Impact of postsurgical rehabilitation on outcomes for degenerative cervical myelopathy.

OBJECTIVE: Despite widespread use, there is limited evidence to support postsurgical rehabilitation to enhance neurological recovery after surgery for degenerative cervical myelopathy (DCM). Outcomes research for DCM seldom accounts for the effect of postsurgical rehabilitation. The aim of this study was to quantify the impact of postsurgical rehabilitation on outcomes after surgery for DCM. METHODS: This was a retrospective analysis of prospectively collected data from a single center. The study enrolled 66 patients who underwent spinal surgery for DCM. In addition to patient demographic, imaging, and surgical data, chart review was performed to document the timing, type, duration, and outcomes of postsurgical rehabilitation therapy. Outcomes were collected prospectively, including the modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI) score, and SF-36 physical component summary (PCS) score. Linear regression models were created to determine the independent effects of type and timing of postsurgical occupational therapy (OT) and physical therapy (PT) on outcomes. RESULTS: A total of 66 patients were included in the analysis. Multivariate regression analysis showed that postsurgical OT was associated with significantly greater improvement in 12-month SF-36 PCS scores (p = 0.009) and mJOA scores (p = 0.019). In the subset of patients who received therapy, delayed therapy (> 42 days after surgery) compared to early therapy (< 42 days after surgery) was associated with less improvement in SF-36 PCS scores (p = 0.03). CONCLUSIONS: Postsurgical outpatient rehabilitation was independently associated with improved postsurgical outcomes within the 1st year after surgery for DCM, and early therapy (< 42 days) was associated with superior outcomes compared to delayed therapy. This is one of the first studies to use a prospective database to demonstrate an independent effect for postsurgical rehabilitation on outcomes after surgery for DCM.

Predicting the geographical distribution and niche characteristics of Cotoneaster multiflorus based on future climate change.

Introduction: Arid and semi-arid regions are climate-sensitive areas, which account for about 40% of the world's land surface area. Future environment change will impact the environment of these area, resulting in a sharp expansion of arid and semi-arid regions. Cotoneaster multiflorus is a multi-functional tree species with extreme cold, drought and barren resistance, as well as ornamental and medicinal functions. It was found to be one of the most important tree species for ecological restoration in arid and semi-arid areas. However, bioclimatic factors play an important role in the growth, development and distribution of plants. Therefore, exploring the response pattern and ecological adaptability of C. multiflorus to future climate change is important for the long-term ecological restoration of C. multiflorus in arid and semi-arid areas. Methods: In this study, we predicted the potential distribution of C. multiflorus in China under different climate scenarios based on the MaxEnt 2.0 model, and discussed its adaptability and the major factors affecting its geographical distribution. Results: The major factors that explained the geographical distribution of C. multiflorus were Annual precipitation (Bio12), Min air temperature of the coldest month (Bio6), and Mean air temperature of the coldest quarter (Bio11). However, C. multiflorus could thrive in environments where Annual precipitation (Bio12) >150 mm, Min air temperature of the coldest month (Bio6) > -42.5°C, and Mean air temperature of the coldest quarter (Bio11) > -20°C, showcasing its characteristics of cold and drought tolerance. Under different future climate scenarios, the total suitable area for C. multiflorus ranged from 411.199×104 km² to 470.191×104 km², which was 0.8~6.14 percentage points higher than the current total suitable area. Additionally, it would further shift towards higher latitude. Discussion: The MaxEnt 2.0 model predicted the potential distribution pattern of C. multiflorus in the context of future climate change, and identified its ecological adaptability and the main climatic factors affecting its distribution. This study provides an important theoretical basis for natural vegetation restoration in arid and semi-arid areas.

Hybrid chiral nanocellulose-cyanidin composite with pH and humidity response for visual inspection and real-time tracking of shrimp quality and freshness.

