The roles of PD-L1 in the various stages of tumor metastasis.

The interaction between tumor programmed death ligand 1 (PD-L1) and T-cell programmed cell death 1 (PD-1) has long been acknowledged as a mechanism for evading immune surveillance. Recent studies, however, have unveiled a more nuanced role of tumor-intrinsic PD-L1 in reprograming tumoral phenotypes. Preclinical models emphasize the synchronized effects of both intracellular and extracellular PD-L1 in promoting metastasis, with intricate interactions with the immune system. This review aims to summarize recent findings to elucidate the spatiotemporal heterogeneity of PD-L1 expression and the pro-metastatic roles of PD-L1 in the entire process of tumor metastasis. For example, PD-L1 regulates the epithelial-to-mesenchymal transition (EMT) process, facilitates the survival of circulating tumor cells, and induces the formation of immunosuppressive environments at pre-metastatic niches and metastatic sites. And the complexed and dynamic regulation process of PD-L1 for tumor metastasis is related to the spatiotemporal heterogeneity of PD-L1 expression and functions from tumor primary sites to various metastatic sites. This review extends the current understandings for the roles of PD-L1 in mediating tumor metastasis and provides new insights into therapeutic decisions in clinical practice.

ZNPs reduce epidermal mechanical strain resistance by promoting desmosomal cadherin endocytosis via mTORC1-TFEB-BLOC1S3 axis.

Zinc oxide nanoparticles (ZNPs) are widely used in sunscreens and nanomedicines, and it was recently confirmed that ZNPs can penetrate stratum corneum into deep epidermis. Therefore, it is necessary to determine the impact of ZNPs on epidermis. In this study, ZNPs were applied to mouse skin at a relatively low concentration for one week. As a result, desmosomes in epidermal tissues were depolymerized, epidermal mechanical strain resistance was reduced, and the levels of desmosomal cadherins were decreased in cell membrane lysates and increased in cytoplasmic lysates. This finding suggested that ZNPs promote desmosomal cadherin endocytosis, which causes desmosome depolymerization. In further studies, ZNPs were proved to decrease mammalian target of rapamycin complex 1 (mTORC1) activity, activate transcription factor EB (TFEB), upregulate biogenesis of lysosome-related organelle complex 1 subunit 3 (BLOC1S3) and consequently promote desmosomal cadherin endocytosis. In addition, the key role of mTORC1 in ZNP-induced decrease in mechanical strain resistance was determined both in vitro and in vivo. It can be concluded that ZNPs reduce epidermal mechanical strain resistance by promoting desmosomal cadherin endocytosis via the mTORC1-TFEB-BLOC1S3 axis. This study helps elucidate the biological effects of ZNPs and suggests that ZNPs increase the risk of epidermal fragmentation.

Tumor-suppressive circRHOBTB3 is excreted out of cells via exosome to sustain colorectal cancer cell fitness.

BACKGROUND & AIMS: To clarify the biological roles, circularization process and secretion pathway of circRHOBTB3 in colorectal cancer (CRC) progression. METHODS: We performed a comprehensive analysis of circRNA levels in serum exosomes from multiple types of cancer patients in public databases and verified the higher level of circRHOBTB3 in CRC sera versus healthy donors by RT-qPCR. Then, the function of circRHOBTB3 in CRC was investigated in vitro and in vivo. RNA-seq and RNA pull-down assays together with mass spectrometry identified the downstream signals and the binding proteins of circRHOBTB3. Finally, Antisense oligonucleotides (ASOs) were designed to target circularization and secretion elements of circRHOBTB3 for CRC therapy. RESULTS: circRHOBTB3 levels were increased in the sera but was downregulated in tissue samples in CRC, and the downregulation was associated with poor prognosis. Furthermore, circRHOBTB3 acts a tumor-suppressive circRNA by repressing metabolic pathways, intracellular ROS production in CRC. Several key elements were discovered to regulate circRHOBTB3 circularization and exosomal secretion. Moreover, SNF8 was identified that sorts circRHOBTB3 into exosomes. Interestingly, we found that CRC cells could actively secrete more circRHOBTB3 than normal cells. According to the sequence of regulatory elements for circularization and exosomal secretion, we designed and synthesized ASOs, which increased circRHOBTB3 expression and blocked circRHOBTB3 exosomal secretion. More importantly, ASOs could inhibit CRC growth and metastasis in vitro and in vivo. CONCLUSIONS: circRHOBTB3 plays a tumor-suppressive role in CRC and has to be excreted out of cells to sustain cancer cell fitness. ASOs targeting regulatory elements for circularization and exosomal secretion will become a novel antitumor strategy.

