Astragaloside IV inhibits inflammation caused by influenza virus via reactive oxygen species/NOD-like receptor thermal protein domain associated protein 3/Caspase-1 signaling pathway.

BACKGROUND: Astragaloside IV (AS-IV) is the most active monomer in the traditional Chinese herbal medicine Radix Astragali, which has a wide range of antiviral, anti-inflammatory, and antifibrosis pharmacological effects, and shows protective effects in acute lung injury. METHODS: This study utilized the immunofluorescence, flow cytometry, enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, western blot, and hematoxylin and eosin staining methods to investigate the mechanism of AS-IV in reducing viral pneumonia caused by influenza A virus in A549 cells and BALB/c mice. RESULTS: The results showed that AS-IV suppressed reactive oxygen species production in influenza virus-infected A549 cells in a dose-dependent manner, and subsequently inhibited the activation of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 inflammasome and Caspase-1, decreased interleukin (IL) -1ß and IL-18 secretion. In BALB/c mice infected with Poly (I:C), oral administration of AS-IV can significantly reduce Poly (I:C)-induced acute pneumonia and lung pathological injury. CONCLUSIONS: AS-IV alleviates the inflammatory response induced by influenza virus in vitro and lung flammation and structural damage caused by poly (I:C) in vivo.

Reduced expression of E-cadherin correlates with poor prognosis and unfavorable clinicopathological features in gastric carcinoma: a meta-analysis.

BACKGROUNDS: Gastric carcinoma (GC) is one of the most fatal human malignancies globally, with a median survival time less than 1 year. E-cadherin exerts a crucial role in the development and progression of GC as an adhesive, invasive suppressor gene. Whether reduced E-cadherin has an impact on prognosis, clinicopathological features for GC has been well studied, but no conclusive results has been obtained. METHODS: Eligible studies and relevant data were obtained from PubMed, Elsevier, Embase, Cochrane Library and Web of Science databases until June 30, 2023. A fixed- or random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Correlation of E-cadherin expression with overall survival (OS), clinicopathological features and risk factors were evaluated. RESULTS: 36 studies fulfilled the selected criteria. 9048 cases were included. This meta-analysis showed that patients with GC with reduced E-cadherin had unfavourable clinicopathological features and poor OS. The pooled ORs of one-, three- and five-year OS were 0.38 (n = 25 studies, 95%CI: 0.25-0.57, Z = 4.61, P < 0.00001), 0.33 (n = 25 studies, 95% CI: 0.23-0.47, Z = 6.22, P < 0.00001), 0.27 (n = 22 studies, 95% CI: 0.18-0.41, Z = 6.23, P < 0.00001), respectively. Moreover, reduced E-cadherin expression significantly correlated with differentiation grade (OR = 0.29, 95% CI: 0.22-0.39, Z = 8.58, P < 0.00001), depth of invasion (OR = 0.49, 95% CI: 0.36-0.66, Z = 4.58, P < 0.00001), lymphatic node metastasis (OR = 0.49, 95% CI: 0.38-0.64, Z = 5.38, P < 0.00001), distant metastasis (OR = 2.24, 95% CI: 1.62-3.09, Z = 4.88, P < 0.00001), peritoneal metastasis (OR = 2.17, 95% CI: 1.39-3.39, Z = 3.40, P = 0.0007), TNM stage (OR = 0.41, 95% CI: 0.28-0.61, Z = 4.44, P < 0.00001), lymphatic vessel invasion (OR = 1.77, 95% CI: 1.11-2.82, Z = 2.39, P = 0.02), vascular invasion (OR = 1.55, 95% CI: 1.22-1.96, Z = 3.58, P = 0.0003), Lauren type (OR = 0.35, 95% CI: 0.21-0.57, Z = 4.14, P < 0.0001), Borrmann classification (OR = 0.50, 95% CI: 0.25-0.99, Z = 1.97, P = 0.048) and tumor size (≥5 cm vs. <5 cm: OR = 1.73, 95% CI: 1.34-2.23, Z = 4.19, P < 0.0001; ≥6 cm vs. <6 cm: OR = 2.29, 95% CI: 1.51-3.49, Z = 3.87, P = 0.0001). No significant association was observed between reduced E-cadherin expression and liver metastasis, perineural invasion, alcohol consumption, smoking status, familial history, Helicobacter pylori (HP) infection. CONCLUSIONS: The reduced expression of E-cadherin is significantly correlated with poor OS and unfavourable clinicopathological features in GC. The expression level of E-cadherin not only serves as a predictor for disease progression and prognosis in GC but also emerges as a novel therapeutic target.

