Contamination-Free Reference Electrode Using Prussian Blue for Small Oxygen Sensors.

In recent years, significant attention has been directed toward advancing compact, point-of-care testing (POCT) devices to better deliver patient care and alleviate the burden on the medical care system. Common POCTs, such as blood oxygen sensors, leverage electrochemical sensing in their design. However, conventional electrochemical devices typically use Ag/AgCl reference electrodes, which are likely to release trace amounts of silver ions that contaminate the working electrode, causing rapid deterioration of the devices. This study proposes an effective reference electrode using graphene-coated porous silica spheres (G/PSS) with embedded Prussian blue (PB), denoted PB/G/PSS, designed specifically for small oxygen sensors. PB is a redox species that is an improvement over Ag/AgCl since it is significantly less water-soluble than AgCl. Since PB is an insulator, we dispersed PB in G/PSS, well-conductive mesoporous matrices, to ensure contact between PB clusters and the electrolytes. Moreover, the monodispersed, spherically shaped PB/G/PSS is an advantageous medium for fabricating POCT devices by screen printing. In this study, the open-circuit potential of the PB/G/PSS electrode remained stable within 30 mV for 31 days. The small oxygen sensor assembled through screen printing using PB/G/PSS demonstrated stable operation for several days or more. In contrast, a similar sensor with Ag/AgCl reference electrode rapidly deteriorated within a day. This PB/G/PSS reference electrode with improved stability is expected to be an excellent alternative to the Ag/AgCl system for small electrochemical-based POCT devices.

Endoplasmic reticulum-targeted iridium(III) photosensitizer induces pyroptosis for augmented tumor immunotherapy.

An ideal tumor treatment strategy involves therapeutic approaches that can enhance the immunogenicity of the tumor microenvironment while simultaneously eliminating the primary tumor. A cholic acid-modified iridium(III) (Ir3) photosensitizer, targeted to the endoplasmic reticulum (ER), has been reported to exhibit potent type I and type II photodynamic therapeutic effects against triple-negative breast cancer (MDA-MB-231). This photosensitizer induces pyroptotic cell death mediated by gasdermin E (GSDME) through photodynamic means and enhances tumor immunotherapy. Mechanistic studies have revealed that complex Ir3 induces characteristics of damage-related molecular patterns (DAMPs) in MDA-MB-231 breast cancer cells under light conditions. These include cell-surface calreticulin (CRT) eversion, extracellular high mobility group box 1 (HMGB1) and ATP release, accompanied by ER stress and increased reactive oxygen species (ROS). Consequently, complex Ir3 promotes dendritic cell maturation and antigen presentation under light conditions, fully activates T cell-dependent immune response in vivo, and ultimately eliminates distant tumors while destroying primary tumors. In conclusion, immune regulation and targeted intervention mediated by metal complexes represent a new and promising approach to tumor therapy. This provides an effective strategy for the development of combined targeted therapy and immunotherapy.

Fabrication of cysteine-modified antibodies with Fc-specific conjugation for covalent and oriented immobilization of native antibodies.

Covalent and oriented immobilization of antibodies (Abs) can substantially improve the sensitivity and stability of solid-phase immunoassays. By modifying the natural Abs with functional groups that provide unique handles for further conjugation, Abs could be immobilized onto the solid matrices with uniform orientation. Herein, an effective approach for Fc-specific modification of Abs was developed for the oriented and covalent immobilization of Abs. Twelve photoreactive Z-domain variants, incorporated with a photoactivable probe (p-benzoyl-L-phenylalanine, Bpa) at different positions and carrying a C-terminal Cys-tag (i.e. ZBpa-Cys variants), were individually constructed and produced in Escherichia coli and tested for photo-cross-linking to various IgGs. The different ZBpa-Cys variants demonstrated large differences in photo-conjugation efficiency for the tested IgGs. The conjugation efficiencies of 17thZBpa-Cys ranged from 90 % to nearly 100 % for rabbit IgG and mouse IgG2a, IgG2b and IgG3. Other variants, including 5thZBpa-Cys, 18thZBpa-Cys, 32thZBpa-Cys, and 35thZBpa-Cys, also displayed conjugation efficiencies of 61 %-83 % for mouse IgG1, IgG2a and IgG3. Subsequently, the photo-modified Abs, namely IgG-Cys conjugates, were covalently immobilized onto a maleimide group-functionalized solid-phase carrier on the basis of the reaction of sulfhydryl and maleimide. Thus, a generic platform for the controlled and oriented immobilization of Abs was developed, and the efficacy and potential of the proposed approach for sensitive immunoassays was demonstrated by detecting human α-fetoprotein.