Biobased multi-stimulation materials have received considerable attention for intelligent packaging and anti-counterfeiting applications. Cellulose nanocrystals (CNCs) and cyanidins are good material candidates for monitoring food freshness as they are eco-friendly natural substances. This work incorporated cyanidin with a CNC-hosting substrate to develop a simple, environment-friendly colorimetric device to visualize food freshness. Across the pH range of 2-13, the indicator exhibited noticeable color changes ranging from red to gray and eventually to orange. The CNC-cyanidin (CC) film exhibited a dramatic color change from blue to dark red and high sensitivity at a relative humidity of 30 %-100 %. In corresponding to the total volatile elemental nitrogen (TVB-N) level of shrimp, the indicator showed distinguishable colors at different stages of shrimp. The findings imply that the samples have substantial potential for use as an intelligent indicator for tracking shrimp freshness.

Ureteroplasty with buccal mucosa graft without omental wrap: an effective method to treat ureteral strictures.

PURPOSE: Successful treatment options for ureteral strictures are limited. Surgical options such as ileal interposition and kidney autotransplantation are difficult and associated with morbidity and complications. Techniques such as Boari flap and psoas hitch are limited to distal strictures. Only limited case studies on the success of open buccal mucosa graft (BMG) ureteroplasty exist to this date. The purpose of this study was to evaluate the success of open BMG ureteroplasty without omental wrap. METHODS: In this single-center retrospective study between July 2020 and January 2023, we included 14 consecutive patients with ureteric strictures who were treated with open BMG ureteroplasty without omental wrap. The primary outcome was the success of open BMG ureteroplasty. Further endpoints were complications and hospital readmission. Outcome variables were assessed by clinical examination, kidney sonography, and patient anamnesis. RESULTS: Out of 14 patients, 13 were stricture and ectasia-free without a double-J stent at a median follow-up of 15 months (success rate 93%). No complications were observed at the donor site, and the complication rate overall was low with 3 out of 14 patients (21%) having mild-to-medium complications. CONCLUSIONS: Open BMG ureteroplasty without omental wrap is a successful and feasible technique for ureteric stricture repair.

Arginine-Nanoenzyme with Timely Angiogenesis for Promoting Diabetic Wound Healing.

The successful treatment of diabetic wounds requires strategies that promote anti-inflammation, angiogenesis, and re-epithelialization of the wound. Excessive oxidative stress in diabetic ulcers (DUs) inhibits cell proliferation and hinders timely vascular formation and macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2, resulting in a persistent inflammatory environment and a nonhealing wound. We designed arginine-nanoenzyme (FTA) with mimic-catalase and arginine-loading. 2,3,4-trihydroxy benzaldehyde and arginine (Arg) were connected by a Schiff base bond, and the nanoassembly of Arg to FTA was driven by the coordination force between a ferric ion and polyphenol and noncovalent bond force such as a hydrogen bond. FTA could remove excess reactive oxygen species at the wound site in situ and convert it to oxygen to improve hypoxia. Meanwhile, Arg was released and catalytically metabolized by NO synthase in M1 to promote vascular repair in the early phase. In the late phase, the metabolite of Arg catalyzed by arginase in M2 was mainly ornithine, which played a vital role in promoting tissue repair, which implemented angiogenesis timely and prevented hypertrophic scars. Mechanistically, FTA activated the cAMP signaling pathway combined with reducing inflammation and ameliorating angiogenesis, which resulted in excellent therapeutic effects on a DU mice model.

Fibration of powdery materials.

Non-destructive processing of powders into macroscopic materials with a wealth of structural and functional possibilities has immeasurable scientific significance and application value, yet remains a challenge using conventional processing techniques. Here we developed a universal fibration method, using two-dimensional cellulose as a mediator, to process diverse powdered materials into micro-/nanofibres, which provides structural support to the particles and preserves their own specialties and architectures. It is found that the self-shrinking force drives the two-dimensional cellulose and supported particles to pucker and roll into fibres, a gentle process that prevents agglomeration and structural damage of the powder particles. We demonstrate over 120 fibre samples involving various powder guests, including elements, compounds, organics and hybrids in different morphologies, densities and particle sizes. Customized fibres with an adjustable diameter and guest content can be easily constructed into high-performance macromaterials with various geometries, creating a library of building blocks for different fields of applications. Our fibration strategy provides a universal, powerful and non-destructive pathway bridging primary particles and macroapplications.

