Hypoxia-Challenged Pancreatic Adenocarcinoma Cell-Derived Exosomal circR3HCC1L Drives Tumor Growth Via Upregulating PKM2 Through Sequestering miR-873-5p.

Pancreatic adenocarcinoma (PAAD) is a fatal disease with poor survival. Increasing evidence show that hypoxia-induced exosomes are associated with cancer progression. Here, we aimed to investigate the function of hsa_circ_0007678 (circR3HCC1L) and hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD progression. Through the exoRBase 2.0 database, we screened for a circular RNA circR3HCC1L related to PAAD. Changes of circR3HCC1L in PAAD samples and cells were analyzed with real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, migration, invasion were analyzed by colony formation, cell counting, and transwell assays. Measurements of glucose uptake and lactate production were done using corresponding kits. Several protein levels were detected by western blotting. The regulation mechanism of circR3HCC1L was verified by dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Exosomes were separated by differential ultracentrifugation. Animal experiments were used to verify the function of hypoxia-derived exosomal circR3HCC1L. CircR3HCC1L was upregulated in PAAD samples and hypoxic PAAD cells. Knockdown of circR3HCC1L decreased hypoxia-driven PAAD cell proliferation, migration, invasion, and glycolysis. Hypoxic PAAD cell-derived exosomes had higher levels of circR3HCC1L, hypoxic PAAD cell-derived exosomal circR3HCC1L promoted normoxic cancer cell malignant transformation and glycolysis in vitro and xenograft tumor growth in mouse models in vivo. Mechanistically, circR3HCC1L regulated pyruvate kinase M2 (PKM2) expression via sponging miR-873-5p. Also, PKM2 overexpression or miR-873-5p silencing offset circR3HCC1L knockdown-mediated effects on hypoxia-challenged PAAD cell malignant transformation and glycolysis. Hypoxic PAAD cell-derived exosomal circR3HCC1L facilitated PAAD progression through the miR-873-5p/PKM2 axis, highlighting the contribution of hypoxic PAAD cell-derived exosomal circR3HCC1L in PAAD.

Lignin derivatives-based hydrogels for biomedical applications.

Recently, numerous studies have been conducted on renewable polymers derived from different natural sources, exploring their suitability for diverse biomedical applications. Lignin as one of the main components of lignocellulosic has garnered significant attention as a promising alternative to petroleum-based polymers. This interest is primarily due to its cost-effectiveness, biocompatibility, eco-friendly nature, as well as its antioxidant and antimicrobial properties. These characteristics could be more beneficial when incorporating lignin into the formulation of value-added products. Although lignin has a chemical structure that is suitable for various applications, these characteristics require modifications to guarantee that the resultant materials display the desired biological, chemical, and physical properties when applied in the creation of biodegradable hydrogels, particularly for biomedical purposes. This study delineates the recent modification approaches that have been employed in the creation of lignin-based hydrogels. These strategies encompass both chemical and physical interactions with other polymers. Additionally, this review encompasses an examination of the current applications of lignin hydrogels, spanning their use as scaffolds for tissue engineering, carriers for pharmaceuticals, materials for wound dressings and biosensors, and elements in flexible and wearable electronics. Finally, we delve into the challenges and constraints associated with these materials, discuss the necessary steps required to attain the appropriate properties for the development of innovative lignin-based hydrogels, and derive conclusions based on the presented findings.

Bovine Pluripotent Stem Cells: Current Status and Prospects.

Pluripotent stem cells (PSCs) can differentiate into three germ layers and diverse autologous cell lines. Since cattle are the most commonly used large domesticated animals, an important food source, and bioreactors, great efforts have been made to establish bovine PSCs (bPSCs). bPSCs have great potential in bovine breeding and reproduction, modeling in vitro differentiation, imitating cancer development, and modeling diseases. Currently, bPSCs mainly include bovine embryonic stem cells (bESCs), bovine induced pluripotent stem cells (biPSCs), and bovine expanded potential stem cells (bEPSCs). Establishing stable bPSCs in vitro is a critical scientific challenge, and researchers have made numerous efforts to this end. In this review, the category of PSC pluripotency; the establishment of bESCs, biPSCs, and bEPSCs and its challenges; and the application outlook of bPSCs are discussed, aiming to provide references for future research.