CaMK4: Structure, physiological functions, and therapeutic potential.

Calcium/calmodulin-dependent protein kinase IV (CaMK4) is a versatile serine/threonine kinase involved in various cellular functions. It regulates T-cell differentiation, podocyte function, tumor cell proliferation/apoptosis, ß cell mass, and insulin sensitivity. However, the underlying molecular mechanisms are complex and remain incompletely understood. The aims of this review are to highlight the latest advances in the regulatory mechanisms of CaMK4 underlying T-cell imbalance and parenchymal cell mass in multiple diseases. The structural motifs and activation of CaMK4, as well as the potential role of CaMK4 as a novel therapeutic target are also discussed.

A comprehensive evaluation of risk factors for mortality, infection and colonization associated with CRGNB in adult solid organ transplant recipients: a systematic review and meta-analysis.

BACKGROUND: The burden of carbapenem-resistant gram-negative bacteria (CRGNB) among solid organ transplant (SOT) recipients has not been systematically explored. Here, we discern the risk factors associated with CRGNB infection and colonization in SOT recipients. METHODS: This study included observational studies conducted among CRGNB-infected SOT patients, which reported risk factors associated with mortality, infection or colonization. Relevant records will be searched in PubMed, Embase and Web of Science for the period from the time of database construction to 1 March 2023. RESULTS: A total of 23 studies with 13,511 participants were included, enabling the assessment of 27 potential risk factors. The pooled prevalence of 1-year mortality among SOT recipients with CRGNB was 44.5%. Prolonged mechanical ventilation, combined transplantation, reoperation and pre-transplantation CRGNB colonization are salient contributors to the occurrence of CRGNB infections in SOT recipients. Renal replacement therapy, post-LT CRGNB colonization, pre-LT liver disease and model for end-stage liver disease score increased the risk of infection. Re-transplantation, carbapenem use before transplantation and ureteral stent utilization increaesd risk of CRGNB colonization. CONCLUSION: Our study demonstrated that SOT recipients with CRGNB infections had a higher mortality risk. Invasive procedure may be the main factor contribute to CRGNB infection.

The effects of flexible short protocol with gonadotropin-releasing hormone antagonist on preventing premature ovulation in poor responders.

PURPOSE: The proportion of patients with poor ovarian response (POR) is increasing, but effective treatment remains a challenge. To control the hidden peaks of luteinizing hormone (LH) and premature ovulation for poor responders, this study investigated the efficacy of flexible short protocol (FSP) with gonadotropin-releasing hormone antagonist (GnRH-ant) on trigger day. METHODS: The 662 cycles of POR patients were retrospectively analyzed. The cohort was divided into control and intervention groups. The intervention group (group A) with 169 cycles received a GnRH-ant given on trigger day. The control (group B) with 493 cycles received only FSP. The clinical outcomes of the two groups were compared. RESULTS: Compared with group B, with gonadotropin-releasing hormone antagonist (GnRH-ant) on trigger day in group A the incidences of spontaneous premature ovulation decreased significantly (2.37% vs. 8.72%, P < 0.05). The number of fresh embryo-transfer cycles was 45 in group A and 117 in group B. There were no significant differences in clinical outcomes, including implantation rate, clinical pregnancy rate, live birth rate and the cumulative live birth rate (12.0% vs. 9.34%; 22.22% vs. 21.93%; 17.78% vs. 14.91%; 20.51% vs. 20%, respectively; P > 0.05) between the two group. CONCLUSION: FSP with GnRH-ant addition on trigger day had no effect on clinical outcomes, but could effectively inhibit the hidden peaks of luteinizing hormone (LH) and spontaneous premature ovulation in POR. Therefore, it is an advantageous option for POR women.

