Molecular Basis of VCPIP1 and P97/VCP Interaction Reveals Its Functions in Post-Mitotic Golgi Reassembly.

The VCPIP1-P97/VCP (Valosin-Containing Protein) complex is required for post-mitotic Golgi cisternae reassembly and maintenance in interphase. However, the organization and mechanism of this complex in regulating Golgi membrane fusion is still elusive. Here, the cryo-electron microscopy (cryo-EM) structures of the human VCPIP1-P97/VCP complex are presented. These studies reveal that three independent VCPIP1 molecules sit over the C-terminal substrate exit tunnel formed by P97/VCP homo-hexamer, resulting in an unusual C3 to C6 symmetric barrel architecture. The UFD1 (unknown function domain 1) from VCPIP1, but not the N-terminal OTU domain and the C-terminal UBL domain, docks to the two adjacent D2 domains of P97/VCP, allosterically causing the cofactors binding domain-NTDs (N-terminal domains) of P97/VCP in a "UP" and D1 domain in an ATPase competent conformation. Conversely, VCPIP1 bound P97/VCP hexamer favors the binding of P47, and thus the intact SNARE complex, promoting Golgi membrane fusion. These studies not only reveal the unexpected organization of humanVCPIP1-P97/VCP complex, but also provide new insights into the mechanism of VCPIP1-P97/VCP mediated Golgi apparatus reassembly, which is a fundamental cellular event for protein and lipid processing.

Simultaneous Characterization of In-Plane and Cross-Plane Resistivities in Highly Anisotropic 2D Layered Heterostructures.

Understanding and characterizing the intrinsic properties of charge carrier transport across the interfaces in van der Waals heterostructures is critical to their applications in modern electronics, thermoelectrics, and optoelectronics. However, there are very few published cross-plane resistivity measurements of thin samples because these inherently 2-probe measurements must be corrected for contact and lead resistances. Here, we present a method to extract contact resistances and metal lead resistances by fitting the width dependence of the contact end voltages of top and bottom electrodes of different contact widths to a model based on current crowding. These contributions are then subtracted from the total 2-probe cross-plane resistance to obtain the cross-plane resistance of the material itself without needing multiple devices and/or etching steps. This approach was used to measure cross-plane resistivities of a (PbSe)1(VSe2)1 heterostructure containing alternating layers of PbSe and VSe2 with random in-plane rotational disorder. Several samples measured exhibited a 4 order of magnitude difference between cross-plane and in-plane resistivities over the 6-300 K temperature range. We also reported the observation of charge density wave transition in the cross-plane transport of the (PbSe)1(VSe2)1 heterostructure. The device fabrication process is fully liftoff compatible, and the method developed enables the straightforward measurement of the resistivity anisotropy of most thin film materials with nm thicknesses.

Camrelizumab, apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib (TRIPLET protocol) is promising for advanced hepatocellular carcinoma (Ad-HCC). However, the usefulness of microwave ablation (MWA) after TRIPLET is still controversial. AIM: To compare the efficacy and safety of TRIPLET alone (T-A) vs TRIPLET-MWA (T-M) for Ad-HCC. METHODS: From January 2018 to March 2022, 217 Ad-HCC patients were retrospectively enrolled. Among them, 122 were included in the T-A group, and 95 were included in the T-M group. A propensity score matching (PSM) was applied to balance bias. Overall survival (OS) was compared using the Kaplan-Meier curve with the log-rank test. The overall objective response rate (ORR) and major complications were also assessed. RESULTS: After PSM, 82 patients were included both the T-A group and the T-M group. The ORR (85.4%) in the T-M group was significantly higher than that (65.9%) in the T-A group (P < 0.001). The cumulative 1-, 2-, and 3-year OS rates were 98.7%, 93.4%, and 82.0% in the T-M group and 85.1%, 63.1%, and 55.0% in the T-A group (hazard ratio = 0.22; 95% confidence interval: 0.10-0.49; P < 0.001). The incidence of major complications was 4.9% (6/122) in the T-A group and 5.3% (5/95) in the T-M group, which were not significantly different (P = 1.000). CONCLUSION: T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

Carbon quantum dots from carbohydrate-rich residue of birch obtained following lignin-first strategy.

