Ingenious designed a HER2-Specific macrophage biomimetic multifunctional nanoplatform for enhanced bio-photothermal synergistic therapy in HER2 positive breast cancer.

Photothermal therapy (PTT) has garnered extensive attention as an efficient strategy for cancer therapy. Unfortunately, there are currently no suitable photothermal agents (PTAs) capable of effectively treating HER2-positive breast cancer (HER2+ BC) due to the challenges in addressing blood circulation and tumor accumulation. Here, we propose a HER2-specific macrophage biomimetic nanoplatform IR820@ZIF-8@EM (AMBP) for enhanced bio-photothermal therapy of HER2+ BC. An anti-HER2 antibody was expressed in engineered macrophages using the transmembrane expression technique. As an efficient PTAs, IR820 dyes were assembled into ZIF-8 as to develop a "nano-thermal-bomb". Homology modeling methods support that the expressed anti-HER2 antibody can specifically recognize the HER2 receptor. Moreover, antibody-dependent cell-mediated cytotoxicity can also be induced in HER2+ BC cells by AMBP. In vitro fluorescence confocal imaging showed that AMBP promoted the uptake of HER2+ cancer cells while in vivo anti-tumor experiments demonstrated that AMBP efficiently accumulates in the tumor regions. Finally, under spatiotemporally controlled near-infrared (NIR) irradiation, three of the six tumors were eradicated in AMBP-treated mice, demonstrating a safe and effective strategy. In conclusion, our research opens a new paradigm for antibody-specific macrophage, and it is expected that these characteristics will have substantial clinical translation potential for BC treatment.

Interfacial polymerization at unconventional interfaces: an emerging strategy to tailor thin-film composite membranes.

Interfacial polymerization is a well-known process to synthesize separation layers for thin film composite membranes at an immiscible organic liquid-aqueous liquid interface. The organic-aqueous interface determines the diffusion dynamics of monomers and the chemical environment for polymerization, exerting a critical influence on the formation of polymer thin films. This review summarizes recent advances in tailoring interfacial polymerization using interfaces beyond the conventional alkane-water interface to achieve high-performance separation films with designed structures. Diverse liquid-liquid interfaces are introduced for synthesizing separation films by adding co-solvents into the organic phase and/or the aqueous phase, respectively, or by replacing one of the liquid phases with other solvents. Innovative liquid-gel and liquid-gas interfaces are then summarized for the synthesis of polymer thin films for separation. Novel strategies to form reaction interfaces, such as spray-coating, are also presented and discussed. In addition, we discuss the details of how a physically or chemically patterned substrate affects interfacial polymerization. Finally, the potential of unconventional interfaces in interfacial polymerization is forecast with both challenges and opportunities.

Molecular Stacking and Aggregation Optimization of Photoactive Layer through Solid Additive Enables High-Performance Organic Solar Cells.

Regulating molecular packing and aggregation of photoactive layer is a critical but challenging issue in developing high-performance organic solar cells. Herein, two structurally similar analogues of anthra[2,3-b : 6,7-b']dithiophene (ADT) and naphtho[1,2-b : 5,6-b']dithiophene (NDT) are developed as solid additive to exploit their effect in regulating the molecular aggregation and π-stacking of photoactive layer. We clarify that the perpendicular arrangements of NDT can enlarge the molecular packing space and improve the face-on stacking of Y6 during the film formation, favoring a more compact and ordered long-range π-π stacking in the out-of-plane direction after the removal of NDT under thermal annealing. The edge-to-face stacked herringbone-arrangement of ADT along with its non-volatilization under thermal annealing can induce the coexistence of face-on and edge-on stacking of blend film. As a result, the NDT treatment shows encouraging effect in improving the photovoltaic performance of devices based on various systems. Particularly, a remarkable PCE of 18.85 % is achieved in the PM6 : L8-BO-based device treated by NDT additive, which is a significant improvement with regard to the PCE of 16.41 % for the control device. This work offers a promising strategy to regulate the molecular packing and aggregation of photoactive layer towards significantly improved performance and stability of organic solar cells.

Engineered Macrophages-Based uPA-Scavenger Load Gemcitabine to Prompt Robust Treating Cancer Metastasis.