Combinational Gene Therapy toward Cancer with Nanoplatform: Strategies and Principles.

Cancer remains a significant threat to human health. While numerous therapies have been developed to combat the disease, traditional treatments such as chemotherapy and radiotherapy are suboptimal and associated with significant side effects. Gene therapy is an emerging therapeutic approach that offers improved targeting and reduced side effects compared with traditional treatments. Using siRNA and other nucleic acid-based drugs in cancer treatment has generated significant interest among researchers. Nanocarriers, such as liposomes, can effectively deliver these agents to tumor sites. However, gene therapy alone is often insufficient to eradicate tumors, and there is a risk of recurrence. Therefore, combining gene therapy with other therapies using nanocarriers, such as phototherapy and magnetic hyperthermia therapy, can lead to synergistic therapeutic effects through different mechanisms. In this review, we summarize various ways in which gene therapy can be combined with other therapies and highlight the role of nanoplatforms in mediating these combined therapies, which would inspire novel design ideas toward combination therapies. Additionally, bottlenecks and barriers to gene therapy should be addressed in the near future to achieve better clinical efficacy.

Influence of Fe2O3 on the Properties and Structure of Iron Coke.

Iron cokes were produced in an electrical furnace from a coal blend containing varying levels of added Fe2O3. The effects of Fe2O3 on the properties and structure of the iron coke were then investigated using the coke for metallurgy determination of mechanical strength, determination of coke reactivity and coke strength after the reaction, X-ray diffraction, Raman spectroscopy, and a method for quantitative analysis of the minerals in coal and coke. Further, the relationships between the properties and structures of iron coke samples were established. The results show that the addition of Fe2O3 can reduce the tumble strength, coke strength after the reaction, aromaticity, microcrystalline size, graphitization degree, crystalline volume, and carbon order degree of the iron coke and increase the abrasion resistance, coke reactivity index, and pulverization rate. Moreover, the degree of influence increases with increasing levels of added Fe2O3. The Fe2O3 is mainly transformed into metallic iron during the coking process, and part of metallic iron is converted into Fe3O4 during iron coke gasification. With an increasing Fe2O3 content, the trend of the change in the minerals from Fe to Fe3O4 becomes much more obvious, resulting in deeper influences on the iron coke thermal properties. There are obvious correlations among the iron coke reactivity and iron coke strength after the reaction and the crystalline volume, carbon order degree, and metallic iron content. It is concluded that the addition of Fe2O3 decreases the crystalline volume and carbon order degree and increases the metallic iron content, resulting in increases in abrasion resistance and coke reactivity and decreases in tumble strength and coke strength after the reaction.

Pre-Induced ICD Membrane-Coated Carrier-Free Nanoparticles for the Personalized Lung Cancer Immunotherapy.