Carbon quantum dots (CQDs) were successfully synthesized from carbohydrate-rich residue of birch obtained following the lignin-first strategy. The optical and physicochemical properties of the CQDs were studied, along with their potential for photocatalytic pollutant degradation. By combining solvothermal and chemical oxidation methods, the product yield of CQDs from carbohydrate-rich residue reached 8.1 wt%. Doping nitrogen enhances the graphitization of CQDs and introduces abundant amino groups to the surface, thereby boosted the quantum yield significantly from 8.9 % to 18.7 %-19.3 %. Nitrogen-doped CQDs exhibited efficient photocatalytic degradation of methylene blue, reaching 37 % within 60 min, with a kinetic degradation rate of 0.00725 min-1. This study demonstrates that carbohydrate-rich residue obtained from lignin-first strategy are ideal precursors for synthesizing CQD with high mass yield and quantum yield by combining solvothermal treatment and chemical oxidation methods, offering a novel approach for the utilization of whole biomass components following the lignin-first strategy.

Pyrrololactam alkaloids with IL-6 inhibitory activities from the sponge Phakellia fusca collected in the South China Sea.

Sixteen undescribed pyrrololactam alkaloids, including five 2-bromopyrrole-ε-lactam (1a, 1b, 4a, 4b and 5), two 3-bromopyrrole-ε-lactam (9 and 10), eight pyrrole-ε-lactam (2a-3 and 6a-8), and one pyrrole-δ-lactam alkaloids (11), along with three previously reported compounds (12-14) were isolated from the marine sponge Phakellia fusca collected in the South China Sea. The planar structures were determined by NMR and MS analyses, while the absolute configurations were clearly elucidated by comparing the experimental and calculated ECD spectra. Compounds 2a, 2b, 4a-7b, 10, 12 and 13 exhibited anti-inflammatory activity in inhibiting the production of inflammatory cytokines IL-6 in LPS-induced RAW264.7 macrophages.

Astragaloside IV Ameliorates Colonic Adenomatous Polyps Development by Orchestrating Gut Bifidobacterium and Serum Metabolome.

Astragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus, has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed [Formula: see text] mice. [Formula: see text] mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. The study assessed CAP proliferation and employed 16S DNA-sequencing and untargeted metabolomics to explore correlations between microbiome and metabolome in CAP development. AS-IV was more effective than Naringin in reducing CAP development, inhibiting colonic proinflammatory cytokines (IL-1[Formula: see text], IL-6, and TNF-[Formula: see text]), tumor associated biomarkers (c-Myc, Cyclin D1), and Wnt/[Formula: see text]-catenin pathway proteins (Wnt3a, [Formula: see text]-catenin). AS-IV also inhibited the proliferative capabilities of human colon cancer cells (HT29, HCT116, and SW620). Multiomics analysis revealed AS-IV increased the abundance of beneficial genera such as Bifidobacterium pseudolongum and significantly modulated serum levels of certain metabolites including linoleate and 2-trans,6-trans-farnesal, which were significantly correlated with the number of CAP. Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed [Formula: see text] mice but could be reinstated following a combined with Bifidobacterium pseudolongum transplant. AS-IV attenuates CAP development in HFD-fed [Formula: see text] mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/[Formula: see text]-catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV's antitumor effects.

Atomic-Scale Characterization of Dilute Dopants in Topological Insulators via STEM-EDS Using Registration and Cell Averaging Techniques.

Magnetic dopants in three-dimensional topological insulators (TIs) offer a promising avenue for realizing the quantum anomalous Hall effect (QAHE) without the necessity for an external magnetic field. Understanding the relationship between site occupancy of magnetic dopant elements and their effect on macroscopic property is crucial for controlling the QAHE. By combining atomic-scale energy-dispersive X-ray spectroscopy (EDS) maps obtained by aberration-corrected scanning transmission electron microscopy (AC-STEM) and novel data processing methodologies, including semi-automatic lattice averaging and frame registration, we have determined the substitutional sites of Mn atoms within the 1.2% Mn-doped Sb2Te3 crystal. More importantly, the methodology developed in this study extends beyond Mn-doped Sb2Te3 to other quantum materials, traditional semiconductors, and even electron irradiation sensitive materials.

Low expression of Lnc-ENST00000535078 inhibits the migration, invasion, and enhances apoptosis of CTPE-induced malignantly transformed BEAS-2B cells.