Bioactive secondary metabolites isolated from the branches and leaves of Pittosporum pulchrum Gagnep.

Five new compounds, including two sesquiterpenoid glycosides (1 and 2), two monoterpenoid glycosides (3 and 4), and a quinovose ester (5), together with four known compounds (6-9) were isolated from branches and leaves of Pittosporum pulchrum Gagnep. Their structures were established by 1D and 2D NMR, HR-ESI-MS, IR and UV spectral analyses. This is the first time to investigate the chemical constituents of P. pulchrum. Subsequently, the anti-inflammatory and antioxidant activities of different solvent fractions of ethanol extract and isolated compounds were evaluated. Dichloromethane and ethyl acetate fractions dramatically inhibited the production of NO in a concentration-dependent manner in LPS-induced RAW264.7 cells. Ethyl acetate and n-butanol fractions showed excellent DPPH radical scavenging activities with IC50 values of 24.31 µg/mL and 27.81 µg/mL, respectively. Compounds 7 and 8 might be potential natural antioxidants with IC50 values of 16.13 µM and 24.81 µM, respectively.

[Intraspinal Metastasis of Thymic Carcinoma:Report of One Case].

Intraspinal metastasis from malignant carcinomas in other body parts is rarely reported.Intraspinal metastases are often epidural,with primary tumors mostly from the lung and prostate.The extramedullary subdural metastasis of thymic carcinoma is particularly rare and prone to misdiagnosis due to overlapping imaging features with primary intraspinal tumors.This article reports one case of intraspinal metastasis of thymic carcinoma,with the main diagnostic clues including a history of thymic carcinoma,fast growth rate,and irregular shape.

Psathrosterols C-E, highly conjugated ergosterol derivatives from Psathyrella rogueiana with anti-inflammatory and immunosuppressive activity.

Three new ergosterols featuring with a highly conjugated ring system, psathrosterols C-E (1-3), have been isolated from the fungus Psathyrella rogueiana. The structures with the absolute configurations were elucidated by means of spectroscopic methods and single crystal X-ray diffraction. Compounds 1-3 exhibit inhibitory activity against NO production with IC50 values ranging from 8.4 to 21.8 µM. Compound 1 inhibits the LPS-induced proliferation of B lymphocyte cells with an IC50 value of 12.3 µM.

An Injectable Hydrogel with Ultrahigh Burst Pressure and Innate Antibacterial Activity for Emergency Hemostasis and Wound Repair.

Uncontrolled bleeding and wound infections following severe trauma pose significant challenges for existing tissue adhesives, primarily due to their weak wet adhesion, slow adhesion formation, cytotoxicity concerns, and lack of antibacterial properties. Herein, an injectable hydrogel (denoted as ES gel) with rapid, robust adhesive sealing and inherent antibacterial activity based on ε-polylysine and a poly(ethylene glycol) derivative is developed. The engineered hydrogel exhibits rapid gelation behavior, high mechanical strength, strong adhesion to various tissues, and can sustain an ultrahigh burst pressure of 450 mmHg. It also presents excellent biocompatibility, biodegradability, antibacterial properties, and on-demand removability. Significantly improved hemostatic efficacy of ES gel compared to fibrin glue is demonstrated using various injury models in rats and rabbits. Remarkably, the adhesive hydrogel can effectively halt lethal non-compressible hemorrhages in visceral organs (liver, spleen, and heart) and femoral artery injury models in fully anticoagulated pigs. Furthermore, the hydrogel outperforms commercial products in sutureless wound closure and repair in the rat liver defect, skin incision, and infected full-thickness skin wound models. Overall, this study highlights the promising clinical applications of ES gel for managing uncontrolled hemorrhage, sutureless wound closure, and infected wound repair.