The majority of cancer patients die of metastasis rather than primary tumors, and most patients may have already completed the cryptic metastatic process at the time of diagnosis, making them intractable for therapeutic intervention. The urokinase-type plasminogen activator (uPA) system is proved to drive cancer metastasis. However, current blocking agents such as uPA inhibitors or antibodies are far from satisfactory due to poor pharmacokinetics and especially have to face multiplex mechanisms of metastasis. Herein, an effective strategy is proposed to develop a uPA-scavenger macrophage (uPAR-MΦ), followed by loading chemotherapeutics with nanoparticles (GEM@PLGA) to confront cancer metastasis. Interestingly, significant elimination of uPA by uPAR-MΦ is demonstrated by transwell analysis on tumor cells in vitro and enzyme-linked immunosorbent assay detection in peripheral blood of mice with metastatic tumors, contributing to significant inhibition of migration of tumor cells and occurrence of metastatic tumor lesions in mice. Moreover, uPAR-MΦ loaded with GEM@PLGA shows a robust antimetastasis effect and significantly prolonged survival in 4T1-tumor-bearing mice models. This work provides a novel living drug platform for realizing a potent treatment strategy to patients suffering from cancer metastasis, which can be further expanded to handle other tumor metastasis markers mediating cancer metastasis.

Reduced bimolecular charge recombination in efficient organic solar cells comprising non-fullerene acceptors.

Bimolecular charge recombination is one of the most important loss processes in organic solar cells. However, the bimolecular recombination rate in solar cells based on novel non-fullerene acceptors is mostly unclear. Moreover, the origin of the reduced-Langevin recombination rate in bulk heterojunction solar cells in general is still poorly understood. Here, we investigate the bimolecular recombination rate and charge transport in a series of high-performance organic solar cells based on non-fullerene acceptors. From steady-state dark injection measurements and drift-diffusion simulations of the current-voltage characteristics under illumination, Langevin reduction factors of up to over two orders of magnitude are observed. The reduced recombination is essential for the high fill factors of these solar cells. The Langevin reduction factors are observed to correlate with the quadrupole moment of the acceptors, which is responsible for band bending at the donor-acceptor interface, forming a barrier for charge recombination. Overall these results therefore show that suppressed bimolecular recombination is essential for the performance of organic solar cells and provide design rules for novel materials.

Morphology Optimization of the Photoactive Layer through Crystallinity and Miscibility Regulation for High-performance Polymer Solar Cells.

On the premise of strongly crystalline materials involved, it is a challenge to control the phase separation of bulk-heterojunction donor/acceptor active layer to fabricate high-performance polymer solar cells (PSCs). Herein, we develop a molecular design strategy of the third component to synthesize three guest materials (namely BTPT, BTP-Th, and BTP-2Th) to address this issue. We investigate and reveal the effect of crystallinity and miscibility of the third component in controlling the phase separation of Y6-derivatives-based blend film. As a result, a remarkable power-conversion efficiency of 18.53 % is obtained in the ternary PSC based on PTQ10 : m-BTP-PhC6 with BTP-Th as the third component, which is a significant improvement with regard to the efficiency of 17.22 % for the control binary device. Our study offers a molecular design strategy to develop a third component for building ternary PSCs in terms of crystallinity and miscibility regulation.

Deep learning architectures for diagnosing the severity of apple frog-eye leaf spot disease in complex backgrounds.

Introduction: In precision agriculture, accurately diagnosing apple frog-eye leaf spot disease is critical for effective disease management. Traditional methods, predominantly relying on labor-intensive and subjective visual evaluations, are often inefficient and unreliable. Methods: To tackle these challenges in complex orchard environments, we develop a specialized deep learning architecture. This architecture consists of a two-stage multi-network model. The first stage features an enhanced Pyramid Scene Parsing Network (L-DPNet) with deformable convolutions for improved apple leaf segmentation. The second stage utilizes an improved U-Net (D-UNet), optimized with bilinear upsampling and batch normalization, for precise disease spot segmentation. Results: Our model sets new benchmarks in performance, achieving a mean Intersection over Union (mIoU) of 91.27% for segmentation of both apple leaves and disease spots, and a mean Pixel Accuracy (mPA) of 94.32%. It also excels in classifying disease severity across five levels, achieving an overall precision of 94.81%. Discussion: This approach represents a significant advancement in automated disease quantification, enhancing disease management in precision agriculture through data-driven decision-making.

Tomato leaf disease recognition based on multi-task distillation learning.

Introduction: Tomato leaf diseases can cause major yield and quality losses. Computer vision techniques for automated disease recognition show promise but face challenges like symptom variations, limited labeled data, and model complexity. Methods: Prior works explored hand-crafted and deep learning features for tomato disease classification and multi-task severity prediction, but did not sufficiently exploit the shared and unique knowledge between these tasks. We present a novel multi-task distillation learning (MTDL) framework for comprehensive diagnosis of tomato leaf diseases. It employs knowledge disentanglement, mutual learning, and knowledge integration through a multi-stage strategy to leverage the complementary nature of classification and severity prediction. Results: Experiments show our framework improves performance while reducing model complexity. The MTDL-optimized EfficientNet outperforms single-task ResNet101 in classification accuracy by 0.68% and severity estimation by 1.52%, using only 9.46% of its parameters. Discussion: The findings demonstrate the practical potential of our framework for intelligent agriculture applications.

