Maintaining moderate levels of hypochlorous acid promotes neural stem cell proliferation and differentiation in the recovery phase of stroke.

JOURNAL/nrgr/04.03/01300535-202503000-00029/figure1/v/2024-06-17T092413Z/r/image-tiff It has been shown clinically that continuous removal of ischemia/reperfusion-induced reactive oxygen species is not conducive to the recovery of late stroke. Indeed, previous studies have shown that excessive increases in hypochlorous acid after stroke can cause severe damage to brain tissue. Our previous studies have found that a small amount of hypochlorous acid still exists in the later stage of stroke, but its specific role and mechanism are currently unclear. To simulate stroke in vivo, a middle cerebral artery occlusion rat model was established, with an oxygen-glucose deprivation/reoxygenation model established in vitro to mimic stroke. We found that in the early stage (within 24 hours) of ischemic stroke, neutrophils produced a large amount of hypochlorous acid, while in the recovery phase (10 days after stroke), microglia were activated and produced a small amount of hypochlorous acid. Further, in acute stroke in rats, hypochlorous acid production was prevented using a hypochlorous acid scavenger, taurine, or myeloperoxidase inhibitor, 4-aminobenzoic acid hydrazide. Our results showed that high levels of hypochlorous acid (200 µM) induced neuronal apoptosis after oxygen/glucose deprivation/reoxygenation. However, in the recovery phase of the middle cerebral artery occlusion model, a moderate level of hypochlorous acid promoted the proliferation and differentiation of neural stem cells into neurons and astrocytes. This suggests that hypochlorous acid plays different roles at different phases of cerebral ischemia/reperfusion injury. Lower levels of hypochlorous acid (5 and 100 µM) promoted nuclear translocation of ß-catenin. By transfection of single-site mutation plasmids, we found that hypochlorous acid induced chlorination of the ß-catenin tyrosine 30 residue, which promoted nuclear translocation. Altogether, our study indicates that maintaining low levels of hypochlorous acid plays a key role in the recovery of neurological function.

Targeted agents plus CHOP compared with CHOP as the first-line treatment for newly diagnosed patients with peripheral T-cell lymphoma (GUIDANCE-03): an open-label, multicentre phase 2 clinical trial.

Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes. We conducted an open-label, phase 2 nonrandomised, externally controlled study to evaluate the efficacy and safety of targeted agents plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) (CHOPX) for PTCL in the front-line setting. Methods: Eligible patients were ≥18 years of age and newly diagnosed PTCL. Patients in the CHOPX group received standard CHOP at Cycle 1. Specific targeted agents were added from Cycle 2, decitabine if TP53 mut, azacytidine if TET2/KMT2D mut, tucidinostat if CREBBP/EP300 mut, and lenalidomide if without mutations above. Patients in the CHOP group received CHOP for 6 cycles. The primary endpoint was the complete response rate (CRR) at the end of treatment (EOT). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov, NCT04480099. Findings: Between July 29, 2020, and Sep 22, 2022, 96 patients were enrolled and included for efficacy and safety analysis with 48 in each group. The study met its primary endpoint. CRR at EOT in the CHOPX group was superior to the CHOP group (64.6% vs. 33.3%, OR 0.27, 95%CI 0.12-0.64; p = 0.004). At a median follow-up of 24.3 months (IQR 12.0-26.7), improved median PFS was observed in the CHOPX group (25.5 vs. 9.0 months; HR 0.57, 95%CI 0.34-0.98; p = 0.041). The median OS was similar between two groups (not reached vs. 30.9 months; HR 0.55, 95%CI 0.28-1.10; p = 0.088). The most common grade 3-4 hematological and non-hematological adverse events in the CHOPX group were neutropenia (31, 65%) and infection (5, 10%). Interpretation: Targeted agents combined with CHOP demonstrated effective and safe as first-line treatment in PTCL. Biomarker-driven therapeutic strategy is feasible and may lead to promising efficacy specifically toward molecular features in PTCL. Funding: This study was supported by the National Key Research and Development Program (2022YFC2502600) and the General Program of the Shanghai Municipal Health Commission (202040400).