Highly Permeable and Regenerative Microhoneycomb Filters.

Allergic reactions can profoundly influence the quality of life. To address the health risks posed by allergens and overcome the permeability limitations of the current filter materials, this work introduces a novel microhoneycomb (MH) material for practical filter applications such as masks. Through a synthesis process integrating ice-templating and a gas-phase post-treatment with silane, MH achieves unprecedented levels of moisture resistance and mechanical stability while preserving the highly permeable microchannels. Notably, MH is extremely elastic, with a 92% recovery rate after being compressed to 80% deformation. The filtration efficiency surpasses 98.1% against pollutant particles that simulate airborne pollens, outperforming commercial counterparts with fifth-fold greater air permeability while ensuring unparalleled user comfort. Moreover, MH offers a sustainable solution, being easily regenerated through back-flow blowing, distinguishing it from conventional nonwoven fabrics. Finally, a prototype mask incorporating MH is presented, demonstrating its immense potential as a high-performance filtration material, effectively addressing health risks posed by allergens and other harmful particles.

Exploring the multicomponent synergy mechanism of Zuogui Wan on postmenopausal osteoporosis by a systems pharmacology strategy.

OBJECTIVE: To explore the multi-component synergistic mechanism of Zuogui Wan (, ZGW) in treating postmenopausal osteoporosis (PMOP). METHODS: The main components and target genes of ZGW were screened via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). In addition, the target gene sets of PMOP were derived from the GeneCards and Online Mendelian Inheritance in Man databases. The search tool for recurring instances of neighbouring genes (STRING) 11.0 software was used to analyze the interaction among intersecting genes. Cytoscape 3.6.1 software and the Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Fifty Sprague-Dawley female rats were randomly divided into the sham-operated (Sham) group and the four ovariectomized (OVX) subgroups. Rats subjected to Sham or OVX were administered with the vehicle (OVX, 1 mL water/100 g weight), 17ß-estradiol (E2, 50 µg·kg-1·d-1), and lyophilized powder of ZGW at a low dose of 2.3 (ZGW-L) and high dose of 4.6 (ZGW-H) g·kg-1·d-1 for three months. The bone density and bone strength were assessed using dual-energy X-ray and three-point bending tests, respectively. Furthermore, enzyme-linked immun-osorbent assay, Hematoxylin-eosin staining, and western blot analysis were used to determine the potential pharmacological mechanisms of action of ZGW in PMOP. RESULTS: A total of 117 active compounds of ZGW were screened from the TCMSP. Furthermore, 108 intersecting genes of drugs and diseases were identified. Using STRING software and the MCC algorithm, ten core genes, including C-X-C chemokine living 8 (CXCL8), C-C chemokine receptor type 2 (CCR2), alpha-2a active receptor (ADRA2A), melatonin receptor type 1B (MTNR1B), and amyloid-beta A4 protein (APP), were identified. The anti-osteoporosis regulation network of ZGW was constructed using the Cytoscape software. The animal experiments demonstrated that ZGW groups significantly reduced the serum levels of ß-C-terminal telopeptide of type I collagen (ß-CTX) and increased serum levels of bone-specific alkaline phosphatase (BALP) (P < 0.05, P < 0.01). The OVX group exhibited a significant decrease in bone mineral density and bone strength compared with the Sham group (P < 0.01). Moreover, treatment with ZGW resulted in increased trabecular thickness, improved arrangement of trabecular structure, and reduced empty bone lacunae. Furthermore, treatment with ZGW significantly increased the protein expression of CXCL8, ADRA2A, and CCR2 (P < 0.05, P < 0.01), and significantly decreased the protein expression of Runx2 (P < 0.01). Furthermore, the ZGW and E2 groups demonstrated significantly increased BMD (P < 0.05, P < 0.01), improved bone strength (P < 0.05, P < 0.01), reduced expression of CXCL8, ADRA2A, and CCR2, and increased runt-related transcription factor 2 levels in bone tissue (P < 0.05, P < 0.01) compared with the OVX group. However, there were no significant differences in MTNR1B and APP expression among the groups. CONCLUSION: ZGW shows synergistic mechanisms in PMOP through multiple components, targets, and pathways.

