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Numerous diseases, such as diabetic retinopathy and age-related macular degeneration, can lead to retinal neovascularization, which can seriously impair the visual function and potentially result in blindness. The presence of the blood-retina barrier makes it challenging for ocularly administered drugs to penetrate physiological barriers and reach the ocular posterior segments, including the retina and choroid. Herein, we developed an innovative bifunctional peptide, Tat-C-RP7, which exhibits excellent penetration capabilities and antiangiogenic properties aimed at treating retinal neovascularization diseases. RP7 is an NRP-1 targeting peptide that blocks vascular endothelial growth factor receptor-2 (VEGFR-2) signaling and inhibits angiogenesis, while Tat facilitates the delivery of various cargoes across biological barriers, such as the blood-retina barrier. By combining these attributes, Tat-C-RP7 is anticipated to traverse ocular barriers via ocular topical administration and exert its antiangiogenic effects in the ocular posterior segment. Experimental results demonstrated that Tat-C-RP7 significantly inhibited the proliferation and migration of rat retinal microvascular endothelial cells and effectively reduced tubule formation in vitro . Its antiangiogenic activity was confirmed in zebrafish. The outstanding penetrative capabilities of FITC-labeled Tat-C-RP7 have been validated through cell uptake assays, in vitro cell barrier models, ex-vivo ocular tissues, and in vivo studies. Besides, the half-life of Tat-C-RP7 was longer than that of RP7. In an oxygen-induced retinopathy model, Tat-C-RP7 was shown to reduce the area of angiogenesis following ocular administration. Additionally, it produced no irritating effects on the eyes of rabbits. Overall, Tat-C-RP7 demonstrates excellent ocular penetrability and antiangiogenic effects and represents a promising therapeutic option for treating retinal neovascularization diseases.

Bacterial keratitis (BK) is a type of corneal inflammation resulting from bacterial infection in the eye. Although nanozymes have been explored as promising materials in corneal wound healing, currently available nanozymes lack sufficient catalytic activity and the ability to penetrate bacterial biofilms, limiting their efficacy against the treatment of BK. To remedy this, ZnFe layered double hydroxide (ZnFe-LDH) nanosheets are loaded with Cu single-atom nanozymes (Cu-SAzymes) and aminated dextran (Dex-NH 2 ), resulting in the formation of the nanozyme DT-ZnFe-LDH@Cu, which possesses peroxidase (POD)-, oxidase (OXD)-, and catalase (CAT)-like catalytic activities. This enables the nanozyme to generate reactive oxygen species (ROS), such as hydroxyl radicals ( • OH), superoxide anion radical (O 2 •- ), and singlet oxygen ( 1 O 2 ) from hydrogen peroxide (H 2 O 2 ), thereby killing the bacteria causing the infections. The surface Dex-NH 2 enabled the DT-ZnFe-LDH@Cu to penetrate the biofilm and adsorb onto extracellular polymeric substances (EPS) produced by bacteria in the biofilm. Additionally, the DT-ZnFe-LDH@Cu successfully repaired P. aeruginosa-infected corneal injury in a BK rabbit model more effectively than commercially available tobramycin eye drops. This was enabled, in part, by the ability of DT-ZnFe-LDH@Cu to reduce inflammation by promoting the polarization of pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2) and decrease the expression of α-smooth muscle actin (α-SMA) to promote wound healing without scar formation. This study provides an innovative concept for the treatment of BK and holds great scientific value and clinical application potential., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Tumor cells transmit various immunosuppressive signals and induce a dysfunctional state in T cells, which essentially leads to immune escape and tumor progression. However, developing effective strategies to counteract the domestication of T cells by tumor cells remains a challenge. Here, we prepared pH-responsive lipid nanoparticles (NL/PLDs) co-loaded with PCSK9 shRNA, lonidamine (LND), and low-dose doxorubicin (DOX). NL/PLDs can awaken domesticated T cells function by sending pro-activation, pro-recognition, and pro-killing signals by increasing tumor immunogenicity, increasing the expression of major histocompatibility complex I (MHC-I) on tumor cells, and alleviating the suppression effect of tumor-secreted lactic acid (LA) on the T cell effector function, respectively. In melanoma-bearing mice, NL/PLDs effectively relieved tumor immunosuppressive microenvironment (TIME) and enhanced the antitumor immunity mediated by CD8 + T cells. Furthermore, when combined with aPD-1, NL/PLDs demonstrated strong antitumor effects and increased immunotherapeutic efficacy. This regulatory strategy provides new insights for enhancing immunotherapy by regulating tumor immunosuppressive signals and shows significant potential for clinical tumor treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Although evidence has been presented for desalination potentials in single-walled carbon nanotubes (SWCNTs), it is still very challenging to overcome the trade-off between ion selectivity and water permeability by simply tuning the carbon nanotube (CNT) size. In this work, we prove that double-walled carbon nanotubes (DWCNTs) can make it. Employing a series of molecular dynamics simulations, we find a striking phenomenon that tuning the combination architecture of DWCNTs can significantly improve the desalination performance, with the salt rejection rate even reaching 100% in some cases while maintaining high levels of water flux. Specifically, under a certain outer CNT (20,20), with the increase in inner CNT radius, the salt rejection rate reaches a maximum for the CNT (9,9), attributed to the small size of the inner CNT and the space between the two CNT walls that significantly impedes the ion passage; however, it still allows the passage of massive water. Furthermore, as the pressure difference increases, the water flux greatly increases, while the salt rejection rate only slightly decreases for the CNTs (8,8) and (9,9), effectively addressing the trade-off between ion selectivity and water permeability. As a result, optimizing the architecture of DWCNTs should be an effective strategy for designing an efficient desalination membrane, which is still a challenge for SWCNTs.

Background: The immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect., Methods: In this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained., Results: The immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet β-cells was increased, and the maturity of the new islet β-cells was increased. The immunogenicity of new islet β-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site., Conclusions: New islet β-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect., Competing Interests: Declarations. Ethics approval and consent to participate: The study is reported in accordance with ARRIVE guidelines ( https://arriveguidelines.org ). All of the dogs were reared, obtained, and housed in accordance with our institute’s laboratory animal requirements. All procedures and the study design were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (Ministry of Science and Technology of China, 2006) and were approved by the Animal Ethical and Welfare Committee of Northwest Agriculture and Forest University (Title of the approved project: Study on anti-graft rejection effect and mechanism of canine gene-edited MSCs and their differentiated cells. Date of approval: September 17, 2022. Approval No: 20220182). No human cells/tissues/samples/cell lines were used in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Heterogeneous cobalt-based catalysts are highly effective in activing peroxymonosulfate (PMS) and produce free radicals to deal with recalcitrant organic pollutants in water. However, unfeasible recyclability and gradual performance degradation remain challenging due to the easy agglomeration and leaching of active cobalt species. Herein, a strategy is proposed to construct stably anchored and highly dispersed Co 2+ sites on dual functional sulfonated covalent organic frameworks (COF-Co). The sulfonic acid groups are able to realize the targeted binding with cobalt ions through a two-step cation-exchange method, leading to strong combination with active Co 2+ sites and utmost utilization efficiencies. Moreover, the super-hydrophility of sulfonic acid groups favors the rapid accessibility of organic molecules to the catalyst and accelerates the degradation. Remarkably, COF-Co exhibits high activity in PMS activation, effective oxidation for tetracycline degradation (92% within 30 min at 30 mg L -1 ) and other coloring contaminants, and excellent recycle stability. This work can guide the rational design of efficient and environmentally friendly PMS-activated catalyst with great potential for application in wastewater treatment., (© 2024 Wiley‐VCH GmbH.)

