Discovery of a novel BTK inhibitor S-016 and identification of a new strategy for the treatment of lymphomas including BTK inhibitor-resistant lymphomas.

Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.

The m6A reader HNRNPC promotes glioma progression by enhancing the stability of IRAK1 mRNA through the MAPK pathway.

Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC-IRAK1-MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.

Clinical characteristics, survival analysis and influencing factors of distant metastasis in patients with acromelanomas: A retrospective study.

The prognosis of acromelanomas (AM) is worse. The objective of this study was to investigate the clinical features of distant metastasis of AM and the factors affecting the survival and prognosis of patients. In this study, a retrospective study was conducted to select 154 AM patients admitted to Nanjing Pukou People's Hospital from January 2018 to April 2021 for clinical research. The clinical characteristics of distant metastasis were statistically analyzed, and the survival curve was drawn with 5-year follow-up outcomes. The median survival time of the patients was calculated, and the clinicopathological features and peripheral blood laboratory indexes of the surviving and dead patients were analyzed. Logistic regression model was used to analyze the risk factors affecting the prognosis of AM patients. In this study, 154 patients with AM were treated, including 88 males and 76 females, aged from 27 to 79 years old, with an average age of (59.3 ±â€…11.7) years old. Among them, 90 cases had distant metastasis. The main metastatic sites were lung (47.78%) and lymph nodes (42.22%). Among them, single site metastasis accounted for 41.11% and multiple site metastasis 58.89%. 89 cases survived and 65 cases died. The survival time was 22 months to 60 months, and the median survival time was 48.0 months. The Breslow thickness, stage at diagnosis, distant metastasis, site of metastasis and ulceration were compared between the survival group and the death group (P < .05). serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR) and lymphocyte monocyte ratio (LMR) were compared between the survival group and the death group (P < .05). The results of Logistic regression model showed that LDH ≥ 281 U/L, NLR ≥ 2.96, LMR ≤ 3.57, newly diagnosed stage > stage II, distant metastasis, multiple site metastasis and tumor ulcer were independent risk factors for poor prognosis of AM patients (P < .05). Patients with AM had a higher proportion of distant metastasis, mainly lung and lymph node metastasis. Increased LDH, increased NLR, decreased LMR, higher initial stage, distant metastasis, multiple site metastasis, and combined tumor ulcer were closely related to the poor prognosis of patients after surgery.

Differentiation of bone marrow mesenchymal stem cells into Leydig-like cells with testicular extract liquid in vitro.

Differentiation of Leydig cells plays a key role in male reproductive function. Bone marrow mesenchymal stem cells (BMSCs) have emerged as a potential cell source for generating Leydig-like cells due to their multipotent differentiation capacity and accessibility. This study aimed to investigate the morphological and genetic expression changes of BMSCs during differentiation into Leydig-like cells. Testicular extract liquid, which simulates the microenvironment in vivo, induced the third passage BMSCs differentiated into Leydig-like cells. Changes in cell morphology were observed by microscopy, the formation of lipid droplets of androgen precursor was identified by Oil Red Staining, and the expression of testicular specific genes 3ß-HSD and SF-1 in testicular stromal cells was detected by RT-qPCR. BMSCs isolated from the bone marrow of Sprague-Dawley (SD) rats were cultured for 3 generations and identified as qualified BMSCs in terms of morphology and cell surface markers. After 14 days of induction with testicular tissue lysate, lipid droplets appeared in the cytoplasm of P3 BMSCs by Oil Red O staining. RT-qPCR detection was performed on BMSCs on the 3rd, 7th, 14th, and 21st day after induction. Relative expression levels of 3ß-HSD mRNA significantly increased after 14 days of induction, while the relative expression of SF-1 mRNA increased after 14 days of induction but was not significant. BMSCs can differentiate into testicular interstitial cells with reserve androgen precursor lipid droplets after induction by testicular tissue lysate. The differentiation ability of BMSCs provides the potential to reconstruct the testicular microenvironment and is expected to fundamentally improve testicular function and provide new treatment options for abnormal spermatogenesis diseases.

Clotting Blood into an Adhesive Gel by Hemostatic Powder Based on Cationic/Anionic Polysaccharides and Laponite.