Heterologous Biosynthesis of Methanobactin from Methylocystis sp. Strain SB2 in Methylosinus trichosporium OB3b.

Aerobic methanotrophs, or methane-consuming microbes, are strongly dependent on copper for their activity. To satisfy this requirement, some methanotrophs produce a copper-binding compound, or chalkophore, called methanobactin (MB). In addition to playing a critical role in methanotrophy, MB has also been shown to have great promise in treating copper-related human diseases, perhaps most significantly Wilson's disease. In this congenital disorder, copper builds up in the liver, leading to irreversible damage and, in severe cases, complete organ failure. Remarkably, MB has been shown to reverse such damage in animal models, and there is a great deal of interest in upscaling MB production for expanded clinical trials. Such efforts, however, are currently hampered as (1) the natural rate of MB production rate by methanotrophs is low, (2) the use of methane as a substrate for MB production is problematic as it is explosive in air, (3) there is limited understanding of the entire pathway of MB biosynthesis, and (4) the most attractive form of MB is produced by Methylocystis sp. strain SB2, a methanotroph that is genetically intractable. Herein, we report heterologous biosynthesis of MB from Methylocystis sp. strain SB2 in an alternative methanotroph, Methylosinus trichosporium OB3b, not only on methane but also on methanol. As a result, the strategy described herein not only facilitates enhanced MB production but also provides opportunities to construct various mutants to delineate the entire pathway of MB biosynthesis, as well as the creation of modified forms of MB that may have enhanced therapeutic value.

Correlation and predictive value of pathological complete response and ultrasound characteristic parameters in neoadjuvant chemotherapy for breast.

BACKGROUND: Breast cancer ranks as one of the most prevalent malignant tumors among women, significantly endangering their health and lives. While radical surgery has been a pivotal method for halting disease progression, it alone is insufficient for enhancing the quality of life for patients. AIM: To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy (NAC). METHODS: Employing a case-control study design, this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022. According to the Miller-Payne grading system, the pathological response, i.e. efficacy, of the NAC in the initial breast lesion after NAC was evaluated. Of these, 59 patients achieved a pathological complete response (PCR), while 119 did not (non-PCR group). Ultrasound characteristics prior to NAC were compared between these groups, and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches. RESULTS: In the PCR group, the incidence of posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II were significantly lower compared to the non-PCR group (P < 0.05). The area under the curve values for predicting NAC efficacy using posterior echo attenuation, lesion diameter, and Alder grade were 0.604, 0.603, and 0.583, respectively. Also, rates of pathological stage II, lymph node metastasis, vascular invasion, and positive Ki-67 expression were significantly lower in the PCR group (P < 0.05). Logistic regression analysis identified posterior echo attenuation, lesion diameter ≥ 2.0 cm, Alder blood flow grade ≥ II, pathological stage III, vascular invasion, and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients (P < 0.05). CONCLUSION: While ultrasound characteristics such as posterior echo attenuation, lesion diameter ≥ 2.0 cm, and Alder blood flow grade ≥ II exhibit limited predictive value for NAC efficacy, they are significantly associated with poor response to NAC in breast cancer patients.

Micropeptide MPM regulates cardiomyocyte proliferation and heart growth via the AKT pathway.

