[Relationship Between the Migration of Endogenous Neural Stem Cells and the Pattern of Change in Immune Cell Phenotypes in the Microenvironment After Intracerebral Hemorrhage in Rats]. / å¤§é¼ è„‘å‡ºè¡€åŽå† æºæ€§ç¥žç»å¹²ç»†èƒžè¿ç§»å’Œå¾®çŽ¯å¢ƒä¸­å ç–«ç»†èƒžè¡¨åž‹å˜åŒ–è§„å¾‹çš„å ³ç³».

Objective: Intracerebral hemorrhage (ICH), the second most common type of stroke, can cause long-lasting disability in the afflicted patients. The study was conducted to examine the patterns of change in endogenous neural stem cells (eNSCs) and in the regenerative microenvironment after ICH, to observe the relationship between the migration of eNSCs and the pattern of change in the polarization state of immune cells in the microenvironment, and provide a research basis for research on clinical nerve repair. Methods: The collagenase injection method was used for modeling. The ICH model was induced in adult female Sprague-Dawley (SD) rats by injecting type VII collagenase (2 U) into the brain tissue of rats. All the experimental rats weighed 280-300 g. In order to simulate the ICU at different time points, including the acute phase (within 1 week), subacute phase (1-3 weeks), and the chronic phase (over 3 weeks), brain tissues were harvested at 3 day post injection (3 DPI), 10 DPI, 20 DPI, and 30 DPI to evaluate the modeling effect. Immunofluorescence staining of the brain tissue sections was performed with DCX antibody to observe the pattern of change in the migration of eNSCs in the brain tissue at different time points. Immunofluorescence staining of brain tissue sections was performed with CD206 antibody and CD86 antibody for respective observation of the pattern of change in pro-inflammatory (M1-type) and anti-inflammatory (M2-type) immune cells in the regenerative microenvironment of the brain tissue after ICM. Results: Spontaneous ICH was successfully induced by injecting type Ⅶ collagenase into the brain tissue of SD rats. The volume of the hematoma formed started to gradually increase at 3 DPI and reached its maximum at 10 DPI. After that, the hematoma was gradually absorbed and was completely absorbed by 30 DPI. Analysis of the pattern of changes in eNSCs in the brain tissue showed that a small number of eNSCs were activated at 3 DPI, but very soon their number started to decrease. By 10 DPI, eNSCs gradually began to increase. A large number of eNSCs migrated to the hemorrhage site at 20 DPI. Then the number of eNSCs decreased significantly at 30 DPI (P<0.01). Analysis of the immune microenvironment of the brain tissue showed that pro-inflammatory (M1 type) immune cells increased significantly at 10 and 20 DPI (P<0.01) and decreased at 30 DPI. Anti-inflammatory (M2 type) immune cells began to increase gradually at 3 DPI, decreased significantly at 20 DPI (P<0.05), and then showed an increase at 30 DPI. Conclusion: After ICH in rats, eNSCs migrating toward the site of ICH first increase and then decrease. The immune microenvironment demonstrates a pattern of change in which inflammation is suppressed at first, then promoted, and finally suppressed again. Inflammation may have a stimulatory effect on the migration of eNSCs, but excessive inflammatory activation has an inhibitory effect on the differentiation and further activation of eNSCs. After ICH, the early stage of repair and protection (10 d) and the subacute phase (20 d) may provide the best opportunities for intervention.

A bioinspired injectable antioxidant hydrogel for prevention of postoperative adhesion.