Long non-coding RNA (LncRNA) plays an important role in malignant transformation of cells. This study aimed to explore the role of Lnc-ENST00000535078 in the malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) induced by coal tar pitch extract (CTPE). The malignant transformation model of BEAS-2B cells exposed to CTPE. Cell proliferation was examined by Cell counting kit-8 (CCK-8) assay. Colony formation assay was used to assess the colony of cells. Cell migration and invasion were detected by Transwell analysis. Cell cycle progression and apoptotic status were assessed by flow cytometry. Differentially expressed genes were screened by RNA sequencing. The results showed that Lnc-ENST00000535078 expression was highest in malignantly transformed BEAS-2B cells passaged to the 30th generation. Knockdown of Lnc-ENST00000535078 inhibited the migration, invasion and anti-apoptotic abilities of malignantly transformed BEAS-2B cells. Transcriptome analysis found 608 differential genes. CCND1 and FOS genes were screened out because of their levels were positive correlation with the expression of Lnc-ENST00000535078, which were consistent with the RNA sequencing results. In conclusion, Low expression of Lnc-ENST00000535078 inhibits the migration and invasion of malignant transformed BEAS-2B cells and promotes apoptosis in these cells. Lnc-ENST00000556926 might affect the malignant transformation of cells through the regulation of CCND1 and FOS. This study may provide a potential target for intervention in CTPE-induced lung cancer.

Biomechanical changes of oblique lumbar interbody fusion with different fixation techniques in degenerative spondylolisthesis lumbar spine: a finite element analysis.

OBJECTIVE: There is a dearth of comprehensive research on the stability of the spinal biomechanical structure when combining Oblique Lumbar Interbody Fusion (OLIF) with internal fixation methods. Hence, we have devised this experiment to meticulously examine and analyze the biomechanical changes that arise from combining OLIF surgery with different internal fixation techniques in patients diagnosed with degenerative lumbar spondylolisthesis. METHODS: Seven validated finite element models were reconstructed based on computed tomography scan images of the L3-L5 segment. These models included the intact model, a stand-alone (S-A) OLIF model, a lateral screw rod (LSR) OLIF model, a bilateral pedicle screw (BPS) OLIF model, an unilateral pedicle screw (UPS) OLIF model, a bilateral CBT (BCBT) OLIF model, and an unilateral CBT(UCBT) OLIF model. The range of motion (ROM), as well as stress levels in the cage, L4 lower endplate, L5 upper endplate, and fixation constructs were assessed across these different model configurations. RESULTS: S-A model had the highest average ROM of six motion modes, followed by LSR, UPS, UCBT, BPS and BCBT. The BCBT model had a relatively lower cage stress than the others. The maximum peak von Mises stress of the fixation constructs was found in the LSR model. The maximum peak von Mises stress of L4 lower endplate was found in the S-A model. The peak von Mises stress on the L4 lower endplate of the rest surgical models showed no significant difference. The maximum peak von Mises stress of the L5 upper endplate was found in the S-A model. The minimum peak von Mises stress of the L5 upper endplate was found in the BCBT model. No significant difference was found for the peak von Mises stress of the L5 upper endplate among LSR, BPS, UPS and UCBT models. CONCLUSION: Among the six different fixation techniques, BCBT exhibited superior biomechanical stability and minimal stress on the cage-endplate interface. It was followed by BPS, UCBT, UPS, and LSR in terms of effectiveness. Conversely, S-A OLIF demonstrated the least stability and resulted in increased stress on both the cage and endplates. Combining OLIF with BCBT fixation technique enhanced biomechanical stability compared to BPS and presented as a less invasive alternative treatment for patients with degenerative lumbar spondylolisthesis.

Measurement of thresholds using Chirp-ABR in children with auditory neuropathy spectrum disorder and sensorineural hearing loss.

AIM: This study explored the value of Chirp-auditory brainstem response (ABR) thresholds in assessing the hearing threshold of children diagnosed with auditory neuropathy spectrum disorder (ANSD). METHODS: A total of 20 children with ANSD (40 ears, aged 1.5-7.0 years, median age 4.5 years) and 31 children with sensorineural hearing loss (SNHL) (52 ears, aged 0.9-8.0 years, median age 3.7 years) were included. Besides, 25 normal children (50 ears, aged 0.8-7.5 years, median age 4.6 years) were used as controls. Chirp-ABR and behavioral audiometry were performed simultaneously among three groups of children, allowing for a comparison of the thresholds obtained through both methods. RESULTS: In ANSD children, the correlation (r-values) between the thresholds obtained from Chirp-ABR and behavioral audiometry at 500-4000 Hz were 0.84, 0.67, 0.59, and 0.60, respectively. The average threshold differences between two methods ranged from 9.7 to 13.3 dB at 500-4000 Hz. Notably, 20 % ears (8/40) exhibited considerable discrepancies (>30 dB) in thresholds at certain frequencies. For SNHL children, the r-values between two methods were 0.84, 0.89, 0.92, and 0.93, respectively. The average threshold differences between two methods were 5.7-8.2 dB at 500-4000 Hz. Similarly, in normal children, the average threshold differences between two methods ranged from 6.1 dB to 7.7 dB, the r-values were 0.81, 0.78, 0.80, and 0.80 at 500-4000 Hz, respectively. CONCLUSION: Chirp-ABR threshold is not suitable to predict the behavioral audiometry threshold in ANSD children. When there is a significant discrepancy (>30 dB) between Chirp-ABR thresholds and behavioral audiometry thresholds in hearing loss, ANSD should be highly suspected.