Immunotherapy is a required adjuvant method in lung cancer therapy clinically. The single immune adjuvant failed to show the expected clinical therapeutic efficacy due to its rapid drug metabolism and inability to accumulate in the tumor site efficiently. Immunogenic cell death (ICD) is a new anti-tumor strategy combined with immune adjuvants. It can provide tumor-associated antigens, activate dendritic cells, and attract lymphoid T cells into the tumor microenvironment. Here doxorubicin-induced tumor membrane-coated iron (II)-cytosine-phosphate-guanine nanoparticles (DM@NPs) are shown for efficient co-delivery of tumor-associated antigens and adjuvant. Higher expression of ICD-related membrane proteins on the surface of the DM@NPs leads to the enhanced uptake of DM@NPs by dendritic cells (DCs), thereby promoting the DCs maturation and pro-inflammatory cytokines release. DM@NPs can remarkably increase the T cell infiltrations, remodel the tumor immune microenvironment and inhibit tumor progression in vivo. These findings reveal that pre-induced ICD tumor cell membrane-encapsulated nanoparticles can enhance immunotherapy responses and provide an effective biomimetic nanomaterial-based therapeutic strategy for lung cancer.

Pregnancy Outcomes after Frozen Embryo Transfer and Fresh Embryo Transfer in Women of Advanced Maternal Age: Single-Center Experience.

Delayed childbearing leads to increased assisted reproductive technology use by women of advanced maternal age (AMA). It is unclear whether fresh or frozen embryo transfer (FET) is the better option. We aimed to assess maternal and neonatal outcomes in patients having their first FET after a freeze-all cycle versus those having their first fresh embryo transfer (ET). We reviewed 720 women of AMA undergoing a first fresh ET (n = 375) or FET (n = 345) between January 2016 and April 2021. No significant difference in the live birth rate was found between FET and fresh ET (19.7% vs. 24.3%, p = 0.141). The clinical pregnancy rate was significantly lower in the FET group than in the fresh ET group (26.4 % (91/345) vs. 33.6% (126/375), p = 0.035), but FET resulted in higher birthweights (3217.16 ± 734.44 vs. 3003.37 ± 635.00, p = 0.037) and was associated with a lower incidence of preterm births (2.6% vs. 5.6%, p = 0.046). The risks of other maternal and neonatal outcomes did not differ significantly between the groups. Among women of AMA, the transfer of frozen embryos did not result in significantly higher rates of live birth than fresh embryos did; however, a freeze-all strategy may not be beneficial for the women of AMA.

Fatal Rickettsia Japonica Infection Complicating Disseminated Intravascular Coagulation in Yichang, China.

Background: Severe complications may cause a fatal or disabling outcome in patients with Rickettsia japonica infection but are poorly understood. Methods: We identified 11 patients with only Rickettsia japonica infection with metagenomics next generation sequencing (mNGS) during April to November 2021 at Yichang Central People's Hospital, China. Clinical data were obtained through review of medical records. Results: Most patients realized that they had symptoms about one or two days after being bitten. Fever (91%), pulmonary effusion (91%), rash or erythema (100%), abnormal urine (100%), neutropenia (100%), lymphopenia (100%), and thrombocytopenia (100%) were the most common clinical signs. Six severely ill patients were admitted to the intensive care unit and five had mild symptoms. Systemic manifestations such as vomiting (83%), neurological manifestations (100%), and disseminated intravascular coagulation (100%) were more frequently observed in the severe cases, 33.3% of whom developed purpura fulminans requiring amputation or skin graft, and 16.6% died two days after admission. Some patients experienced sequelae. Conclusion: Our study found that patients with critical Rickettsia japonica infection complicating disseminated intravascular coagulation had high risk of poor outcome.

A Meta-Analysis of How Nonalcoholic Fatty Liver Disease Affect Antiviral Treatment of Patients with e Antigen-Positive Chronic Hepatitis B.