The role of micropeptide in cardiomyocyte proliferation remains unknown. We found that MPM (micropeptide in mitochondria) was highly expressed in cardiomyocytes. Compared to MPM+/+ mice, MPM knockout (MPM-/-) mice exhibited reduction in left ventricular (LV) mass, myocardial thickness and LV fractional shortening. RNA-sequencing analysis in H9c2, a rat cardiomyocyte cell line, identified downregulation of cell cycle-promoting genes as the most significant alteration in MPM-silencing cells. Consistently, gain- and loss-of-function analyses in H9c2 cells revealed that cardiomyocyte proliferation was repressed by silencing MPM but was promoted by overexpressing MPM. Moreover, the cardiomyocytes in the hearts of MPM-/- mice displayed reduced proliferation rates. Mechanism investigations disclosed that MPM is crucial for AKT activation in cardiomyocytes. We also identified an interaction between MPM and PTPMT1, and found that silencing PTPMT1 attenuated the effect of MPM in activating the AKT pathway, whereas inhibition of the AKT pathway abrogated the role of MPM in promoting cardiomyocyte proliferation. Collectively, these results indicate that MPM may promote cardiomyocyte proliferation and thus heart growth by interacting with PTPMT1 to activate the AKT pathway. Our findings identify the novel function and regulatory network of MPM and highlight the importance of micropeptides in cardiomyocyte proliferation and heart growth.

A multicenter study on deep learning for glioblastoma auto-segmentation with prior knowledge in multimodal imaging.

A precise radiotherapy plan is crucial to ensure accurate segmentation of glioblastomas (GBMs) for radiation therapy. However, the traditional manual segmentation process is labor-intensive and heavily reliant on the experience of radiation oncologists. In this retrospective study, a novel auto-segmentation method is proposed to address these problems. To assess the method's applicability across diverse scenarios, we conducted its development and evaluation using a cohort of 148 eligible patients drawn from four multicenter datasets and retrospective data collection including noncontrast CT, multisequence MRI scans, and corresponding medical records. All patients were diagnosed with histologically confirmed high-grade glioma (HGG). A deep learning-based method (PKMI-Net) for automatically segmenting gross tumor volume (GTV) and clinical target volumes (CTV1 and CTV2) of GBMs was proposed by leveraging prior knowledge from multimodal imaging. The proposed PKMI-Net demonstrated high accuracy in segmenting, respectively, GTV, CTV1, and CTV2 in an 11-patient test set, achieving Dice similarity coefficients (DSC) of 0.94, 0.95, and 0.92; 95% Hausdorff distances (HD95) of 2.07, 1.18, and 3.95 mm; average surface distances (ASD) of 0.69, 0.39, and 1.17 mm; and relative volume differences (RVD) of 5.50%, 9.68%, and 3.97%. Moreover, the vast majority of GTV, CTV1, and CTV2 produced by PKMI-Net are clinically acceptable and require no revision for clinical practice. In our multicenter evaluation, the PKMI-Net exhibited consistent and robust generalizability across the various datasets, demonstrating its effectiveness in automatically segmenting GBMs. The proposed method using prior knowledge in multimodal imaging can improve the contouring accuracy of GBMs, which holds the potential to improve the quality and efficiency of GBMs' radiotherapy.

Bioinspired molecular catalysts with a unique tricopper architecture for highly efficient oxygen reduction reaction.

In situ growth of intertwined trinuclear copper complexes (nCu3) on a cellulose-derived carbon support (CMC) produced a high-performance electrocatalyst (CMC-nCu3) for the oxygen reduction reaction (ORR), which demonstrated superior performance in zinc-air batteries compared to a commercial Pt/C catalyst. This work highlights the importance of copper-based molecular catalysts with rich and intertwined tricopper structures for boosting both ORR activity and stability.

Convergent synthesis of glycoalkaloids solasonine and its saponin derivative.

We present a practical and convergent synthesis of glycoalkaloids solasonine 1 and its saponin derivative 2, incorporating a {3-O-α-L-rhamnopyranosyl-(1→2)-O-[ß-D-glucopyranosyl-(1→3)]-ß-D-galactopyranoside} moiety. The key features of this strategy include the following: (1) AuCl3-tBuCN cooperative catalysis enabling 1,2-trans stereoselective glycosidation of 2-branched trisaccharide trichloroacetimidate donors with steroidal aglycons, in the absence of neighboring group participation; (2) "cyanide effect" mediated regioselective benzoylation of the 4- and 6-hydroxyl groups of galactopyranosyl disaccharide; and (3) an effective approach to prevent orthoester byproduct formation.