The quantifying relationship between the remission duration and the cardiovascular and kidney outcomes in the patients with primary nephrotic syndrome.

BACKGROUND: Patients with persistent nephrotic-range proteinuria have a high risk of kidney dysfunction and cardiovascular events. Recently, the maintenance of proteinuria remission has been demonstrated to reduce the risk of kidney endpoint. However, the effect of remission duration on cardiovascular outcomes remains unclear. METHODS: This study enrolled 982 patients with primary nephrotic syndrome who had achieved clinical remission. Remission duration was defined as the maintenance time (months) of the first remission. Arteriosclerotic cardiovascular disease (ASCVD) and kidney dysfunction (ESKD or eGFR reduction >50%) were the endpoints. Survival curves, Cox regression models, restricted cubic spline analysis were used and the cutoff time points were determined. RESULTS: During the 38.3 months of follow-up, 161 (16.4%) patients developed ASCVD (51.3 per 1000 patient-years) and 52 (5.3%) patients developed kidney dysfunction (15.3 per 1000 patient-years). Multivariate analysis showed that remission duration was an independently protective factor to ASCVD, in which each one-year extension associated with a 15% reduction of the risk (HR, 0.854; 95% CI, 0.776 ∼ 0.940, p = .001). The initial time point was seven months for remission to present the protective effect to ASCVD and the maximum time point was 36 months. Remission duration was also an independently protective factor to kidney dysfunction. This effect was shown from the beginning of remission and reached the maximum at 26 months. CONCLUSIONS: The maintenance of proteinuria remission was crucial for the improvement of cardiovascular and kidney outcomes in nephrotic syndrome patients.

Nanomaterial-mediated autophagy: coexisting hazard and health benefits in biomedicine.

BACKGROUND: Widespread biomedical applications of nanomaterials (NMs) bring about increased human exposure risk due to their unique physicochemical properties. Autophagy, which is of great importance for regulating the physiological or pathological activities of the body, has been reported to play a key role in NM-driven biological effects both in vivo and in vitro. The coexisting hazard and health benefits of NM-mediated autophagy in biomedicine are nonnegligible and require our particular concerns. MAIN BODY: We collected research on the toxic effects related to NM-mediated autophagy both in vivo and in vitro. Generally, NMs can be delivered into animal models through different administration routes, or internalized by cells through different uptake pathways, exerting varying degrees of damage in tissues, organs, cells, and organelles, eventually being deposited in or excreted from the body. In addition, other biological effects of NMs, such as oxidative stress, inflammation, necroptosis, pyroptosis, and ferroptosis, have been associated with autophagy and cooperate to regulate body activities. We therefore highlight that NM-mediated autophagy serves as a double-edged sword, which could be utilized in the treatment of certain diseases related to autophagy dysfunction, such as cancer, neurodegenerative disease, and cardiovascular disease. Challenges and suggestions for further investigations of NM-mediated autophagy are proposed with the purpose to improve their biosafety evaluation and facilitate their wide application. Databases such as PubMed and Web of Science were utilized to search for relevant literature, which included all published, Epub ahead of print, in-process, and non-indexed citations. CONCLUSION: In this review, we focus on the dual effect of NM-mediated autophagy in the biomedical field. It has become a trend to use the benefits of NM-mediated autophagy to treat clinical diseases such as cancer and neurodegenerative diseases. Understanding the regulatory mechanism of NM-mediated autophagy in biomedicine is also helpful for reducing the toxic effects of NMs as much as possible.

Neuroinflammation is induced by tongue-instilled ZnO nanoparticles via the Ca2+-dependent NF-κB and MAPK pathways.