Postoperative adhesions, a prevalent complication following abdominal surgery, affect 90% of patients undergoing abdominal surgical procedures. Currently, the primary approach to prevent postoperative adhesions involves physical isolation of the surgical site and surrounding tissues using a hydrogel; however, this method represents a rudimentary strategy. Herein, considering the impact of oxidative stress and free radicals on postoperative adhesion during wound healing, an injectable antioxidant hydrogel, named PU-OHA-D, was successfully synthesized, which is formed by the crosslinking of dopamine-modified oxidized hyaluronic acid (OHA-D) and dihydrazide-terminated polyurethane (PU-ADH) through hydrazone bonding. PU-OHA-D hydrogel possesses versatile characteristics such as rapid gel formation, injectability, self-repair capability and biodegradability. Additionally, they exhibit an excellent ability to clear free radicals and superior tissue adhesion. PU-OHA-D can be injected in situ to form a hydrogel to prevent abdominal wall-cecum adhesion. Importantly, it can effectively eliminate free radicals and inhibit oxidative stress at the wound site. Thereby, it leads to collagen physiological degradation and prevents the occurrence of postoperative adhesions. The bioinspired hydrogel demonstrates its great potential in preventing postoperative adhesion and promoting wound healing.

Temperature-Sensitive Materials for Oil and Gas Drilling Applications.

With the vigorous development of the petroleum industry, improving the efficiency of oil and gas exploitation has become an important issue. Temperature-sensitive materials show great potential for application in the development and production of oil and gas fields due to their unique temperature-responsive properties. This paper reviews the application of temperature-sensitive materials in oil and gas drilling and introduces the characteristics of three types of temperature-sensitive materials: N-substituted acrylamide polymers, amphiphilic block copolymers, and peptides. Because these materials can change their physical state at specific temperatures, this paper discusses in detail the role of various temperature-sensitive materials as plugging agent, thickener, oil displacing agent, flocculant, and tackifier in oil and gas field operations, as well as the mechanism of action and performance of temperature-sensitive materials in practical oil and gas drilling operations. As we have not yet seen relevant similar literature, this paper aims to discuss the innovative application of temperature-sensitive materials in the oil and gas drilling process, and at the same time points out the problems in the current research and applications as well as future development directions. Through analysis and comparison, we provide an efficient and environmentally friendly materials selection option for the petroleum industry in order to promote the progress and sustainable development of oil and gas extraction processes.

Imparting Chemiresistor with Humidity-Independent Sensitivity toward Trace-Level Formaldehyde via Substitutional Doping Platinum Single Atom.

The modification of metal oxides with noble metals is one of the most effective means of improving gas-sensing performance of chemiresistors, but it is often accompanied by unintended side effects such as sensor resistance increases up to unmeasurable levels. Herein, a carbonization-oxidation method is demonstrated using ultrasonic spray pyrolysis technique to realize platinum (Pt) single atom (SA) substitutional doping into SnO2 (named PtSA-SnO2 ). The substitutional doping strategy can obviously enhance gas-sensing properties, and meanwhile decrease sensor resistance by two orders of magnitude (decreased from ≈850 to ≈2 MΩ), which are attributed to the tuning of band gap and fermi-level position, efficient single atom catalysis, and the raising of adsorption capability of formaldehyde, as validated by the state-of-the-art characterizations, such as spherical aberration-corrected scanning transmission electron microscopy (Cs -corrected STEM), in situ diffuse reflectance infrared Fourier transformed spectra (in situ DRIFT), CO temperature-programmed reduction (CO-TPR), and theoretical calculations. As a proof of concept, the developed PtSA-SnO2 sensor shows humidity-independent (30-70% relative humidity) gas-sensing performance in the selective detection of formaldehyde with high response, distinguishable selectivity (8< Sformaldehyde /Sinterferant <14), and ultra-low detection limit (10 ppb). This work presents a generalized and facile method to design high-performance metal oxides for chemical sensing of volatile organic compounds (VOCs).

Thyroid dysfunction induced by anti-PD-1 therapy is associated with a better progression-free survival in patients with advanced carcinoma.

