Epoxy-based multifunctional re-bondable polymer with self-healing, shape memory and superb bonding properties.

Thermoset epoxy resin-based materials are widely used, but their permanent cross-linked network limits their processability and reusability, which can lead to environmental burdens. In this work, by exploiting the weak reactivity of aniline to design appropriate reaction ratios, we achieved a linear link between the epoxy resin and the curing agent. This linear link, along with the crosslinking points provided by the flexibly branched polyurethanes, avoids the inherent brittleness associated with the highly crosslinked network of conventional epoxy resins. As a result, the adhesive exhibits extraordinary improvements in extensibility and toughness. The lap shear strength, tensile strength and elongation at break reach 11.9 MPa, 14.4 MPa and 607 %, respectively. The fracture toughness is as high as 109.6 kJ/m2, far beyond the existing epoxy adhesives. The synergistic effect of disulfide bonds and hydrogen bonds confers the adhesive with self-healing and repeatable bonding characteristics. The multi-level hydrogen bonding and appropriate phase separation structure are key to optimizing toughness, resulting in excellent comprehensive performance. The introduction of polyurethane not only improves toughness but also enhances the interfacial bonding force between the adhesive and the substrate, broadening the scope of applications. The prepared high-performance polymers provide new insights into reusable epoxy adhesives.

Integration of bioinformatics and multi-layered experimental validation reveals novel functions of acetylation-related genes in intervertebral disc degeneration.

BACKGROUND: The molecular mechanisms underlying intervertebral disc degeneration (IDD) remain poorly understood. The purpose of this work is to elucidate key molecules and investigate the roles of acetylation-related RNAs and their associated pathways in IDD. METHOD: Datasets GSE70362 and GSE124272 were obtained from the Gene Expression Omnibus (GEO) and combined to investigate differentially expressed genes (DEGs) associated with acetylation in IDD patients compared to healthy controls. Critical genes were pinpointed by integrating GO, KEGG and PPI networks. Furthermore, CIBERSORTx analysis was used to investigate the differences in immune cell infiltration between different groups and the biological processes (BP), cellular components (CC) and molecular functions (MF) were calculated by GSEA and GSVA. In addition, The single-cell database GSE165722 was incorporated to validate the specific expression patterns of hub genes in cells and identify distinct cell subtypes. This provides a theoretical basis for a more in-depth understanding of the roles played by critical cell subtypes in the process of IDD. Subsequently, tissues from IVD with varying degrees of degeneration were collected to corroborate the key DEGs using western blot, RT-qPCR, and immunofluorescence staining. RESULTS: By integrating various datasets and references, we identified a total of 1620 acetylation-related genes. These genes were subjected to a combined analysis with the DEGs from the databases included in this study, resulting in the discovery of 358 acetylation-related differentially expressed genes (ARDEGs). A comparative analysis with differentially expressed genes obtained from three databases yielded 19 ARDEGs. The PPI network highlighted the top 10 genes (IL1B, LAMP1, PPIA, SOD2, LAMP2, FBL, MBP, SELL, IRF1 and KHDRBS1) based on their protein interaction relationships. CIBERSORTx immune infiltration analysis revealed a moderate positive correlation between the gene IL1ß and Mast.cells.activated, as well as a similar correlation between the gene IRF1 and Mast.cells.activated. Single-cell dataset was used to identify cell types and illustrate the distribution of hub genes in different cell types. The two cell types with the highest AUCell scores (Neutrophils and Monocytes) were further explored, leading to the subdivision of Neutrophils into two new cell subtypes: S100A9-type Neutrophils and MARCKS-type Neutrophils. Monocytes were labeled as HLA-DRA9-type Monocytes and IGHG3-type Monocytes. Finally, molecular biology techniques were employed to validate the expression of the top 10 hub genes. Among them, four genes (IL1ß, SOD2, LAMP2, and IRF1) were confirmed at the gene level, while two (IL1ß and SOD2) were validated at the protein level. CONCLUSION: In this study, we carried out a thorough analysis across three databases to identify and compare ARDEGs between IDD patients and healthy individuals. Furthermore, we validated a subset of these genes using molecular biology techniques on clinical samples. The identification of these differently expressed genes has the potential to offer new insights for diagnosing and treating IDD.