BACKGROUND: The extensive biological applications of zinc oxide nanoparticles (ZnO NPs) in stomatology have created serious concerns about their biotoxicity. In our previous study, ZnO NPs were confirmed to transfer to the central nervous system (CNS) via the taste nerve pathway and cause neurodegeneration after 30 days of tongue instillation. However, the potential adverse effects on the brain caused by tongue-instilled ZnO NPs are not fully known. METHODS: In this study, the biodistribution of Zn, cerebral histopathology and inflammatory responses were analysed after 30 days of ZnO NPs tongue instillation. Moreover, the molecular mechanisms underlying neuroinflammation in vivo were further elucidated by treating BV2 and PC12 cells with ZnO NPs in vitro. RESULTS: This analysis indicated that ZnO NPs can transfer into the CNS, activate glial cells and cause neuroinflammation after tongue instillation. Furthermore, exposure to ZnO NPs led to a reduction in cell viability and induction of inflammatory response and calcium influx in BV2 and PC12 cells. The mechanism underlying how ZnO NPs induce neuroinflammation via the Ca2+-dependent NF-κB, ERK and p38 activation pathways was verified at the cytological level. CONCLUSION: This study provided a new way how NPs, such as ZnO NPs, induce neuroinflammation via the taste nerve translocation pathway, a new mechanism for ZnO NPs-induced neuroinflammation and a new direction for nanomaterial toxicity analysis.

Potential Links between Cytoskeletal Disturbances and Electroneurophysiological Dysfunctions Induced in the Central Nervous System by Inorganic Nanoparticles.

Inorganic nanomaterials have been widely applied in biomedicine. However, several studies have noted that inorganic nanoparticles can enter the brain and induce cytoskeletal remodeling, as well as electrophysiological alterations, which are related to neurodevelopmental disorders and neurodegenerative diseases. The toxic effects of inorganic nanomaterials on the cytoskeleton and electrophysiology are summarized in this review. The relationships between inorganic NPs-induced cytoskeletal and electrophysiological alterations in the central nervous system remain obscure. We propose several potential relationships, including those involving N-methyl-D-aspartate receptor function, ion channels, transient receptor potential channels, and the Rho pathway.

Fabrication of Natural Sensitizer Extracted from Mixture of Purple Cabbage, Roselle, Wormwood and Seaweed with High Conversion Efficiency for DSSC.

This study aims to deal with the influence of different solvent in extraction of natural sensitizer and different thickness of photoelectrode thin film on the photoelectric conversion efficiency and the electron transport properties for the prepared dye-sensitized solar cells (DSSC). The natural dyes of anthocyanin and chlorophyll dyes are extracted from mixture of purple cabbage and roselle and mixture of wormwood and seaweed, respectively. The experimental results show the cocktail dye extracted with ethanol and rotating speed of spin coating at 1000 rpm can achieve the greatest photoelectric conversion efficiency up to 1.85%. Electrochemical impedance result shows that the effective diffusion coefficient for the prepared DSSC with the thickness of photoelectrode thin film at 21 microm are 5.23 x 10(-4) cm2/s.

Reduced threshold of optically pumped amplified spontaneous emission and narrow line-width electroluminescence at cutoff wavelength from bilayer organic waveguide devices.

We present a detailed study of the optically and electrically pumped emission in the BSB-Cz/PVK bilayer waveguide devices. By optical pumping we demonstrate that PVK as a spacer between fluorescent BSB-Cz and ITO electrode allows the significant reduction of the threshold for amplified spontaneous emission (ASE) of BSB-Cz. The simulation provides a better understanding of how the PVK thickness affects the waveguide mode field distribution and hence the ASE threshold of BSB-Cz. On the other hand, the BSB-Cz/PVK bilayer OLED exhibits the external quantum efficiency of >1% and anisotropic electroluminescence with spectrally narrowed edge emission at the cutoff wavelength controlled by the BSB-Cz thickness. When tuning the cutoff wavelength to match the peak gain of BSB-Cz, we demonstrate an intense, particularly narrow edge emission (~5 nm) without obvious degradation of efficiency at a high current density of 1000 mA/cm2, suggesting a reliable device performance for high-power applications and further exploration of electrically-pumped ASE.