Single-Cell RNA Sequencing Transcriptomics Revealed HCMV IE2-Related Microglia Responses in Alzheimer's-Like Disease in Transgenic Mice.

    Although multiple factors are known to concur with Alzheimer's disease (AD), the relationship between human cytomegalovirus (HCMV) and AD-like disease is unclear. Here, we propose a hypothesis that HCMV immediate-early 2 (IE2) protein promotes microglia activation and thus leads to AD-like disease. We successfully constructed IE2 transgenic mice expressing IE2 in the hippocampus. Single-cell sequencing analysis revealed that IE2 promoted the activation of microglia and upregulated the expression of disease-associated microglia genes. Differentially expressed gene analysis and pathway enrichment revealed that IE2 upregulated immune and nervous system disease-related genes. Immunohistochemical analysis showed that the expressions of both amyloid precursor protein (APP) and p-Tau were significantly upregulated in the brains of IE2 mice and were markers of AD. Taken together, these findings provide useful insights into AD-like disease activated by HCMV IE2.

Recent developments in lignin-based fluorescent materials.

Biomass-based fluorescent materials are an alternative to plastic-based materials for their multifunctional applications. Lignin, an inexpensive and easily available raw material, demonstrates outstanding environment-responsive properties such as pH, metal ions, dyes sensing, bioimaging and so on. To date, only a little work has been reported on the synthesis of lignin-based fluorescent materials. In this review report, synthetic approaches and light-responsive applications of lignin-based fluorescent carbon dots and other materials are summarized. The results reveal that lignin-based fluorescent carbon dots are prepared by hydrothermal method, exhibit small size <10 nm, reveal significant quantum yield, biocompatibility, non-toxicity, photostability and display substantial tunable emission and can be efficiently employed for sensing, bioimaging and energy storage applications. Finally, the forthcoming challenges, investigations, and options open for the chemical and/or physical modification of lignin into fluorescent materials for future applications are well-addressed. To our knowledge, this is the first comprehensive review report on lignin-based fluorescent materials and their light-responsive applications. In addition, this review will attract remarkable consideration and thrust for the researchers and biochemical technologists working with the preparation of lignin-based fluorescent materials for broad applications.

Integrative analysis reveals key mRNA and long non-coding RNA interaction in idiopathic pulmonary arterial hypertension.

Introduction: Idiopathic pulmonary arterial hypertension (IPAH) is a rare and sporadic form of pulmonary arterial hypertension (PAH), characterized by elevated pulmonary arterial resistance leading to right heart failure. However, molecular mechanisms of PAH development are still not completely understood. Material and methods: In this study, we aimed to uncover key mRNAs and long non-coding RNA (lncRNAs), functional modules and pathways. Moreover, to detect the dysregulated pathway or biological function, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. PPI and co-expression networks were constructed to reveal the potential roles of PAH-related mRNAs and lncRNAs. Results: A total of 3,134 genes, including 945 up-regulated and 2,189 down-regulated genes, were identified to be differentially expressed in IPAH by differential expression analysis. We identified T cell differentiation and the T cell receptor signaling pathway as up-regulated in IPAH by using GO and KEGG analysis. Based on the PPI module analysis, we identified that the pro-inflammatory genes, such as OAS1, CXCL10, STAT1 and TLR4, were the hub genes in the PPI modules. To link the lncRNAs to the PPI modules, we calculated the Spearman correlation coefficient for lncRNA-DE-mRNA pairs to identify the modules with high correlation with each lncRNA. Conclusions: Notably, 6 of these lncRNAs were associated with modules characterized by the NOD-like receptor signaling pathway and chemokine signaling pathway, suggesting that these lncRNAs may promote the occurrence of IPAH via participating in the pro-inflammatory pathways. In conclusion, our systematic analysis not only improved our understanding of the molecular mechanism, but also provided potential lncRNA biomarkers for further research.

Low-temperature pretreatment by AlCl3-catalyzed 1,4-butanediol solution for producing 'ideal' lignin with super-high content of ß-O-4 linkages.