PURPOSE: Thyroid dysfunction is the most common immune-related adverse event during anti-programmed cell death 1 (anti-PD-1) therapy. In this study, we monitored patients with advanced malignant tumors who received anti-PD-1 therapy to observe the characteristic of anti-PD-1 therapy-induced thyroid dysfunction and its correlation with prognosis. METHODS: Patients with advanced carcinoma treated with anti-PD-1 therapy were evaluated for thyroid function at baseline and after treatment initiation from August 2020 to March 2022. Seventy-three patients were finally included in the study. RESULTS: Among these patients, 19 (26.03%) developed thyroid dysfunction after receiving anti-PD-1 therapy. Primary hypothyroidism and thyrotoxicosis were the most common clinical manifestation. Anti-PD-1-induced thyroid dysfunction occurred 63 (26-131) days after administration; thyrotoxicosis appeared earlier than primary hypothyroidism. In Kaplan-Meier survival analysis, the progression-free survival (PFS) of the thyroid dysfunction group was better than that of the no thyroid dysfunction group (227 (95% confidence interval (CI) 50.85-403.15) days vs 164 (95% CI 77.76-250.24) days, p = 0.026). Male patients had better PFS than female patients (213 (95% CI 157.74-268.26) days vs 74 (95% CI 41.23-106.77) days, p = 0.031). In cox proportional hazards regression model, anti-PD-1-induced thyroid dysfunction remained an independent predictor of better PFS (hazard ratio (HR) = 0.339(0.136-0.848), p = 0.021). CONCLUSION: Thyroid dysfunction is a common immune-related adverse events in advanced cancer patients treated with anti-PD-1 therapy and predicts a better prognosis. TRIAL REGISTRATION: This study was retrospectively registered with Trial ClinicalTrials.gov (NCT05593744) on October 25, 2022.

Janus functional electrospun polyurethane fibrous membranes for periodontal tissue regeneration.

The guided tissue regeneration (GTR) technique with GTR membranes is an efficient method for repairing periodontal defects. Conventional periodontal membranes act as physical barriers that resist the growth of fibroblasts, epithelial cells, and connective tissue. However, they cannot facilitate the regeneration of periodontal tissue. To address this issue, the exploitation of novel GTR membranes with bioactive functions based on therapeutic requirements is critical. Herein, we exploited a biodegradable bilayer polyurethane fibrous membrane by uniaxial electrostatic spinning to construct two sides with Janus properties by integrating the bioactive molecule dopamine (DA) and antimicrobial Gemini quaternary ammonium salt (QAS). The DA-containing side, located inside the injury, can effectively promote cell adhesion and mesenchymal stem cell growth as well as support mineralization and antioxidant properties, which are beneficial for bone regeneration. The QAS-containing side, located on the outer surface of the injury, endows antibacterial properties and limits fibroblast adhesion and growth on its surface owing to its strong hydrophilicity. An in vivo study demonstrates that the Janus polyurethane fibrous membrane can significantly promote the regeneration of periodontal defects in rats. Owing to its superior mechanical properties and biocompatibility, this polyurethane fibrous membrane has potential applications in the field of periodontal regeneration.

Performance-Advantaged Stereoregular Recyclable Plastics Enabled by Aluminum-Catalytic Ring-Opening Polymerization of Dithiolactone.

Chemically recyclable polymers that can depolymerize into their constituent monomers are attractive candidates to replace non-recyclable petroleum-derived plastics. However, the physical properties and mechanical strengths of depolymerizable polymers are commonly insufficient for practical applications. Here we demonstrate that by proper ligand design and modification, aluminum complexes can catalyse stereoretentive ring-opening polymerization of dithiolactone, yielding highly isotactic polythioesters with molar masses up to 45.5 kDa. This material can form crystalline stereocomplex with a Tm of 94.5 °C, and exhibits mechanical performances comparable to petroleum-based low density polyethylene. Exposure of the polythioester to aluminum precatalyst used to synthesized it resulted in depolymerization to pristine chiral dithiolactone. Experimental and computational studies suggest that aluminum complexes have appropriate binding affinity with sulfide propagating species, thereby avoiding catalyst poisoning and minimizing epimerization reactions, which has not been accessible using other metal catalysts. Overall, aluminum catalysis provides access to performance-advantaged stereoregular recyclable plastics as a promising alternative to petrochemical plastics, thus incentivizing improved plastic sustainability.