Research progress and application of bacterial traceability technology.

Bacterial traceability refers to the use of a range of techniques to trace the origins and transmission pathways of bacteria. It is crucial in controlling the spread of diseases, analyzing bioterrorism incidents, and advancing microbial forensics. In recent years, the frequency and scope of bacterial outbreaks have continued to escalate, exerting significant impacts on global biosecurity, public health, and other areas. Consequently, it is required to process traceability of bacteria timely and accurately around the globe. The rapid development of biological and physicochemical traceability techniques provides convenience for tracing bacteria. These techniques not only surpass traditional methods in terms of sensitivity, traceability and throughput, but also find more extensive applications in elucidating bacterial growth mechanisms, transmission routes, and geographical origins. This paper systematically reviews the latest research progress and applications of technologies of bacterial traceability, highlighting key advancements and projecting future trends, with the intent of providing a valuable reference for researchers, facilitating further studies and innovations in this field.

Insights into the mechanisms of serplulimab: a distinctive anti-PD-1 monoclonal antibody, in combination with a TIGIT or LAG3 inhibitor in preclinical tumor immunotherapy studies.

With more than 20 anti-PD-1/PD-L1 antibodies currently marketed, anti-PD-1 therapy has become a cornerstone of tumor immunotherapy. These agents, however, exhibit notable disparities in their characteristics and clinical performance. For instance, in the field of small cell lung cancer (SCLC) where the majority of anti-PD-1 antibodies have yielded limited success, serplulimab produced impressive survival improvements and was approved for this indication by China's National Medical Products Administration. Serplulimab's marketing authorization application also received a positive opinion from the European Medicines Agency. Nevertheless, the molecular mechanism underpinning serplulimab's superiority over its competitors remains elusive. We characterized the differences between serplulimab with approved PD-1/PD-L1 inhibitors (pembrolizumab and nivolumab) in terms of their binding features and functions in vitro and anti-tumor activity in vivo. Cellular pathways underlying the efficacy of serplulimab were also investigated. In comparison to competitors, serplulimab robustly induces PD-1 receptor endocytosis while fostering weaker PD-1-CD28 cis interactions. This phenomenon could mitigate the dephosphorylation of CD28 by SHP2, thereby facilitating sustained and robust T cell activation. While serplulimab and pembrolizumab exhibited similar performance in vitro and in vivo studies, serplulimab consistently demonstrated superior tumor killing efficacy compared to pembrolizumab upon co-administration with anti-TIGIT or anti-LAG3 inhibitors. Mechanistically, the serplulimab combination effectively reduces tumor microenvironment Treg cell populations, augments effector and memory T cell populations, and more potently modulates genes associated with diverse facets of the immune system, surpassing the effects of the pembrolizumab combination. In summary, our data underscore serplulimab as a differentiated PD-1 monoclonal antibody with best-in-class therapeutic potential.

Acupuncture and Moxibustion in the Treatment of Gynecological Perioperative Anxiety: A Systematic Review and Meta-Analysis.