High contents of internal ß-O-4 linkages in lignin are critical for high-yield production of high-value aromatic monomers by depolymerization. However, it remains great challenge due to lack of suitable protection strategy. In this work, a very effective lignin-first strategy was developed to produce ideal lignin with a super high content of ß-O-4 linkages (up to 72 %) from poplar, in which the pretreatment was undertaken at low temperatures of 90-130 °C with the use of AlCl3-catalyzed 1, 4-butanediol solution. 2D-HSQC NMR spectra revealed that lignin ß-O-4 linkages were protected from etherification of the OH group by 1, 4-butanediol at the α position of lignin aliphatic chains. Besides, the OH groups at the γ position of lignin was also etherified, leading the formation of a structure of Ph-CH=CHCH2O(CH2)4OH. Interestingly, structure protection facilitated the formation of lignin nanoparticles via self-assembly (<100 nm). In addition, it was observed from pyrolysis results that addition of 1, 4-butanediol remarkably protected the structure of lignin by avoiding condensation, promoting the production of aromatics. The cellulose-rich fraction possessed a high cellulose digestibility of 91.64 % by enzymatic hydrolysis at a cellulase dosage of 15 FPU/g cellulose, approximately 6-fold untreated poplar (15.91 %). This low-temperature lignin-first strategy was of great importance for multi-products biorefining lignocellulose because it leads to the production of both lignin with super high content of ß-O-4 linkages for depolymerization and highly digestible cellulose for sugar production.

Development of a novel patient-reported outcome measure for orthognathic surgery.

OBJECTIVES: This study aimed to develop a new patient-reported outcome measure (PROM) to systematically and scientifically evaluate patients' subjective feelings after orthognathic surgery. METHODS: A literature review and semi-structured interviews were conducted to construct a conceptual framework and an item pool, followed by expert and patient surveys for measure construction. We conducted a clinical investigation to test the feasibility, reliability, and content validity of this measure. RESULTS: The conceptual framework included four domains: psychological health, physiological health, social function, and satisfaction, and 33 items were included in the survey. Following the expert analysis, 31 items remained in the draft. The clinical investigation showed a 100% recovery and completion rate and good reliability, with Cronman-Brown formula coefficients of 0.893 and 0.944, respectively. CONCLUSIONS: A new outcome measure to evaluate patients' subjective feelings after orthognathic surgery was successfully developed, and the clinical investigation demonstrated that the PROM had satisfactory feasibility, reliability, and validity. Further studies are possible based on our PROM, and data on a larger scale may reveal more information on patients' subjective feelings about orthognathic surgery. CLINICAL SIGNIFICANCE: The novel PROM provides a systematic and scientific way to evaluate the patient's subjective feelings to help surgeons obtain complete patient-reported information after orthognathic surgery. Additionally, standardised multicentre research on patients' subjective feelings using our PROM is possible and could improve the effectiveness of the evaluation and help maintain treatment quality.

Expression of Phospholipase D Family Member 6 in Bovine Testes and Its Molecular Characteristics.

Spermatogonial stem cells (SSCs) are the only primitive spermatogonial cells in males that can naturally transmit genetic information to their offspring and replicate throughout their lives. Phospholipase D family member 6 (PLD6) has recently been found to be a surface marker for SSCs in mice and boars; however, it has not been validated in cattle. The results of reversed transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR (qRT-PCR) found that the relative expression of the PLD6 gene in the testicular tissues of two-year-old Simmental calves was significantly higher than that of six-month-old calves. Immunofluorescent staining further verified the expression of PLD6 protein in bovine spermatogenic cells like germ cell marker DEAD box helicase 4 (DDX4, also known as VASA). Based on multiple bioinformatic databases, PLD6 is a conservative protein which has high homology with mouse Q5SWZ9 protein. It is closely involved in the normal functioning of the reproductive system. Molecular dynamics simulation analyzed the binding of PLD6 as a phospholipase to cardiolipin (CL), and the PLD6-CL complex showed high stability. The protein interaction network analysis showed that there is a significant relationship between PLD6 and piwi-interacting RNA (piRNA) binding protein. PLD6 acts as an endonuclease and participates in piRNA production. In addition, PLD6 in bovine and mouse testes has a similar expression pattern with the spermatogonium-related genes VASA and piwi like RNA-mediated gene silencing 2 (PIWIL2). In conclusion, these analyses imply that PLD6 has a relatively high expression in bovine testes and could be used as a biomarker for spermatogenic cells including SSCs.