The tandem CD33-CLL1 CAR-T as an approach to treat acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is characterized by high heterogeneity, poor long-term survival, and a propensity for relapse. Exceptional efficacy in treating recurrent or refractory B-lymphoid malignancies has been demonstrated by Chimeric antigen receptor T cells (CAR-T cells). Given the therapeutic potential of targeting both CD33 and C-type lectin-like molecule-1 (CLL1) in AML, the development of a dual-targeting CD33-CLL1 CAR-T cells assumes significant importance. MATERIALS AND METHODS: The expressions of CD33 and CLL-1 antigens in peripheral blood cells and bone marrow cells from AML patients was assessed. Subsequently, a Chimeric Antigen Receptor (CAR) incorporating a dual-specific single-chain variable fragment targeting CLL1 and CD33 (CD33-CLL1-CAR-T) was engineered. The anti-tumor efficacy and potential side effects of CD33-CLL1-CAR-T cells were comprehensively investigated in both in vitro and in vivo settings. RESULTS: The constructed tandem CD33-CLL1 CAR-T exhibited potent cytotoxicity against leukemia cell lines and human primary AML cells in vitro. Co-cultivation of AML blasts with CD33-CLL1-CAR-T cells resulted in effective proliferation and the secretion of substantial quantities of GM-CSF and IFN-γ. Importantly, the impact of CD33-CLL1-CAR-T cells on normal hematopoietic stem cells was minimal, ensuring safety in vivo mouse models. Notably, significant anti-leukemic activity was observed in the mouse model, with CD33-CLL1-CAR-T cells leading to tumor eradication and prolonged survival. DISCUSSION: The tandem CD33-CLL1 CAR-T cells not only efficiently eliminated AML blasts but also exhibited low cytotoxicity toward normal hematopoietic stem cells (HSCs). These findings underscore the potential clinical applicability of the tandem CD33-CLL1 CAR-T cells as an effective and safe treatment strategy for AML, representing a noteworthy advancement in the field of CAR-T cells therapy.

KMT2D mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-induced regulatory T cell trafficking via FBXW7-NOTCH-MYC/TGF-ß1 axis.

Histone methyltransferase KMT2D is one of the most frequently mutated genes in diffuse large B-cell lymphoma (DLBCL) and has been identified as an important pathogenic factor and prognostic marker. However, the biological relevance of KMT2D mutations on tumor microenvironment remains to be determined. KMT2D mutations were assessed by whole-genome/exome sequencing (WGS/WES) in 334 patients and by targeted sequencing in 427 patients with newly diagnosed DLBCL. Among all 761 DLBCL patients, somatic mutations in KMT2D were observed in 143 (18.79%) patients and significantly associated with advanced Ann Arbor stage and MYC expression ≥ 40%, as well as inferior progression-free survival and overall survival. In B-lymphoma cells, the mutation or knockdown of KMT2D inhibited methylation of lysine 4 on histone H3 (H3K4), downregulated FBXW7 expression, activated NOTCH signaling pathway and downstream MYC/TGF-ß1, resulting in alterations of tumor-induced regulatory T cell trafficking. In B-lymphoma murine models established with subcutaneous injection of SU-DHL-4 cells, xenografted tumors bearing KMT2D mutation presented lower H3K4 methylation, higher regulatory T cell recruitment, thereby provoking rapid tumor growth compared with wild-type KMT2D via FBXW7-NOTCH-MYC/TGF-ß1 axis.

Enhancing Multichannel Fiber Optic Sensing Systems with IFFT-DNN for Remote Water Level Monitoring.

This paper proposes a novel approach to enhance the multichannel fiber optic sensing systems by integrating an Inverse Fast Fourier Transform-based Deep Neural Network (IFFT-DNN) to accurately predict sensor responses despite signals overlapping and crosstalk between sensors. The IFFT-DNN leverages both frequency and time domain information, enabling a comprehensive feature extraction which enhances the prediction accuracy and reliability performance. To investigate the IFFT-DNN's performance, we propose a multichannel water level sensing system based on Free Space Optics (FSO) to measure the water level at multiple points in remote areas. The experimental results demonstrate the system's high precision, with a Mean Absolute Error (MAE) of 0.07 cm, even in complex conditions. Hence, this system provides a cost-effective and reliable remote water level sensing solution, highlighting its practical applicability in various industrial settings.