Precision Synthesis of Polypeptides via Living Anionic Ring-Opening Polymerization of N-Carboxyanhydrides by Tri-thiourea Catalysts.

The chemistry of α-amino acid N-carboxyanhydrides (NCAs) has a history of over 100 years, but precise and efficient ring-opening polymerization methods for NCAs remain highly needed to facilitate the studies of polypeptides─that is, mimics of natural proteins─in various disciplines. Moreover, the universally accepted NCA polymerization mechanisms are largely limited to the "amine" and the "activated monomer" mechanisms, and the anionic ring-opening polymerization of NCAs has so far not been invoked. Herein, we show an unprecedented anion-binding catalytic system combining tripodal tri-thiourea with sodium thiophenolate that enables the fast and selective anionic ring-opening polymerization of NCAs. This method leads to the precision construction of various polypeptides with living polymerization behavior and is evidenced by narrow molecular weight distributions (Mw/Mn < 1.2), chain extension experiments, and minimal "activated monomer" pathway. Calculations and experimental results elucidate a living anionic polymerization mechanism, and high selectivities for monomer propagation relative to other deleterious side reactions, such as the "activated monomer" pathway, are attributed to the enhanced stabilization of the propagating carbamate anion, which is enforced by an intramolecular hydrogen bond within the tri-thiourea structure.

Circular RNA circSDHC (hsa_circ_0015004) regulates tumor growth and angiogenesis via regulating centrosomal protein 55 expression in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the main aggressive subtype of kidney cancer. Circular RNAs have been shown to exert critical roles in RCC. However, little is known about the regulatory mechanism of hsa_circ_0015004 (circSDHC) in RCC. METHODS: 35 patients with RCC were recruited in the research. Expression changes of circSDHC were determined by real-time quantitative polymerase chain reaction (RT-qPCR). The effects of circSDHC inhibition on cell proliferation, apoptosis, angiogenesis, migration, and invasion were analyzed. The regulation mechanism of circSDHC was surveyed by bioinformatics analysis. The effect of circSDHC on tumorigenesis was validated by xenograft assay. RESULTS: We observed an observable elevation in circSDHC expression in RCC tissues and cell lines. Functionally, circSDHC silencing decreased xenograft tumor growth and induced RCC cell apoptosis, repressed RCC cell proliferation, angiogenesis, migration, and invasion in vitro. Mechanically, circSDHC modulated centrosomal protein 55 (CEP55) expression by functioning as a miR-130a-3p sponge. Also, miR-130a-3p silencing offset circSDHC knockdown-mediated impacts on malignant phenotypes and angiogenesis of RCC cells. Furthermore, exogenetic expression of CEP55 counteracted miR-130a-3p overexpression-mediated effects on malignant phenotypes and angiogenesis of RCC cells. CONCLUSION: Silencing of circSDHC restrained cell malignant phenotypes and angiogenesis via reducing CEP55 expression by releasing miR-130a-3p in RCC, providing a new mechanism for understanding the progression of RCC.

Water-Triggered Stiffening of Shape-Memory Polyurethanes Composed of Hard Backbone Dangling PEG Soft Segments.

Shape-memory polymers (SMPs) induced by heat or water are commonly used candidates for biomedical applications. Shape recovery inevitably leads to a dramatic decrease of Young's modulus due to the enhanced flexibility of polymer chains at the transition temperature. Herein, the principle of phase-transition-induced stiffening of shape-memory metallic alloys (SMAs) is introduced to the design of molecular structures for shape-memory polyurethane (SMPUs), featuring all-hard segments composed of main chains that are attached with poly(ethylene glycol) (PEG) dangling side chains. Different from conventional SMPs, they achieve a soft-to-stiff transition when shape recovers. The stiffening process is driven by water-triggered segmental rearrangement due to the incompatibility between the hard segments and the soft PEG segments. Upon hydration, the extent of microphase separation is enhanced and the hard domains are transformed to a more continuous morphology to realize more effective stress transfer. Meanwhile, such segmental rearrangement facilitates the shape-recovery process in the hydrated state despite the final increased glass transition temperature (Tg ). This work represents a novel paradigm of simultaneously integrating balanced mechanics, shape-memory property, and biocompatibility for SMPUs as materials for minimally invasive surgery such as endoluminal stents.