Exosome-transmitted hsa_circ_0012634 suppresses pancreatic ductal adenocarcinoma progression through regulating miR-147b/HIPK2 axis.

Circular RNA (circRNA) has been confirmed to play a vital role in pancreatic ductal adenocarcinoma (PDAC) progression. However, the function and regulatory mechanism of hsa_circ_0012634 in PDAC progression remain unclear. Quantitative real-time PCR was used to measure the expression of hsa_circ_0012634, microRNA (miR)-147b and homeodomain interacting protein kinase 2 (HIPK2). Cell function was assessed by cell counting kit 8 assay, EdU assay, colony formation assay and flow cytometry. Glucose uptake and lactate production were evaluated to determine cell glycolysis ability. Protein expression was examined by western blot analysis. RNA interaction was confirmed by RNA pull-down assay and dual-luciferase reporter assay. Exosomes were isolated from serums and cell culture supernatant using ultracentrifugation and identified by transmission electron microscopy. Animal experiments were conducted using nude mice. Hsa_circ_0012634 was downregulated in PDAC tissues and cells, and its overexpression suppressed PDAC cell proliferation, glycolysis and enhanced apoptosis. MiR-147b was targeted by hsa_circ_0012634, and its inhibitors repressed PDAC cell growth and glycolysis. HIPK2 could be targeted by miR-147b, and hsa_circ_0012634 regulated miR-147b/HIPK2 to suppress PDAC cell progression. Hsa_circ_0012634 was lowly expressed in serum exosomes of PDAC patients. Exosomal hsa_circ_0012634 inhibited PDAC cell growth and glycolysis in vitro, as well as tumorigenesis in vivo. Exosomal hsa_circ_0012634 restrained PDAC progression via the miR-147b/HIPK2 pathway, confirming that hsa_circ_0012634 might serve as a diagnosis and treatment biomarker for PDAC.

Method for Diagnosing Bearing Faults in Electromechanical Equipment Based on Improved Prototypical Networks.

Due to the complexity of electromechanical equipment and the difficulties in obtaining large-scale health monitoring datasets, as well as the long-tailed distribution of data, existing methods ignore certain characteristics of health monitoring data. In order to solve these problems, this paper proposes a method for the fault diagnosis of rolling bearings in electromechanical equipment based on an improved prototypical network-the weight prototypical networks (WPorNet). The main contributions of this paper are as follows: (1) the prototypical networks, which perform well on small-sample classification tasks, were improved by calculating the different levels of influence of support sample distributions in order to achieve the prototypical calculation. The change in sample influence was calculated using the Kullback-Leibler divergence of the sample distribution. The influence change in a specific sample can be measured by assessing how much the distribution changes in the absence of that sample; and (2) The Gramian Angular Field (GAF) algorithm was used to transform one-dimensional time series into two-dimensional vibration images, which greatly improved the application effect of the 2D convolutional neural network (CNN). Through experiments on MAFAULDA and CWRU bearing datasets, it was shown that this network effectively solves the shortcomings of a small number of valid samples and a long-tail distribution in health monitoring data, it enhances the dependency between the samples and the global data, it improves the model's feature extraction ability, and it enhances the accuracy of model classification. Compared with the prototypical network, the improved network model increased the performance of the 2-way 10-shot, 2-way 20-shot, and 2-way 50-shot classification tasks by 5.23%, 5.74%, and 4.37%, respectively, and it increased the performance of the 4-way 10-shot, 4-way 20-shot, and 4-way 50-shot classification tasks by 12.02%, 10.47%, and 4.66%, respectively. Experimental results show that the improved prototypical network model has higher sample classification accuracy and stronger anti-interference ability compared with traditional small-sample classification models.