A novel grading approach predicts worse outcomes in stage pT1 non-muscle-invasive bladder cancer.

OBJECTIVE: To develop a prognostically relevant scoring system for stage pT1 non-muscle-invasive bladder cancer (NMIBC) incorporating tumour budding, growth pattern and invasion pattern because the World Health Organisation grading system shows limited prognostic value in such patients. PATIENTS AND METHODS: The tissue specimens and clinical data of 113 patients with stage pT1 NMIBC who underwent transurethral resection of bladder tumour were retrospectively investigated. Tumour budding, and growth and invasion patterns were evaluated and categorised into two grade groups (GGs). GGs and other clinical and histopathological variables were investigated regarding recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS) using univariable and multivariable Cox regression analyses. RESULTS: The integration of two tumour budding groups, two growth patterns, and two invasion patterns yielded an unfavourable GG (n = 28; 24.7%) that had a high impact on oncological outcomes. The unfavourable GG was identified as an independent RFS and OS predictor (P = 0.004 and P = 0.046, respectively) and linked to worse PFS (P = 0.001) and CSS (P = 0.001), irrespective of the European Association of Urology risk group. The unfavourable GG was associated with higher rates of BCG-unresponsive tumours (P = 0.006). Study limitations include the retrospective, single-centre design, diverse therapies and small cohort. CONCLUSIONS: We present a morphology-based grading system for stage pT1 NMIBC that correlates with disease aggressiveness and oncological patient outcomes. It therefore identifies a highest risk group of stage pT1 NMIBC patients, who should be followed up more intensively or receive immediate radical cystectomy. The grading incorporates objective variables assessable on haematoxylin and eosin slides and immunohistochemistry, enabling an easy-to-use low-cost approach that is applicable in daily routine. Further studies are needed to validate and confirm these results.

PIM3 regulates myocardial ischemia/reperfusion injury via ferroptosis.

BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury is closely related with cardiovascular diseases; however, the underlying pathogenic mechanisms remain not fully understood. This study sought to investigate the effect and mechanisms of PIM3 implicated in myocardial I/R injury using a rat model of myocardial I/R injury and a cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) induction. METHODS: The morphology changes were detected by HE staining while cell viability was accessed by the CCK-8 method. The characteristics of ferroptosis were evaluated by ROS production, MDA content, SOD level, iron content, TfR1, FTH1, and GPX4 expression. RESULTS: Myocardial I/R operation increased myocardial tissue damage in rats, while OGD/R treatment reduced the viability of H9c2 cells. Both myocardial I/R operation and OGD/R stimulation increased ferroptosis, as demonstrated by elevated ROS, MDA, iron content, decreased SOD level, upregulation of TfR1, and downregulation of FTH1 and GPX4. Additionally, myocardial I/R modeling or OGD/R treatment enhanced the expression of PIM3. Silencing of PIM3 inhibited ferroptosis, which resulted in alleviated myocardial I/R-induced damage and improved H9c2 cell survival. CONCLUSIONS: Our findings highlight a vital role of PIM3 in myocardial I/R injury, indicating that PIM3-targeting ferroptosis may be a promising target for the development of novel therapies of myocardial I/R injury-associated diseases.

Antioxidant-Engineered Milk-Derived Extracellular Vesicles for Accelerating Wound Healing via Regulation of the PI3K-AKT Signaling Pathway.