Objective: This systematic review and meta-analysis aims to investigate the effectiveness and safety of acupuncture and moxibustion in managing perioperative anxiety during gynecological surgery. Methods: Relevant studies published from the establishment of the databases to March 20, 2023, were searched in PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM. Literature screening and data extraction were independently conducted by two investigators. The Cochrane risk-of-bias tool 2.0 was utilized to assess the risk of bias in the included studies. Data analysis was carried out using Stata 15.1 software. Results: The analysis included a total of 3254 patients from twenty studies. It was found that acupuncture and moxibustion therapy resulted in a reduction of postoperative State-Trait Anxiety Inventory (STAI-S) scores (mean difference [MD] = -3.50, 95% confidence interval [CI] [-6.93 to -0.07], P = 0.046), as well as both preoperative and postoperative Visual Analogue Scale-Anxiety (VAS-anxiety) and Self-Rating Anxiety Scale (SAS) scores (pre-operation: SMD = -1.04, 95% CI [-1.73 to -0.35], P = 0.003; post-operation: SMD = -0.78, 95% CI [-1.21 to -0.35], P < 0.001) in comparison to the control group. Nonetheless, no significant variances were noted between the two groups with regards to preoperative and intraoperative STAI-S scores (pre-operation: MD = -3.38, 95% CI [-9.58 to 2.82], P = 0.286; intraoperative: MD = -1.09, 95% CI [-7.32 to 5.13], P = 0.730), and intraoperative VAS-anxiety and SAS scores (SMD = -0.44, 95% CI [-1.51 to 0.64], P = 0.427). Conclusion: During the perioperative period of gynecological surgery, acupuncture and moxibustion therapy show potential in alleviating anxiety in patients. It is noteworthy that the current level of evidence is limited by the small sample size. Therefore, further validation of these findings is necessary.

Contrast-Enhanced Ultrasound for Diagnosing Thyroid Nodules With Indeterminate Cytology: A Retrospective Study.

BACKGROUND: A small number of thyroid nodules cannot be clearly diagnosed using ultrasound-guided fine needle aspiration biopsy. Contrast-enhanced ultrasound (CEUS) has high diagnostic performance for thyroid nodules. We explored the value of CEUS for diagnosing thyroid nodules with indeterminate cytology. METHODS: Between September 2019 and July 2022, 27,646 patients with thyroid nodule(s) underwent conventional ultrasound (CUS) in our hospital. From these patients, 597 nodules were subjected to CEUS and ultrasound-guided fine needle aspiration biopsy and 116 thyroid nodules with indeterminate cytology diagnose were enrolled in this study. The independent risk factors for predicting malignancy were determined using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were drawn for CUS, CEUS, and CEUS combined with CUS. The area under the curve (AUC) was calculated and compared. RESULTS: Of the 116 thyroid nodules, 40 (34.5%) were benign and 76 (65.5%) were malignant. Univariate analysis showed that the shape, echogenicity, margin, microcalcification, enhancement intensity, enhancement homogeneity, wash in, and wash out were significantly different between benign and malignant thyroid nodules (all p < 0.05). Multivariate logistic regression analysis showed that taller-than-wide, irregular margin, microcalcification, hypo-enhancement, heterogeneity enhancement, synchronous/slower wash in, and synchronous/slower wash out were independent risk factors for malignancy (all p < 0.05). ROC curve analysis showed that the AUC of CUS and CEUS were 0.769 and 0.848, respectively. No significant difference was observed in the AUC between the two modalities (p > 0.05). However, the AUC (0.934) of the CUS combined with CEUS was significantly higher than that of CEUS or CUS alone (both p < 0.05). CONCLUSIONS: CEUS is helpful in diagnosing thyroid nodules with indeterminate cytology. CUS combined with CEUS is highly valuable for predicting malignancy.

Efficacy and Safety of Chlortalidone and Hydrochlorothiazide in Prevention of Cardiovascular Diseases.