A comprehensive study on three typical photoacid generators using photoelectron spectroscopy and ab initio calculations.

Conducting a comprehensive molecular-level evaluation of a photoacid generator (PAG) and its subsequent impact on lithography performance can facilitate the rational design of a promising 193 nm photoresist tailored to specific requirements. In this study, we integrated spectroscopy and computational techniques to meticulously investigate the pivotal factors of three prototypical PAG anions, p-toluenesulfonate (pTS-), 2-(trifluoromethyl)benzene-1-sulfonate (TFMBS-), and triflate (TF-), in the lithography process. Our findings reveal a significant redshift in the absorption spectra caused by specific PAG anions, attributed to their involvement in electronic transition processes, thereby enhancing the transparency of the standard PAG cation, triphenylsulfonium (TPS+), particularly at ∼193 nm. Furthermore, the electronic stability of PAG anions can be enhanced by solvent effects with varying degrees of strength. We observed the lowest vertical detachment energy of 6.6 eV of pTS- in PGMEA solution based on the polarizable continuum model, which prevents anion loss at 193 nm lithography. In addition, our findings indicate gas-phase proton affinity values of 316.4 kcal/mol for pTS-, 308.1 kcal/mol for TFMBS-, and 303.2 kcal/mol for TF-, which suggest the increasing acidity strength, yet even the weakest acid pTS- is still stronger than strong acid HBr. The photolysis of TPS+-based PAG, TPS+·pTS-, generated an excited state leading to homolysis bond cleavage with the lowest reaction energy of 83 kcal/mol. Overall, the PAG anion pTS- displayed moderate acidity, possessed the lowest photolysis reaction energy, and demonstrated an appropriate redshift. These properties collectively render it a promising candidate for an effective acid producer.

Preoperative computed tomography-guided localization for pulmonary nodules: comparison between hook-wire and anchored needle localization.

Introduction: Both hook-wire (HW) and anchored needle (AN) techniques can be used for preoperative computed tomography (CT)-guided localization for pulmonary nodules (PNs). But the outcomes associated with these two materials remain unclear. Aim: To assess the relative safety and efficacy of preoperative CT-guided HW and AN localization for PNs. Material and methods: This was a retrospective analysis of data collected from two institutions. Consecutive patients with PNs between January 2020 and December 2021 who underwent preoperative CT-guided HW or AN localization followed by video-assisted thoracoscopic surgery (VATS) procedures were included in these analyses, which compared the safety and clinical efficiency of these two localization strategies. Results: In total, 98 patients (105 PNs) and 93 patients (107 PNs) underwent CT-guided HW and AN localization procedures, respectively. The HW and AN groups exhibited similar rates of successful PN localization (95.2% vs. 99.1%, p = 0.117), but the dislodgement rate in the HW group was significantly higher than that for the AN group (4.8% vs. 0.0%, p = 0.029). The mean pain score of patients in the HW group was significantly higher than that for the AN group (p = 0.001). HW and AN localization strategies were associated with comparable pneumothorax (21.4% vs. 16.1%, p = 0.349) and pulmonary hemorrhage (29.6% vs. 23.7%, p = 0.354) rates. All patients other than 1 individual in the HW group successfully underwent VATS-guided limited resection. Conclusions: These data suggest that AN represents a safe, well-tolerated, feasible preoperative localization strategy for PNs that may offer value as a replacement for HW localization.

The predictors of fungal infections after liver transplantation and the influence of fungal infections on outcomes.