Hemostatic powder is widely employed for emergency bleeding control due to its ability to conform to irregularly shaped wounds, ease of use, and stable storage. However, current powders exhibit limited tissue adhesion and insufficient support for thrombus formation, making them easily washed away by blood. In this study, a hybrid powder (QAL) was produced by mixing quaternized chitosan (QCS) powder, catechol-modified alginate (Cat-SA) powder, and laponite (Lap) powder. Upon addition of QAL, the blood quickly transformed to a robust and adhesive blood gel. The adhesion strength of the blood gel was up to 31.33 ± 1.56 kPa. When compared with Celox, QAL showed superior performance in promoting hemostasis. Additionally, QAL exhibited effectiveness in eliminating bacteria while also demonstrating outstanding biocompatibility with cells and blood. These favorable properties, including strong coagulation, adhesion to wet tissue, antibacterial activity, biosafety, ease of use, and stable storage, make QAL a promising emergency hemostatic agent.

First report of leaf spot on Daphniphyllum macropodum caused by Neopestalotiopsis clavispora in China.

Daphniphyllum macropodum Miq., an evergreen arbor, is widely cultivated in southern China for its ornamental and medicinal value (Su et al. 2013). In October 2019, a severe leaf spot was observed on D. macropodum in Jinggangshan National Nature Reserve in Ji'an city, Jiangxi, China (114°06'23″E, 26°32'25″N). The plants were about 15 years old, and the disease incidence was estimated to be 15% (4/26 plants). The disease primarily appeared as small black spots on the leaves. At the late stage, the spots enlarged and coalesced into regular or irregular gray necrotic lesions with dark margins. We collected five samples per plant and total 20 samples were collected to isolated the pathogen strains. The margin of the diseased tissues was cut into 5 mm × 5 mm pieces; surface disinfected with 70% ethanol and 2% NaOCl for 30 s and 60 s, respectively; and rinsed thrice with sterile water. Tissues were placed on potato dextrose agar (PDA) and incubated at 25°C in the dark. Pure cultures were obtained by single-spore isolation method, and the representative isolates, JRM3, JRM6, and JRM8 were used for morphological studies and phylogenetic analyses. The colonies of three isolates grown on PDA were white, cottony, and flocculent, contained undulate edges with dense aerial mycelium on the surface at 25 °C. Conidiomata was black conidial masses on PDA. Conidia were 5-celled, clavate to fusiform, smooth, 19.3 to 24.4 long × 6.1 to 8.6 µm wide (n = 50). The 3 median cells were dark brown to olivaceous, the central cell was darker than the other 2 cells, and the basal and apical cells were hyaline. All conidia developed one basal appendage (3.4 to 8.3 µm long; n = 50), and 2 to 3 apical appendages (18 to 32 µm long; n = 50), filiform. The morphological characteristics of the isolates are comparable with those of the genus Neopestalotiopsis (Maharachchikumbura et al. 2014). The internal transcribed spacer (ITS) regions, ß-tubulin 2 (TUB2) and translation elongation factor 1-alpha (TEF1-α) were amplified from genomic DNA for the three isolates using primers ITS1/ITS4, T1/Bt-2b, EF1-728F/EF-2 (Maharachchikumbura et al. 2014), respectively. The sequences of the isolates were submitted to GenBank (ITS, OQ372202 to OQ372204; TUB2, OQ390129 to OQ390131; TEF1-α, OQ390126 to OQ390128). A maximum likelihood and Bayesian posterior probability analyses using IQtree v. 1.6.8 and Mr. Bayes v. 3.2.6 with the concatenated sequences placed JRM3, JRM6, and JRM8 in the clade of N. clavispora. Based on the multi-locus phylogeny and morphology, three isolates were identified as N. clavispora. To confirm pathogenicity, eight healthy 10-year-old D. macropodum plants growing in the field were chosen, and 4 leaves per plant were wounded with a sterile needle and inoculated with 10 µL conidial suspension per leaf (106 conidia/ml). Eight plants inoculated with sterile water were used as control. All the inoculated leaves were covered with plastic bags to maintian a humidity environment for 2 days. The leaves inoculated with conidial suspension showed similar symptoms to those observed in the field, whereas control leaves were asymptomatic for 10 days. The same fungus were re-isolated from the lesions, whereas no fungus was isolated from control leaves. N. clavispora was determined as the pathogen of a variety of plant diseases, including Kadsura coccinea (Xie et al. 2018), Dendrobium officinale (Cao et al. 2022), Macadamia integrifolia (Santos et al. 2019). However, this is the first report of N. clavispora infecting D. macropodum in China. This work provided crucial information for epidemiologic studies and appropriate control strategies for this newly emerging disease.