Biomimetic design and impact simulation of Al2O3/Al composite armor based on armadillo shell.

The advancement of lightweight protective armors holds critical importance for enhancing the maneuverability and combat capabilities of helicopters. Leveraging insights from bionics, it provides a new idea for high-performance armor design. In this study, a new type of composite armor was designed by referring to the structural characteristics of hard phase-protection, soft phase-buffering of unitization armadillo shell. Through the numerical study, the anti-ballistic performance of armor with varying thickness ratios of the dense ceramic layer to the interpenetrating layer is obtained, and the influence of different structures of armor on the anti-ballistic performance is analyzed. The results show that compared with the traditional laminated composite armor, the Al2O3/Al biomimetic composite armor not only improves the separation phenomenon caused by wave impedance mismatch, but also greatly improves the speed drop in resisting high-speed and penetrating bullets. When the thickness ratio is 2:1, the armor has higher ballistic protection performance.

Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.

Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC ('EC alone'; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607 .

Leader ethical voice and subordinate job performance: the chain mediating role of subordinate identification with leader and leader-member exchange.

Introduction: Ethical voice is a valuable ethical behavior that enables organizations to promptly recognize and rectify unethical issues and practices, thus preventing severe dilemmas and crises. Despite its importance, the extant literature has yet to fully explore the impact of a leader's ethical voice on subordinate outcomes. This study bridges this gap by integrating social identity theory and social exchange theory to scrutinize the process by which a leader's ethical voice affects subordinate task performance. Methods: We employ a serial mediation model to explore the mechanisms by which a leader's ethical voice enhances subordinates' task performance. Our theoretical framework is empirically validated using a dataset that includes 449 subordinate-leader pairings from Chinese enterprises. Results: The survey results demonstrate that a leader's ethical voice has a significant positive impact on subordinate task performance. Subordinate identification with leader and leader-member exchange not only individually mediate the effects of a leader's ethical voice on subordinate task behavior but also jointly serve as a chain-mediated mechanism in the influence of a leader's ethical voice on subordinate task behavior. Discussion: These findings illuminate the substantial effects that ethical leadership behaviors exert on employee performance and offer fresh perspectives on the intricate dynamics that govern this influence.

Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury.

Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to the myocardium. This phenomenon is known as myocardial ischemia-reperfusion injury (MIRI), which includes oxidative stress, inflammation, and further cell death. microRNA-146a (miR-146a) is known to play a significant role in regulating the immune response and inflammation, and has been studied for its potential impact on the improvement of heart function after myocardial injury. However, the delivery of miR-146a to the heart in a specific and efficient manner remains a challenge as extracellular RNAs are unstable and rapidly degraded. Milk exosomes (MEs) have been proposed as ideal delivery platform for miRNA-based therapy as they can protect miRNAs from RNase degradation. In this study, the effects of miR-146a containing MEs (MEs-miR-146a) on improvement of cardiac function were examined in a rat model of MIRI. To enhance the targeting delivery of MEs-miR-146a to the site of myocardial injury, the ischemic myocardium-targeted peptide IMTP was modified onto the surfaces, and whether the modified MEs-miR-146a could exert a better therapeutic role was examined by echocardiography, myocardial injury indicators and the levels of inflammatory factors. Furthermore, the expressions of miR-146a mediated NF-κB signaling pathway-related proteins were detected by western blotting and qRT-PCR to further elucidate its mechanisms. MiR-146 mimics were successfully loaded into the MEs by electroporation at a square wave 1000 V voltage and 0.1 ms pulse duration. MEs-miR-146a can be up-taken by cardiomyocytes and protected the cells from oxygen glucose deprivation/reperfusion induced damage in vitro. Oral administration of MEs-miR-146a decreased myocardial tissue apoptosis and the expression of inflammatory factors and improved cardiac function after MIRI. The miR-146a level in myocardium tissues was significantly increased after the administration IMTP modified MEs-miR-146a, which was higher than that of the MEs-miR-146a group. In addition, intravenous injection of IMTP modified MEs-miR-146a enhanced the targeting to heart, improved cardiac function, reduced myocardial tissue apoptosis and suppressed inflammation after MIRI, which was more effective than the MEs-miR-146a treatment. Moreover, IMTP modified MEs-miR-146a reduced the protein levels of IRAK1, TRAF6 and p-p65. Therefore, IMTP modified MEs-miR-146a exerted their anti-inflammatory effect by inhibiting the IRAK1/TRAF6/NF-κB signaling pathway. Taken together, our findings suggested miR-146a containing MEs may be a promising strategy for the treatment of MIRI with better outcome after modification with ischemic myocardium-targeted peptide, which was expected to be applied in clinical practice in future.