Sesamol suppresses the inflammatory response by inhibiting NF-κB/MAPK activation and upregulating AMP kinase signaling in RAW 264.7 macrophages.

OBJECTIVES AND DESIGN: Sesamol is a lignan isolated from sesame seed oil. In recent years, it was found that sesamol could decrease lung inflammation and lipopolysaccharide (LPS)-induced lung injury in rats. In this study, we investigated whether sesamol exhibited anti-inflammatory activity in LPS-stimulated macrophages. MATERIALS AND METHODS: RAW 264.7 cells were treated with sesamol, then treated with LPS to induce inflammation. The levels of proinflammatory cytokines were analyzed with ELISA. The gene and protein expression of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), and nuclear factor erythroid-2-related factor 2 (Nrf2) were evaluated with real-time PCR and Western blots, respectively. We also examined inflammatory signaling pathways, including nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. RESULTS: Sesamol inhibited production of nitric oxide, prostaglandin E2 (PGE2), and proinflammatory cytokines. Sesamol markedly suppressed mRNA and protein expression of iNOS and COX-2. Sesamol enhanced the protective antioxidant pathway represented by Nrf2 and HO-1. Moreover, sesamol suppressed NF-κB transport into the nucleus and decreased MAPK activation, but it promoted adenosine monophosphate-activated protein kinase (AMPK) activation. CONCLUSIONS: These data suggested that sesamol ameliorated inflammatory and oxidative damage by upregulating AMPK activation and Nrf2 signaling and blocking the NF-κB and MAPK signaling pathways.

Pt/ZnO nanoarray nanogenerator as self-powered active gas sensor with linear ethanol sensing at room temperature.

A self-powered gas sensor that can actively detect ethanol at room temperature has been realized from a Pt/ZnO nanoarray nanogenerator. Pt nanoparticles are uniformly distributed on the whole surface of ZnO nanowires. The piezoelectric output of Pt/ZnO nanoarrays can act not only as a power source, but also as a response signal to ethanol at room temperature. Upon exposure to dry air and 1500 ppm ethanol at room temperature, the piezoelectric output of the device under the same compressive strain is 0.672 and 0.419 V, respectively. Moreover, a linear dependence of the sensitivity on the ethanol concentration is observed. Such a linear ethanol sensing at room temperature can be attributed to the atmosphere-dependent variety of the screen effect on the piezoelectric output of ZnO nanowires, the catalytic properties of Pt nanoparticles, and the Schottky barriers at Pt/ZnO interfaces. The present results can stimulate research in the direction of designing new material systems for self-powered room-temperature gas sensing.

Outcomes of stage 1-5 chronic kidney disease in Mainland China.

OBJECTIVE: This study aims to quantify and compare the risks of death and end stage renal disease (ESRD) in a prospective cohort of patients with chronic kidney disease (CKD) stages 1-5 under renal management clinic at Peking University Third Hospital and to evaluate the risk factors associated with these two outcomes. METHOD: This was a prospective cohort study. Finally, 1076 patients at CKD stage 1-5 short of dialysis were recruited from renal management clinic. Patients were monitored for up to Dec, 2011 or until ESRD and death. Glomerular filtration rate was estimated (eGFR) according to the using the CKD Epidemiology Collaboration (CKD-EPI) formula. RESULTS: At the end of follow-up, 111 patients (10.1%) developed ESRD (initiated dialysis or kidney transplantation (ESRD)) and 24 patients (2.2%) had died. There were more ESRD occurrence rate in patients with baseline diabetic nephropathy, lower eGFR, hemoglobin <100 g/L and 24 h urinary protein excretion ≥ 3.0 g. By multivariate Cox regression model, having heavy proteinuria and CKD stage were the risk factors of ESRD. For all-cause mortality, the most common cause was cardiovascular disease, followed by infectious disease and cancer. But we failed to conclude any significant variable as risk factors for mortality in multivariate analysis. CONCLUSIONS: Our study indicated that baseline diabetic nephropathy, lower hemoglobin level, lower baseline GFR and heavy proteinuria were the risk factors of ESRD. In this CKD cohort, patients were more likely to develop ESRD than mortality, and cardiovascular mortality was the leading cause of death, and then followed by infectious diseases and cancer in this population.