Background: The variance between guideline recommendations and real-world usage might stem from the perception that chlorthalidone poses a higher risk of adverse effects, although there is no clear evidence of disparities in cardiovascular outcomes. It is crucial to assess both the clinical cardiovascular effects and adverse reactions of both drugs for clinical guidance. In this study, we present a comprehensive and updated analysis comparing the efficacy and safety of chlorthalidone (CHLOR) versus hydrochlorothiazide (HCTZ) for the prevention of cardiovascular diseases through lower the blood pressure. Methods: We conducted a systematic literature search using reputable databases including PubMed, Embase, Cochrane, and Web of Science up to April 2023, to identify studies that compared the efficacy and safety of CHLOR versus HCTZ for the long term prognosis of cardiovascular disease. This analysis represents the most up-to-date and systematic evidence on the comparative efficacy and safety of CHLOR and HCTZ for cardiovascular diseases. Results: Our review included a total of 6 eligible articles with a cohort of 368,066 patients, of which 36,999 were treated with CHLOR and 331,067 were treated with HCTZ. The primary diagnosis studied in six articles was hypertension. Initial features between the two different groups were comparable across every possible outcome. These papers followed patients using the two drugs over a long period of time to compare the differences in the occurrence of cardiovascular disease, and the results were as follows, the confidence interval is described in square brackets, followed by the p-value: We measured the outcomes of myocardial infarction with an odds ratio (OR) of 0.80 [0.56, 1.14], p = 0.41, heart failure with an OR of 0.86 [0.64, 1.14], p = 0.05, cardiovascular events with an OR of 1.85 [0.53, 6.44], p = 0.34, non-cancer-related death with an OR of 1.02 [0.56, 1.85], p = 0.45, death from any cause with an OR of 1.95 [0.52, 7.28], p = 0.32, complication rate, stroke with an OR of 0.94 [0.80, 1.10], p = 0.45, hospitalization for acute kidney injury with an OR of 1.38 [0.40, 4.78], p = 0.61 and hypokalemia with an OR of 2.10 [1.15, 3.84], p = 0.01. Pooled analyses of the data revealed that CHLOR was associated with a higher incidence of hypokalemia compared to HCTZ and the results were statistically significant. Conclusions: CHLOR and HCTZ are comparable in efficacy for prevention cardiovascular diseases, with the only difference being a higher incidence of hypokalemia in patients using CHLOR compared to those using HCTZ. Considering the potential heterogeneity and bias in the analytical studies, these results should be interpreted with caution.

Alpine and subalpine plant microbiome mediated plants adapt to the cold environment: A systematic review.

With global climate change, ecosystems are affected, some of which are more vulnerable than others, such as alpine ecosystems. Microbes play an important role in environmental change in global ecosystems. Plants and microbes are tightly associated, and symbiotic or commensal microorganisms are crucial for plants to respond to stress, particularly for alpine plants. The current study of alpine and subalpine plant microbiome only stays at the community structure scale, but its ecological function and mechanism to help plants to adapt to the harsh environments have not received enough attention. Therefore, it is essential to systematically understand the structure, functions and mechanisms of the microbial community of alpine and subalpine plants, which will be helpful for the conservation of alpine and subalpine plants using synthetic microbial communities in the future. This review mainly summarizes the research progress of the alpine plant microbiome and its mediating mechanism of plant cold adaptation from the following three perspectives: (1) Microbiome community structure and their unique taxa of alpine and subalpine plants; (2) The role of alpine and subalpine plant microbiome in plant adaptation to cold stress; (3) Mechanisms by which the microbiome of alpine and subalpine plants promotes plant adaptation to low-temperature environments. Finally, we also discussed the future application of high-throughput technologies in the development of microbial communities for alpine and subalpine plants. The existing knowledge could improve our understanding of the important role of microbes in plant adaptation to harsh environments. In addition, perspective further studies on microbes' function confirmation and microbial manipulations in microbiome engineering were also discussed.

A phase II study of anlotinib plus whole brain radiation therapy for patients with NSCLC with multiple brain metastases.

