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Antibodies have been developed as therapeutic agents for the treatment of cancer, infection, and inflammation. In addition to binding activity toward the target, antibodies also exhibit effector-mediated activities through the interaction of the Fc glycan and the Fc receptors on immune cells. To identify the optimal glycan structures for individual antibodies with desired activity, we have developed an effective method to modify the Fc-glycan structures to a homogeneous glycoform. In this study, it was found that the biantennary N-glycan structure with two terminal alpha-2,6-linked sialic acids is a common and optimized structure for the enhancement of antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antiinflammatory activities.

A new class of broadly neutralizing antibodies (bNAbs) from HIV donors has been reported to target the glycans on gp120—a glycoprotein found on the surface of the virus envelope—thus renewing hope of developing carbohydrate-based HIV vaccines. However, the version of gp120 used in previous studies was not from human T cells and so the glycosylation pattern could be somewhat different to that found in the native system. Moreover, some antibodies recognized two different glycans simultaneously and this cannot be detected with the commonly used glycan microarrays on glass slides. Here, we have developed a glycan microarray on an aluminium-oxide-coated glass slide containing a diverse set of glycans, including homo- and mixed N -glycans (high-mannose, hybrid and complex types) that were prepared by modular chemo-enzymatic methods to detect the presence of hetero-glycan binding behaviours. This new approach allows rapid screening and identification of optimal glycans recognized by neutralizing antibodies, and could speed up the development of HIV-1 vaccines targeting cell surface glycans. The glycoprotein gp120 is found on the surface of the HIV viron; it is essential for virus entry into cells. Now, an efficient modular synthesis of N -glycans and the preparation of a mixed-glycan array on aluminium-oxide-coated glass slide is described. This is a vital step in understanding the complex compositions of gp120 and thus important for the development of new HIV therapies.

Radiation-induced lung injury (RILI) remains a dose-limiting and life-threatening complication of thoracic radiotherapy. The present study aimed to evaluate the therapeutic efficacy and mechanism of the naturally extracted flavonoid, 5,7,8-trimethoxyflavone (HY-N7656), in inhibiting RILI. Lung injury in mice was evaluated using micro-computed tomography, histopathological analysis, enzyme-linked immunosorbent assay and western blotting. Network pharmacology was conducted to predict the potential therapeutic targets and signaling pathways of HY-N7656 in RILI. Cell Counting Kit-8, wound healing, immunofluorescence, reverse transcription-quantitative (RT-q) PCR and protein expression analyses were carried out in vitro using TGF-β-stimulated A549 cells to evaluate epithelial-mesenchymal transition (EMT) and signaling activity. Results of the present study revealed that HY-N7656 markedly alleviated pulmonary inflammation and fibrosis in irradiated mice, leading to a reduction in α-smooth muscle actin expression. In addition, EMT was effectively reversed following treatment with HY-N7656 in A549 alveolar epithelial cells treated with TGF-β, accompanied by restoration of E-cadherin expression and downregulation of mesenchymal markers, such as N-cadherin and vimentin. Network pharmacology analysis and molecular docking validation identified the PI3K/Akt pathway as a central target, which was subsequently confirmed via western blot analysis. Moreover, results of the present study demonstrated that HY-N7656 inhibited radiation-induced activation of PI3K and Akt. To the best of the authors' knowledge, the present study was the first to demonstrate that HY-N7656 modulates the PI3K/Akt signaling pathway to suppress the progression of EMT in RILI, establishing HY-N7656 as a multi-target inhibitor of RILI. These findings present a potential strategy to enhance the safety of radiotherapy, warranting further preclinical and clinical evaluation.

Anticancer therapies are often compromised by nonspecific effects and challenged by tumour environments’ inherent physicochemical and biological characteristics. Often, therapeutic effect can be increased by addressing multiple parameters simultaneously. Here we report on exploiting extravasation due to inherent vascular leakiness for the delivery of a pH-sensitive polymer carrier. Tumours’ acidic microenvironment instigates a charge reversal that promotes cellular internalization where endosomes destabilize and gene delivery is achieved. We assess our carrier with an aggressive non-small cell lung carcinoma (NSCLC) in vivo model and achieve >30% transfection efficiency via systemic delivery. Rejuvenation of the p53 apoptotic pathway as well as expression of KillerRed protein for sensitization in photodynamic therapy (PDT) is accomplished. A single administration greatly suppresses tumour growth and extends median animal survival from 28 days in control subjects to 68 days. The carrier has capacity for multiple payloads for greater therapeutic response where inter-individual variability can compromise efficacy. Alterations of p53 are associated with more than half of all human cancers. Here the authors present a new pH-sensitive nanoparticle that is delivered via systemic circulation and combines gene delivery to restore p53 with expression of Killerred protein to induce photosensitization.