Novel Carbon Quantum Dots Precisely Trigger Ferroptosis in Cancer Cells through Antioxidant Inhibition Synergistic Nanocatalytic Activity.

High levels of glutathione (GSH) are an important characteristic of malignant tumors and a significant cause of ineffective treatment and multidrug resistance. Although reactive oxygen species (ROS) therapy has been shown to induce tumor cell death, the strong clearance effect of GSH on ROS significantly reduces its therapeutic efficacy. Therefore, there is a need to develop new strategies for targeting GSH. In this study, novel carbon quantum dots derived from gentamycin (GM-CQDs) were designed and synthesized. On the basis of the results obtained, GM-CQDs contain sp2 and sp3 carbon atoms as well as nitrogen oxygen groups, which decrease the intracellular levels of GSH by downregulating SLC7A11, thereby disrupting redox balance, mediating lipid peroxidation, and inducing ferroptosis. Transcriptome analysis demonstrated that GM-CQDs downregulated the expression of molecules related to GSH metabolism while significantly increasing the expression of molecules related to ferroptosis. The in vivo results showed that the GM-CQDs exhibited excellent antitumor activity and immune activation ability. Furthermore, because of their ideal biological safety, GM-CQDs are highly promising for application as drugs targeting GSH in the treatment of malignant tumors.

Physiologically-based pharmacokinetic modeling to predict drug-drug interactions of dabigatran etexilate and rivaroxaban in the Chinese older adults.

INTRODUCTION: Drug-drug interaction (DDI) is one of the major concerns for the clinical use of NOACs in the older adults considering that coexistence of multiple diseases and comorbidity were common. Current guidelines on the DDI management were established based on clinical studies conducted in healthy adults and mainly focus on the Caucasians, whereas systemic and ethnic differences may lead to distinct management in the Chinese older adults. OBJECTIVES: To investigate the impact of aging on the DDI magnitude between P-gp and/or CYP3A4 inhibitors with dabigatran etexilate and rivaroxaban in older adults, providing additional information for the use in clinical practice. RESULTS: Compared with the simulated adult, the AUC of the simulated older adults increased by 42-88% (DABE) and 21-60% (rivaroxaban), respectively, during NOACs monotherapy. Simulation on DDIs predicted that verapamil and clarithromycin further increase the exposure of dabigatran by 29-72% and 40-47%, whereas clarithromycin, fluconazole, and ketoconazole increase the exposure of rivaroxaban by 21-30%, 16-24%, and 194-247% in the older adults. Overall, our simulation result demonstrated that aging and DDIs both increased the exposure of NOACs. However, aging does not have a drastic impact on the extent of DDIs. The DDI ratios of young and old older adults were similar to the adults and were also similar between Caucasians and Chinese. DISCUSSION: We further simulated the interactions under steady-state based on the EHRA guideline (2021). Our simulation results revealed that recommended reduced dosing regimen of dabigatran etexilate during comedication with verapamil and clarithromycin (110 and 75 mg BID for Chinese young and old older adults) will result in exposure (trough concentration) that was either slightly higher or similar to the trough concentration of patients with any bleeding events. Routine monitoring of bleeding risk is encouraged. Further studies on the use of rivaroxaban in Chinese older adults are warranted. CONCLUSION: Aging and DDI increases exposure of drug in Chinese older adults. However, aging does not have a drastic impact on the extent of DDIs. Clinical management of DDIs in Chinese older adults in the absence of complex polypharmacy can a priori be similar to the EHRA guideline but routine monitoring of bleeding risk is encouraged when dabigatran etexilate given with verapamil and clarithromycin.

Physiologically Based Pharmacokinetic Model for Older Adults and Its Application in Geriatric Drug Research.