The primary objective of this study was to assess the incidence, timing, risk factors of fungal infections (FIs) within 3 months after liver transplantation (LT). The secondary objective was to evaluate the impact of FIs on outcomes. Four hundred and ten patients undergoing LT from January 2015 until January 2023 in a tertiary university hospital were included in the present retrospective cohort study to investigate the risk factors of FIs and to assess the impacts of FIs on the prognosis of LT recipients using logistic regression. The incidence of FIs was 12.4% (51/410), and median time from LT to the onset of FIs was 3 days. By univariate analysis, advanced recipient age, prolonged hospital stay prior to LT, high Model for End Stage Liver Disease (MELD) score, use of broad-spectrum antibiotics, and elevated white blood cell (WBC) count, increased operating time, massive blood loss and red blood cell transfusion, elevated alanine aminotransferase on day 1 and creatinine on day 3 after LT, prolonged duration of urethral catheter, prophylactic antifungal therapy, the need for mechanical ventilation and renal replacement therapy were identified as factors of increased post-LT FIs risk. Multivariate logistic regression analysis identified that recipient age ≥ 55 years[OR = 2.669, 95%CI: 1.292-5.513, P = 0.008], MELD score at LT ≥ 22[OR = 2.747, 95%CI: 1.274-5.922, P = 0.010], pre-LT WBC count ≥ 10 × 109/L[OR = 2.522, 95%CI: 1.117-5.692, P = 0.026], intraoperative blood loss ≥ 3000 ml [OR = 2.691, 95%CI: 1.262-5.738, P = 0.010], post-LT duration of urethral catheter > 4 d [OR = 3.202, 95%CI: 1.553-6.602, P = 0.002], and post-LT renal replacement therapy [OR = 5.768, 95%CI: 1.822-18.263, P = 0.003] were independently associated with the development of post-LT FIs. Post-LT prophylactic antifungal therapy ≥ 3 days was associated with a lower risk of the development of FIs [OR = 0.157, 95%CI: 0.073-0.340, P < 0.001]. As for clinical outcomes, FIs had a negative impact on intensive care unit (ICU) length of stay ≥ 7 days than those without FIs [OR = 3.027, 95% CI: 1.558-5.878, P = 0.001] but had no impact on hospital length of stay and 1-month all-cause mortality after LT. FIs are frequent complications after LT and the interval between the onset of FIs and LT was short. Risk factors for post-LT FIs included high MELD score at LT, advanced recipient age, pre-LT WBC count, massive intraoperative blood loss, prolonged post-LT duration of urethral catheter, and the need for post-LT renal replacement therapy. However, post-LT prophylactic antifungal therapy was independently associated with the reduction in the risk of FIs. FIs had a significant negative impact on ICU length of stay.

Pro-survival signaling regulates lipophagy essential for multiple myeloma resistance to stress-induced death.

Pro-survival metabolic adaptations to stress in tumorigenesis remain less well defined. We find that multiple myeloma (MM) is unexpectedly dependent on beta-oxidation of long-chain fatty acids (FAs) for survival under both basal and stress conditions. However, under stress conditions, a second pro-survival signal is required to sustain FA oxidation (FAO). We previously found that CD28 is expressed on MM cells and transduces a significant pro-survival/chemotherapy resistance signal. We now find that CD28 signaling regulates autophagy/lipophagy that involves activation of the Ca2+→AMPK→ULK1 axis and regulates the translation of ATG5 through HuR, resulting in sustained lipophagy, increased FAO, and enhanced MM survival. Conversely, blocking autophagy/lipophagy sensitizes MM to chemotherapy in vivo. Our findings link a pro-survival signal to FA availability needed to sustain the FAO required for cancer cell survival under stress conditions and identify lipophagy as a therapeutic target to overcome treatment resistance in MM.

Structural characteristics of cell wall pectic polysaccharides from wampee and their decreased binding with pectinase by wampee polyphenol.