Designing Dual-Responsive Drug Delivery Systems: The Role of Phase Change Materials and Metal-Organic Frameworks.

Stimuli-responsive drug delivery systems (DDSs) offer precise control over drug release, enhancing therapeutic efficacy and minimizing side effects. This review focuses on DDSs that leverage the unique capabilities of phase change materials (PCMs) and metal-organic frameworks (MOFs) to achieve controlled drug release in response to pH and temperature changes. Specifically, this review highlights the use of a combination of lauric and stearic acids as PCMs that melt slightly above body temperature, providing a thermally responsive mechanism for drug release. Additionally, this review delves into the properties of zeolitic imidazolate framework-8 (ZIF-8), a stable MOF under physiological conditions that decomposes in acidic environments, thus offering pH-sensitive drug release capabilities. The integration of these materials enables the fabrication of complex structures that encapsulate drugs within ZIF-8 or are enveloped by PCM layers, ensuring that drug release is tightly controlled by either temperature or pH levels, or both. This review provides comprehensive insights into the core design principles, material selections, and potential biomedical applications of dual-stimuli responsive DDSs, highlighting the future directions and challenges in this innovative field.

Case report: a cataract induced by bleomycin in a patient with testicular cancer.

Background: Bleomycin is a glycopeptide antibiotic with outstanding anti-tumor effects. A major adverse effect of bleomycin is lung fibrosis. However, the development of cataracts as a severe adverse effect has not been reported. Case summary: Herein, we describe the first case of cataract induced by bleomycin therapy in a 22-year-old male with testicular cancer. After surgical intervention and following five successive chemotherapy cycles of the BEP regimen, including bleomycin, etoposide and cisplatin, the patient reported a gradual painless loss of vision, with substantial decline in visual ability, especially in the right eye. Following comprehensive eye examinations, a cataract was diagnosed. Eventually, the patient underwent phacoemulsification and received replacement of the intraocular lenses. Conclusion: Bleomycin can cause cataracts, which induces a significant loss of vision. Therefore, clinicians should observe early symptoms and properly adjust treatment to prevent aggravation of symptoms.

Degradation of Isotianil in Water and Soil: Kinetics, Degradation Pathways, Mechanisms, and Ecotoxicity Assessments.

Pesticides are transported and transformed in soil and can enter surface water through various pathways. They undergo hydrolysis, oxidation, and photoconversion in surface water. Isotianil is a new fungicide that effectively controls rice blast. However, there are limited reports on its degradation. Herein, the hydrolysis and photolysis of isotianil in water and its degradation in soil samples from five provinces of China were investigated. The degradation products of isotianil were identified using ultrahigh-performance liquid chromatography-Q exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry, and four compounds were discovered for the first time. The degradation pathways of isotianil were inferred, and the reaction active site and degradation mechanism of isotianil were clarified based on density functional theory calculations. The ecotoxicity of the degradation product M118 (aminobenzonitrile) was found to be moderate toward Daphnia magna, which was predicted and confirmed by Ecological Structure Activity Relationships and the experiment, respectively. The results of this study will contribute to a better understanding of the fate of isotianil in the environment.

Enhancing the Inhibition of Corneal Neovascularization Efficacy by Self-Assembled into Supramolecular Hydrogel of Anti-Angiogenic Peptide.