Mussel-inspired lignin decorated cellulose nanocomposite tough organohydrogel sensor with conductive, transparent, strain-sensitive and durable properties.

A novel gel-based wearable sensor with environment resistance (anti-freezing and anti-drying), excellent strength, high sensitivity and self-adhesion was prepared by introducing biomass materials including both lignin and cellulose. The introduction of lignin decorated CNC (L-CNC) to the polymer network acted as nano-fillers to improve the gel's mechanical with high tensile strength (72 KPa at 25 °C, 77 KPa at -20 °C), excellent stretchability (803 % at 25 °C, 722 % at -20 °C). The abundant catechol groups formed in the process of dynamic redox reaction between lignin and ammonium persulfate endowed the gel with robust tissue adhesiveness. Impressively, the gel exhibited outstanding environment resistance, which could be stored for a long time (>60 days) in an open-air environment with a wide work temperature range (-36.5 °C-25 °C). Based on these significant properties, the integrated wearable gel sensor showed superior sensitivity (gauge factor = 3.11 at 25 °C and 2.01 at -20 °C) and could detect human activities with excellent accuracy and stability. It is expected that this work will provide a promising platform for fabricating and application of a high-sensitive strain conductive gel with long-term usage and stability.

Gut microbiota induces hepatic steatosis by modulating the T cells balance in high fructose diet mice.

Metabolic diseases are often associated with high fructose (HF) consumption. HF has also been found to alter the gut microbiota, which then favors the development of nonalcoholic fatty liver disease. However, the mechanisms underlying of the gut microbiota on this metabolic disturbance are yet to be determined. Thus, in this study, we further explored the effect the gut microbiota concerning the T cells balance in an HF diet mouse model. We fed mice 60% fructose-enriched diet for 12 weeks. At 4 weeks, HF diet did not affect the liver, but it caused injury to the intestine and adipose tissues. After 12 weeks, the lipid droplet aggregation was markedly increased in the liver of HF-fed mice. Further analysis of the gut microbial composition showed that HF decreased the Bacteroidetes/Firmicutes ratio and increased the levels of Blautia, Lachnoclostridium, and Oscillibacter. In addition, HF can increase the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in the serum. T helper type 1 cells were significantly increased, and regulatory T(Treg) cells were markedly decreased in the mesenteric lymph nodes of the HF-fed mice. Furthermore, fecal microbiota transplantation alleviates systemic metabolic disorder by maintaining liver and intestinal immune homeostasis. Overall, our data indicated that intestinal structure injury and intestinal inflammation might be early, and liver inflammation and hepatic steatosis may be a subsequent effect following HF diets. Gut microbiota disorders impairing the intestinal barrier function and triggering immune homeostasis imbalance may be an importantly responsible for long-term HF diets induced hepatic steatosis.

Mesothelioma patient and carer experience research: A research prioritisation exercise.

OBJECTIVES: Incidence of mesothelioma worldwide is growing and the UK reports the highest global incidence. Mesothelioma is an incurable cancer with a high symptom burden. However, it is under researched when compared to other cancers. The aim of this exercise was to identify unanswered questions about the mesothelioma patient and carer experience in the UK and to prioritise research areas of most importance through consultation with patients, carers and professionals. MATERIALS AND METHODS: A virtual Research Prioritisation Exercise was conducted. This involved a review of mesothelioma patient and carer experience literature to identify research gaps and a national online survey to identify and rank research gaps. Following this, a modified consensus method with mesothelioma experts (patients, carers and professionals from healthcare, legal, academic and volunteer organisations) was undertaken to reach a consensus regarding mesothelioma patient and carer experience research priorities. RESULTS: Survey responses were received from 150 patients, carers and professionals and 29 research priorities were identified. During consensus meetings, 16 experts refined these into a list of 11 key priorities. The five most urgent priorities were symptom management, receiving a mesothelioma diagnosis, palliative and end of life care, treatment experiences, barriers and facilitators to joined up service provision. CONCLUSION: This novel priority setting exercise will shape the national research agenda, contribute knowledge to inform nursing and wider clinical practice and ultimately improve the experiences of mesothelioma patients and carers.