Mechanism of Jinteng Qingbi granules in the treatment of rheumatoid arthritis using metabolomics analysis.

This study investigated the differential metabolites after rheumatoid arthritis (RA) rats were treated with Jinteng Qingbi granules. Collagen-induced arthritis rats were divided into three groups, namely normal group, model group, and Jinteng Qingbi granules group. Serum compounds were identified, annotated, and classified using metabolomics to explain the physicochemical properties and biological functions. The metabolites were screened using univariate and multivariate statistical analyses. There were differences in serum metabolites between RA and normal rats; Jinteng Qingbi granules improved RA and recovered the metabolite levels to normal. Compared to the normal group, 51 differential ions were screened, and 108 ions were changed in the Jinteng Qingbi granules group compared to the RA model. Eight metabolites were upregulated in the RA model group compared to the normal group, whereas 10 metabolites were downregulated. Treatment with Jinteng Qingbi granules increased the levels of 12 metabolites such as cinnamate and decreased the levels of 16 metabolites such as allamandin in the RA model. Differential ion enrichment was mainly related to the histidine metabolic pathway in amino acid metabolism. Jinteng Qingbi granules resulted in improvements in the RA model, which were mainly associated with lipids and lipid-like molecules, organic acids, and derivatives, providing a new possibility and basis for screening biomarkers for the diagnosis and treatment of RA.

A preliminary study on the normal values of the thoracic Haller index in children.

OBJECTIVES: The Haller index (HI) is widely utilized as a quantitative indicator to assess the extent of the pectus excavatum (PE) deformity, which is the most common chest wall abnormality in children. Both preoperative correction planning and postoperative follow-up need to be based on the standard of normal thoracic growth and development. However, there is currently no established reference range for the HI in children. Consequently, the goal of this study was to conduct a preliminary investigation of normal HI values among children to understand thoracic developmental characteristics. METHODS: Chest computed tomography images obtained from January 2012 to March 2022 were randomly selected from the imaging system of the Children's Hospital of Chongqing Medical University. We divided the images of children into a total of 19 groups: aged 0-3 months (1 group), 4-12 months (1 group) and 1 year to 17 years (17 groups), with 50 males and 50 females, totaling 100 children in each group. HI was measured in the plane where the lowest point of the anterior thoracic wall was located and statistically analysed using SPSS 26.0 software. RESULTS: A total of 1900 patients were included in the study. Our results showed that HI, transverse diameter and anterior-posterior diameter were positively correlated with age (P < 0.05). Using age as the independent variable and HI as the dependent variable, the best-fit regression equations were HI-male = 2.047 * Age0.054(R2 = 0.276, P<0.0001) and HI-female = 2.045 * Age0.067(R2 = 0.398, P<0.0001). Males had significantly larger thoracic diameters than females, and there was little difference in the HI between the 2 sexes. CONCLUSIONS: The HI rapidly increases during the neonatal period, slowly increases during infancy and stops increasing during puberty, with no significant differences between the sexes.

Deep Learning-Assisted Spectrum-Structure Correlation: State-of-the-Art and Perspectives.

Spectrum-structure correlation is playing an increasingly crucial role in spectral analysis and has undergone significant development in recent decades. With the advancement of spectrometers, the high-throughput detection triggers the explosive growth of spectral data, and the research extension from small molecules to biomolecules accompanies massive chemical space. Facing the evolving landscape of spectrum-structure correlation, conventional chemometrics becomes ill-equipped, and deep learning assisted chemometrics rapidly emerges as a flourishing approach with superior ability of extracting latent features and making precise predictions. In this review, the molecular and spectral representations and fundamental knowledge of deep learning are first introduced. We then summarize the development of how deep learning assist to establish the correlation between spectrum and molecular structure in the recent 5 years, by empowering spectral prediction (i.e., forward structure-spectrum correlation) and further enabling library matching and de novo molecular generation (i.e., inverse spectrum-structure correlation). Finally, we highlight the most important open issues persisted with corresponding potential solutions. With the fast development of deep learning, it is expected to see ultimate solution of establishing spectrum-structure correlation soon, which would trigger substantial development of various disciplines.