Inspired by the experience of relieving inflammation in infants with milk, antioxidant-engineered milk-derived extracellular vesicles (MEVs) are developed to evaluate their potential for accelerating wound healing. In this work, MEVs with polydopamines (PDA) are engineered using the co-extrusion method. Subsequently, the authors incorporated them into a Schiff-based crosslink hydrogel, forming a skin dosage form that could facilitate the wound healing process. The antioxidant properties of PDA assist in the anti-inflammatory function of engineered MEVs, while the gel provides better skin residency. The PDA@MEVs+GEL formulation exhibits excellent biocompatibility, pro-angiogenic capacity, and antioxidant ability in vitro. Furthermore, in vivo experiments demonstrate its efficacy in wound repair and inflammation inhibition. Mechanistically, PDA@MEVs+GEL simultaneously promotes the growth, migration, and anti-inflammation of 3T3 cells by activating PI3K-AKT pathway. Moreover, PDA@MEVs+GEL exhibits enhanced functionality in promoting wound healing in vivo, attributed to its ability to inhibit inflammation, stimulate angiogenesis, and promote collagen synthesis. In conclusion, this study delves into the mechanism of MEVs and underscores the improved efficacy of engineered extracellular vesicles. Additionally, the feasibility and prospect of engineered MEVs in treating skin wounds are verified, suggesting that antioxidant-engineered MEVs could be a promising therapeutic agent for wound healing applications.

Effectiveness of smartphone-assisted cardiac rehabilitation: a systematic review and meta-analysis.

PURPOSE: To explore the effectiveness of smartphone-assisted home cardiac rehabilitation and whether it can be used as a remote detection method to promote home cardiac rehabilitation. METHODS: Four databases were searched to collect randomized controlled trials (RCTs) about smartphone-assisted cardiac rehabilitation. The Cochrane risk-of-bias tool was used to assess the methodological quality of the included studies. Two independent investigators performed the literature screening, information extraction, and risk of bias assessment. Any disagreements were resolved by a third investigator. Meta-analysis and systematic review were performed. Sensitivity analysis and subgroup analysis were carried out to explore the sources of heterogeneity. RESULTS: A total of 14 RCTs involving 1962 patients were included. Meta-analysis showed that compared with conventional cardiac rehabilitation/usual care, smartphone-assisted cardiac rehabilitation significantly improved VO2peak in patients with cardiovascular disease (WMD= 1.32, 95%CI:0.82 to 1.81, p > 0.05) and enhanced their treatment compliance (RR = 1.62, 95%CI:1.21 to 2.17, p > 0.05). There were no significant differences in six-minute walk distance (WMD = 12.88, 95%CI:-0.82 to 26.57, p > 0.05), body mass index (BMI) (WMD=-0.14, 95%CI:-0.34 to 0.06, p > 0.05), life quality, psychological status, and other cardiovascular risks. CONCLUSION: Smartphone-assisted cardiac rehabilitation showed significant improvement in exercise capacity and treatment compliance in patients with cardiac rehabilitation but did not improve BMI, quality of life, psychological status, or reduce other cardiovascular risks. Smartphone-based cardiac rehabilitation is increasingly used as a remote detection method for cardiac rehabilitation in middle-income countries, which provides new insights into home cardiac rehabilitation.

Smartphone-assisted cardiac rehabilitation showed significant improvement in exercise capacity and treatment compliance in patients with cardiac rehabilitation.Smartphone-assisted cardiac rehabilitation showed no significant improvements in body mass index, quality of life, psychological status, and other cardiovascular risk.Smartphone-based cardiac rehabilitation is increasingly used as a remote detection method for cardiac rehabilitation in middle-income countries, which provides new insights into home cardiac rehabilitation.

NF-κB pathway affects silica nanoparticle-induced fibrosis via inhibited inflammatory response and epithelial-mesenchymal transition in 3D co-culture.