Cytokine release syndrome (CRS) can occur following cancer immunotherapies, but is most often mild and of limited duration. International Classification of Diseases (ICD)-10 codes allowing identification of CRS were introduced in 2020 but may be underutilized. We evaluated the performance of a published claims-based algorithm to detect CRS (any grade) and high-grade CRS (HG, grades 2-5), as well as identified indicators of HG CRS in retrospective data. Adults with low-grade and HG CRS during an encounter coinciding with administrations of blinatumomab or chimeric antigen receptor-T therapy were identified in three types of retrospective databases (hospital chargemaster data, electronic health records, and administrative claims). The algorithm's sensitivity in detecting any CRS and HG CRS was reported. A least absolute shrinkage and selection operator (LASSO) regression model was developed to identify indicators of HG CRS. Performance of the model was evaluated using area under the curve (AUC). The sensitivity of the algorithm to detect any grade CRS ranged between 77%-100% and between 8%-80% for HG CRS, depending on the type of database. The LASSO model identified hypotension, positive pressure (including mechanical ventilation), tocilizumab, and vasopressors as indicators of HG CRS. AUC varied between 60% and 75%. The algorithm accurately detected any grade CRS for over three-quarters of instances, but was not as reliable for HG CRS. Results varied based on database attributes. Hypotension, vasopressors, positive pressure, and tocilizumab were associated with HG CRS and may be methodologically helpful signals of CRS severity in retrospective data., (© 2024 Janssen Scientific Affairs, LLC. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Photodynamic therapy is an efficient approach to promote cytotoxic T lymphocyte tumor infiltration to convert immunologically cold tumors into hot tumors through the induction of immunogenic cell death . However, tumors usually overexpress immune checkpoints such as PD-L1 to suppress T lymphocyte antitumor activity and evade immune surveillance. Therefore, the design of efficient photosensitizers to overcome checkpoint-mediated immune evasion is highly necessary. In this work, we report the design of BRD-PS , a BRD4-targeting photosensitizer, as a new class of immunomodulatory photosensitizer termed an immune checkpoint-modulating photosensitizer, to solve this issue. On one hand, BRD-PS induces immunogenic pyroptosis and ferroptosis to promote the activation and tumor infiltration of cytotoxic T cells. On the other hand, BRD-PS suppresses the expression of PD-L1 to avoid immune evasion. This work demonstrated the feasibility of utilizing a single photosensitizer to simultaneously induce immunogenic cell death and PD-L1 downregulation for synergistic cancer photoimmunotherapy.

Objectives: Recently, more and more evidences suggest that β-glucans can induce trained immunity and non-specific protections against pathogens. However, most of the reports evaluated the immunological activities of β-glucans through injection route but no nasal inhalation. In this study, the effects of curdlan sulfate-based nanoparticles, CS/O-HTCC on trained immunity through intranasal administration were evaluated., Methods: Macrophages were treated with CS/O-HTCC and the metabolisms of the macrophages were detected. Mice were intranasal administered with CS/O-HTCC for 3 times with a 14 days interval, then the antitumor or infection prevention effects were assessed., Results: In vitro, CS/O-HTCC enhanced the macrophage metabolism significantly through upregulating glycolysis (26.1 ± 4.3 mpH/min) and oxidative phosphorylation (36.0 ± 9.0 pmol/min) compared with that of negative group (7.5 ± 2.3 mpH/min and 19.5 ± 4.9 pmol/min). In vivo, CS/O-HTCC inhibited lung metastasis of B16F10 tumor cells and improved the survival time (26.5 days) of the nmice compared with negative group (19.5 days). Moreover, CS/O-HTCC prevented the lung infections by Escherichia coli or Streptococcus pneumoniae (less bacterial residual) and reduced lung damages., Conclusions: CS/O-HTCC can induce trained immunity through enhancing the metabolism of macrophages and enhance the non-specific protection against pathogens through intranasal immunization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o -nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors.)

Monomeric flavan-3-ols are important copigments in red wines, due to their superior copigmentation ability and high concentration. In this work, a systematic study was conducted on the copigmentation effects of eight common monomeric flavan-3-ols with malvidin-3-O-glucoside, using experimental and theoretical methods. The results revealed that the addition of a hydroxy group to the B ring and the attachment of a galloyl group at the 3-O position of monomeric flavan-3-ols both contributed to enhance copigmentation, with the latter exerting a more pronounced effect. Regarding stereoisomerism, it was observed that the cis-configuration of the B ring and 3-O-hydroxy group favored copigmentation. However, the cis-configuration of the B ring and 3-O-galloyl group was disadvantageous due to steric hindrance, in contrast to when these moieties occupied opposing sides (i.e., the 2,3-trans configuration). These results highlight the crucial role played by both substitution patterns and conformational arrangements in determining the copigmentation ability of monomeric flavan-3-ols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The surface wetting or coating of materials by polymers is crucial for designing functional interfaces and various industrial applications. However, the underlying mechanisms remain elusive. In this study, the wetting behavior of hydroxyl-terminated polybutadiene (HTPB) on a quartz surface was systematically investigated using computer simulation methods. A notable tip-dominant surface adsorption mode of HTPB was identified, where the hydroxyl group at the end of the polymer chain binds to the surface to initiate the wetting process. Moreover, it was found that with the increase in the degree of polymerization (e.g., from DP = 10 to 30), spontaneous adsorption of HTPB becomes increasingly difficult, with a three-fold increase in the adsorption time. These results suggest a competition mechanism between enthalpy (e.g., adhesion between the polymer and the surface) and entropy (e.g., conformational changes in polymer chains) that underlies the wetting behavior of HTPB. Based on this mechanism, two strategies were employed: altering the degree of polymerization of HTPB and/or regulating the amount of interfacial water molecules (e.g., above or below the threshold amount of 350 on a 10 × 10 nm 2 surface). These strategies effectively modulate HTPB's surface wetting process. This study provides valuable insights into the mechanisms underlying the surface adsorption behavior of HTPB and offers guidance for manipulating polymer wetting processes at interfaces., Competing Interests: The authors declare no conflicts of interest.

Background: The immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect., Methods: In this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained., Results: The immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet β-cells was increased, and the maturity of the new islet β-cells was increased. The immunogenicity of new islet β-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site., Conclusions: New islet β-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dai, Qi, Zhu, Du, Wang, Gao, Li, Feng and Zhang.)

Objective: Talquetamab is the first-in-class GPRC5DxCD3 bispecific antibody for relapsed/refractory multiple myeloma. Given limited real-world data, this study was conducted with US healthcare providers (HCPs) to understand real-world talquetamab dosing and symptom management., Methods: In February/March 2024, individual in-depth interviews (IDIs; n  = 10) were conducted with HCPs administering talquetamab in real-world settings. A subsequent expert panel ( n  = 6) further discussed current practices., Results: The IDIs reported a variety of settings for step-up dosing (SUD), including inpatient ( n  = 5), outpatient ( n  = 3), and hybrid models ( n  = 2), with a trend toward shorter SUD length to reduce healthcare resource utilization. Most HCPs used a biweekly (Q2W) schedule in SUD ( n  = 7) and treatment phases ( n  = 8). Six participants explored reducing dose frequency to every 4 weeks (Q4W) in patients following positive disease response to treatment, considering patient convenience and relieving GPRC5D-related symptoms. Panelists recommended symptom management and prophylactic strategies, such as dexamethasone and nystatin mouthwash or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms., Conclusion: This study outlines current real-world practices for talquetamab. Findings indicate variation in the SUD care setting. The 0.8 mg/kg Q2W dosing schedule was most common, although switching to Q4W is a real-world symptom management strategy for some patients with responses to therapy. GPRC5D-related symptom management approaches are evolving; prophylactic use of dexamethasone and nystatin mouthwash or zinc and vitamin B complex may be effective strategies to alleviate oral symptoms. Further real-world evidence is needed to inform optimal dosing schedules while mitigating symptom impact.

Cytotherapy is a strategy to deliver modified cells to a diseased tissue, but targeting solid tumours remains challenging. Here we design macrophages, harbouring a surface glypican-3-targeting peptide and carrying a cargo to combat solid tumours. The anchored targeting peptide facilitates tumour cell recognition by the engineered macrophages, thus enhancing specific targeting and phagocytosis of tumour cells expressing glypican-3. These macrophages carry a cargo of the TLR7/TLR8 agonist R848 and INCB024360, a selective indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, wrapped in C16-ceramide-fused outer membrane vesicles (OMV) of Escherichia coli origin (RILO). The OMVs facilitate internalization through caveolin-mediated endocytosis, and to maintain a suitable nanostructure, C16-ceramide induces membrane invagination and exosome generation, leading to the release of cargo-packed RILOs through exosomes. RILO-loaded macrophages exert therapeutic efficacy in mice bearing H22 hepatocellular carcinomas, which express high levels of glypican-3. Overall, we lay down the proof of principle for a cytotherapeutic strategy to target solid tumours and could complement conventional treatment., (© 2024. The Author(s).)

