV. Among them, KIF26B and CREB3L1 can affect the proliferation, migration, and invasion of SKOV3 cells by the Wnt/ß-catenin pathway. Conclusions: The local infection or inflammation of ovarian may affect the immunity of OV. KIF26B and CREB3L1 are expected to be potential targets for the immunotherapy of OV.