Enhancing antitumor immunity with stimulus-responsive mesoporous silicon in combination with chemotherapy and photothermal therapy.

Due to the immunosuppressive tumor microenvironment (TME) and potential systemic toxicity, chemotherapy often fails to elicit satisfactory anti-tumor responses, so how to activate anti-tumor immunity to improve the therapeutic efficacy remains a challenging problem. Photothermal therapy (PTT) serves as a promising approach to activate anti-tumor immunity by inducing the release of tumor neoantigens in situ. In this study, we designed tetrasulfide bonded mesoporous silicon nanoparticles (MSNs) loaded with the traditional drug doxorubicin (DOX) inside and modified their outer layer with polydopamine (DOX/MSN-4S@PDA) for comprehensive anti-tumor studies in vivo and in vitro. The MSN core contains GSH-sensitive tetrasulfide bonds that enhance DOX release while generating hydrogen sulfide (H2S) to improve the therapeutic efficacy of DOX. The polydopamine (PDA) coating confers acid sensitivity and mild photothermal properties upon exposure to near-infrared (NIR) light, while the addition of hyaluronic acid (HA) to the outermost layer enables targeted delivery to CD44-expressing tumor cells, thereby enhancing drug accumulation at the tumor site and reducing toxic side effects. Our studies demonstrate that DOX/MSN@PDA-HA can reverse the immunosuppressive tumor microenvironment in vivo, inducing potent immunogenic cell death (ICD) of tumor cells and improving anti-tumor efficacy. In addition, DOX/MSN@PDA-HA significantly suppresses tumor metastasis to the lung and liver. In summary, DOX/MSN@PDA-HA exhibits controlled drug release, excellent biocompatibility, and remarkable tumor inhibition capabilities through synergistic chemical/photothermal combined therapy.

Successful secukinumab treatment of generalized pustular psoriasis.

Generalized pustular psoriasis is a rare variant of psoriasis. Evidence recommending generalized pustular psoriasis treatment with secukinumab is limited. This report aims to evaluate the use of secukinumab in two patients with generalized pustular psoriasis. The standard treatment regimen for secukinumab was as follows: 300mg subcutaneously once weekly in weeks 0-4, followed by 300mg every four weeks. The efficacy was evaluated by analyzing the psoriasis area and severity index (PASI) and dermatology life quality index (DLQI). One patient had generalized pustular psoriasis, which had developed from palmoplantar pustulosis over 12 years. The second patient was an adolescent with recurrent generalized pustular psoriasis. The first patient achieved PASI-75 response by week 3 and both PASI-90 and a DLQI score of 0 were observed by week 8. The second patient achieved PASI-75 response by week 4 and complete clinical resolution, except for nail changes, and a DLQI of 0 by week 8, without any adverse events.

The origin of exceptionally large ductility in molybdenum alloys dispersed with irregular-shaped La2O3 nano-particles.

Molybdenum and its alloys are known for their superior strength among body-centered cubic materials. However, their widespread application is hindered by a significant decrease in ductility at lower temperatures. In this study, we demonstrate the achievement of exceptional ductility in a Mo alloy containing rare-earth La2O3 nanoparticles through rotary-swaging, a rarity in Mo-based materials. Our analysis reveals that the large ductility originates from substantial variations in the electronic density of states, a characteristic intrinsic to rare-earth elements. This characteristic can accelerate the generation of oxygen vacancies, facilitating the amorphization of the oxide-matrix interface. This process promotes vacancy absorption and modification of dislocation configurations. Furthermore, by inducing irregular shapes in the La2O3 nanoparticles through rotary-swaging, incoming dislocations interact with them, creating multiple dislocation sources near the interface. These dislocation sources act as potent initiators at even reduced temperatures, fostering diverse dislocation types and intricate networks, ultimately enhancing dislocation plasticity.

Development of a nine-variant reference material panel to standardize cell-free DNA detection.