Background: The poor overall survival of osteosarcoma (OS) underscores the need to explore new therapeutic avenues. Tumor necrosis rate (TNR) after neoadjuvant chemotherapy predicts prognosis., Aims: The study was to investigate safety and activity of neoadjuvant chemotherapy with camrelizumab (a humanized antibody against PD-1) in patients with resectable OS., Materials & Methods: We conducted a prospective, single-arm, exploratory phase II trial in OS patients. Eligible patients received camrelizumab combined with doxorubicin or liposomal doxorubicin, cisplatin, methotrexate, ifosfamide with mesna. Surgery was performed 12-14 days after neoadjuvant therapy and adjuvant therapy starting 2-3 weeks postoperatively. The primary endpoint was the rate of good tumor necrosis (TNR ≥90%) after neoadjuvant therapy, and the secondary outcomes were safety, 2-year progression free survival and 2-year overall survival., Results: Seventy-five patients were recruited to the study. Subsequently, 64 patients completed neoadjuvant therapy and underwent surgery. Thirty-one patients (48.4%) have a good TNR to neoadjuvant therapy. With a median follow-up of 22.4 months (range 2.2-44.9 months), the estimated 2-year PFS was 69.6% and the estimated 2-year overall survival was 89.4%. Grade 3 or 4 treatment-related adverse events were noticed in 62.7% of the patients. Frequent grade 3 or 4 adverse events were decreased platelet count (45.3%), decreased white blood cell count (36%). No immune-related serious adverse events were observed., Discussion: Our study had limitations. First, it was limited by its non-randomized design. Besides, stromal tumor-infiltrating lymphocytes was comprehensively analyzed in this study., Conclusions: This study demonstrated that amrelizumab combined with adriamycin, cisplatin, methotrexate, and ifosfamide in the neoadjuvant treatment of resectable OS was safe and tolerable. This combined therapeutic strategy may not increase TNR, but the long-term survival benefit remains to be followed up., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Chitosan and its derivatives are ideal nasal vaccine adjuvant to deliver antigens to immune cells. Previously, we successfully used a chitosan derivative, O-(2-Hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (O-HTCC), and a β-glucan derivative, curdlan sulfate (CS), to prepare a nanoparticle adjuvant CS/O-HTCC which could deliver ovalbumin to antigen presenting cells (APCs) through nasal inhalation. In this article, we used SARS-CoV-2 spike receptor binding domain (S-RBD) as the antigen and CS/O-HTCC nanoparticles as the adjuvant to develop a nasal mucosal protein subunit vaccine, CS/S-RBD/O-HTCC. The humoral immunity, cell-mediated immunity and mucosal immunity induced by vaccines were evaluated. The results showed that CS/S-RBD/O-HTCC could induce desirable immunization with single or bivalent antigen through nasal inoculation, giving one booster vaccination with mutated S-RBD (beta) could bring about a broad cross reaction with ancestral and different mutated S-RBD, and vaccination of the BALB/c mice with CS/S-RBD/O-HTCC containing S-RBD mix antigens (ancestral and omicron) could induce the production of binding and neutralizing antibodies against both of the two antigens. Our results indicate that CS/O-HTCC is a promising nasal mucosal adjuvant to prepare protein subunit vaccine for both primary and booster immunization, and the adjuvant is suitable for loading more than one antigen for preparing multivalent vaccines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tartaric acid is one of the characteristic acids in wine, playing a crucial role in wine characteristics. However, superabundant tartaric acid will form insoluble salts and precipitate in the form of crystals, affecting consumers' purchasing appetite. Therefore, tartaric stability is also one of the important indices for controlling the wine quality. At present, the main processing methods for tartaric stability include cold stabilization, ion exchange treatment, electrodialysis and the addition of exogenous components (gum arabic, metatartaric acid, carboxymethyl cellulose, mannoprotein and potassium polyaspartate). This review summarizes and analyzes the origin of tartaric acid in wine, factors influencing the tartaric stability, detection methods, treatments for tartaric stabilization, and the effects of these methods on the sensory quality of wine. Comparing the effects of these methods on wine quality can provide a basis for the further study of tartaric stabilization methods in order to select an appropriate tartaric stabilization method., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

Bacterial keratitis is among the most prevalent causes of blindness. Currently, the abuse of antibiotics in clinical settings not only lacks bactericidal effects but also readily induces bacterial resistance, making the clinical treatment of bacterial keratitis a significant challenge. In this study, we present an injectable hydrogel (GS-PNH-FF@CuS/MnS) containing self-assembled diphenylalanine dipeptide (FF) and CuS/MnS nanocomposites (CuS/MnS NCs) that destroy bacterial cell walls through a synergistic combination of mild photothermal therapy (PTT), chemodynamic therapy (CDT), ion release chemotherapy, and self-assembled dipeptide contact, thereby eliminating Pseudomonas aeruginosa. Under 808 nm laser irradiation, the bactericidal efficiency of GS-PNH-FF@CuS/MnS hydrogel against P. aeruginosa in vitro reach up to 96.97 %. Furthermore, GS-PNH-FF@CuS/MnS hydrogel is applied topically to kill bacteria, reduce inflammation, and promote wound healing. Hematoxylin-eosin (H&E) staining, Masson staining, immunohistochemistry and immunofluorescence staining are used to evaluate the therapeutic effect on infected rabbit cornea models in vivo. The GS-PNH-FF@CuS/MnS demonstrate good biocompatibility with human corneal epithelial cells and exhibit no obvious eyes side effects. In conclusion, the GS-PNH-FF@CuS/MnS hydrogel in this study provides an effective and safe treatment strategy for bacterial keratitis through a multimodal approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Eomecon chionantha Hance, an endemic species in China, has a long medical history in Chinese ethnic minority medicine and is known for its anti-inflammatory and analgesic effects. However, studies of E. chionantha are lacking. In this study, we investigated the characteristics of the E. chionantha chloroplast genome and determined the taxonomic position of E. chionantha in Papaveraceae via phylogenetic analysis. In addition, we determined molecular markers to identify E. chionantha at the molecular level by comparing the chloroplast genomes of E. chionantha and its closely related species. The complete chloroplast genomic information indicated that E. chionantha chloroplast DNA (178,808 bp) contains 99 protein-coding genes, 8 rRNAs, and 37 tRNAs. Meanwhile, we were able to identify a total of 54 simple sequence repeats through our analysis. Our findings from the phylogenetic analysis suggest that E. chionantha shares a close relationship with four distinct species, namely Macleaya microcarpa, Coreanomecon hylomeconoides, Hylomecon japonica, and Chelidonium majus. Additionally, using the Kimura two-parameter model, we successfully identified five hypervariable regions (ycf4-cemA, ycf3-trnS-GGA, trnC-GCA-petN, rpl32-trnL-UAG, and psbI-trnS-UGA). To the best of our knowledge, this is the first report of the complete chloroplast genome of E. chionantha, providing a scientific reference for further understanding of E. chionantha from the perspective of the chloroplast genome and establishing a solid foundation for the future identification, taxonomic determination and evolutionary analysis of this species., (© 2024. The Author(s) under exclusive licence to The Botanical Society of Japan.)