Bioorthogonally activatable cyanine dye with torsion-induced disaggregation for in vivo tumor imaging.

Advancement of bioorthogonal chemistry in molecular optical imaging lies in expanding the repertoire of fluorophores that can undergo fluorescence signal changes upon bioorthogonal ligation. However, most available bioorthogonally activatable fluorophores only emit shallow tissue-penetrating visible light via an intramolecular charge transfer mechanism. Herein, we report a serendipitous "torsion-induced disaggregation (TIDA)" phenomenon in the design of near-infrared (NIR) tetrazine (Tz)-based cyanine probe. The TIDA of the cyanine is triggered upon Tz-transcyclooctene ligation, converting its heptamethine chain from S-trans to S-cis conformation. Thus, after bioorthogonal reaction, the tendency of the resulting cyanine towards aggregation is reduced, leading to TIDA-induced fluorescence enhancement response. This Tz-cyanine probe sensitively delineates the tumor in living mice as early as 5 min post intravenous injection. As such, this work discovers a design mechanism for the construction of bioorthogonally activatable NIR fluorophores and opens up opportunities to further exploit bioorthogonal chemistry in in vivo imaging.

Mitogen-activating protein kinase kinase kinase kinase-3, inhibited by Astragaloside IV through H3 lysine 4 monomethylation, promotes the progression of diabetic nephropathy by inducing apoptosis.

Astragaloside IV (AS-IV) is a bioactive saponin extracted from the Astragalus root and has been reported to exert a protective effect on diabetic nephropathy (DN). However, the underlying mechanism remains unclear. Herein, we found that AS-IV treatment alleviated DN symptoms in DN mice accompanied by reduced metabolic parameters (body weight, urine microalbumin and creatinine, creatinine clearance, and serum urea nitrogen and creatinine), pathological changes, and apoptosis. Epigenetic histone modifications are closely related to diabetes and its complications, including H3 lysine 4 monomethylation (H3K4me1, a promoter of gene transcription). A ChIP-seq assay was conducted to identify the genes regulated by H3K4me1 in DN mice after AS-IV treatment and followed by a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The results showed that there were 16 common genes targeted by H3K4me1 in normal and AS-IV-treated DN mice, 1148 genes were targeted by H3K4me1 only in DN mice. From the 1148 genes, we screened mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3) for the verification of gene expression and functional study. The results showed that MAP4K3 was significantly increased in DN mice and high glucose (HG)-treated NRK-52E cells, which was reversed by AS-IV. MAP4K3 silencing reduced the apoptosis of NRK-52E cells under HG condition, as evidenced by decreased cleaved caspase 3 and Bax (pro-apoptotic factors), and increased Bcl-2 and Bcl-xl (anti-apoptotic factors). Collectively, AS-IV may downregulate MAP4K3 expression by regulating H3K4me1 binding and further reducing apoptosis, which may be one of the potential mechanisms that AS-IV plays a protective effect on DN.

Molecular Optimization on Polymer Acceptor Enables Efficient All-Polymer Solar Cell with High Open-Circuit Voltage of 1.10 V.

Currently, rational design of polymer acceptors is desirable but there is still a challenge to develop high-performance all-polymer solar cells (all-PSCs). In this work, brominated thienyl-fused malononitrile-based monomer is employed to copolymerize with indacenodithiophene (IDT) and benzodithiophene (BDT)-based linking units to develop two polymerized small molecule acceptors (PSMAs) PIDT and PBDT, respectively, for all-PSCs. The two PSMAs show similar absorption edges, while PBDT shows a slightly higher lowest unoccupied molecular orbital (LUMO) energy level than PIDT. Benefitted from the relatively high LUMO levels of the two polymer acceptors, notable open-circuit voltage (Voc ) values over 1.0 V are achieved when using them as acceptor to blend with PTQ10 as polymer donor. Particularly, the all-PSC based on PTQ10:PIDT demonstrates a power conversion efficiency of 10.19%, with an outstanding Voc of 1.10 V benefitted from the higher LUMO energy level of PIDT acceptor. The results demonstrate a feasible strategy to design PSMAs by selecting appropriate linking units for increasing the Voc and improving the efficiency of all-PSCs.