Drug-related adverse events are higher in older patients than in non-older patients, increasing the risk of medication and reducing compliance. Aging is accompanied by a decline in physiological functions and metabolic weakening. Most tissues and organs undergo anatomical and physiological changes that may affect the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of drugs. Clinical trials are the gold standard for selecting appropriate dosing regimens. However, older patients are generally underrepresented in clinical trials, resulting in a lack of evidence for establishing an optimal dosing regimen for older adults. The physiologically based pharmacokinetic (PBPK) model is an effective approach to quantitatively describe the absorption, distribution, metabolism, and excretion of drugs in older adults by integrating physiological parameters, drug physicochemical properties, and preclinical or clinical PK data. The PBPK model can simulate the PK/PD characteristics of clinical drugs in different scenarios, ultimately compensating for inadequate clinical trial data in older adults, and is recommended by the Food and Drug Administration for clinical pharmacology studies in older adults. This review describes the effects of physiological changes on the PK/PD process in older adults and summarises the research progress of PBPK models. Future developments of PBPK models are also discussed, together with the application of PBPK models in older adults, aiming to assist the development of clinical study strategies in older adults.

Long-term visit-to-visit variability in low-density lipoprotein cholesterol is associated with poor cardiovascular and kidney outcomes in patients with primary nephrotic syndrome.

PURPOSE: It is unclear whether long-term variability in low-density lipoprotein cholesterol (LDL-C) is associated with clinical outcomes in patients with nephrotic syndrome (NS). METHODS: A large cohort of 1100 patients with primary NS underwent treatment and regular follow-up. Long-term variability in LDL-C was assessed by calculating its weighted standard deviation (w-SD). The primary endpoints of this study were the occurrence of arteriosclerotic cardiovascular disease (ASCVD) or kidney dysfunction. Factors associated with the w-SD of LDL-C were evaluated by linear regression. Associations of the w-SD of LDL-C with clinical outcomes were evaluated by Cox proportional hazards regression. RESULTS: Over a median follow-up of 44.8 (interquartile range, 26.8, 70.1) months, 198 patients developed ASCVD (45.9 cases per 1,000 patient-years), and 84 patients developed kidney dysfunction (17.6 cases per 1,000 patient-years). The incidence rates of the primary outcomes increased across the quartiles of the w-SD of LDL-C (log-rank, P < 0.001). Multivariate Cox regression analysis showed that higher LDL-C variability was associated with an increased risk of ASCVD [hazard ratio (HR), 2.236; 95% confidence interval (CI), 1.684-2.969, P < 0.001] and an increased risk of kidney dysfunction (HR, 3.047; 95% CI 2.240-4.144, P < 0.001). The results were similar after adjusting the w-SD of LDL-C by its related parameters (baseline and mean LDL-C as well as mean total cholesterol), although the mean LDL-C was also an independent risk factor for ASCVD and kidney dysfunction. CONCLUSION: Long-term variability in LDL-C was independently associated with the risk of ASCVD and kidney dysfunction in NS patients.

Specific intracellular retention of circSKA3 promotes colorectal cancer metastasis by attenuating ubiquitination and degradation of SLUG.

Our previous study demonstrated that tumor-suppressor circular RNAs (circRNAs) can be specifically secreted outside of colorectal cancer (CRC) cells within exosomes to maintain tumor cell fitness. However, whether tumor-driving circRNAs can be specifically retained in cells to facilitate tumor progression remains unknown. In this study, circRNA-seq showed that circSKA3 was significantly upregulated in CRC tissues but downregulated in serum samples from CRC patients. In addition, circSKA3 promoted CRC progression in vitro and in vivo and was retained in CRC cells via a specific cellmotif element. Interestingly, the cellmotif element was also the site of interaction of circSKA3 with SLUG, which inhibited SLUG ubiquitination degradation and promoted CRC epithelial-mesenchymal transition (EMT). Moreover, FUS was identified as a key circularization regulator of circSKA3 that bound to the key element. Finally, we designed and synthesized specific antisense oligonucleotides (ASOs) targeting circularization and cellmotif elements, which repressed circSKA3 expression, abolished the SLUG-circSKA3 interaction, and further inhibited CRC EMT and metastasis in vitro and in vivo.

Graphene-Based Material-Mediated Immunomodulation in Tissue Engineering and Regeneration: Mechanism and Significance.