Feline chronic gingivostomatitis (FCGS) is an ulcerative and/or proliferative disease that typically affects the palatoglossal folds. Because of its unknown pathogenesis and long disease course, it is difficult to treat and has a high recurrence rate. Most of the bacteria in the oral microbiota exist in the mouth symbiotically and maintain a dynamic balance, and when the balance is disrupted, they may cause disease. Disturbance of the oral microbiota may play an important role in the development of FCGS. In this study, the medical records of 3109 cats in three general pet hospitals in Xi 'an were collected. Sixty-one cats with FCGS were investigated via questionnaires, routine oral examinations and laboratory examinations. Oral microbiota samples were collected from 16 FCGS-affected cats, and microbial species were identified by 16S rDNA sequencing. The results showed that the incidence of FCGS had no significant correlation with age, sex or breed. However, the incidence of FCGS was associated with immunization, a history of homelessness and multicat rearing environments. The number of neutrophils and the serum amyloid A concentration were increased, and the percentage of cells positive for calicivirus antigen was high in all cases. All the cats had different degrees of dental calculus, and there were problems such as loss of alveolar bone or tooth resorption. Compared with those in healthy cats, the bacterial diversity and the abundance of anaerobic bacteria were significantly increased in cats with FCGS. Porphyromonas , Treponemas and Fusobacterium were abundant in the mouths of the affected cats and may be potential pathogens of FCGS. After tooth extraction, a shift could be seen in the composition of the oral microbiota in cats with FCGS. An isolated bacteria obtained from the mouths of the affected cats was homologous to P. gulae . Both the identified oral microbiota and the isolated strain of the cats with FCGS had high sensitivity to enrofloxacin and low sensitivity to metronidazole. This study provides support to current clinical criteria in diagnosing FCGS and proposes a more suitable antibiotic therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dai, Yang, Du, Wang, Chen, Feng, Chen and Zhang.)

Mesenchymal Stem Cells are ideal seed cells for tissue repair and cell therapy and have promising applications in regenerative medicine and tissue engineering. Using Platelet-Rich Plasma as an adjuvant to create and improve the microenvironment for Mesenchymal Stem Cells growth can enhance the biological properties of Mesenchymal Stem Cells and improve the efficacy of cell therapy. However, the mechanism by which Platelet-Rich Plasma improves the biological performance of Mesenchymal Stem Cells is still unknown. In this study, by examining the effects of Platelet-Rich Plasma on the biological performance of Mesenchymal Stem Cells, combined with multiomics analysis (Transcriptomics, Proteomics and Metabolomics) and related tests, we analyzed the specific pathways, related mechanisms and metabolic pathways of Platelet-Rich Plasma to improve the biological performance of Mesenchymal Stem Cells. In an in vitro cell culture system, the biological performance of Mesenchymal Stem Cells was significantly improved after replacing Foetal Bovine Serum with Platelet-Rich Plasma, and the genes (ESM1, PDGFB, CLEC7A, CCR1 and ITGA6 et al.) related to cell proliferation, adhesion, growth, migration and signal transduction were significantly upregulated. Platelet-Rich Plasma can enhance the secretion function of MSC exosomes, significantly upregulate many proteins related to tissue repair, immune regulation and anti-infection, and enhance the repair effect of exosomes on skin injury. After replacing Foetal Bovine Serum with Platelet-Rich Plasma, Mesenchymal Stem Cells underwent metabolic reprogramming, the metabolism of amino acids and fatty acids and various signaling pathways were changed, the anabolic pathways of various proteins were enhanced. These results provide a theoretical and technical reference for optimizing the Mesenchymal Stem Cells culture system, improving the biological characteristics and clinical application effects of Mesenchymal Stem Cells., (© 2024. The Author(s).)

Transcriptomics and metabolomics offer distinct advantages in investigating the differentially expressed genes and cellular entities that have the greatest influence on end-phenotype, making them crucial techniques for studying plant quality and environmental responses. While numerous relevant articles have been published, a comprehensive summary is currently lacking. This review aimed to understand the global and longitudinal research trends of transcriptomics and metabolomics in plant quality and environmental response (TMPQE). Utilizing bibliometric methods, we presented a comprehensive science mapping of the social structure, conceptual framework, and intellectual foundation of TMPQE. We uncovered that TMPQE research has been categorized into three distinct stages since 2020. A citation analysis of the 29 most cited articles, coupled with a content analysis of recent works (2020-2023), highlight five potential research streams in plant quality and environmental responses: (1) biosynthetic pathways, (2) abiotic stress, (3) biotic stress, (4) development and ripening, and (5) methodologies and tools. Current trends and future directions are shaped by technological advancements, species diversity, evolving research themes, and an environmental ecology focus. Overall, this review provides a novel and comprehensive perspective to understand the longitudinal trend on TMPQE.

Tert-butylhydroquinone (tBHQ) has emerged as a promising candidate for mitigating the adverse effects of T-2-induced reproductive toxicity. The protective effects of tBHQ on rat sperm quality, testicular injury, apoptosis, and inflammation induced by T-2 toxin exposure were investigated. Histopathological examination of testicular tissues revealed severe damage in the T-2-treated group, characterized by disorganized germ cell arrangement, thinning of the convoluted seminiferous tubule walls, and significant cellular necrosis. However, tBHQ administration, either as a preventive or therapeutic measure, mitigated this structural damage. Image analysis confirmed an increase in the cross-sectional area and height of the convoluted seminiferous tubules in the tBHQ-treated groups compared to the T-2-treated group ( p < 0.05), indicating tBHQ's efficacy in alleviating testicular damage. Additionally, tBHQ treatment significantly inhibited T-2-induced apoptosis of testicular tissue cells, as evidenced by the results showing reduced apoptotic cell counts and downregulation of the BAX/BCL2 ratio and caspase-3 expression ( p < 0.05). tBHQ significantly increased the concentrations of the antioxidant factors SOD, CAT, TAC, and GSH-PX. Furthermore, tBHQ attenuated the inflammatory response induced by T-2 exposure, as indicated by the decreased mRNA expression of the proinflammatory cytokines Tnf , Il1 , and Il10 in testicular tissue ( p < 0.05). Additionally, tBHQ treatment alleviated the decline in serum testosterone induced by the T-2 and promoted testosterone synthesis gene expression, including for the genes 17β-HSD and Cyp11a1 , in rat testes ( p < 0.05). These findings underscore tBHQ's role as a therapeutic agent combatting T-2-induced reproductive toxicity, highlighting its antioxidative, anti-apoptotic, and anti-inflammatory properties. Further elucidation of tBHQ's mechanisms of action may offer novel strategies for preventing and treating reproductive disorders induced by environmental toxins.

Accurate intraoperative differentiation of primary central nervous system lymphoma (PCNSL) remains pivotal in guiding neurosurgical decisions. However, distinguishing PCNSL from other lesions, notably glioma, through frozen sections challenges pathologists. Here we sought to develop and validate a deep learning model capable of precisely distinguishing PCNSL from non-PCNSL lesions, especially glioma, using hematoxylin and eosin (H&E)-stained frozen whole-slide images. Also, we compared its performance against pathologists of varying expertise. Additionally, a human-machine fusion approach integrated both model and pathologic diagnostics. In external cohorts, LGNet achieved AUROCs of 0.965 and 0.972 in distinguishing PCNSL from glioma and AUROCs of 0.981 and 0.993 in differentiating PCNSL from non-PCNSL lesions. Outperforming several pathologists, LGNet significantly improved diagnostic performance, further augmented to some extent by fusion approach. LGNet's proficiency in frozen section analysis and its synergy with pathologists indicate its valuable role in intraoperative diagnosis, particularly in discriminating PCNSL from glioma, alongside other lesions., (© 2024. The Author(s).)

Addressing soil salinization and implementing sustainable practices for cultivating cash crops on saline-alkali land is a prominent global challenge. Cynomorium songaricum is an important salt-alkali tolerant medicinal plant capable of adapting to saline-alkali environments. In this study, two typical ecotypes of C. songaricum from the desert-steppe (DS) and saline-alkali land (SAL) habitats were selected. Through the integration of multi-omics with machine learning, the rhizosphere microbial communities, genetic maps, and metabolic profiles of two ecotypes were created and the crucial factors for the adaptation of C. songaricum to saline-alkali stress were identified, including 7 keystone OTUs (i.e. Novosphingobium sp., Sinorhizobium meliloti, and Glycomyces sp.), 5 core genes (cell wall-related genes), and 10 most important metabolites (i.e. cucurbitacin D and 3-Hydroxybutyrate) were identified. Our results indicated that under saline-alkali environments, the microbial competition might become more intense, and the microbial community network had the simple but stable structure, accompanied by the changes in the gene expression related to cell wall for adaptation. However, this regulation led to the reduction in active ingredients, such as the accumulation of flavonoids and organic acid, and enhanced the synthesis of bitter substances (cucurbitacin D), resulting in the decrease in the quality of C. songaricum. Therefore, compared to the SAL ecotype, the DS was more suitable for the subsequent development of medicinal and edible products of C. songaricum. Furthermore, to explore the reasons for this quality variation, we constructed a comprehensive microbial-genetic-metabolic regulatory network, revealing that the metabolism of C. songaricum was primarily influenced by genetic factors. These findings not only offer new insights for future research into plant salt-alkali tolerance strategies but also provide a crucial understanding for cultivating high-quality medicinal plants., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024. Published by Elsevier B.V.)