Human Cytomegalovirus IE2 Disrupts Neural Progenitor Development and Induces Microcephaly in Transgenic Mouse.

Human cytomegalovirus (HCMV) is a significant contributor to congenital birth defects. Limited by the lack of animal models, the pathogenesis of neurological damage in vivo caused by HCMV infection and the role of individual viral genes remain to be elucidated. Immediate early (IE2) protein may play a function in neurodevelopmental problems caused by HCMV infection. Here, this study intended to investigate IE2's long-term effects on development of the brain in IE2-expressing transgenic mice (Rosa26-LSL-IE2+/-, Camk2α-Cre) aimed to observe the phenotype of postnatal mice. The expression of IE2 in transgenic mice was confirmed by PCR and Western blot technology. We collected mouse brain tissue at 2, 4, 6, 8, and 10 days postpartum to analyze the developmental process of neural stem cells by immunofluorescence. We discovered that transgenic mice (Rosa26-LSL-IE2+/-, Camk2α-Cre) can reliably produce IE2 in the brain at various postpartum phases. Furthermore, we also observed the symptoms of microcephaly in postnatal transgenic mice, and IE2 can damage the amount of neural stem cells, prevent them from proliferating and differentiating, and activate microglia and astrocytes, creating an unbalanced environment in the brain's neurons. In conclusion, we demonstrate that long-term expression of HCMV-IE2 can cause microcephaly through molecular mechanisms affecting the differentiation and development of neural stem cells in vivo. This work establishes a theoretical and experimental foundation for elucidating the molecular mechanism of fetal microcephaly brought by HCMV infection in throughout the period of neural development of pregnancy.

Construction of Cu-N coordination into natural biopolymer lignin backbone for highly efficient and selective removal of cationic dyes.

Here, a Cu2+-doped lignin-based adsorbent (Cu-AL) was fabricated via the amination and Cu2+-doping of industrial alkali lignin for massive and selective adsorption of cationic dyes azure B (AB) and saffron T (ST). The Cu-N coordination structures endowed Cu-AL with stronger electronegativity and higher dispersity. Through the electrostatic attraction, π-π interaction, H-bonding, and Cu2+ coordination, the adsorption capacities of AB and ST reached up to 1168 and 1420 mg g-1, respectively. The pseudo-second-order model and Langmuir isotherm model were more relevant to the AB and ST adsorption on Cu-AL. Based on the thermodynamic study, the adsorption progresses were endothermic, spontaneous, and feasible. The Cu-AL maintained high removal efficiency to dyes after 4 reuses (>80%). Importantly, the Cu-AL could efficiently remove and separate AB and ST from dye mixtures even in real time. All the above characteristics demonstrated that Cu-AL was an excellent adsorbent for fast wastewater treatment.

CRM197-conjugated peptides vaccine of HCMV pp65 and gH induce maturation of DC and effective viral-specific T cell responses.

Human cytomegalovirus (HCMV) infection is prevalent worldwide, and there is currently no licenced HCMV vaccine to control it. Therefore, developing an effective HCMV vaccine is a significant priority. Because of their excellent immunogenicity, the crucial components of HCMV, phosphoprotein 65 (pp65) and glycoproteins H (gH) are potential target proteins for HCMV vaccine design. In this study, we predicted and screened the dominant antigenic epitopes of B and T cells from pp65 and gH conjugated with the carrier protein cross-reacting material 197 (CRM197) to form three peptide-CRM197 vaccines (pp65-CRM197, gH-CRM197, and pp65-CRM197+gH-CRM197). Furthermore, the immunogenicity of the peptide-CRM197 vaccines and their effects on dendritic cells (DCs) were explored. The results showed that three peptide-CRM197 vaccines could induce maturation of DCs through the p38 MAPK signalling pathway and promote the release of proinflammatory factors, such as TNF-α and interleukin (IL) -6. Meanwhile, the peptide-CRM197 vaccines could effectively activate T cell and humoral immunity, which were far better than the inactivated HCMV vaccine. In conclusion, we constructed three peptide-CRM197 vaccines, which could induce multiple immune effects, providing a novel approach for HCMV vaccine design.