BACKGROUND: Whole brain radiotherapy (WBRT) is the mainstay of treatment for patients with non-small cell lung cancer (NSCLC) with multiple brain metastases (BMs); however, the BRAIN study showed that the efficacy of WBRT is unsatisfactory. This prospective phase II study aimed to evaluate the efficacy and safety of WBRT combined with anlotinib, a novel anti-angiogenic multi-target tyrosine kinase inhibitor (TKI), in patients with multiple BMs (>3) from advanced NSCLC. METHODS: Patients with advanced NSCLC with multiple BMs who had received two or more lines of treatment were eligible for enrolment into this study. All patients were treated with anlotinib (8-12 mg, QD, on days 1-14 of a 21-day cycle) combined with WBRT (DT 30 Gy/12 F), followed by maintenance therapy with anlotinib until disease progression or treatment intolerance. The primary endpoint of this study was the intracranial progression-free survival (iPFS). The secondary endpoints were intracranial objective response rate (iORR), intracranial disease control rate (iDCR), overall survival (OS) and treatment safety. RESULTS: Between May 2019 and January 2021, 28 patients were enrolled, all of whom were evaluable for efficacy and safety. The median age was 57.7 years, and 46.4% were male. Twenty-five patients had adenocarcinoma (89.3%), six had EGFR mutations (21.4%) and two had ALK mutations (7.1%). The median iPFS was 11.1 months (95% confidence interval (CI): 5.4-16.8 months) and the median OS was 13.4 months (95% CI: 5.2-21.6 months). The iORR was 71.4% (six complete responses + 14 partial responses). The most frequently observed adverse events (AEs) were hypertension (71.4%), fatigue (64.3%), anorexia (46.4%), and foot and hand skin reactions (25.0%). No patients developed ≥ grade 4 AEs. No intracranial haemorrhages occurred during treatment. Dose adjustment due to AEs occurred in 17.9% of patients. CONCLUSIONS: Anlotinib combined with WBRT is effective and well-tolerated in patients with NSCLC with multiple BMs.

HLX07 alone or combined with serplulimab, cisplatin and 5-fluorouracil for advanced esophageal squamous cell carcinoma: A phase 2 study.

BACKGROUND: The combination of anti-PD-1 antibody serplulimab and chemotherapy is considered standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), but few later-line treatments are available. Here we evaluated the therapeutic efficacy of the recombinant, humanized anti-EGFR antibody HLX07 when used alone or together with serplulimab and chemotherapy against advanced ESCC. METHODS: This open-label, non-randomized, two-cohort, phase 2 trial involved patients 18-75 years old with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients who had failed first-line immuno-chemotherapy or at least two lines of other systemic therapy received HLX07 monotherapy intravenously at a dose of 1,000 mg once every 2 weeks (Q2W). Patients with no prior systemic therapy received HLX07 (1,000 mg, day 1) and serplulimab (200 mg, day 1) intravenously Q2W for up to 2 years, concurrently with cisplatin (50 mg/m2, day 1) for up to 8 cycles and 5-fluorouracil (1,200 mg/m2, days 1-2) for up to 12 cycles intravenously Q2W. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). RESULTS: Overall, 50 patients were enrolled. In the HLX07 monotherapy group, ORR was 15.0% (3/20), and the median PFS was 1.5 months (95% confidence interval [CI], 1.3 to 3.7). The median duration of response was not reached, and the rate of patients showing an objective response lasting at least 6 months was 66.7% (95% CI, 5.4 to 94.5). Two (10.0%, 2/20) patients experienced grade 3-4 treatment-related adverse events (TRAEs), including hypomagnesemia, hypocalcemia, and fatigue. No patient experienced grade 5 TRAEs. In the HLX07 combination group, the ORR was 60.0% (18/30), and the median PFS was 7.8 months (95% CI, 3.3 to 9.1). Fourteen (46.7%, 14/30) patients experienced grade 3-4 TRAEs, and one (3.3%, 1/30) patient died due to serplulimab-related pneumonitis. CONCLUSIONS: HLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomized controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC. TRIAL REGISTRATION: This trial was registered at Clinicaltrials.gov (NCT05221658).

Effects of the co-exposure of microplastic/nanoplastic and heavy metal on plants: Using CiteSpace, meta-analysis, and machine learning.