Improving the ionic rectification in nanochannels enables versatile applications such as biosensors, energy harvesting, and fluidic diodes. While previous work mostly focused on the effect of channel geometry and surface charge, in this work via a series of molecular dynamics simulations, we find a striking phenomenon that the ionic current rectification (ICR) ratio in Janus graphene oxide (GO) channels can be tremendously promoted by lateral electric fields. First, under a given axial electric field, an additional lateral electric field can improve the ICR ratio by several times to an order, depending on the channel symmetry. The symmetric channel has an obviously greater ICR ratio because it maintains a more pronounced ion transport disparity at opposite axial fields. The underlying mechanism for the function of the lateral electric field is that it promotes the lateral migration of ions and thus amplifies the ion-residue electrostatic interaction at opposite axial fields, enlarging the ion dynamical difference. Furthermore, for different axial electric fields, the ICR ratio can always be improved by lateral electric fields (up to two orders), suggesting that the ICR improvement is universal. Our results demonstrate that applying a lateral electric field could be a new method to improve the rectification performance of nanochannels, providing valuable guidance for the design of efficient ionic diode devices.

Accurate tumor diagnosis by pathologists relies on identifying specific morphological characteristics. However, summarizing these unique morphological features in tumor classifications can be challenging. Although deep learning models have been extensively studied for tumor classification, their indirect and subjective interpretation obstructs pathologists from comprehending the model and discerning the morphological features accountable for classifications. In this study, we introduce a new approach utilizing Style Generative Adversarial Networks, which enables a direct interpretation of deep learning models to detect significant morphological characteristics within datasets representing patients with deficient mismatch repair/microsatellite instability-high gastric cancer. Our approach effectively identifies distinct morphological features crucial for tumor classification, offering valuable insights for pathologists to enhance diagnostic accuracy and foster professional growth., Competing Interests: All authors declare no financial or non-financial competing interests., (© 2024 The Author(s).)

This study aimed to determine the effect of prostaglandin F 2α (PGF 2α ) analog ( D -cloprostenol sodium and DL -cloprostenol sodium) administration on the milk yield of multiparous sows (MS) and piglet growth performance. In total, 320 Landrace×Yorkshire parturient MS were randomly divided into three groups on day 115 of pregnancy: without treatment ( N  = 50), with 75 μg D -cloprostenol sodium ( N  = 137), and with 200 μg DL -cloprostenol sodium ( N  = 133). After delivery, the sows treated with D -cloprostenol sodium and DL -cloprostenol sodium were randomly allocated into three subgroups, respectively: (i) no additional treatment after farrowing; (ii) administration of cloprostenol sodium at 3 h and 5 days after farrowing; and (iii) administration of cloprostenol sodium at 3 h, 5 days, and 10 days after farrowing. Cloprostenol sodium effectively induced sows to synchronize parturition approximately 23 h after administration and increased the daytime delivery rates ( p  < 0.05). Compared with DL -cloprostenol sodium, D -cloprostenol sodium shortened the farrowing duration and birth interval of sows for inducing farrowing ( p  < 0.05). Moreover, we observed that a single administration of both D -cloprostenol sodium and DL -cloprostenol sodium a day before delivery significantly reduced the rates of stillborn piglets type II in MS ( p  < 0.05). Compared to no treatment and single treatment with cloprostenol sodium, quartic treatments with cloprostenol sodium significantly increased the daily feed intake of MS, litter weight after weaning, and average daily gain of piglets ( p  < 0.05). Cloprostenol sodium improved the 21-day milk yield, with D -cloprostenol sodium showing the best effect, which increased lactation ability by 30.30% (176.72 kg vs. 135.63 kg) ( p  < 0.05). DL -cloprostenol sodium followed closely, increasing lactation ability by approximately 25.00% (169.71 kg vs. 135.63 kg) ( p  < 0.05). During lactation, sows administered with D -cloprostenol sodium observed increased serum prolactin levels. Compared to untreated sows, the sows administered with D -cloprostenol sodium and multiple DL -cloprostenol sodium visibly shortened the weaning-to-estrus interval (WEI) and weaning-to-service interval (WSI) ( p  < 0.05). Furthermore, quartic injections of D -cloprostenol sodium resulted in an 18 percentage point increase in the pregnancy rate of breeding sows compared to controls (82.61% vs. 64.58%) ( p  > 0.05). In summary, cloprostenol sodium could enhance the reproductive performance of MS, particularly in terms of lactation performance. Additionally, the effect of quartic injections of D -cloprostenol sodium was the most pronounced., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Zhang, Zhang, Li, Li, Zhang, Li, Meng, Wei and Zhang.)

Nepeta bracteata (N. bracteata) is an important medicinal plant used by Chinese ethnic minorities. However, the lack of knowledge regarding the chloroplast genome of N. bracteata has imposed current limitations on our study. Here, we used Next-generation sequencing to obtain the chloroplast genome of N. bracteata. The findings suggested that the 151,588 bp cp genome of N. bracteata comprises 130 genes, including 35 tRNA genes and 87 protein-coding genes. And its chloroplast genome exhibits a typical quadripartite structure, the largest single copy (LSC; 82,819 bp) and the smallest single copy (SSC; 17,557 bp) separate a pair of inverted repeats IR regions (IRa and IRb; 25,606 bp) from one another. Interestingly, palindromic repeats are more common, as shown by the examination of repetition. In the interim, 18 SSRs were discovered in the interim, the bulk of which were Adenine-Thymine (A-T) mononucleotides. Meanwhile, we compared it with five other species from the Nepeta genus. Five hypervariable areas were found by the study, including ndhH-rps15, accD-psal, ndhG-ndhl, trnH-GUG-psbA, and rpoC1-rpoB. Furthermore, the phylogenetic study revealed that N. bracteata and Nepeta stewartiana (N. stewartiana) were linked to each other most closely. In summary, our findings enrich the resources available for chloroplast genomes in the Nepeta genus. Moreover, these hypervariable regions have the potential to be developed into molecular markers, enabling the rapid identification of species within the Nepeta genus. Comparative analysis of species within the Nepeta genus can help enhance our study of their phylogenetic relationships, potential medicinal properties and bioprospecting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Improving the desalination performance of membranes is always in the spotlight of scientific research; however, Janus channels with polarized surface charge as nanofiltration membranes are still unexplored. In this work, using molecular dynamics simulations, we demonstrate that Janus graphene oxide (GO) channels with appropriate geometry and surface charge can serve as highly efficient nanofiltration membranes. We observe that the water permeability of symmetric Janus GO channels is significantly superior to that of asymmetric channels without sacrificing much ion rejection, owing to weakened ion blockage and electrostatic effects. Furthermore, in symmetric Janus GO channels, the transport of water and ions is sensitive to the charge polarity of the channel inner surface, which is realized by tuning the ratio of cationic and anionic functionalization. Specifically, with the increase in cationic functionalization, the water flux decreases monotonously, while ion rejection displays an interesting maximum behavior that indicates desalination optimization. Moreover, the trade-off between water permeability and ion rejection suggests that the Janus GO channels have an excellent desalination potential and are highly tunable according to the specific water treatment requirements. Our work sheds light on the key role of channel geometry and charge polarity in the desalination performance of Janus GO channels, which paves the way for the design of novel desalination devices.