Tissue engineering and regenerative medicine hold promise for improving or even restoring the function of damaged organs. Graphene-based materials (GBMs) have become a key player in biomaterials applied to tissue engineering and regenerative medicine. A series of cellular and molecular events, which affect the outcome of tissue regeneration, occur after GBMs are implanted into the body. The immunomodulatory function of GBMs is considered to be a key factor influencing tissue regeneration. This review introduces the applications of GBMs in bone, neural, skin, and cardiovascular tissue engineering, emphasizing that the immunomodulatory functions of GBMs significantly improve tissue regeneration. This review focuses on summarizing and discussing the mechanisms by which GBMs mediate the sequential regulation of the innate immune cell inflammatory response. During the process of tissue healing, multiple immune responses, such as the inflammatory response, foreign body reaction, tissue fibrosis, and biodegradation of GBMs, are interrelated and influential. We discuss the regulation of these immune responses by GBMs, as well as the immune cells and related immunomodulatory mechanisms involved. Finally, we summarize the limitations in the immunomodulatory strategies of GBMs and ideas for optimizing GBM applications in tissue engineering. This review demonstrates the significance and related mechanism of the immunomodulatory function of GBM application in tissue engineering; more importantly, it contributes insights into the design of GBMs to enhance wound healing and tissue regeneration in tissue engineering.

Improvement of synaptic plasticity by nanoparticles and the related mechanisms: Applications and prospects.

Synaptic plasticity is an important basis of learning and memory and participates in brain network remodelling after different types of brain injury (such as that caused by neurodegenerative diseases, cerebral ischaemic injury, posttraumatic stress disorder (PTSD), and psychiatric disorders). Therefore, improving synaptic plasticity is particularly important for the treatment of nervous system-related diseases. With the rapid development of nanotechnology, increasing evidence has shown that nanoparticles (NPs) can cross the blood-brain barrier (BBB) in different ways, directly or indirectly act on nerve cells, regulate synaptic plasticity, and ultimately improve nerve function. Therefore, to better elucidate the effect of NPs on synaptic plasticity, we review evidence showing that NPs can improve synaptic plasticity by regulating different influencing factors, such as neurotransmitters, receptors, presynaptic membrane proteins and postsynaptic membrane proteins, and further discuss the possible mechanism by which NPs improve synaptic plasticity. We conclude that NPs can improve synaptic plasticity and restore the function of damaged nerves by inhibiting neuroinflammation and oxidative stress, inducing autophagy, and regulating ion channels on the cell membrane. By reviewing the mechanism by which NPs regulate synaptic plasticity and the applications of NPs for the treatment of neurological diseases, we also propose directions for future research in this field and provide an important reference for follow-up research.

ZnO NPs delay the recovery of psoriasis-like skin lesions through promoting nuclear translocation of p-NFκB p65 and cysteine deficiency in keratinocytes.

BACKGROUND: This study aimed to evaluate the safety of applying zinc oxide nanoparticles (ZnO NPs) to pathological skin. The majority of previous studies confirmed the safety of applying ZnO NPs to normal skin. However, we know very little about the risks of using sunscreen, cosmetics and topical drugs containing ZnO NPs for individuals with skin diseases. RESULTS: ZnO NPs passed through gaps between keratinocytes and entered stratum basale of epidermis and dermis in imiquimod-induced psoriasis-like skin lesions. Application of a ZnO NP-containing suspension for 3 connective days delayed the healing of the epidermal barrier; increased the expression levels of inflammatory cytokines; promoted keratinocyte apoptosis and disturbed redox homeostasis. In TNF-α-stimulated HaCaT cells, QNZ and JSH-23 (NFκB inhibitors) blocked ZnO NP-induced inflammation. JSH-23 and NAC (a precursor of cysteine) inhibited ZnO NP-induced nuclear translocation of p-NFκB p65, cysteine deficiency and apoptosis. Additionally, ZnO NPs decreased CD98 level in main pathway and failed to activate transsulfuration pathway in cysteine biosynthesis. CONCLUSIONS: ZnO NPs can enter psoriasis-like skin lesions and promote inflammation and keratinocyte apoptosis through nuclear translocation of p-NFκB p65 and cysteine deficiency. This work reminds the public that ZnO NPs have harmful effects on the recovery of inflammatory skin diseases.