Effect of repetitive transcranial magnetic stimulation on patients with severe depression: a study protocol for systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Depression is characterised by easy recurrence, high disability and high burden, and antidepressant therapy is the standard treatment. However, its treatment effect on patients with severe depressive disorder has been unsatisfactory. Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS), as a neurotherapy, can effectively mitigate the severity of depressive symptoms. Yet, more evidence is still required for TMS to treat severe depression. This study will be the first systematic review of the efficacy and tolerability of TMS for treating severe depression. We expect it to guide future clinical practice of TMS for the treatment of psychiatric disorders. METHODS AND ANALYSIS: We will search for the randomised controlled trial (RCT) involving rTMS for treating depression in eight electronic databases, including PubMed, Web of Science, EMBASE, the Cochrane Library and Wanfang Database, from publication up to September 2021. We will define Improvement in depressive symptoms, the difference between pretreatment (baseline) and post-treatment as the primary outcomes. The difference between pretreatment and post-treatment changes in resting state fMRI will be regarded as the secondary outcomes. Quality assessment of the included articles will be independently performed according to the Cochrane Risk of Bias tool. ETHICS AND DISSEMINATION: Ethical approval is not essential because there is no need to collect individual patient data. And this study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42020211460.

Volatilizable Solid Additive-Assisted Treatment Enables Organic Solar Cells with Efficiency over 18.8% and Fill Factor Exceeding 80.

Controlling the self-assembling of organic semiconductors to form well-developed nanoscale phase separation in the bulk-heterojunction active layer is critical yet challenging for building high-performance organic solar cells (OSCs). Particularly, the similar anisotropic conjugated structures between nonfullerene acceptors and p-type organic semiconductor donors raise more complexity on manipulating their aggregation toward appropriate phase separation. Herein, a new approach to tune the morphology of photoactive layer is developed by utilizing the synergistic effect of dithieno[3,2-b:2',3'-d]thiophene (DTT) and 1-chloronaphthalene (CN). The volatilizable solid additive DTT with high crystallinity can restrict the over self-assembling of nonfullerene acceptors during the film casting process, and then allowing the refining of phase separation and molecular packing with the simultaneous volatilization of DTT under thermal annealing. Consequently, the PTQ10:m-BTP-PhC6:PC71 BM-based ternary OSCs processed by the dual additives of CN and DTT record a notable power-conversion efficiency of 18.89%, with a remarkable FF of 80.6%.

Indacenodithiophene-based small-molecule donor with strong crystallinity for efficient organic solar cells.

Two indacenodithiophene (IDT)-based small-molecule analogues (IDBT and IDBT-Cl) are designed as donor materials for organic solar cells. Relative to the amorphous IDBT-Cl, the IDBT with strong crystallinity shows overall better photovoltaic performance when blended with a Y6 acceptor. The results demonstrate the great potential of IDT units in designing efficient small-molecule donors.

Regioselective synthesis and structures of anti-cancer 20(R)-ginsenoside Rg3 derivatives.

Regioselective synthesis of three novel palmitates of 20(R)-ginsenoside Rg3 was accomplished via a facile strategy, along with complete assignment of their 1H and 13C NMR resonances by 1D and 2D NMR (1H-1H COSY, DEPT 135, HSQC, HMBC, and NOESY) techniques. The derivatives were tested for in vitro anti-proliferative activities against pancreatic cancer PANC-1 cells. Compounds 2, 3, and 4 exhibited more potent activity than did 20(R)-ginsenoside Rg3.

Irregular structural networks of gray matter in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) induces dementia and cognitive decrements indicating the impairment of the central nervous system. While there is evidence showing abnormalities in white-matter structural networks in T2DM, the topological features of gray matter are still unknown. The study enrolled 30 right-handed T2DM patients and 20 healthy control subjects with matched age, gender, handedness, and education. Graph theoretical analysis of magnetic resonance imaging on gray matter volume was conducted to explore large-scale structural networks of brain. Although retaining small-worldness characteristics, the structural networks of grey matter in the T2DM group exhibited an increased clustering coefficient, prolonged characteristic path, decreased global efficiency, and more vulnerability to random failures or targeted attacks compared with controls. Additionally, the degree of structural networks in both T2DM and control groups was distributed exponentially in truncated power law. Our findings suggest that T2DM disturbed the overall topological features of gray matter networks, which provides a novel insight into the neurobiological mechanisms accounting for the cognitive impairment of T2DM patients.

Astragaloside IV protects against diabetic nephropathy via activating eNOS in streptozotocin diabetes-induced rats.