Long-term inhalation of silica nanoparticles (SiNPs) can induce pulmonary fibrosis (PF), nevertheless, the potential mechanisms remain elusive. Herein, we constructed a three-dimensional (3D) co-culture model by using Matrigel to investigate the interaction among different cells and potential regulatory mechanisms after SiNPs exposure. Methodologically, we dynamically observed the changes in cell morphology and migration after exposure to SiNPs by co-culturing mouse monocytic macrophages (RAW264.7), human non-small cell lung cancer cells (A549), and medical research council cell strain-5 (MRC-5) in Matrigel for 24 h. Subsequently, we detected the expression of nuclear factor kappa B (NF-κB), inflammatory factor and epithelial-mesenchymal transition (EMT) markers. The results showed that SiNPs produced toxic effects on cells. In the 3D co-culture state, the cell's movement velocity and displacement increased, and the cell migration ability was enhanced. Meanwhile, the expression of inflammatory factor tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) were upregulated, the epithelial marker E-cadherin (E-cad) was downregulated, the mesenchymal marker N-cadherin (N-cad) and myofibroblast marker alpha-smooth muscle actin (α-SMA) expression were upregulated, while NF-κB expression was also upregulated after SiNPs exposure. We further found that cells were more prone to transdifferentiate into myofibroblasts in the 3D co-culture state. Conversely, utilizing the NF-κB-specific inhibitor BAY 11-7082 effectively downregulated the expression of TNF-α, IL-6, interleukin-1ß (IL-1ß), N-cad, α-SMA, collagen-I (COL I), and fibronectin (FN), the expression of E-cad was upregulated. These findings suggest that NF-κB is involved in regulating SiNPs-induced inflammatory, EMT, and fibrosis in the 3D co-culture state.

A Versatile 2D Cellulose Platform Strategy from Natural Wood Scaffold.

A wood cell wall with cellulose as the key scaffold is a natural hierarchical lamellar structure. This wood-derived cellulose scaffold has recently attracted enormous attention and interest, but almost all efforts have been devoted to its whole tissue functionalization. Here, we report the short ultrasonic processing of a wood cellulose scaffold to directly generate 2D cellulose materials. The obtained 2D cellulose nanosheets consist of many highly oriented fibrils densely arranged and can be further converted to ultrathin 2D carbon nanosheets. The nanoparticles, nickel-iron layer double hydroxide nanoflowers, manganese dioxide nanorods, and zinc oxide nanostars, are successfully loaded in the 2D nanosheet, providing a versatile 2D platform strategy for excellent 2D hybrid nanomaterials.

Gilteritinib-induced severe immune-related enteritis: a possible case report.

Gilteritinib is currently approved in China for relapsed/refractory FLT3-mutated acute myeloid leukemia, and it is very important to monitor and report its adverse drug reaction (ADR) after post-marketing. This case report describes a patient who was diagnosed with acute myeloid leukemia harboring FLT3 mutations and developed a severe suspected immune-related enteritis during treatment with gilteritinib for maintenance therapy following allo-hematopoietic stem cell transplantation. According to the Naranjo probability scale, gilteritinib was defined as a 'possible' cause of ADR. Another suspicious inducement, graft-versus-host disease, can not be eluted and might represent a limitation in this case. To the best of our knowledge, this is the first report on gilteritinib-induced severe enteritis and will help physicians to keep vigilant, and detect and deal with time for possible ADR.

Dual-Network Structured Nanofibrous Membranes with Superelevated Interception Probability for Extrafine Particles.

Airborne particulate matter (PM) pollution has caused a public health threat, including nanoscale particles, especially with emerging infectious diseases and indoor and vehicular environmental pollution. However, most existing indoor air filtration units are expensive, energy-intensive, and bulky, and there is an unavoidable trade-off between low-efficiency PM0.3/pathogen interception, PM removal, and air resistance. Herein, we designed and synthesized a two-dimensional continuous cellulose-sheath/net with a unique dual-network corrugated architecture to manufacture high-efficiency air filters and even N95 particulate face mask. Combined with its sheath/net structured pores (size 100-200 nm) consisting of a cellulose framework (1-100 nm diameter), the cellulose sheath/net filter offers high-efficiency air filtration (>99.5338%, Extrafine particles; >99.9999%, PM2.5), low-pressure drops, and a robustness quality factor of >0.14 Pa-1, utilizing their ultralight weight of 30 mg/m2 and physical adhesion and sieving behaviors. Simultaneously, masks prepared with cellulose-sheath/net filters are more likely to capture and block smaller particles than the N95 standard. The synthesis of such materials with their nanoscale features and designed macrostructures may suggest new design criteria for a novel generation of high-efficiency air filter media for different applications such as personal protection products and industrial dust removal.

Epoxy-functionalized polyethyleneimine modified epichlorohydrin-cross-linked cellulose aerogel as adsorbents for carbon dioxide capture.