Detection of specific gene mutations in cell-free DNA (cfDNA) serves as a valuable cancer biomarker and is increasingly being explored as an appealing alternative to tissue-based methods. However, the lack of available reference materials poses challenges in accurately evaluating the performance of different assays. In this study, we present the development of a comprehensive reference material panel for cfDNA detection, encompassing nine hotspot mutations in KRAS/BRAF/EGFR/PIK3CA at three variant allele frequencies (VAFs), ranging from 0.33 to 23.9%. To mimic cfDNA, these reference materials were generated by enzymatically digesting cell-line DNA into approximately 154-bp to 173-bp fragments using a laboratory-developed reaction system. The VAFs for each variation were precisely determined through validated digital PCR assays with high accuracy. Furthermore, the reliability and applicability of this panel were confirmed through two independent NGS assays, yielding concordant results. Collectively, our findings suggest that this novel reference material panel holds great potential for validation, evaluation, and quality control processes associated with liquid biopsy assays.

The association analysis between fatigue and body composition loss in patients with nasopharyngeal carcinoma during radiotherapy: An observational longitudinal study.

PURPOSE: This study aimed to reveal the association of fatigue with weekly changes in the body composition in patients with nasopharyngeal carcinoma (NPC) and identified the independent strength. METHODS: Four body composition indexes and fatigue were assessed before treatment (T0, baseline) and once a week throughout radiotherapy (T1-T7). Generalized additive mixed models (GAMMs) were used to explore the trajectories and longitudinal relationships of fatigue and weekly changes in body composition. The marginal structural model (MSM) was used to control the effect of depression and anxiety. RESULTS: The trajectories of fatigue in 105 participants reached a peak in the fifth week, and changes in body composition started appearing from the second week. Four body composition indexes, weight, body mass index (BMI), body fat rate, and lean body weight loss weekly were positively associated with fatigue. High magnitude of effects was revealed when anxiety and depression were controlled as time-dependent confounders. The positive associations with fatigue were manifested in patients aged >53 years, those with senior high and above education, no drinking, >5000 Y/month of family inflow, ≥ stage III, or those receiving a dose of ≥70 Gy, ≥3 cycles of induced chemotherapy, and ≤1 cycle of concurrent chemotherapy. CONCLUSIONS: Loss of weight, BMI, body fat rate, and lean body weight could be used to independently evaluate the development of fatigue in patients with NPC during radiotherapy. Positive associations between fatigue and weekly body composition loss were found in patients with certain characteristics.

The Truncated Peptide AtPEP1(9-23) Has the Same Function as AtPEP1(1-23) in Inhibiting Primary Root Growth and Triggering of ROS Burst.

Currently, the widely used active form of plant elicitor peptide 1 (PEP1) from Arabidopsis thaliana is composed of 23 amino acids, hereafter AtPEP1(1-23), serving as an immune elicitor. The relatively less conserved N-terminal region in AtPEP family indicates that the amino acids in this region may be unrelated to the function and activity of AtPEP peptides. Consequently, we conducted an investigation to determine the necessity of the nonconserved amino acids in AtPEP1(1-23) peptide for its functional properties. By assessing the primary root growth and the burst of reactive oxygen species (ROS), we discovered that the first eight N-terminal amino acids of AtPEP1(1-23) are not crucial for its functionality, whereas the conserved C-terminal aspartic acid plays a significant role in its functionality. In this study, we identified a truncated peptide, AtPEP1(9-23), which exhibits comparable activity to AtPEP1(1-23) in inhibiting primary root growth and inducing ROS burst. Additionally, the truncated peptide AtPEP1(13-23) shows similar ability to induce ROS burst as AtPEP1(1-23), but its inhibitory effect on primary roots is significantly reduced. These findings are significant as they provide a novel approach to explore and understand the functionality of the AtPEP1(1-23) peptide. Moreover, exogenous application of AtPEP1(13-23) may enhance plant resistance to pathogens without affecting their growth and development. Therefore, AtPEP1(13-23) holds promise for development as a potentially applicable biopesticides.

Low-Temperature Cross-Linked Hole Transport Layer for High-Performance Blue Quantum-Dot Light-Emitting Diodes.

Quantum-dot light-emitting diodes (QLEDs), a kind of promising optoelectronic device, demonstrate potential superiority in next-generation display technology. Thermal cross-linked hole transport materials (HTMs) have been employed in solution-processed QLEDs due to their excellent thermal stability and solvent resistance, whereas the unbalanced charge injection and high cross-linking temperature of cross-linked HTMs can inhibit the efficiency of QLEDs and limit their application. Herein, a low-temperature cross-linked HTM of 4,4'-bis(3-(((4-vinylbenzyl)oxy)methyl)-9H-carbazol-9-yl)-1,1'-biphenyl (DV-CBP) with a flexible styrene side chain is introduced, which reduces the cross-linking temperature to 150 °C and enhances the hole mobility up to 1.01 × 10-3 cm2 V-1 s-1. More importantly, the maximum external quantum efficiency of 21.35% is successfully obtained on the basis of the DV-CBP as a cross-linked hole transport layer (HTL) for blue QLEDs. The low-temperature cross-linked high-mobility HTL using flexible side chains could be an excellent alternative for future HTL development.