Identification of Prostate Cancer Risk Genetics Biomarkers Based on Intergraded Bioinformatics Analysis.

Background: Prostate cancer (PCa) is one of the most popular cancer types in men. Nevertheless, the pathogenic mechanisms of PCa are poorly understood. Hence, we aimed to identify the potential genetic biomarker of PCa in the present study. Methods: High-throughput data set GSE46602 was obtained from the comprehensive gene expression database (GEO) for screening differentially expressed genes (DEGs). The common DEGs were further screened out using The Cancer Genome Atlas (TCGA) dataset. Functional enrichment analysis includes Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to study related mechanisms. The Cox and Lasso regression analyses were carried out to compress the target genes and construct the high-risk and low-risk gene model. Survival analyses were performed based on the gene risk signature model. The CIBERSORT algorithm was performed to clarify the correlation of the high- and low-risk gene model in risk and infiltration of immune cells in PCa. Results: A total of 385 common DEGs were obtained. The results of functional enrichment analysis show that common DEGs play an important role in PCa. A three-gene signature model (KCNK3, AK5, and ARHGEF38) was established, and the model was significantly associated with cancer-related pathways, overall survival (OS), and tumor microenvironment (TME)-related immune cells in PCa. Conclusion: This new risk model may contribute to further investigation in the immune-related pathogenesis in progression of PCa.

Identification of three novel antioxidative peptides from Auxenochlorella pyrenoidosa protein hydrolysates based on a peptidomics strategy.

Auxenochlorella pyrenoidosa is recognized as a potential sustainable protein material in food industry, however, its application remains still very limited. Herein, this study aimed to investigate the antioxidative properties of Auxenochlorella pyrenoidosa protein hydrolysates and identify novel antioxidative peptides from protein hydrolysates through a workflow mainly including enzymatic hydrolysis, peptidome quantification, quantitative structure-activity relationship (QSAR) modeling, in silico screening, and validation. Three novel antioxidative peptides including AGWACLVG, IDLAY and YPLDL were identified from protein hydrolysates by papain with the hydrolysis time of 4 h, in which, AGWACLVG showed strong 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity with the IC50 value of 68.88 µM and Trolox equivalent antioxidative capacity of 6.20 ± 0.23 mmol TE/g. This study suggested that Auxenochlorella pyrenoidosa protein hydrolysates could be used as potential antioxidative ingredients in food industry, and the identification of novel antioxidative peptides would contribute to the construction of more robust QSAR models in the future.

Preclinical pharmacology and toxicology evaluation of an anti-CD52 monoclonal antibody produced by perfusion fermentation process.

Anti-cluster of differentiation 52 (CD52) monoclonal antibody (mAb) has been employed in the treatment of chronic lymphoblastic leukemia and multiple sclerosis. Previously we developed a perfusion process to produce the biosimilar mAb named "Mab-TH." A series of quality assessments was conducted in the fields of structural identification, purity analysis, and activity measurement. After these quality researches, this report laid emphasis on preclinical pharmacology and toxicology evaluation. Mab-TH was characterized in biological, pharmacological, and toxicological properties in comparison with the original drug, alemtuzumab. Binding activity and immune-dependent toxicity as in vitro activity were evaluated. Severe immunodeficient mice transplanted with a human leukemia cell line were also used as an in vivo pharmacological model and a 4-week repeated dosing study in cynomolgus monkeys was conducted to evaluate the safety differences. Our results demonstrated that Mab-TH, the anti-CD52 antibody generated by a perfusion process, had high similarity in in vitro and in vivo activities compared with alemtuzumab in relevant preclinical models. The results supported it as a biosimilar candidate for clinical evaluation.