Developing affordable and effective carbon dioxide (CO2) capture technology has attracted substantial intense attention due to the continued growth of global CO2 emissions. The low-cost and biodegradable cellulosic materials are developed into CO2 adsorbent recently. Epoxy-functionalized polyethyleneimine modified epichlorohydrin-cross-linked cellulose aerogel (EBPCa) was synthesized from alkaline cellulose solution, epoxy-functionalized polyethyleneimine (EB-PEI), and epichlorohydrin (ECH) through the freezing-thawing processes and freeze-drying. The Fourier transform infrared spectroscopy confirmed that the cellulose aerogel was successfully modified by EB-PEI. The X-ray photoelectron spectroscopy analyses confirmed the presence of N 1s and Cl 2p in EBPCa, meaning that the chlorine of ECH and the amino groups of EB-PEI exist in the cellulose surface. The obtained sample has a rich porous structure with a specific surface area in the range of 97.5-149.5 m2/g. Owing to its uniformly three-dimensional porous structure, the sample present preferable rigidity and carrying capacity, which 1 g of sample could easily carry the weight of a 3000 ml Erlenmeyer flask filled with water (total 4 kg). The sample showed good adsorption performance, with a maximum adsorption capacity of 6.45 mmol/g. This adsorbent has broad prospects in the CO2 capture process.

Labeling Assembly of Hydrophilic Methionine into Nanoparticle for Mild-Heat Mediated Immunometabolic Therapy.

Methionine metabolism has a significant impact on T cells' survival and activation even in comparison to arginine, a well-documented amino acid in metabolic therapy. However, hydrophilic methionine is hardly delivered into TME due to difficult loading and rapid diffusion. Herein, the labeling assembly of methionine into nanoparticle is developed to overcome high hydrophilicity for mild-heat mediated immunometabolic therapy. The strategy is to first label methionine with protocatechualdehyde (as the tag) via reversible Schiff-base bond, and then drive nanoassembly of methionine (MPC@Fe) mediated by iron ions. In this fashion, a loading efficiency of 40% and assembly induced photothermal characteristics can be achieved. MPC@Fe can accumulate persistently in tumor up to 36 h due to tumor-selective aggregation in acidic TME. A mild heat of 43 °C on tumor by light irradiation stimulated the immunogenic cell death and effectively generated CD8+ T cells. Notably, MPC@Fe assisted by mild heat promoted 4.2-fold of tumor-infiltrating INF-γ+ CD8+ T cells, leading to an inhibition ratio of 27.3-fold versus the free methionine. Such labeling assembly provides a promising methionine delivery platform to realize mild heat mediated immunometabolic therapy, and is potentially extensible to other amino acids.

Microenvironment-Based Diabetic Foot Ulcer Nanomedicine.

Diabetic foot ulcers (DFU), one of the most serious complications of diabetes, are essentially chronic, nonhealing wounds caused by diabetic neuropathy, vascular disease, and bacterial infection. Given its pathogenesis, the DFU microenvironment is rather complicated and characterized by hyperglycemia, ischemia, hypoxia, hyperinflammation, and persistent infection. However, the current clinical therapies for DFU are dissatisfactory, which drives researchers to turn attention to advanced nanotechnology to address DFU therapeutic bottlenecks. In the last decade, a large number of multifunctional nanosystems based on the microenvironment of DFU have been developed with positive effects in DFU therapy, forming a novel concept of "DFU nanomedicine". However, a systematic overview of DFU nanomedicine is still unavailable in the literature. This review summarizes the microenvironmental characteristics of DFU, presents the main progress of wound healing, and summaries the state-of-the-art therapeutic strategies for DFU. Furthermore, the main challenges and future perspectives in this field are discussed and prospected, aiming to fuel and foster the development of DFU nanomedicines successfully.

Dynamic tagging to drive arginine nano-assembly to metabolically potentiate immune checkpoint blockade therapy.