Micro/nanoplastics (MNPs) and heavy metals (HMs) coexist worldwide. Existing studies have reported different or even contradictory toxic effects of co-exposure to MNPs and HMs on plants, which may be related to various influencing factors. In this study, existing publications were searched and analyzed using CiteSpace, meta-analysis, and machine learning. CiteSpace analysis showed that this research field was still in the nascent stage, and hotspots in this field included accumulation, cadmium (Cd), growth, and combined toxicity. Meta-analysis revealed the differential association of seven influencing factors (MNP size, pollutant treatment duration, cultivation media, plant species, MNP type, HM concentration, and MNP concentration) and 8 physiological parameters receiving the most attention. Co-exposure of the two contaminants had stronger toxic effects than HM treatment alone, and phytotoxicity was generally enhanced with increasing concentrations and longer exposure durations, especially when using nanoparticles, hydroponic medium, dicotyledons producing stronger toxic effects than microplastics, soil-based medium, and monocotyledons. Dry and fresh weight analysis showed that co-exposure to MNPs and Cd resulted in significant phytotoxicity in all classifications. Concerning the MNP types, polyolefins partially attenuated plant toxicity, but both modified polystyrene (PS) and biodegradable polymers exacerbated joint phytotoxicity. Finally, machine learning was used to fit and predict plant HM concentrations, showing five classifications with an accuracy over 80 %, implying that the polynomial regression model could be used to predict HM content in plants under complex pollution conditions. Overall, this study identifies current knowledge gaps and provides guidance for future research.

Distinct roles of COMPASS subunits to Drosophila heart development.

The multiprotein complexes known as the complex of proteins associated with Set1 (COMPASS) play a crucial role in the methylation of histone 3 lysine 4 (H3K4). In Drosophila, the COMPASS series complexes comprise core subunits Set1, Trx, and Trr, which share several common subunits such as ash2, Dpy30-L1, Rbbp5, and wds, alongside their unique subunits: Wdr82 for Set1/COMPASS, Mnn1 for Trx/COMPASS-like, and Ptip for Trr/COMPASS-like. Our research has shown that flies deficient in any of these common or unique subunits exhibited high lethality at eclosion (the emergence of adult flies from their pupal cases) and significantly shortened lifespans of the few adults that do emerge. Silencing these common or unique subunits led to severe heart morphological and functional defects. Moreover, specifically silencing the unique subunits of the COMPASS series complexes, Wdr82, Mnn1, and Ptip, in the heart results in decreased levels of H3K4 monomethylation and dimethylation, consistent with effects observed from silencing the core subunits Set1, Trx, and Trr. These findings underscore the critical roles of each subunit of the COMPASS series complexes in regulating histone methylation during heart development and provide valuable insights into their potential involvement in congenital heart diseases, thereby informing ongoing research in heart disease.

The role of uric acid in the risk of hypertension developed from prehypertension: a five-year Chinese urban cohort study.

BACKGROUND: Uric acid as a prominent causal factor in the pathogenesis of hypertension is well recognized. Nevertheless, the influence of uric acid on the transition from prehypertension to hypertension within the Chinese population remains understudied. METHODS: A cohort of 1,516 prehypertensive individuals, aged 35 to 84 years, underwent recruitment following a comprehensive health assessment in 2017 and subsequent re-evaluation in 2022. Baseline characteristics and relevant clinical data were collected. The analytical approach encompassed multiple logistic regression and propensity score matching. RESULTS: Over 5 years, the cumulative incidence of hypertension amounted to 35.1%, with 33.9% in males and 37.3% in females, respectively. Notably, prehypertensive subjects concomitant with hyperuricemia exhibited a higher cumulative incidence of hypertension in comparison to the non-hyperuricemic counterparts (40.7% vs. 34.0%, p = 0.041). Multiple logistic regression unveiled a significant association between hyperuricemia and heightened hypertension risk (adjusted odds ratio [OR] = 1.44; 95% confidence interval [CI], 1.05-1.98; p = 0.022). Nonetheless, this association did not reach statistical significance when examining female subjects (adjusted OR = 1.10; 95% CI, 0.58-2.09; p = 0.781) or participants aged ≥ 60 years (adjusted OR = 1.07; 95% CI, 0.61-1.88; p = 0.814). Further validation through propensity score matching affirmed that subjects afflicted by hyperuricemia experienced a substantially elevated risk of transitioning from prehypertension to hypertension over the course of five years compared with the non-hyperuricemic counterparts (41.3% vs. 32.3%, p = 0.045), after adjusting for 12 covariates including age and gender. Hyperuricemia emerged as an independent risk factor predisposing individuals to the development of hypertension from a prehypertensive state. CONCLUSION: This observation prompted the formulation of a hypothesis suggesting that ameliorating elevated uric acid levels may potentially mitigate the progression from prehypertension to hypertension.