Background: Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB) are both the most common underlying diseases leading to cirrhosis and hepatocellular carcinoma, and NAFLD and HBV infection are the first and second leading causes of chronic liver disease in China. However, there are still a lot of controversies about whether the combined presence of CHB and NAFLD will affect the course or outcome of liver disease together with HBV, and how the two affect each other. Objective: To investigate the effect of nonalcoholic fatty liver disease (NAFLD) on antiviral therapy in patients with chronic hepatitis B (CHB). Methods: Computer searches of databases such as PubMed, CNKI, VIP.com, and Wanfang Data Knowledge Service Platform were used. The time frame was from the creation of the database to June 2022. The search subject terms were hepatitis B, CHB, or NAFLD. The observation group consisted of patients with e antigen-positive CHB with NAFLD, and the control group consisted of patients with e-antigen + CHB. Extracts including title, name, date of publication, number of samples, antiviral drugs, and outcome indicators were used for Meta-analysis. Funnel plots were drawn to analyze literature bias. Results: Seven papers including 1348 patients with HBeAg + CHB (observation group: n = 547, control group: n = 801) were finally included. Results: Seven papers including 1348 patients with HBeAg + CHB (observation group: n = 547, control group: n = 801) were finally included. Results. Meta-analysis showed that CHB patients with NAFLD had lower efficacy than CHB patients after 48 weeks of antiviral treatment with nucleotide analogs, as measured by three outcome indicators HBV DNA conversion rate, ALT-normalization, and HBeAg conversion rate. Conclusion: NAFLD reduces the effect of antiviral therapy in CHB patients, and the clinicopathological features of patients with NAFLD combined with chronic hepatitis B are different from those of patients with chronic hepatitis B alone, so early diagnosis by liver histological examination should be actively performed and reasonable antiviral therapy should be administered.

Vibration Analysis of a 1-DOF System Coupled with a Nonlinear Energy Sink with a Fractional Order Inerter.

The fluid inerter described by the fractional derivative model is introduced into the traditional nonlinear energy sink (NES), which is called fractional-order NES in this paper. The slowly varying dynamic equation (SVDE) of the system coupled with fractional-order NES is obtained by the complex averaging method, in which the fractional derivative term is treated using the fractional Leibniz theorem. Then, the discriminants (Δ, Δ1, and Δ2) of the number of equilibrium points are derived. By using the variable substitution method, the characteristic equation for judging the stability is established. The results show: (1) the approximate SVDE is sufficient to reflect the slowly varying characteristics of the system, which shows that the mathematical treatment of the fractional derivative term is reliable; (2) the discriminant conditions (Δ1, Δ2) can accurately reflect the number of equilibrium points, and the corresponding range of nonlinear parameter κ can be calculated when the system has three equilibrium points. The expressions of Δ1, Δ2 are simpler than Δ, which is suitable for analysis and design parameters; (3) the stability discrimination methods of schemes 1 and 2 are accurate. Compared with scheme 2, scheme 1 is more prone to various responses, especially various strongly and weakly modulated responses. In scheme 2, the inertia effect of mass can be completely replaced by integer order inerter. Compared with integer order inerter, the introduction of fractional order inerter, whether in series or in parallel, means that the amplitude of the equilibrium point on the NES vibrator is smaller, but it is also for this reason that it is not easy to produce a modulated response with scheme 2, and the vibration suppression effect of the main structure is not good.

The evolution of conglobation in Ceratocanthinae.

Conglobation is an adaptive behaviour occurring independently in various animal groups. Here, we study the evolution of conglobation in Ceratocanthinae, a beetle group with the ability to roll three body segments into a tight ball. It is here implied that this ability evolved only once in the Mesozoic. Evidence is offered suggesting that the high defensive strength of Ceratocanthinae is due not only to the spherical body shape but also to the thickness and stronger mechanical properties of the dorsal cuticle. We further validate five adaptive characters including the allometrically thickened body wall and find that the specific adaptation of different body segments are likely separate evolutionary events. Finally, we propose an "attackers stress" hypothesis to explain the origin of conglobation behaviours. This work contributes to understanding how and why conglobation behaviour may have evolved in this group.

MiR-223 as a Regulator and Therapeutic Target in Liver Diseases.