Biodegradable polyurethane nerve guide conduits with different moduli influence axon regeneration in transected peripheral nerve injury.

Nerve guide conduits (NGCs) can replace autogenous nerve grafting in the treatment of peripheral nerve system (PNS) injury. However, the modulus of polyurethane NGCs that affects the outcome of PNS repair has been rarely elucidated in vivo. In this study, we developed biodegradable waterborne polyurethane (BWPU) NGCs with an outer BWPU membrane and an inner three-dimensional scaffold structure. The mechanical properties of BWPU NGCs can be modified by adjusting the molar content of polyethylene glycol (PEG) in the soft segments within the BWPU. Two types of BWPU NGCs with different moduli were prepared, containing 17% and 25% PEG in BWPU (termed as BWPU 17 NGCs and BWPU 25 NGCs, respectively). In rat sciatic nerves with 10-mm transected injury, mechanically stronger BWPU 17 NGCs exhibited superior nerve repair, which was similar to that obtained by the current gold standard autograft implantation, whereas weaker BWPU 25 NGCs displayed an unsatisfactory effect. Histological results revealed that both BWPU NGCs had anti-inflammatory effects and altered the activation state of macrophages to M2 phenotypes to enhance PNS regeneration. The analysis of growth-associated protein 43 expression, which regulates axon growth, revealed that the mechanical properties of BWPU NGCs influence the outcome of PNS regeneration by affecting the formation and extension of axons. These findings suggest that the mechanical properties of NGCs could play a key role in regulating PNS repair and should be considered in future biomaterial NGC designs.

Efficacy and Safety of Cetuximab Plus Cisplatin Alone or in Combination With Paclitaxel in Patients With Head and Neck Squamous Cell Carcinoma: A Randomized Trial.

OBJECTIVES: The aim of this study was to assess the clinical usefulness of cetuximab and cisplatin alone or in combination with paclitaxel as the first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). METHODOLOGY: Three hundred patients with confirmed HNSCC from 20 different hospitals were included in this study. Patients in group I underwent a 2-hour infusion of 400 mg/m2 cetuximab (day 1), followed by a 1-hour infusion of 250 mg/m2 cetuximab weekly and 1-hour infusion of 100 mg/m2 cisplatin (days 1 and 21) per treatment cycle. Patients in group II were treated with a combination of cetuximab, cisplatin, and paclitaxel. Patients received 6 cycles of 175 mg/m2 paclitaxel given on days 1 and 21. The primary outcome of the study was progression-free survival (PFS); overall survival (OS) and objective response rate (ORR) were the secondary endpoints. RESULTS: The median PFS was 5 months and 8 months for patients in groups I and II, respectively (HR, 0.93; 95% CI, 0.85-1.78; P > 0.05). Similarly, we found no significant differences in OS between the 2 groups (median OS, 13 vs. 11 months, respectively; HR, 0.67; 95% CI, 0.42-1.43; P = 0.198). Moreover, we observed no significant difference in ORR between the 2 groups (ORR, 63.3% vs 69.9%, respectively; HR, 0.87; 95% CI, 0.36-1.67; P = 0.231). CONCLUSIONS: The combination of paclitaxel with cetuximab and cisplatin did not improve patient outcomes compared to cetuximab plus cisplatin alone. Therefore, the 2-drug regimen could be used as first-line treatment in patients with recurrent or metastatic HNSCC.

CircSMARCA5 Facilitates the Progression of Prostate Cancer Through miR-432/PDCD10 Axis.