Effect of Polygonatum sibiricum on biological toxicity of zinc oxide nanoparticles during respiratory exposure.

Although zinc oxide nanoparticles (ZnO NPs) with distinct physicochemical properties have attracted great attention, the application of ZnO NPs is still limited due to their potential biotoxicity. In this work, ZnO-Polygonatum sibiricum (PS) NPs are synthesized to overcome this challenge. The ZnO NPs stably combine with PS according to microstructural observation, particle size distribution, zeta potential results and Fourier transform infrared spectroscopy analysis. The cytotoxicity of ZnO NPs is alleviated by combining them with PS as a consequence of the diminished generation of reactive oxygen species and reinforced superoxide dismutase activity. Furthermore, the respiratory index and histopathologic results of mice exposed to NPs manifest that the pulmonary dysfunction caused by ZnO NPs is avoided in the ZnO-PS NPs group. This study provides the foundations for the amelioration and universal utilization of ZnO NPs and emphasizes the potential of ZnO-PS NPs in biomedical applications.

Rnf111 has a pivotal role in regulating development of definitive hematopoietic stem and progenitor cells through the Smad2/3-Gcsfr/NO axis in zebrafish.

The ubiquitination or SUMOylation of hematopoietic related factors plays pivotal roles in hematopoiesis. RNF111, known as a ubiquitin ligase (Ubl), is a newly discovered SUMO-targeted ubiquitin ligase (STUbl) involved in multiple signaling pathways mediated by TGF-ß family members. However, its role in hematopoiesis remains unclear. Herein, a heritable Rnf111 mutant zebrafish line was generated by CRISPR/Cas9-mediated genome editing. Impaired hematopoietic stem and progenitor cells (HSPC) of definitive hematopoiesis was found in Rnf111 deficient mutants. Ablation of Rnf111 resulted in decreased phosphorylation of Smad2/3 in HSPC. Definitive endoderm 2 inducer (IDE2), which specifically activates TGF-ß signaling and downstream Smad2 phosphorylation, can restore the definitive hematopoiesis in Rnf111-deficient embryos. Further molecular mechanism studies revealed that Gcsfr/NO signaling was an important target pathway of Smad2/3 involved in Rnf111-mediated HSPC development. In conclusion, our study demonstrated that Rnf111 contributes to the development of HSPC by maintaining Smad2/3 phosphorylation and the Gcsfr/NO signaling pathway activation. Keywords: Rnf111, Ubiquitin ligase (UbL), HSPC, Smad2/3, Gcsfr/NO.

Long-term rice-crayfish farming alters soil dissolved organic carbon quality and biodegradability by regulating microbial metabolism and iron oxidation.