A cDNA encoding a bifunctional acetylxylan esterase/xylanase, XynS20E, was cloned from the ruminal fungus Neocallimastix patriciarum. A putative conserved domain of carbohydrate esterase family 1 was observed at the N-terminus and a putative conserved domain of glycosyl hydrolase family 11 was detected at the C-terminus of XynS20E. To examine the enzyme activities, XynS20E was expressed in Escherichia coli as a recombinant His₆ fusion protein and purified by immobilized metal ion-affinity chromatography. Response surface modeling combined with central composite design and regression analysis was then applied to determine the optimal temperature and pH conditions of the recombinant XynS20E. The optimal conditions for the highest xylanase activity of the recombinant XynS20E were observed at a temperature of 49°C and a pH of 5.8, while those for the highest carbohydrate esterase activity were observed at a temperature of 58°C and a pH of 8.2. Under the optimal conditions for the enzyme activity, the xylanase and acetylxylan esterase specific activities of the recombinant XynS20E toward birchwood xylan were 128.7 and 873.1 U mg⁻¹, respectively. To our knowledge, this is the first report of a bifunctional xylanolytic enzyme with acetylxylan esterase and xylanase activities from rumen fungus.

Streptococcus pyogenes is a group A streptococcus (GAS) and an important human pathogen that causes a variety of diseases. Streptococcal pyrogenic exotoxin B (SPE B) and streptolysin S (SLS) are important virulence factors involved in GAS infection, but it is not clear which one is more virulent. Using an air pouch infection model, the wild-type strain NZ131, its isogenic mutants, and complementary mutants were used to examine the effects of SPE B and SLS on GAS infection. The results of the skin lesion and mouse mortality assays showed that although SPE B and SLS had a synergistic effect on GAS infection, SPE B played a more important role in local tissue damage while SLS had a more prominent effect on mouse mortality. Surveys of the exudates from the air pouch revealed that the expression of inflammatory cytokines was significantly inhibited in the sagB / speB- double-mutant JM4-infected mice. Furthermore, in vivo and in vitro studies showed that the isogenic mutant strains were more susceptible to the immune cell killing than the wild-type strain and that the sagB / speB- double-mutant JM4 was the most sensitive among these strains. Moreover, infection with the sagB / speB- double-mutant JM4 strain caused the least amount of macrophage apoptosis compared to infection with the wild-type NZ131 and the other complementary strains, which express only SPE B or SLS or both. Taken together, these results indicate that both SPE B and SLS contributed to GAS evasion from immune cell killing, local tissue damage, and mouse mortality.

This study aims to find out the optimum extraction time varied from 5 min to 60 min for extracellular polymeric substances (EPS) from sewage sludge pretreated at 80 °C. The change of the contents of EPS and its components under different time limit were recorded and compared. The results showed: the contents of soluble protein, TOC, soluble sugar and DNA was increased by 579.17 mg/l, 514.25 mg/l, 132.79 mg/l, and 34.69 mg/l, respectively, with the increase of thermal pre-treatment time during the process, and the DNA content increased the least, which indicating that the effect of thermal pre-treatment at 80 °C on cell lysis of sewage sludge was small. The EPS content, as a whole, was increased with the increase of thermal pre-treatment time. By analyzing the experimental data with the Analytic Hierarchy Process Model, which was used to identify the optimum thermal pre-treatment time of extracting EPS, the results showed that the effectiveness of EPS extraction from sludges was 30 min>60 min>50 min>20 min>40 min>10 min>5 min. Therefore, the 30 min was choosed as the optimum thermal pre-treatment time.