L-arginine metabolism is essential for the activation, survival, and effector function of the T lymphocytes and critical in eliminating tumors via T-cell-mediated immunotherapy, such as immune checkpoint blockade (ICB). Unfortunately, efficient delivery of hydrophilic L-arginine to the tumor microenvironment (TME) has met tremendous difficulties because of the limited loading efficacy and rapid diffusion. Inspired by the small-molecule prodrug nanoassemblies with ultrahigh drug-loading, we screen out aromatic aldehydes compounds to be used as dynamic tags to decorate L-arginine (reversible imine). Nano-Arginine (ArgNP, 104 nm) was created based on dynamic tag-mediated self-assembly. Molecular dynamics simulations indicate that the driving force of this self-assembly process is intermolecular hydrogen bonds, π-π stacking, and cation-π interactions. Notably, ArgNP metabolic synergy with anti-PD-L1 antibody (aPDL1) can promote tumor-infiltrating T cells (3.3-fold than aPDL1), resulting in a tumor inhibition ratio of 2.6-fold than aPDL1. Besides, such a strategy efficiently reduces the myeloid-derived suppressor cells, increases the M1-macrophages against the tumor, and induces the production of memory T cells. Furthermore, this synergistic therapy effectively restrains lung metastasis and prolongs mouse survival (60% survival ratio). The study highlights the dynamic tags strategy with facility and advance to deliver L-arginine that can metabolically promote ICB therapy.

Silica nanoparticle exposure inhibits surfactant protein A and B in A549 cells through ROS-mediated JNK/c-Jun signaling pathway.

Exposure to silica nanoparticles (SiNPs) is related to the dysregulation of pulmonary surfactant that maintains lung stability and function. Nevertheless, there are limited studies concerning the interaction and influence between SiNPs and pulmonary surfactant, and the damage and mechanism are still unclear. Herein, we used A549 cells to develop an in vitro model, with which we investigated the effect of SiNPs exposure on the expression of pulmonary surfactant and the potential regulatory mechanism. The results showed that SiNPs were of cytotoxicity in regarding of reduced cell viability and promoted the production of excessive reactive oxygen species (ROS). Additionally, the JNK/c-Jun signaling pathway was activated, and the expression of surfactant protein A (SP-A) and surfactant protein B (SP-B) was decreased. After the cells being treated with N-acetyl-L-cysteine (NAC), we found that the ROS content was effectively downregulated, and the expression of proteins related to JNK and c-Jun signaling pathways was suppressed. In contrast, the expression of SP-A and SP-B was enhanced. Furthermore, we treated the cells with JNK inhibitor and c-Jun-siRNA and found that the expression of protein related to JNK and c-Jun signaling pathways, as well as SP-A and SP-B, changed in line with that of NAC treatment. These findings suggest that SiNPs exposure can upregulate ROS and activate the JNK/c-Jun signaling pathway in A549 cells, thereby inhibiting the expression of SP-A and SP-B proteins.

NF-κB mediates silica-induced pulmonary inflammation by promoting the release of IL-1ß in macrophages.

Long-term exposure to respirable silica particles causes pulmonary inflammation and fibrosis primarily promoted by cytokines released from alveolar macrophages, yet the underlying mechanism is still unclear. From the perspective of nuclear factor kappa B (NF-κB), we studied the mechanism of IL-1ß biosynthesis and release. Utilizing BAY 11-7082, an NF-κB specific inhibitor, we showed the alteration of macrophage viability and examined the expression of both IL-1ß and NF-κB in vitro. We found that silica nanoparticles (SiNPs) were internalized by macrophages and caused damage to cell integrity. The immunofluorescence assay showed that SiNPs exposure enhanced the expression of IL-1ß and NF-κB, which could be effectively suppressed by BAY 11-7082. Besides, we built silica exposure mouse model by intratracheally instilling 5 mg of SiNPs and checked the effect of silica exposure on pulmonary pathological changes. Consistently, we found an upregulation of IL-1ß and NF-κB after SiNPs exposure, along with the aggravated inflammatory cell infiltration, thickened alveolar wall, and enhanced expression of collagens. In conclusion, SiNPs exposure causes pulmonary inflammation and fibrosis that is regulated by NK-κB through upregulating IL-1ß in alveolar macrophages.