To investigate the structural characteristics of cell wall pectic polysaccharides from wampee, water soluble pectin (WSP), chelator-soluble pectin (CSP) and sodium carbonate-soluble pectin (SSP) were purified. And the inhibitory effects of wampee polyphenol (WPP) on pectinase when these cell wall pectic polysaccharides were used as substrates were also explored. Purified WSP (namely PWSP) had the lowest molecular weight (8.47 × 105 Da) and the highest GalA content (33.43%). While purified CSP (called PCSP) and SSP contained more abundant rhamnogalacturonan I side chains. All of them were low-methoxy pectin (DE < 50%). Enzyme activity and kinetics analysis showed that the inhibition of pectinase by wampee polyphenol was reversible and mixed type. When SSP was used as the substrate, WPP had the strongest inhibition (IC50 = 1.96 ± 0.06 mg/mL) on pectinase. Fluorescence quenching results indicated that WPP inhibited enzyme activity by interacting with substrates and enzymes. Therefore, WPP has the application potential in controlling softening of fruits and vegetables.

Immunological characteristics of a recombinant alphaherpesvirus with an envelope-embedded Cap protein of circovirus.

Introduction: Variant pseudorabies virus (PRV) is a newly emerged zoonotic pathogen that can cause human blindness. PRV can take advantage of its large genome and multiple non-essential genes to construct recombinant attenuated vaccines carrying foreign genes. However, a major problem is that the foreign genes in recombinant PRV are only integrated into the genome for independent expression, rather than assembled on the surface of virion. Methods: We reported a recombinant PRV with deleted gE/TK genes and an inserted porcine circovirus virus 2 (PCV2) Cap gene into the extracellular domain of the PRV gE gene using the Cre-loxP recombinant system combined with the CRISPR-Cas9 gene editing system. This recombinant PRV (PRV-Cap), with the envelope-embedded Cap protein, exhibits a similar replication ability to its parental virus. Results: An immunogenicity assay revealed that PRV-Cap immunized mice have 100% resistance to lethal PRV and PCV2 attacks. Neutralization antibody and ELISPOT detections indicated that PRV-Cap can enhance neutralizing antibodies to PRV and produce IFN-γ secreting T cells specific for both PRV and PCV2. Immunological mechanistic investigation revealed that initial immunization with PRV-Cap stimulates significantly early activation and expansion of CD69+ T cells, promoting the activation of CD4 Tfh cell dependent germinal B cells and producing effectively specific effector memory T and B cells. Booster immunization with PRV-Cap recalled the activation of PRV-specific IFN-γ+IL-2+CD4+ T cells and IFN-γ+TNF-α+CD8+ T cells, as well as PCV2-specific IFN-γ+TNF-α+CD8+ T cells. Conclusion: Collectively, our data suggested an immunological mechanism in that the recombinant PRV with envelope-assembled PCV2 Cap protein can serve as an excellent vaccine candidate for combined immunity against PRV and PCV2, and provided a cost-effective method for the production of PRV- PCV2 vaccine.

Exploring Geometric Chirality in Nanocrystals for Boosting Solar-to-Hydrogen Conversion.

Advancing catalyst design is pivotal for the enhancement of photocatalytic processes in renewable energy conversion. The incorporation of structural chirality into conventional inorganic solar hydrogen nanocatalysts promises a significant transformation in catalysis, a feature absent in this field. Here we unveil the unexplored potential of geometric chirality by creating a chiral composite that integrates geometric chiral Au nanoparticles (NPs) with two-dimensional C3N4 nanosheets, significantly boosting photocatalytic H2 evolution beyond the achiral counterparts. The superior performance is driven by the geometric chirality of Au NPs, which facilitates efficient charge carrier separation through the favorable C3N4-chiral Au NP interface and chiral induced spin polarization, and exploits high-activity facets within the concave surfaces of chiral Au NPs. The resulting synergistic effect leads to a remarkable increase in photocatalytic H2 evolution, with an apparent quantum yield of 44.64% at 400 nm. Furthermore, we explore the selective polarized photo-induced carrier separation behavior, revealing a distinct chiral-dependent photocatalytic HER performance. Our work advances the design and utilization of chiral inorganic nanostructures for superior performance in energy conversion processes.