Developing a Portable Fluorescence Imaging Device for Fish Freshness Detection.

Rapid detection of fish freshness is of vital importance to ensuring the safety of aquatic product consumption. Currently, the widely used optical detecting methods of fish freshness are faced with multiple challenges, including low detecting efficiency, high cost, large size and low integration of detecting equipment. This research aims to address these issues by developing a low-cost portable fluorescence imaging device for rapid fish freshness detection. The developed device employs ultraviolet-light-emitting diode (UV-LED) lamp beads (365 nm, 10 W) as excitation light sources, and a low-cost field programmable gate array (FPGA) board (model: ZYNQ XC7Z020) as the master control unit. The fluorescence images captured by a complementary metal oxide semiconductor (CMOS) camera are processed by the YOLOv4-Tiny model embedded in FPGA to obtain the ultimate results of fish freshness. The circuit for the YOLOv4-Tiny model is optimized to make full use of FPGA resources and to increase computing efficiency. The performance of the device is evaluated by using grass carp fillets as the research object. The average accuracy of freshness detection reaches up to 97.10%. Moreover, the detection time of below 1 s per sample and the overall power consumption of 47.1 W (including 42.4 W light source power consumption) indicate that the device has good real-time performance and low power consumption. The research provides a potential tool for fish freshness evaluation in a low-cost and rapid manner.

Bioorthogonal/Ultrasound Activated Oncolytic Pyroptosis Amplifies In Situ Tumor Vaccination for Boosting Antitumor Immunity.

Personalized in situ tumor vaccination is a promising immunotherapeutic modality. Currently, seeking immunogenic cell death (ICD) to generate in situ tumor vaccines is still mired by insufficient immunogenicity and an entrenched immunosuppressive tumor microenvironment (TME). Herein, a series of tetrazine-functionalized ruthenium(II) sonosensitizers have been designed and screened for establishing a bioorthogonal-activated in situ tumor vaccine via oncolytic pyroptosis induction. Based on nanodelivery-augmented bioorthogonal metabolic glycoengineering, the original tumor is selectively remolded to introduce artificial target bicycle [6.1.0] nonyne (BCN) into cell membrane. Through specific bioorthogonal ligation with intratumoral BCN receptors, sonosensitizers can realize precise membrane-anchoring and synchronous click-activation in desired tumor sites. Upon ultrasound (US) irradiation, the activated sonosensitizers can intensively disrupt the cell membrane with dual type I/II reactive oxygen species (ROS) generation for a high-efficiency sonodynamic therapy (SDT). More importantly, the severe membrane damage can eminently evoke oncolytic pyroptosis to maximize tumor immunogenicity and reverse immunosuppressive TME, ultimately eliciting powerful and durable systemic antitumor immunity. The US-triggered pyroptosis is certified to effectively inhibit the growths of primary and distant tumors, and suppress tumor metastasis and recurrence in "cold" tumor models. This bioorthogonal-driven tumor-specific pyroptosis induction strategy has great potential for the development of robust in situ tumor vaccines.

Naturally Derived Injectable Dual-Cross-Linked Adhesive Hydrogel for Acute Hemorrhage Control and Wound Healing.

Developing biocompatible injectable hydrogels with high mechanical strength and rapid strong tissue adhesion for hemostatic sealing of uncontrolled bleeding remains a prevailing challenge. Herein, we engineer an injectable and photo-cross-linkable hydrogel based on naturally derived gelatin methacrylate (GelMA) and N-hydroxysuccinimide-modified poly(γ-glutamic acid) (γPGA-NHS). The chemically dual-cross-linked hydrogel rapidly forms after UV light irradiation and covalently bonds to the underlying tissue to provide robust adhesion. We demonstrate a significantly improved hemostatic efficacy of the hydrogel using various injury models in rats compared to the commercially available fibrin glue. Notably, the hydrogel can achieve hemostasis in porcine liver and spleen incision, and femoral artery puncture models. Moreover, the hydrogel is used for sutureless repair of the liver defect in a rat model with a significantly suppressed inflammatory response, enhanced angiogenesis, and superior healing efficacy compared to fibrin glue. Together, this study offers a promising bioadhesive for treating severe bleeding and facilitating wound repair.