Background: Circular RNAs (circRNAs) have been reported to be implicated in the pathogenesis of prostate cancer (PCa). Herein, the authors explore the role and molecular mechanism of circRNA SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (circSMARCA5) in PCa. Materials and Methods: The levels of circSMARCA5, SMARCA5, miR-432, and programmed cell death 10 (PDCD10) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The circular structure and stability of circSMARCA5 were validated by qRT-PCR using Oligo dT primer, transcriptional inhibitor actinomycin D, or RNase R treatment, respectively. Cell proliferation, migration, invasion, epithelial/mesenchymal transition (EMT), and glycolysis were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell migration and invasion assays, Western blot assay, and Glucose or Lactate Detection Kit, respectively. The target relationship between miR-432 and circSMARCA5 or PDCD10 was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Western blot was performed to detect the protein expression of PDCD10 in PCa cells. Results: CircSMARCA5 was aberrantly upregulated, and was a circular and stable RNA in PCa cells. CircSMARCA5 accelerated the proliferation, metastasis, and glycolysis of PCa cells. MiR-432 was a direct target of circSMARCA5, and circSMARCA5 accelerated the development of PCa through miR-432 in PCa cells. PDCD10 was a direct target of miR-432, and PDCD10 addition reversed the inhibitory effects of miR-432 accumulation on the proliferation, metastasis, and glycolysis of PCa cells. CircSMARCA5 upregulated the expression of PDCD10 through sponging miR-432 in PCa cells. Conclusion: CircSMARCA5 deteriorated PCa through the miR-432/PDCD10 axis. CircSMARCA5/miR-432/PDCD10 axis might be an underlying therapeutic target for PCa treatment.

ι-Carrageenan Tetrasaccharide from ι-Carrageenan Inhibits Islet ß Cell Apoptosis Via the Upregulation of GLP-1 to Inhibit the Mitochondrial Apoptosis Pathway.

ι-Carrageenan performs diversified biological activities but has low bioavailability. ι-Carrageenan tetrasaccharide (ιCTs), a novel marine oligosaccharide prepared by the marine enzyme Cgi82A, was investigated for its effects on insulin resistance in high-fat and high-sucrose diet mice. Oral administration of ιCTs (ιCTs-L 30.0 mg/kg·bw, ιCTs-H 90.0 mg/kg·bw) decreased fasting blood glucose by 35.1% ± 1.41 (P < 0.01) and 27.4% ± 0.420 (P < 0.05), and enhanced glucose tolerance. Besides, ιCTs-L ameliorated islet vacuolization, decreased the ß cell apoptosis by 21.8% ± 0.200 (P < 0.05), and promoted insulin secretion by 5.41% ± 0.0173 (P < 0.01) through pancreatic hematoxylin and eosin (H&E) staining, TUNEL staining, and insulin-glucagon immunostaining analysis. Interestingly, ιCTs-L and ιCTs-H treatment increased the incretin GLP-1 content in serum by 22.1% ± 0.402 (P < 0.01) and 10.7% ± 0.0935 (P < 0.05) respectively, through regulating the bile acid levels, which contributed to the inhibition of ß cell apoptosis. Mechanically, ιCTs upregulated the expression of the GLP-1 receptor (GLP-1R) and protein kinase A (PKA) in the GLP-1/cAMP/PKA signaling pathway, and further inhibited the expression of cytochrome C and caspase 3 in the mitochondrial apoptotic pathway. In conclusion, this study suggested that ιCTs alleviated insulin resistance by GLP-1-mediated inhibition of ß cell apoptosis and proposed a new strategy for developing potential functional foods that prevent insulin resistance.

A waterborne polyurethane 3D scaffold containing PLGA with a controllable degradation rate and an anti-inflammatory effect for potential applications in neural tissue repair.