The biodegradability of dissolved organic carbon (DOC) is a crucial process in the migration and transformation of soil organic carbon (SOC), and play a vital role in the global soil carbon (C) cycle. Although the significance of DOC in SOC transportation and microbial utilization is widely acknowledged, the impact of long-term rice-crayfish (RC) farming on the content, quality, and biodegradability of DOC in paddy soils, as well as regulatory mechanisms involved, remains unclear. To address this gap, a space-for-time method was employed to investigate the effects of different RC farming durations (1-, 5-, 10-, 15-, and 20- years) on the quality and biodegradability of DOC, as well as their relationship with soil microbial metabolism and minerals in this study. The results revealed that continuous RC farming increased the soil DOC content, but reduced DOC biodegradability. Specifically, after 20 years of continuous RC farming, the DOC content increased by 52.7% compared to the initial year, whereas the DOC biodegradability decreased by 63.4%. Analysis using three-dimensional fluorescence and ultraviolet spectroscopy demonstrated that continuous RC farming resulted in a decrease in the relative abundance of humus-like fractions, humification, and aromaticity indexes in DOC, but increased the relative abundance of protein-like fractions, biological, and fluorescence index, indicating that long-term RC farming promoted the simple depolymerization of the molecular structure of DOC. Continuous RC farming increased the activity of hydrolase involved in soil nitrogen (N) and phosphorus (P) cycles and oxidase, but decreasing the hydrolase C/N and C/P acquisition ratios; moreover, it also stimulated an increase in soil iron oxides and exchangeable calcium content. Structural equation modeling suggests that soil hydrolases and iron oxides are the primary drivers of DOC quality change, with DOC biodegradability being driven solely by soil iron oxides and not regulated by DOC quality. In conclusion, long-term RC farming promotes the catalytic decomposition of DOC aromatic substances and the production of DOC protein-like components by increasing soil oxidase activity and decreasing the hydrolase C/N acquisition ratio; these processes collectively contribute to the simple depolymerization of DOC molecular structure. Additionally, long-term RC farming induced legacy effects of soil iron oxides and enhanced chemical protection role leading to reduced DOC biodegradability. These findings suggested that long-term RC farming may reduce the rapid turnover and loss of DOC, providing a negative feedback on climate warming.

Nitrogen-doped graphene quantum dot-intensified tungsten oxide nanosheets as a SERS substrate for antibiotics detection.

In this study, tungsten oxide nanosheets loaded with nitrogen-doped graphene oxide quantum dots (NGQDs/WO3 NSs) were fabricated as SERS substrates. The promoted photo-induced charge transfer (PICT) and the strong π-π stacking effect resulting from the unique structure of the NGQDs contributed to the enhanced SERS signal.

Strength in Numbers: A Giant NIR-II AIEgen with One-for-All Phototheranostic Features for Exceptional Orthotopic Bladder Cancer Treatment.

One-for-all phototheranostics that allows the simultaneous implementations of multiple optical imaging and therapeutic modalities by utilizing a single component, is growing into a sparkling frontier in cancer treatment. Of particular interest is phototheranostic agent with emission in the second near-infrared (NIR-II) window. Nevertheless, the practical uses of those conventional NIR-II agents are severely impeded by their unsatisfactory features including insufficient stability, low synthetic yield, to be extended absorption/ emission wavelengths, and inefficient phototheranostic outcomes. Developing exceptional phototheranostic agents is thus highly desirable yet remains formidably challenging. Herein, we synthesized two novel N-heteroacenes-based NIR-II luminogens, namely 2TT-PPT and 4TT-PBPT, by respectively employing pyrene-fused phenaziothiadiazoles and pyrene-fused bisphenaziothiadiazoles as acceptor skeletons. There is strength in numbers by increasing the fusing rings in N-heteroacenes moieties and numbers of appended donors. Compared to less ring-fused 2TT-PPT, the giant molecule 4TT-PBPT shows improved photophysical characteristics, such as enhanced light absorbance, red-shifted wavelengths, higher brightness, favorable reactive oxygen species (ROS) generation, and elevated photothermal conversion efficiency, which render 4TT-PBPT nanoparticles excellent fluorescence-photoacoustic-photothermal trimodal imaging guided photodynamic-photothermal synergistic therapy for orthotopic bladder cancer.