How the chemical structure of phosphoramides affect the fire retardancy and mechanical properties of polylactide?

Phosphoramides, as a kind of high-efficient fire retardants, have been designed in many structures and endowed exceptional fire retardancy to polylactide (PLA). However, due to ignorance of the structure-property correlation, the effect of phosphoramides' structure on the fire retardancy and mechanical properties of PLA is still unclear. Herein, a series of biobased phosphoramides (phosphoramide (V1), linear polyphosphoramide (V2) and hyperbranched polyphosphamide (V3)) were designed and incorporated into PLA, and the structural effect of phosphoramides on the fire-retardant and mechanical properties of PLA was deeply researched. Among three kinds of phosphoramides, the hyperbranched polyphosphoramide is more effective than the corresponding linear polyphosphoramide and phosphoramide in improving the fire-retardant and anti-dripping properties of PLA, and only linear polyphosphoramide shows a positive effect in the mechanical strength of PLA. This work provides a feasible strategy for creating mechanically robust and fire-retardant polymer composites by molecularly tailoring the structure of fire retardants and uncovering their structure-property relationship.

Randomized Double-Blinded Comparison of Intermittent Boluses Phenylephrine and Norepinephrine for the Treatment of Postspinal Hypotension in Patients with Severe Pre-Eclampsia During Cesarean Section.

Background: Norepinephrine has fewer negative effects on heart rate (HR) and cardiac output (CO) for treating postspinal hypotension (PSH) compared with phenylephrine during cesarean section. However, it remains unclear whether fetuses from patients with severe pre-eclampsia could benefit from the superiority of CO. The objective of this study was to compare the safety and efficacy of intermittent intravenous boluses of phenylephrine and norepinephrine used in equipotent doses for treating postspinal hypotension in patients with severe pre-eclampsia during cesarean section. Methods: A total of 80 patients with severe pre-eclampsia who developed PSH predelivery during cesarean section were included. Eligible patients were randomized at a 1:1 ratio to receive either phenylephrine or norepinephrine for treating PSH. The primary outcome was umbilical arterial pH. Secondary outcomes included other umbilical cord blood gas values, Apgar scores at 1 and 5 min, changes in hemodynamic parameters including CO, mean arterial pressure (MAP), HR, stroke volume (SV), and systemic vascular resistance (SVR), the number of vasopressor boluses required, and the incidence of bradycardia, hypertension, nausea, vomiting, and dizziness. Results: No significant difference was observed in umbilical arterial pH between the phenylephrine and norepinephrine groups (7.303±0.38 vs 7.303±0.44, respectively; P=0.978). Compared with the phenylephrine group, the overall CO (P=0.009) and HR (P=0.015) were greater in the norepinephrine group. The median [IQR] total number of vasopressor boluses required was comparable between the two groups (2 [1 to 3] and 2 [1 to 3], respectively; P=0.942). No significant difference was found in Apgar scores or the incidence of maternal complications between groups. Conclusion: A 60 µg bolus of phenylephrine and a 4.5 µg bolus of norepinephrine showed similar neonatal outcomes assessed by umbilical arterial pH and were equally effective when treating PSH during cesarean section in patients with severe pre-eclampsia. Norepinephrine provided a higher maternal CO and a lower incidence of bradycardia.

Total iridoid glycoside extract of Lamiophlomis rotata (Benth) Kudo accelerates diabetic wound healing by the NRF2/COX2 axis.