Fucosylated glycans on glycoproteins and glycolipids play critical roles in functional regulations, significantly impacting hu-man health and disease. Fucosylated glycans in humans are categorized into three types: core fucose, terminal fucose, and O-linked fucose, with each type contributing uniquely to physiological and pathological processes. Fucosylation is associated with various conditions, including cancer, autoimmune diseases, and developmental disorders, and it can also affect the effi-cacy of therapeutic antibodies. To investigate aberrant fucosylation in disease progression, azido- and alkynyl-fucose analogs have been utilized as orthogonal clickable probes. However, it remains unclear whether all human fucosyltransferases (FUTs) can accept these probes. In this study, we evaluated the utilization of GDP-fucose analogs, including GDP-6-azidofucose (GDP-6-Az-Fuc), GDP-6-alkynyl fucose (GDP-6-Alk-Fuc), and GDP-7-alkynyl fucose (GDP-7-Alk-Fuc) as donor substrates and natural N-glycans as acceptors and compared their specificity with GDP-fucose for nine human FUTs (FUT1-9) that are involved in the biosynthesis of glycoproteins. We determined key kinetic parameters and catalytic efficiencies of individual FUTs for their fucosylation of specific biantennary N-glycan acceptors to assess their incorporation of these ana-logs into glycoprotein N-glycans. Compared to GDP-fucose, all analogs were much weaker substrates for FUTs except FUT4 which exhibited better tolerance toward the analogs especially GDP-7-Alk-Fuc. Notably, GDP-7-Alk-Fuc was better accepted than GDP-6-Alk-Fuc and GDP-6-Az-Fuc as substrates for these nine human FUTs. These findings reveal the variability in the acceptance specificity and catalytic efficiency of the human FUT family toward the probes and emphasize the potential bias in identifying fucosylated glycans as therapeutic targets.Competing Interest StatementThe authors have declared no competing interest.Funder Information DeclaredNational Institutes of Health, https://ror.org/01cwqze88, AI-130227

● Agricultural activities may promote the conversion of inorganic Hg to MeHg in soil. ● Hg and As present an extremely and a moderately contaminated level, respectively. ● The human health risks posed by As, Hg, and Ni merit more attention. ● Pokeweed may be considered as a potential Hg hyperaccumulator. Soil pollution caused by potentially toxic metal(loid)s (PTMs) near mercury (Hg) mines has attracted extensive attention, yet the status and potential health risks of PTM contamination in soils near Hg mining sites have rarely been investigated on a large scale. Global data on methylmercury (MeHg), Hg, Cd, Cr, As, Pb, Cu, Zn, Mn, and Ni concentrations in soils from Hg mining areas were obtained from published research articles (1999-2023). Based on the database, pollution levels, spatial distributions, and potential health risks were investigated. Results indicated that the average percentage of MeHg to total Hg in agricultural soils (0.19%) was significantly higher than that in non-agricultural soils (0.013%). Indeed, 72.4% of these study sites were extremely contaminated with Hg. Approximately 45% of the examined sites displayed a moderate level of As contamination or even more. Meanwhile, the examined sites in Spain and Turkey exhibited considerably higher pollution levels of Hg and As than other regions. The mean hazard indices of the nine PTMs were 2.91 and 0.59 for children and adults, with 85.6% and 13.3% of non-carcinogenic risks for children and adults that exceeded the safe level of 1, respectively. In addition, 70.2% and 56.7% of the total cancer risks through exposure to five carcinogenic PTMs in children and adults, respectively, exceeded the safety level. As and Hg showed a high exceedance of non-carcinogenic risks, while As and Ni were the leading contributors to carcinogenic risks. This study demonstrates the urgent necessity for controlling PTM pollution and reducing the health risks in soils near Hg mining sites and provides an important basis for soil remediation.

Aim： To analyze the volatile chemical components of the herbal pair Rhizoma Ligustici Chuanxiong-Radix Paeoniae Rubra （RLC-RPR） and compare them with those of each of the herbs alone. Methods＂ Gas chromatography-mass spectrometry （GC-MS）, a chemometric resolution technique using the heuristic evolving latent projections （HELP） method, and the overall volume integration method were used. Results： In total, 52, 38, and 61 volatile chemical components in RLC, RPR, and RLC-RPR essential oils were determined, respectively, accounting for 95.14%, 95.19%, and 89.68% of the total contents of essential oil of RLC, RPR, and RLC-RPR, respectively. The main volatile chemical components were butyldienephthalide （20.65%） and ligustilide （50.15%） for RLC; and n-hexadecanoic acid （20.18%）, [Z,Z]9,12-octadecadienoic acid （30.11%）, 2-hydroxy-benzaldehyde （17.08%） for RPR, and butyldienephthalide （14.80%）, and ligustilide （38.91%） for RLC-RPR. The main volatile chemical components of RLC-RPR were almost the same as those of RLC, but the relative amounts were altered. Conclusion： The number of volatile chemical components in RLC-RPR was almost equal to the sum of the number in the 2 constituent herbs, but the relative amounts were altered. Furthermore, an acid-base reaction takes place during the process of decocting the herbs. The data gathered in this study may be helpful for understanding the synergistic nature of this herb pair in traditional Chinese medicine.