MicroRNAs (miRNAs) are endogenous non-coding single-stranded small molecule RNAs consisting of 20-24 nucleotides that are highly conserved in species evolution. Expression of miRNAs is strictly tissue-specific, and it is chronological in fungi and plants, as well as in animals. MiR-223 has been shown to play a key role in innate immunity, and dysregulation of its expression contributes to the pathogenesis of multiple inflammatory diseases, and cancers. In this article the biosynthesis and functions of miR-223 in innate immunity are reviewed, and the role of miR-223 in liver physiopathology and therapeutic prospects are highlighted.

Is traumatic meniscal lesion associated with acute fracture morphology changes of tibia plateau? A series of arthroscopic analysis of 67 patients.

BACKGROUND: Computed tomography (CT) has become a routine preoperative examination for tibial plateau fractures (TPFs). Assessing the location of the fragment and intercondylar eminence fracture can provide clinicians with valuable information; however, the evaluation of traumatic meniscal lesion (TML) and arthroscopic management are controversial. AIM: To predict TML by three-dimensional skeletal anatomy changes in unilateral TPF and bilateral TPF on preoperative thin layer CT. METHODS: Acute fracture of tibial plateau patients undergoing arthroscopic surgery between December 2017 and December 2019 were included in this retrospective study. The type, zone, and location of TMLs were diagnosed based on the operation records and/or arthroscopic videos. Measurement of three-dimensional fracture morphology included the following: Frontal fragment width of plateau, sagittal fragment subsiding distance (FSD), sagittal fracture line distance, sagittal posterior tibial slope, and transversal area ratio of fragment area) on preoperative CT three-dimensional plane. The correlation of TML with skeletal values was calculated according to unicondylar TPFs and bicondylar TPFs. RESULTS: A total of 67 patients were enrolled in this study, among which 30 patients had TMLs, lateral/medial (23/7). FSD was a particularly positive factor to predict TML, with odds ratio of 2.31 (1.26-5.63). On sagittal view of CT, FSD degree of 8 mm and posterior tibial slope exceeding 11.74° implied enhanced risk of TML in bicondylar TPFs. On coronal view, once fragment width of plateau surpassed 3 cm, incidence of TML reached 100%. On transverse view, area ratio of fragment as enhanced risk of 5.5% and FSD > 4.3 mm for predicting TML were observed in unicondylar TPFs. CONCLUSION: TML can be predicted by different parameters on preoperative CT views according to unicondylar fractures and bicondylar TPFs.

A new Himalayan species of Alfieriella (Coleoptera: Cryptophagidae).

A new species of Alfieriella Wittmer, 1935 (Coleoptera, Cryptophagidae), Alfieriella senguptai sp. n. from China and India, is described. This is the first formal record of the genus Alfieriella and the tribe Hypocoprini from the Himalayan region. Alfieriella senguptai is the largest member of Alfieriella, and its presence in a cold, high-altitude environment conforms to Bergmann's rule. The distribution of the genus Alfieriella may be associated with the breakup of the Tethys Ocean and the origin of A. senguptai influenced by the Himalayan orogeny. A distribution map and a key to species of Alfieriella are also provided.

Cellular Responses to Exposure to Outdoor Air from the Chinese Spring Festival at the Air-Liquid Interface.

The Spring Festival is the most important holiday in China. During this time, the levels of particulate matter (PM) as well as gaseous copollutants significantly increase because of the widespread enjoyment of fireworks. The expression patterns of microRNAs may serve as valuable signatures of exposure to environmental constituents. We exposed macrophages to the whole stream of outdoor air at the air-liquid interface aiming at closely approximating the physiological conditions and the inhalation situation in the lung. 58 miRNAs were up-regulated, and 68 miRNAs were down-regulated in the night of the New Year's Eve (exposure group E2N1) compared to filtered-air exposed control cells. The target genes of the up-regulated miRNAs were enriched in immunity- and inflammation-linked pathways, such as the TLR-NF-κB pathway. Compared to the E2N1 group, 29 miRNAs were up-regulated, and 23 miRNAs were down-regulated in the cells exposed to air from the daytime of the Chinese New Year with higher concentrations of particles, SO2, and nitrogen oxide. The target genes of the up-regulated miRNAs were mostly enriched in apoptosis, adhesion, and junction-related pathways. These results preliminarily unravel part of the toxic mechanisms of air constituents and provide clues for discovering the main drivers of air pollution-induced disorders.