BACKGROUND: Astragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), however, the underlying mechanisms still remain unclear. The aim of the present study is to investigate whether AS-IV ameliorates DN via the regulation of endothelial nitric oxide synthase (eNOS). METHODS: DN model was induced in Sprague-Dawley (SD) male rats by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Rats in the AS-IV treatment group were orally gavaged with 5 mg/kg/day or 10 mg/kg/day AS-IV for eight consecutive weeks. Body weight, blood glucose, blood urea nitrogen (BUN), Serum creatinine (Scr), proteinuria and Glycosylated hemoglobin (HbA1c) levels were measured. Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) staining were used to detect the renal pathology. The apoptosis status of glomerular cells was measured by TUNEL assay. The phosphorylation and acetylation of eNOS were detected by western blot. The effects of AS-IV on high-glucose (HG)-induced apoptosis and eNOS activity were also investigated in human renal glomerular endothelial cells (HRGECs) in vitro. RESULTS: Treatment with AS-IV apparently reduced DN symptoms in diabetic rats, as evidenced by reduced BUN, Scr, proteinuria, HbA1c levels and expanding mesangial matrix. AS-IV treatment also promoted the synthesis of nitric oxide (NO) in serum and renal tissues and ameliorated the phosphorylation of eNOS at Ser 1177 with decreased eNOS acetylation. Moreover, HG-induced dysfunction of HRGECs including increased cell permeability and apoptosis, impaired eNOS phosphorylation at Ser 1177, and decreased NO production, were all reversed by AS-IV treatment. CONCLUSIONS: These novel findings suggest that AS-IV ameliorates functional abnormalities of DN through inhibiting acetylation of eNOS and activating its phosphorylation at Ser 1177. AS-IV could be served as a potential therapeutic drug for DN.

Surface degeneration of W crystal irradiated with low-energy hydrogen ions.

The damage layer of a W (100) crystal irradiated with 120 eV hydrogen ions at a fluence of up to 1.5 × 10(25)/m(2) was investigated by scanning electron microscopy and conductive atomic force microscopy (CAFM). The periodic surface degeneration of the W crystal at a surface temperature of 373 K was formed at increasing hydrogen fluence. Observations by CCD camera and CAFM indicate the existence of ultrathin surface layers due to low-energy H irradiation. The W surface layer can contain a high density of nanometer-sized defects, resulting in the thermal instability of W atoms in the surface layer. Our findings suggest that the periodic surface degeneration of the W crystal can be ascribed to the lateral erosion of W surface layers falling off during the low-energy hydrogen irradiation. Our density functional theory calculations confirm the thermal instability of W atoms in the top layer, especially if H atoms are adsorbed on the surface.

Nanostructured fuzz growth on tungsten under low-energy and high-flux He irradiation.

We report the formation of wave-like structures and nanostructured fuzzes in the polycrystalline tungsten (W) irradiated with high-flux and low-energy helium (He) ions. From conductive atomic force microscope measurements, we have simultaneously obtained the surface topography and current emission images of the irradiated W materials. Our measurements show that He-enriched and nanostructured strips are formed in W crystal grains when they are exposed to low-energy and high-flux He ions at a temperature of 1400 K. The experimental measurements are confirmed by theoretical calculations, where He atoms in W crystal grains are found to cluster in a close-packed arrangement between {101} planes and form He-enriched strips. The formations of wave-like structures and nanostructured fuzzes on the W surface can be attributed to the surface sputtering and swelling of He-enriched strips, respectively.

Altered default mode network functional connectivity in schizotypal personality disorder.

The default mode network (DMN) has been identified to play a critical role in many mental disorders, but such abnormalities have not yet been determined in patients with schizotypal personality disorder (SPD). The purpose of this study was to analyze the alteration of the DMN functional connectivity in subjects with (SPD) and compared it to healthy control subjects. Eighteen DSM-IV diagnosed SPD subjects (all male, average age: 19.7±0.9) from a pool of 3000 first year college students, and eighteen age and gender matched healthy control subjects were recruited (all male, average age: 20.3±0.9). Independent component analysis (ICA) was used to analyze the DMN functional connectivity alteration. Compared to the healthy control group, SPD subjects had significantly decreased functional connectivity in the frontal areas, including the superior and medial frontal gyrus, and greater functional connectivity in the bilateral superior temporal gyrus and sub-lobar regions, including the bilateral putamen and caudate. Compared to subjects with SPD, the healthy control group showed decreased functional connectivity in the bilateral posterior cingulate gyrus, but showed greater functional connectivity in the right transverse temporal gyrus and left middle temporal gyrus. The healthy control group also showed greater activation in the cerebellum compared to the SPD group. These findings suggest that DMN functional connectivity, particularly that involving cognitive or emotional regulation, is altered in SPD subjects, and thus may be helpful in studying schizophrenia.