Background: Corneal neovascularization (CNV) is a common eye disease that leads to blindness. New treatment strategies are urgently needed due to the limitations of current treatment methods. Methods: We report the synthesis of peptide Nap-FFEEPCAIWF ( Comp.3 ) via chemical conjugation of Nap-FFEE ( Comp.2 ) to antiangiogenic peptide PCAIWF (Comp.1). Comp.3 self-assembled into a hydrogel ( gel of 3 ) composed of nanofibers, which enhanced the antiangiogenic function of the epitope. Results: We developed a novel peptide with an amphiphilic framework, Comp.3 , which could self-assemble into a supramolecular hydrogel with a well-ordered nanofiber structure. The nanofibers exhibited good biocompatibility with corneal epithelial cells, presenting a promising strategy to enhance the efficacy of free peptide-based drugs in the treatment of ocular vascular diseases, such as CNV and other angiogenesis-related diseases. Conclusion: Nap-FFEEPCAIWF nanofibers provide an alternative approach to enhancing the therapeutic efficiency of free peptide-based drugs against ocular vascular diseases.

Comprehensive evaluation of phosphate deficiency tolerance in common vetch germplasms and the adaption mechanism to phosphate deficiency.

Common vetch (Vicia sativa L.) is widely planted as forage, green manure and food. Phosphate (Pi) deficiency is an important constraint for legume crop production. In this study, P-deficiency tolerance in 40 common vetch collections was evaluated under hydroponic condition. The collections were clustered into three groups based on the tolerance level. Physiological responses to P-deficiency in two tolerant collections (418 and 426) in comparison with one sensitive collection (415) were investigated. Greater growth inhibition was observed in sensitive collection compared with two tolerant collections, although the inorganic phosphorus (P) content in sensitive collection was higher than those in tolerant collections. The internal and external purple acid phosphatase activity in plants showed no significant difference between 418 and 415 under low phosphate condition. Transcriptomic analysis in the tolerant collection 426 in response to Pi starvation showed that many common adaptive strategies were applied and PHOSPHATE STARVATION RESPONSE (PHR)-related Pi signaling and transporter genes were altered. VsPHT1.2 had the highest expression level in root among all VsPHT1s, and it was remarkably upregulated after short time of P-deficiency treatment in tolerant collections compared with sensitive collection. In conclusion, common vetch response to P starvation by altering the expressions of core genes involved in Pi transport and signaling, and the elevated expression of VsPHT1.2 gene might contribute to higher Pi acquisition efficiency in P-deficiency tolerant collections.

Integrated biomarker-based ecological risks assessment of tadpole responses to tris(2-chloroethyl) phosphate, tris(1-chloro-2-propyl) phosphate, and their combined environmental exposure.

Tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propyl) phosphate (TCPP) are common chlorinated organophosphorus flame retardants (OPFRs) used in industry. They have been frequently detected together in aquatic environments and associated with various hazardous effects. However, the ecological risks of prolonged exposure to these OPFRs at environmentally relevant concentrations in non-model aquatic organisms remain unexplored. This study investigated the effects of long-term exposure (up to 25 days) to TCEP and TCPP on metamorphosis, hepatic antioxidants, and endocrine function in Polypedates megacephalus tadpoles. Exposure concentrations were set at 3, 30, and 90 µg/L for each substance, conducted independently and in equal-concentration combinations, with a control group included for comparison. The integrated biomarker response (IBR) method developed an optimal linear model for predicting the overall ecological risks of TCEP and TCPP to tadpoles in potential distribution areas of Polypedates species. Results showed that: (1) Exposure to environmentally relevant concentrations of TCEP and TCPP elicited variable adverse effects on tadpole metamorphosis time, hepatic antioxidant enzyme activity and related gene expression, and endocrine-related gene expression, with their combined exposure exacerbating these effects. (2) The IBR value of TCEP was consistently greater than that of TCPP at each concentration, with an additive effect observed under their combined exposure. (3) The ecological risk of tadpoles exposed to the combined presence of TCEP and TCPP was highest in China's Taihu Lake and Vietnam's Hanoi than in other distribution locations. In summary, prolonged exposure to environmentally relevant concentrations of TCEP and TCPP presents potential ecological risks to amphibian tadpoles, offering insights for the development of policies and strategies to control TCEP and TCPP pollution in aquatic ecosystems. Furthermore, the methodology employed in establishing the IBR prediction model provides a methodological framework for assessing the overall ecological risks of multiple OPFRs.