Large-scale 3D imaging of insects with natural color.

High-resolution 3D imaging technology has found a number of applications in many biological fields. However, the existing 3D imaging tools are often too time-consuming to use on large-scale specimens, such as centimeter-sized insects. In addition, most 3D imaging systems discard the natural color information of the specimens. To surmount these limitations, we present a structured illumination-based approach capable of delivering large field-of-view three-dimensional images. With this approach, 580nm lateral resolution full-color 3D images and 3D morphological data in the size range of typical insect samples can be obtained. This method provides a promising approach that can be used to support many different types of entomological investigations, including taxonomy, evolution, bionics, developmental biology, functional morphology, paleontology, forestry, etc.

Nano-liposomes of lycopene reduces ischemic brain damage in rodents by regulating iron metabolism.

In order to discover new drug delivery approaches and to understand the mechanism of iron overload in cerebral ischemia/reperfusion (I/R), we aimed to investigate the effects of lycopene (LYC) in the form of nano-liposomes (L-LYC) on iron-regulating proteins and ischemic brain injury. We found that L-LYC significantly increased the LYC content in serum and the brain. Adult male Sprague-Dawley rats treated with L-LYC for 14 days were subjected to 60 min of ischemia and 7 days of reperfusion. The effects of L-LYC were evaluated by infarction volume, neurological score, neuronal apoptosis, and markers for oxidative stress. Levels of iron-regulating protein such as hepcidin and ferroportin (FPN1) were examined. L-LYC reduced cerebral infarction and improved neurobehavior of the rats more efficiently than "naked" LYC. L-LYC reduced protein levels of oxidases (e.g. nitric oxide synthase and NOX2), increased the level of Bcl-2, lowered caspase-3, and suppressed apoptosis through inhibiting MAPK-JNK. Furthermore, L-LYC suppressed hepcidin-mediated decrease in FPN1, a sole iron exporter, and normalized the levels of iron. We further demonstrated that the effect of L-LYC on hepcidin expression might result from its ability to attenuate the release of the inflammatory factor interleukin 6. The results demonstrated that nano-liposomal encapsulation significantly improved LYC efficacy in providing neuronal protection against I/R injury. The data also revealed a novel mechanism of L-LYC's neuroprotection by regulating iron metabolism in an ischemic brain.

An Experimental and Computational Approach to the Development of ZnO Nanoparticles that are Safe by Design.

Zinc oxide nanoparticles have found wide application due to their unique optoelectronic and photocatalytic characteristics. However, their safety aspects remain of critical concern, prompting the use of physicochemical modifications of pristine ZnO to reduce any potential toxicity. However, the relationships between these modifications and their effects on biology are complex and still relatively unexplored. To address this knowledge gap, a library of 45 types of ZnO nanoparticles with varying particle size, aspect ratio, doping type, doping concentration, and surface coating is synthesized, and their biological effects measured. Three biological assays measuring cell damage or stress are used to study the responses of human umbilical vein endothelial cells (HUVECs) or human hepatocellular liver carcinoma cells (HepG2) to the nanoparticles. These experimental data are used to develop quantitative and predictive computational models linking nanoparticle properties to cell viability, membrane integrity, and oxidative stress. It is found that the concentration of nanoparticles the cells are exposed to, the type of surface coating, the nature and extent of doping, and the aspect ratio of the particles make significant contributions to the cell toxicity of the nanoparticles tested. Our study shows that it is feasible to generate models that could be used to design or optimize nanoparticles with commercially useful properties that are also safe to humans and the environment.