Currently, implanting tissue engineering scaffolds is one of the treatment methods for the regeneration of damaged tissues. The matching of the degradation rate of the scaffolds with the regeneration rate of the damaged zone is a big challenge in tissue engineering. Here, we have synthesized a series of biodegradable waterborne polyurethane emulsions and fabricated three-dimensional (3D) connected porous polyurethane scaffolds by freeze-drying. The degradation rate of the scaffolds was controlled by adjusting the relative ratio of poly-ε-caprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) in the soft segment. The degradation rate of the scaffolds gradually accelerated with the increase of the relative proportion of PLGA. By co-culture with BV2 microglia, the scaffolds promoted the differentiation of BV2 into an anti-inflammatory M2 phenotype rather than a pro-inflammatory M1 phenotype as the proportion of PLGA increases. When the BV2 cells were stimulated with lipopolysaccharide (LPS), the scaffolds with a higher PLGA ratio showed a much stronger anti-inflammatory effect. Then, we demonstrated that the scaffolds could promote the PC12 neurons to differentiate into neurites. Therefore, we believe that the polyurethane scaffolds have a promising potential application in neural tissue repair.

A robust and stable reporter gene bioassay for anti-IgE antibodies.

Immunoglobin E (IgE)-related allergy constitutes a high proportion in allergic diseases. The production of specific IgE is key to evoking serial cascades and pathological reactions. Thus, targeting IgE is a different therapeutic approach from symptomatic treatments. Monoclonal antibodies (mAbs) against IgE were developed and a humanized antibody, omalizumab, was approved by five countries. It could inhibit the binding of IgE with epsilon receptor I of crystallizable fragment (FcεRI), thus preventing anaphylactic reactions. However, no bioactivity assay, which is the critical quality attribute and should thoroughly reflect the clinical mechanism, has been established to date. In commercial lot release, only the enzyme-linked immunosorbent assay (ELISA) method was applied, which only reflects the binding of omalizumab to IgE but not the subsequent reaction. In scientific research works, human FcεRI-transfected RBL-2H3 cells were used to indicate degranulation based on the detection of ß-hexosaminidase. Nevertheless, this method needs much work to stabilize the response and, hence, is not suitable for routine usage in commercial production and control of antibodies. To evaluate the bioactivity of anti-IgE antibodies including omalizumab using a simple assay that reflects the following mechanism of actions (MOA) after binding, we established an RBL-2H3 cell line transfected with both the α subunit of human FcεRI and nuclear factor-activated T cell (NFAT) response elements, the latter is conjugated with a luciferase gene, which could shed luminescence when substrates exist. The method was proven to possess good specificity, accuracy, linearity, and precision and may be utilized as a supplement to anti-IgE antibody bioactivity assays in terms of development, lot release, stability, and comparability studies. Graphical abstract The mechanism sketch of reporter gene assay for bioactivity determination of anti-IgE antibodies by RBL-2H3/FcεRIα/NFAT-Luc cells (left) and representative curves generated by the reporter gene assay (right).

Comparison of radiologic characteristics and pathological presentations of primary pulmonary lymphoma in 22 patients.

OBJECTIVE: This study was performed to compare the radiologic characteristics and pathological presentations of primary pulmonary lymphoma (PPL), explore the possible mechanism underlying its development, summarize its radiologic characteristics, and improve the accuracy of its diagnosis. METHODS: The medical records of 22 patients pathologically diagnosed with PPL were retrospectively analyzed. RESULTS: Chest computed tomography (CT) demonstrated single or multiple nodules and masses in the lungs, patchy opacities or consolidation along the bronchovascular bundle, and no significantly enlarged mediastinal or hilar lymph nodes. All 22 cases of PPL were classified as non-Hodgkin's lymphoma (NHL) by transbronchial biopsy, CT-guided needle biopsy, and postoperative pathology. Most (16 cases) were marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT). Twelve patients had air bronchograms within the lesion, and 13 showed ill-defined lesions with ground-glass brush-like changes. CONCLUSION: PPL is a rare lung tumor, and most are classified as MALT lymphoma, a subtype of NHL. Chest CT can help to diagnose this disease. Positron emission tomography (PET)/CT is of great clinical value for evaluation of the lesion and patient's general condition. The possibility of PPL should be considered in patients with characteristic CT and PET/CT findings and mild clinical symptoms, and early treatment should be administered.