Preparation of Rehmanniae Radix Praeparata polysaccharide iron(III) complex and evaluation of its biological activity.

This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its iron(III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1→3; 1→2, 3; and 1→2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×104 Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties.

Recent research advances in polysaccharide-based hemostatic materials: A review.

Massive bleeding resulting from civil and martial accidents can often lead to shock or even death, highlighting the critical need for the development of rapid and efficient hemostatic materials. While various types of hemostatic materials are currently utilized in clinical practice, they often come with limitations such as poor biocompatibility, toxicity, and biodegradability. Polysaccharides, such as alginate (AG), chitosan (CS), cellulose, starch, hyaluronic acid (HA), and dextran, have exhibit excellent biocompatibility and in vivo biodegradability. Their degradation products are non-toxic to surrounding tissues and can be absorbed by the body. As a result, polysaccharides have been extensively utilized in the development of hemostatic materials and have gained significant attention in the field of in vivo hemostasis. This review offers an overview of the different forms, hemostatic mechanisms, and specific applications of polysaccharides. Additionally, it discusses the future opportunities and challenges associated with polysaccharide-based hemostats.

Localized surface plasmon resonance (LSPR) excitation on single silver nanoring with nanoscale surface roughness.

With the expansion of the application of high-sensitivity Surface-enhanced Raman scattering (SERS) technique, micro SERS-active substrates with rich optical properties and high-level functions are desired. In this study, silver nanorings with nanoscale surface roughness were fabricated as a new type of enclosed quasi-2D micro-SERS-active substrate. Highly-crystalline spherical and hemispherical silver nanoprotrusions were densely and uniformly distributed over the entire surface of the nanorings. The SERS signals were significantly enhanced on the roughened silver nanorings which were mainly derived from the maximal localized surface plasmon resonance (LSPR) points at the junctions between adjacent coupled nanoprotrusions on the roughened nanorings. The mapping image shows a uniform and intense LSPR enhancement over the nanorings, owing to the uniform and dense distribution of silver nanoprotrusions and the resulting uniform distribution of maximal LSPR points on the roughened nanorings. The dark-field spectra further indicated that the single roughened silver nanoring had significant LSPR enhancement, a wide LSPR frequency-range response, and adaptability for SERS enhancement. Notably, both the measured and simulated results demonstrate that the maximal LSPR enhancement at the junctions between the nanoprotrusions, which are distributed on the inner surface of the silver nanoring, is higher than that on the outer surface because of the plasmon-focusing effect of the enclosed silver nanoring, which leads to the lateral asymmetrical distribution of LSPR intensity, indicating more LSPR and SERS features. These results indicate that single roughened silver nanorings exhibit excellent performance as a new type of enclosed quasi-2D silver nanoring micro-SERS-active substrate, microzone LSPR catalysis, and micro/nanodevices.

Coagulating blood into adhesive gel by hybrid powder based on oppositely charged polysaccharide/tannic acid-modified mesoporous bioactive glass.

Hemostatic powder is widely utilized in emergency situations to control bleeding due to its ability to work well on wounds with irregular shapes, ease of application, and long-term stability. However, traditional powder often suffers from limited tissue adhesion and insufficient support for blood clot formation, leaving it susceptible to displacement by the flow of blood. This study introduces a hemostatic powder composed of tannic modified mesoporous bioactive glass (TMBG), cationic quaternized chitosan (QCS), and anionic hyaluronic acid modified with catechol group (HADA). The resulting TMBG/QCS/HADA based hemostatic powder (TMQH) rapidly absorbs plasma, concentrating blood coagulation factors. Simultaneously, the water-soluble QCS and HADA interact to form a 3D network structure, which can be strengthened by crosslinking with TMBG. This network effectively captures clustered blood coagulation factors, leading to a strong and adhesive thrombus that resists disruption from blood flow. TMQH exhibits superior efficacy in promoting hemostasis compared to Celox™ both in rat arterial injuries and non-compressible liver puncture wounds. TMQH demonstrates excellent antibacterial activity, cytocompatibility, and blood compatibility. These outstanding superiorities in blood clotting capability, wet tissue adhesion, antibacterial activity, safety for living organisms, ease of application, and long-term stability, make TMQH highly suitable for emergency hemostasis.