Tumor cell vaccine combined with Newcastle disease virus promote immunotherapy of lung cancer.

Lung cancer is a fatal disease with the highest worldwide morbidity and mortality rates. Despite recent advances in targeted therapy and immune checkpoint inhibitors for cancer, their efficacy remained limited. Therefore, we designed a Newcastle disease virus (NDV)-modified tumor whole-cell vaccine as a therapeutic vaccine and identified its antigen presentation level to develop effective immunotherapy. Then, we calculated the therapeutic and immune-stimulating effects of NDV-modified lung cancer cell vaccine and intratumoral NDV injection combination on tumor-bearing mice. The results showed that the immunogenic cell death (ICD) expression in NDV-modified lung cancer cell vaccine stimulates dendritic cell maturation and T cell activation in vivo and in vitro. Moreover, NDV-modified lung cancer cell vaccine combined with intratumoral NDV injection could significantly inhibit tumor growth and enhance the differentiation of Th1 cells and Inflammatory cell infiltration in vivo, leading to an excellent immunotherapeutic effect. Therefore, our results revealed that NDV-modified lung cancer cell vaccine combined with intratumoral NDV injection could promote antigen presentation and induce a strong antitumor immune response, which provided a promising combined therapy strategy for tumor immunotherapy.

Antimicrobial Peptide MPX with Broad-Spectrum Bactericidal Activity Promotes Proper Abscess Formation and Relieves Skin Inflammation.

Bacteria have developed antibiotic resistance during the large-scale use of antibiotics, and multidrug-resistant strains are common. The development of new antibiotics or antibiotic substitutes has become an important challenge for humankind. MPX is a 14 amino acid peptide belonging to the MP antimicrobial peptide family. In this study, the antibacterial spectrum of the antimicrobial peptide MPX was first tested. The antimicrobial peptide MPX was tested for antimicrobial activity against the gram-positive bacterium S. aureus ATCC 25923, the gram-negative bacteria E. coli ATCC 25922 and Salmonella enterica serovar Typhimurium CVCC541, and the fungus Candida albicans ATCC 90029. The results showed that MPX had good antibacterial activity against the above four strains, especially against E. coli, for which the MIC was as low as 15.625 µg/mL. The study on the bactericidal mechanism of the antimicrobial peptide revealed that MPX can destroy the integrity of the cell membrane, increase membrane permeability, and change the electromotive force of the membrane, thereby allowing the contents to leak out and mediating bacterial death. A mouse acute infection model was used to evaluate the therapeutic effect of MPX after acute infection of subcutaneous tissue by S. aureus. The study showed that MPX could promote tissue repair in S. aureus infection and alleviate lung damage caused by S. aureus. In addition, skin H&E staining showed that MPX treatment facilitated the formation of appropriate abscesses at the subcutaneous infection site and facilitated the clearance of bacteria by the skin immune system. The above results show that MPX has good antibacterial activity and broad-spectrum antibacterial potential and can effectively prevent the invasion of subcutaneous tissue by S. aureus, providing new ideas and directions for the immunotherapy of bacterial infections.

Advances in organosolv modified components occurring during the organosolv pretreatment of lignocellulosic biomass.

The valorization of organosolv pretreatment (OP) is a required approach to the industrialization of the current enzyme-mediated lignocellulosic biorefinery. Recent literature has demonstrated that the solvolysis happening in the OP can modify the soluble components into value-added active compounds, namely organosolv modified lignin (OML) and organosolv modified sugars (OMSs), in addition to protecting them against excessive degradation. Among them, the OML is coincidental with the "lignin-first" strategy that should render a highly reactive lignin enriched with ß-O-4 linkages and less condensed structure by organosolv grafting, which is desirable for the transformation into phenolic compounds. The OMSs are valuable glycosidic compounds mainly synthesized by trans-glycosylation, which can find potential applications in cosmetics, foods, and healthcare. Therefore, a state-of-the-art OP holds a big promise of lowering the process cost by the valorization of these active compounds. Recent advances in organosolv modified components are reviewed, and perspectives are made for addressing future challenges.