BACKGROUND: Lamiophlomis rotata (Benth.) Kudo (L. rotata), the oral Traditional Tibetan herbal medicine, is adopted for treating knife and gun wounds for a long time. As previously demonstrated, total iridoid glycoside extract of L. rotata (IGLR) induced polarization of M2 macrophage to speed up wound healing. In diabetic wounds, high levels inflammatory and chemotactic factors are usually related to high reactive oxygen species (ROS) levels. As a ROS target gene, nuclear factor erythroid 2-related factor 2 (NRF2), influences the differentiation of monocytes to M1/M2 macrophages. Fortunately, iridoid glycosides are naturally occurring active compounds that can be used as the oxygen radical scavenger. Nevertheless, the influence of IGLR in diabetic wound healing and its associated mechanism is largely unclear. MATERIALS AND METHODS: With macrophages and dermal fibroblasts in vitro, as well as a thickness excision model of db/db mouse in vivo, the role of IGLR in diabetic wound healing and the probable mechanism of the action were investigated. RESULTS: Our results showed that IGLR suppressed oxidative distress and inflammation partly through the NRF2/cyclooxygenase2 (COX2) signaling pathway in vitro. The intercellular communication between macrophages and dermal fibroblasts was investigated by the conditioned medium (CM) of IGLR treatment cells. The CM increased the transcription and translation of collagen I (COL1A1) and alpha smooth muscle actin (α-SMA) within fibroblasts. With diabetic wound mice, the data demonstrated IGLR activated the NRF2/KEAP1 signaling and the downstream targets of the pathway, inhibited COX2/PEG2 signaling and decreased the interaction inflammatory targets of the axis, like interleukin-1beta (IL-1ß), interleukin 6 (IL-6), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase1 (caspase1) and NOD-like receptor-containing protein 3 (NLRP3).In addition, the deposition of COL1A1, and the level of α-SMA, and Transforming growth factor-ß1 (TGF-ß1) obviously elevated, whereas that of pro-inflammatory factors reduced in the diabetic wound tissue with IGLR treatment. CONCLUSION: IGLR suppressed oxidative distress and inflammation mainly through NRF2/COX2 axis, thus promoting paracrine and accelerating wound healing in diabetes mice.

Conditioned Media from Deer Antler Stem Cells Effectively Alleviate Type 1 Diabetes Mellitus Possibly via Inhibiting the NF-κB Signaling Pathway.

BACKGROUND: Type 1 diabetes mellitus (T1D) represents a severe threat to human health. Persistent hyperglycemia and dyslipidemia can lead to damaged liver function, while effective interventions for these complications are currently lacking. Deer antler stem cells (AnSCs), a novel type of adult stem cells, significantly reduced liver injury, which was speculated to be achieved through the paracrine pathway. METHODS: In this study, AnSC-conditioned medium (AnSC-CM) was used to treat C57BL/6 mice with T1D symptoms induced by streptozotocin (STZ). The therapeutic effects of AnSC-CM on T1D were evaluated, and the underlying mechanism was investigated. RESULTS: It was shown that AnSC-CM alleviated the T1D symptom: decreased body weight, increased blood glucose levels and islet lesions, and reduced insulin secretion. Moreover, AnSC-CM treatment improved liver function and mitigated liver injury in T1D mice. Impressively, the therapeutic effects of AnSC-CM on T1D were better than those of bone marrow mesenchymal stem cell-CM (BMSC-CM). The mechanistic study revealed that AnSC-CM significantly downregulated the NF-κB signaling pathway in both pancreatic and liver tissues. CONCLUSIONS: Therapeutic effects of AnSC-CM on STZ-induced T1D and liver injury may be achieved through targeting the NF-κB signaling pathway.

Rational design of ICD-inducing nanoparticles for cancer immunotherapy.

Nanoparticle-based cancer immunotherapy has shown promising therapeutic potential in clinical settings. However, current research mainly uses nanoparticles as delivery vehicles but overlooks their potential to directly modulate immune responses. Inspired by the endogenous endoplasmic reticulum (ER) stress caused by unfolded/misfolded proteins, we present a rationally designed immunogenic cell death (ICD) inducer named NanoICD, which is a nanoparticle engineered for ER targeting and retention. By carefully controlling surface composition and properties, we have obtained NanoICD that can effectively accumulate in the ER, induce ER stress, and activate ICD-associated immune responses. In addition, NanoICD is generally applicable to various proteins and enzymes to further enhance the immunomodulatory capacity, exemplified by encapsulating catalase (CAT) to obtain NanoICD/CAT, effectively alleviated immunosuppressive tumor microenvironment and induced robust antitumor immune responses in 4T1-bearing mice. This work demonstrates engineered nanostructures' potential to autonomously regulate biological processes and provides insights into the development of advanced nanomedicines for cancer treatment.