Photosynthetic Bacteria-Hitchhiking 2D iMXene-mRNA Vaccine to Enable Photo-Immunogene Cancer Therapy.

Therapeutic mRNA vaccines have become powerful therapeutic tools for severe diseases, including infectious diseases and malignant neoplasms. mRNA vaccines encoding tumor-associated antigens provide unprecedented hope for many immunotherapies that have hit the bottleneck. However, the application of mRNA vaccines is limited because of biological instability, innate immunogenicity, and ineffective delivery in vivo. This study aims to construct a novel mRNA vaccine delivery nanosystem to successfully co-deliver a tumor-associated antigen (TAA) encoded by the Wilms' tumor 1 (WT1) mRNA. In this system, named PSB@Nb1.33C/mRNA, photosynthetic bacteria (PSB) efficiently delivers the iMXene-WT1 mRNA to the core tumor region using photo-driven and hypoxia-driven properties. The excellent photothermal therapeutic (PTT) properties of PSB and 2D iMxene (Nb1.33C) trigger tumor immunogenic cell death, which boosts the release of the WT1 mRNA. The released WT1 mRNA is translated, presenting the TAA and amplifying immune effect in vivo. The designed therapeutic strategy demonstrates an excellent ability to inhibit distant tumors and counteract postsurgical lung metastasis. Thus, this study provides an innovative and effective paradigm for tumor immunotherapy, i.e., photo-immunogene cancer therapy, and establishes an efficient delivery platform for mRNA vaccines, thereby opening a new path for the wide application of mRNA vaccines.

Amphiphilic AIE Fluorescent Probe: A Dual-Functionality Strategy for Efficient Antibacterial Therapy Fluorescence Bioimaging against Staphylococcus aureus.

Drug-resistant bacteria present a grave threat to human health. Fluorescence imaging-guided photodynamic antibacterial therapy holds enormous potential as an innovative treatment in antibacterial therapy. However, the development of a fluorescent material with good water solubility, large Stokes shift, bacterial identification, and high photodynamic antibacterial efficiency remains challenging. In this study, we successfully synthesized an amphiphilic aggregation-induced emission (AIE) fluorescent probe referred to as NPTPA-QM. This probe possesses the ability to perform live-bacteria fluorescence imaging while also exhibiting antibacterial activity, specifically against Staphylococcus aureus (S. aureus). We demonstrate that NPTPA-QM can eliminate S. aureus at a very low concentration (2 µmol L-1). Moreover, it can effectively promote skin wound healing. Meanwhile, this NPTPA-QM exhibits an excellent imaging ability by simple mixing with S. aureus. In summary, this research presents a straightforward and highly effective method for creating "amphiphilic" AIE fluorescent probes with antibacterial properties. Additionally, it offers a rapid approach for imaging bacteria utilizing red emission.

Photothermal Synergic Cross-Linking Hole Transport Layer for Highly Efficient RGB QLEDs.

Developing an insoluble cross-linkable hole transport layer (HTL) plays an important role for solution-processed quantum dots light-emitting diodes (QLEDs) to fabricate a multilayer device with separated quantum dots layers and HTLs. In this work, a facile photothermal synergic cross-linking strategy is simultaneous annealing and UV irradiation to form the high-quality cross-linked film as the HTL without any photoinitiator, which efficiently reduces the cross-linking temperature to the low temperature of 130 °C and enhances the hole mobility of the 3-vinyl-9-{4-[4-(3-vinylcarbazol-9-yl)phenyl]phenyl}carbazole (CBP-V) thin films. The obtained high-quality cross-linked CBP-V films exhibited smooth morphology, excellent solvent resistance, and high mobility. Moreover, the high-performance red, green, and blue (RGB) QLEDs are successfully fabricated by using the photothermal synergic cross-linked HTLs, which achieved the maximum external quantum efficiency of 25.69, 24.42, and 16.51%, respectively. This work presents a strategy of using the photothermal synergic cross-linked HTLs for fabrication of high-performance QLEDs and advancing their related device applications.