Many customers prefer goji berry pulp, well-known for its high nutritional content, over fresh goji berries. However, there is limited research on its sensory lexicon and distinctive flavor compounds. This study focused on developing a sensory lexicon for goji berry pulp and characterizing its aroma by sensory and instrumental analysis. Sensory characteristics of goji berry pulp were evaluated by our established lexicon. A total of 83 aromatic compounds in goji berry pulp were quantified using HS-SPME-GC-Orbitrap-MS. By employing OAV in combination, we identified 17 aroma-active compounds as the key ingredients in goji berry pulp. Then, we identified the potentially significant contributors to the aroma of goji berry pulp by combining principal component analysis and partial least squares regression (PLSR) models of aroma compounds and sensory attributes, which included 3-ethylphenol, methyl caprylate, 2-hydroxy-4-methyl ethyl valerate, benzeneacetic acid, ethyl ester, hexanal, (E,Z) -2,6-nonadienal, acetylpyrazine, butyric acid, 2-ethylhexanoic acid, 2-methyl-1-propanol, 1-pentanol, phenylethyl alcohol, and 2-nonanone. This study provides a theoretical basis for improving the quality control and processing technology of goji berry pulp.

Geum japonicum (Rosaceae) has been widely used in China as a traditional herbal medicine due to its high economic and medicinal value. However, the appearance of Geum species is relatively similar, making identification difficult by conventional phenotypic methods, and the studies of genomics and species evolution are lacking. To better distinguish the medicinal varieties and fill this gap, we carried out relevant research on the chloroplast genome of G. japonicum. Results show a typical quadripartite structure of the chloroplast genome of G. japonicum with a length of 156,042 bp. There are totally 131 unique genes in the genome, including 87 protein-coding genes, 36 tRNA genes, and 8 rRNA genes, and there were also 87 SSRs identified and mostly mononucleotide Adenine-Thymine. We next compared the plastid genomes among four Geum species and obtained 14 hypervariable regions, including ndhF, psbE, trnG-UCC, ccsA, trnQ-UUG, rps16, psbK, trnL-UAA, ycf1, ndhD, atpA, petN, rps14, and trnK-UUU. Phylogenetic analysis revealed that G. japonicum is most closely related to Geum aleppicum, and possibly has some evolutionary relatedness with an ancient relic plant Taihangia rupestris. This research enriched the genome resources and provided fundamental insights for evolutionary studies and the phylogeny of Geum., (© 2023. The Author(s) under exclusive licence to The Botanical Society of Japan.)

During the construction of tissue-engineered meniscus, the low porosity of extracellular matrix restricts the flow of nutrient solution and the migration and proliferation of cells, thus affecting the tissue remodeling after transplantation. In this study, the canine allogeneic meniscus was drilled first and then decellularized. The drilled tissue-engineered menisci (Drilled Allogeneic Acellular Meniscus + Bone Marrow Mesenchymal Stem Cells, BMSCs) were transplanted into the knee joints of model dogs. On the basis of ensuring the mechanical properties, the number of the porosity and the cells implanted in allogeneic acellular meniscus was significantly increased. The expression levels of glycosaminoglycans and type II collagen in the drilled tissue-engineered meniscus were also improved. It was determined that the animals in the experimental group recovered well-compared with those in the control group. The graft surface was covered with new cartilage, the retraction degree was small, and the tissue remodeling was good. The surface wear of the femoral condyle and tibial plateau cartilage was light. The results of this study showed that increasing the porosity of allogeneic meniscus by drilling could not only maintain the mechanical properties of the meniscus and increase the number of implanted cells but also promote cell proliferation and differentiation. After transplantation, the drilled tissue-engineered meniscus provided a good remodeling effect in vivo and played a positive role in repairing meniscal injury, protecting articular cartilage and restoring knee joint function., Competing Interests: YZ was employed by Baiopai (Tianjin) Biotechnology Co., LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dai, Zou, Zhao, Lv, Gao, Ruan, Zhang, Zhang and Zhang.)

Bronchiolar adenoma (BA) is a rare lung tumor that has recently been clearly named, including the previous ciliated muconodular papillary tumor (CMPT) and the so-called nonclassical CMPT. The most prominent histological feature of BA is a double-layer cell structure composed of a continuous basal cell layer and a luminal cell layer. BA lined purely by mucinous luminal cells is very rare, and only one case has been reported in the English literature. This type of BA can easily be misdiagnosed as early mucinous adenocarcinoma. This article analyzes the clinicopathological characteristics of a newly discovered case of BA lined purely by mucinous luminal cells and fully integrated with the literatures., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Guangjie Liao and Xinke Zhang.)

This study aimed to achieve toxicity control of sulfadiazine (SDZ) and pirimiphos-methyl (PMM) via the UV/H 2 O 2 process by optimizing the reaction parameters. The results show that both drugs had a good degradation effect under the following parameters: a H 2 O 2 molar ratio of 1:200, and neutral conditions. SDZ and PMM could be degraded by more than 99% within 3 min, respectively. In the Daphnia magna acute toxicity assay and Vibrio fischeri inhibition assay, both SDZ and PMM exhibited a phenomenon of increasing toxicity. Additionally, through the use of density functional theory (DFT) calculation and HPLC-QTOF-MS, 21 transformation products (TPs) were identified, and the principal degradation pathways were proposed. The toxicity of the TPs was determined by comparing the QSAR prediction results with toxicity test data. As a result, under the higher UV light intensity (2300 μW/cm 2 ) and neutral conditions, SDZ showed highest toxicity, whereas PMM showed lowest toxicity under the lowest UV light intensity (450 μW/cm 2 ) and neutral conditions. Four main toxic TPs were identified, and their yields could be reduced by adjusting the reaction parameters. Therefore, the selection of appropriate reaction parameters could reduce the production of toxic TPs and ensure the safety of water environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

ALES is a rare subtype that demonstrates the EWSR1-FLI1 translocation characteristic of ES and demonstrates complex epithelial differentiation including diffuse cytokeratin and p40 expression. It has predominantly recognized in the head and neck and is common in middle-aged population. This case is the first case of ALES reported in the pancreatic tail, sharing some morphological characteristics with ALES in the head and neck, including monotonous cytology, infiltrative growth pattern, and complex epithelioid differentiation, but ALES in the head and neck often has high-grade histological features (e.g., necrosis, high mitotic rate, etc.), and sudden keratinization can also occur, but these features were not reflected in this primary pancreatic tail ALES. Although ALES arising in the pancreatic tail and in the head and neck sites share the immunohistochemical and molecular profile, our case can provide new ideas in differential diagnosis of ALES arising in pancreatic tail and promote increased recognition and understanding of ALES., (© 2023. The Author(s).)

Introduction: Plant microorganism is critical to plant health, adaptability, and productive forces. Intriguingly, the metabolites and microorganisms can act upon each other in a plant. The union of metabolomics and microbiome may uncover the crucial connections of the plant to its microbiome. It has important benefits for the agricultural industry and human being health, particularly for Chinese medical science investigation., Methods: In this last 2 years study, on the strength of the UPLC-MS/MS detection platform, we accurately qualitatively, and quantitatively measured the Cistanche sinensis fleshy stems of two ecotypes. Thereafter, through high-throughput amplicon sequencing 16S/ITS sequences were procured., Results: PhGs metabolites including echinacoside, isoacteoside, and cistanoside A were significantly downregulated at two ecotypes of C. sinensis . Add up to 876 metabolites were monitored and 231 differential metabolites were analyzed. Further analysis of 34 core differential metabolites showed that 15 compounds with up-regulated belonged to phenolic acids, flavonoids, and organic acids, while 19 compounds with down-regulated belonged to phenolic acids, flavonoids, alkaloids, amino acids, lipids, and nucleotides. There was no noteworthy discrepancy in the endophytic bacteria's α and β diversity between sandy and loam ecotypes. By comparison, the α and β diversity of endophytic fungi was notably distinct. The fungal community of the loam ecotype is more abundant than the sandy ecotype. However, there were few such differences in bacteria. Most abundant genera included typical endophytes such as Phyllobacterium , Mycobacterium , Cistanche , Geosmithia, and Fusarium . LEfSe results revealed there were 11 and 20 biomarkers of endophytic bacteria and fungi in C. sinensis at two ecotypes, respectively. The combination parsing of microflora and metabolites indicated noteworthy relativity between the endophytic fungal communities and metabolite output. Key correlation results that Anseongella was positive relation with Syringin, Arsenicitalea is negative relation with 7-methylxanthine and Pseudogymnoascus is completely positively correlated with nepetin-7- O -alloside., Discussion: The aim of this research is: (1) to explore firstly the influence of ecotype on C. sinensis from the perspective of endophytes and metabolites; (2) to investigate the relationship between endophytes and metabolites. This discovery advances our understanding of the interaction between endophytes and plants and provides a theoretical basis for cultivation of C. sinensis in future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Miao, Zhang, Sun, Li and Huang.)

Introduction: Small cell lung cancer (SCLC) is a subtype of lung cancer, the second most common cancer diagnosis worldwide. Currently, there is little published qualitative research that provides insight into the disease-related symptoms and impacts that are relevant to patients living with SCLC as directly reported by patients themselves., Methods: This qualitative, cross-sectional, noninterventional, descriptive study included concept elicitation interviews with participants diagnosed with SCLC and the development of a conceptual model of clinical treatment benefit., Results: Concept elicitation interview data from 26 participants with SCLC were used to develop a conceptual model of clinical treatment benefit that organized 28 patient-reported concepts into two domains: disease-related symptoms (organ-specific and systemic) and impacts. Organ-specific symptoms included cough, chest pain, and difficulty breathing. Systemic symptoms included pain, fatigue, appetite loss, and dizziness. Impacts included physical functioning, role functioning, reduced movement, impact on sleep, and weight loss., Conclusion: As evidenced by this study, people with SCLC experience considerable and significant symptoms and impacts, including physical and role functioning challenges, that affect their quality of life. This conceptual model will inform the design of a patient-reported outcome (PRO) questionnaire for a future SCLC clinical trial, helping to establish the content validity of the items and questionnaires used in the trial and ensuring that the questionnaires and items selected are appropriately targeted to the population. This conceptual model could also be used to inform future SCLC clinical trials., (© 2023. The Author(s).)

The high vascularization of glioma highlights the potential value of anti-angiogenic therapeutics for glioma treatment. Previously, we designed a novel vascular-targeting and blood-brain barrier (BBB)-penetrating peptide, TAT-AT7, by attaching the cell-penetrating peptide TAT to a vascular-targeting peptide AT7, and we demonstrated that TAT-AT7 could target binding to the vascular endothelial growth factor receptor 2 (VEGFR-2) and Neuropilin-1 (NRP-1), which are both highly expressed in endothelial cells. TAT-AT7 has been proven to be a good targeting peptide which could effectively deliver the secretory endostatin gene to treat glioma via the TAT-AT7-modified polyethyleneimine (PEI) nanocomplex. In the current study, we further explored the molecular binding mechanisms of TAT-AT7 to VEGFR-2 and NRP-1 and its anti-glioma effects. Accordingly, TAT-AT7 was proven to competitively bind to VEGFR-2 and NRP-1 and prevent VEGF-A165 binding to the receptors by the surface plasmon resonance (SPR) assay. TAT-AT7 inhibited endothelial cells' proliferation, migration, invasion, and tubule formation, as well as promoted endothelial cells' apoptosis in vitro. Further research revealed that TAT-AT7 inhibited the phosphorylation of VEGFR-2 and its downstream PLC-γ, ERK1/2, SRC, AKT, and FAK kinases. Additionally, TAT-AT7 significantly inhibited angiogenesis of zebrafish embryo. Moreover, TAT-AT7 had a better penetrating ability and could penetrate the BBB into glioma tissue and target glioma neovascularization in an orthotopic U87-glioma-bearing nude mice model, and exhibited the effect of inhibiting glioma growth and angiogenesis. Taken together, the binding and function mechanisms of TAT-AT7 were firstly revealed, and TAT-AT7 was proven to be an effective and promising peptide for the development of anti-angiogenic drugs for targeted treatment of glioma.

Exosomes are small membrane vesicles secreted by most cell types, and widely exist in cell supernatants and various body fluids. They can transmit numerous bioactive elements, such as proteins, nucleic acids, and lipids, to affect the gene expression and function of recipient cells. Mesenchymal stem cells (MSCs) have been confirmed to be a potentially promising therapy for tissue repair and regeneration. Accumulating studies demonstrated that the predominant regenerative paradigm of MSCs transplantation was the paracrine effect but not the differentiation effect. Exosomes secreted by MSCs also showed similar therapeutic effects as their parent cells and were considered to be used for cell-free regenerative medicine. However, the inefficient and limited production has hampered their development for clinical translation. In this review, we summarize potential methods to efficiently promote the yield of exosomes. We mainly focus on engineering the process of exosome biogenesis and secretion, altering the cell culture conditions, cell expansion through 3D dynamic culture and the isolation of exosomes. In addition, we also discuss the application of MSCs-derived exosomes as therapeutics in disease treatment., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Charged asymmetric channels are extensively investigated for the design of artificial biological channels, ionic diodes, artificial separation films, etc. These applications are attributed to the unique ionic current rectification phenomenon, where the surface charge density of the channel has a deep influence. In this work, we use molecular dynamics simulations to study the rectification phenomenon in asymmetric graphene oxide channels. A fascinating finding is that the ionic current rectification direction reverses from the negative to positive electric field direction with an increase in surface charge density. Specifically, at low charge density, the ionic flux reaches greater values in the negative electric field due to the enrichment of cations and anions, which provides a sufficient electrostatic shielding effect inside the channel and increases the possibility of ion release by the residues. However, at high charge density, the extremely strong residue attraction induces a Coulomb blockade effect in the negative electric field, which seriously impedes the ion transport and eventually leads to a smaller ionic current. Consequently, this ionic current order transition ultimately results in the rectification reversion phenomenon, providing a new route for the design of some novel nanofluidic devices.

The differences in chemical and sensory characteristics between Marselan and Cabernet Sauvignon in China were investigated with gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QqQ-MS/MS), combined with color parameters and sensory data. The paired t -test results showed that terpenoids, higher alcohols, and aliphatic lactones were significantly different according to the grape variety. Meanwhile, terpenoids could be considered as marker aroma compounds to distinguish Marselan wines from Cabernet Sauvignon, which could explain the distinct floral note in Marselan wines. The mean concentrations of the mv-vsol, mv-vgol, mv-vcol, mvC-vgol, mv-v(e)cat, mvC-v(e)cat, mv-di(e)cat, and cafA were higher in Marselan wines than Cabernet Sauvignon wines, and these compounds might confer Marselan wines with a deeper color, more red hue, and higher tannin quality. The phenolic profiles of Marselan and Cabernet Sauvignon wines were influenced by the winemaking process, mitigating the varietal differences. As for sensory evaluation, the intensities of herbaceous, oak, and astringency of Cabernet Sauvignon were more pronounced than Marselan, whereas the Marselan wines were characterized by a high color intensity and more redness, together with floral, sweet, and roasted sweet potato attributes, and tannin roughness.

Background: Cutaneous infections are important diseases in captive and free-ranging pinnipeds and are associated with various causative agents. Some special agents, such as fungi, morbillivirus and mycobacteria, can cause cutaneous specific granulomatous inflammation., Objectives: To identity the cause of chronic dermatitis in a spotted seal in an aquarium., Methods: Herein, we analyze the clinical history and cutaneous samples of the spotted seal through differential diagnosis (histopathology, microorganism culture, special histochemical staining methods, PCR), and antibiotic susceptibility test., Results: This is a rare pyogranulomatous dermatitis case caused by E. faecalis in a captive adult male spotted seal (Phoca largha) in an aquarium., Conclusions: We provide a meaningful approach to the diagnosis and treatment of bacterial dermatitis in pinnipeds., (© 2022 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Acute lung injury (ALI) is a clinically severe lung illness with high incidence rate and mortality. Especially, coronavirus disease 2019 (COVID-19) poses a serious threat to world wide governmental fitness. It has distributed to almost from corner to corner of the universe, and the situation in the prevention and control of COVID-19 remains grave. Traditional Chinese medicine plays a vital role in the precaution and therapy of sicknesses. At present, there is a lack of drugs for treating these diseases, so it is necessary to develop drugs for treating COVID-19 related ALI. Fagopyrum dibotrys (D. Don) Hara is an annual plant of the Polygonaceae family and one of the long-history used traditional medicine in China. In recent years, its rhizomes (medicinal parts) have attracted the attention of scholars at home and abroad due to their significant anti-inflammatory, antibacterial and anticancer activities. It can work on SARS-COV-2 with numerous components, targets, and pathways, and has a certain effect on coronavirus disease 2019 (COVID-19) related acute lung injury (ALI). However, there are few systematic studies on its aerial parts (including stems and leaves) and its potential therapeutic mechanism has not been studied. The phytochemical constituents of rhizome of F. dibotrys were collected using TCMSP database. And metabolites of F. dibotrys ' s aerial parts were detected by metabonomics. The phytochemical targets of F. dibotrys were predicted by the PharmMapper website tool. COVID-19 and ALI-related genes were retrieved from GeneCards. Cross targets and active phytochemicals of COVID-19 and ALI related genes in F. dibotrys were enriched by gene ontology (GO) and KEGG by metscape bioinformatics tools. The interplay network entre active phytochemicals and anti COVID-19 and ALI targets was established and broke down using Cytoscape software. Discovery Studio (version 2019) was used to perform molecular docking of crux active plant chemicals with anti COVID-19 and ALI targets. We identified 1136 chemicals from the aerial parts of F. dibotrys , among which 47 were active flavonoids and phenolic chemicals. A total of 61 chemicals were searched from the rhizome of F. dibotrys , and 15 of them were active chemicals. So there are 6 commonly key active chemicals at the aerial parts and the rhizome of F. dibotrys , 89 these phytochemicals's potential targets, and 211 COVID-19 and ALI related genes. GO enrichment bespoken that F. dibotrys might be involved in influencing gene targets contained numerous biological processes, for instance, negative regulation of megakaryocyte differentiation, regulation of DNA metabolic process, which could be put down to its anti COVID-19 associated ALI effects. KEGG pathway indicated that viral carcinogenesis, spliceosome, salmonella infection, coronavirus disease - COVID-19, legionellosis and human immunodeficiency virus 1 infection pathway are the primary pathways obsessed in the anti COVID-19 associated ALI effects of F. dibotrys . Molecular docking confirmed that the 6 critical active phytochemicals of F. dibotrys , such as luteolin, (+) -epicatechin, quercetin, isorhamnetin, (+) -catechin, and (-) -catechin gallate, can combine with kernel therapeutic targets NEDD8, SRPK1, DCUN1D1, and PARP1. In vitro activity experiments showed that the total antioxidant capacity of the aerial parts and rhizomes of F. dibotrys increased with the increase of concentration in a certain range. In addition, as a whole, the antioxidant capacity of the aerial part of F. dibotrys was stronger than that of the rhizome. Our research afford cues for farther exploration of the anti COVID-19 associated ALI chemical compositions and mechanisms of F. dibotrys and afford scientific foundation for progressing modern anti COVID-19 associated ALI drugs based on phytochemicals in F. dibotrys . We also fully developed the medicinal value of F. dibotrys ' s aerial parts, which can effectively avoid the waste of resources. Meanwhile, our work provides a new strategy for integrating metabonomics, network pharmacology, and molecular docking techniques which was an efficient way for recognizing effective constituents and mechanisms valid to the pharmacologic actions of traditional Chinese medicine., (© 2023 The Authors.)

The objective of this study was to investigate the effect of modified carbonic maceration technique (MCM) on the chemical and sensory characteristics of 'Cabernet Sauvignon' wines at an industrial production scale. Wines made from MCM and cold maceration technique (COM, control) were analyzed chemically and sensorially. Wines made by MCM demonstrated higher L* and a* values but lower b* values, and higher anthocyanin concentrations, which indicated that MCM wines had a greater color intensity, more reddish and bluish hues compared to COM wines. MCM wines contained more flavonols but lower flavan-3-ols. MCM treatment reduced the concentration of C 6 alcohols and some higher alcohols, and increased the concentration of esters, especially acetates. Moreover, sensory evaluation showed the MCM treatment increased the overall aroma intensity, due to the increase of black fruit and fresh fruit notes and the decrease of green note. In addition, MCM wines had lower astringency and persistence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Triple-negative breast cancer (TNBC) is an extremely aggressive subtype associated with a poor prognosis. At present, the treatment for TNBC mainly relies on surgery and traditional chemotherapy. As a key component in the standard treatment of TNBC, paclitaxel (PTX) effectively inhibits the growth and proliferation of tumor cells. However, the application of PTX in clinical treatment is limited due to its inherent hydrophobicity, weak penetrability, nonspecific accumulation, and side effects. To counter these problems, we constructed a novel PTX conjugate based on the peptide-drug conjugates (PDCs) strategy. In this PTX conjugate, a novel fused peptide TAR consisting of a tumor-targeting peptide, A7R, and a cell-penetrating peptide, TAT, is used to modify PTX. After modification, this conjugate is named PTX-SM-TAR, which is expected to improve the specificity and penetrability of PTX at the tumor site. Depending on hydrophilic TAR peptide and hydrophobic PTX, PTX-SM-TAR can self-assemble into nanoparticles and improve the water solubility of PTX. In terms of linkage, the acid- and esterase-sensitive ester bond was used as the linking bond, with which PTX-SM-TAR NPs could remain stable in the physiological environment, whereas PTX-SM-TAR NPs could be broken and PTX be released at the tumor site. A cell uptake assay showed that PTX-SM-TAR NPs were receptor-targeting and could mediate endocytosis by binding to NRP-1. The vascular barrier, transcellular migration, and tumor spheroids experiments showed that PTX-SM-TAR NPs exhibit great transvascular transport and tumor penetration ability. In vivo experiments, PTX-SM-TAR NPs showed higher antitumor effects than PTX. As a result, PTX-SM-TAR NPs may overcome the shortcomings of PTX and present a new transcytosable and targeted delivery system for PTX in TNBC treatment.

Background: Rhizosphere and plant microbiota are assumed to play an essential role in deciding the well-being of hosts, but effects of parasites on their host microbiota have been rarely studied. Also, the characteristics of the rhizosphere and root microbiota of parasites and hosts under parasitism is relatively unknown. In this study, we used Cistanche deserticola and Haloxylon ammodendron from cultivated populations as our model parasites and host plants, respectively. We collected samples from BULK soil (BULK), rhizosphere soil of H. ammodendron not parasitized (NCD) and parasitized (RHA) to study how the parasite influenced the rhizosphere microbiota of the host. We also collected samples from the rhizosphere soil and roots of C. deserticola (RCD and ECD) and Haloxylon ammodendron (RHA and EHA) to explore the difference between the microbiota of the parasite and its host under parasitism., Results: The parasite reduced the compositional and co-occurrence network complexities of bacterial and fungal microbiota of RHA. Additionally, the parasite increased the proportion of stochastic processes mainly belonging to dispersal limitation in the bacterial microbiota of RHA. Based on the PCoA ordinations and permutational multivariate analysis of variance, the dissimilarity between microbiota of C. deserticola and H. ammodendron were rarely evident (bacteria, R 2  = 0.29971; fungi, R 2  = 0.15631). Interestingly, four hub nodes of H. ammodendron in endosphere fungal microbiota were identified, while one hub node of C. deserticola in endosphere fungal microbiota was identified. It indicated that H. ammodendron played a predominant role in the co-occurrence network of endosphere fungal microbiota. Source model of plant microbiome suggested the potential source percentage from the parasite to the host (bacteria: 52.1%; fungi: 16.7%) was lower than host-to-parasite (bacteria: 76.5%; fungi: 34.3%), illustrating that microbial communication was bidirectional, mainly from the host to the parasite., Conclusions: Collectively, our results suggested that the parasite C. deserticola shaped the diversity, composition, co-occurrence network, and community assembly mechanisms of the rhizosphere microbiota of H. ammodendron. Additionally, the microbiota of C. deserticola and H. ammodendron were highly similar and shared. Our findings on parasite and host microbiota provided a novel line of evidence supporting the influence of parasites on the microbiota of their hosts., (© 2023. The Author(s).)

A gold-catalyzed oxidative three-component reaction of terminal alkynes with alcohols and quinone monoimines has been disclosed, affording α-ketoacetals in good to excellent yields. By using quinone monoimines as electrophiles for the interception of the in situ generated gold enolate intermediate, this one-pot process provides an unprecedented method for the polyfunctionalization of terminal alkynes through an oxidation-oxyalkylation-aryloxylation sequence, installing three oxygen atoms on the C-C triple bond.