Deposition patterns formed by the evaporation of linear diblock copolymer solution nanodroplets on solid surfaces.

The evaporation-induced deposition pattern of the linear diblock copolymer solution has attracted attention in recent years. Given its critical applications, we study deposition patterns of the linear diblock copolymer solution nanodroplet on a solid surface (the wall) by molecular dynamics simulations. This study focuses on the influence of the nonbonded interaction strength, including the interaction between the wall and polymer blocks (ɛAW and ɛBW), the interaction between the solvent and the wall (ɛSW), and the interaction between polymer blocks (ɛAB). Conditions leading to diverse deposition patterns are explored, including the coffee-ring and the volcano-like structures. The formation of the coffee-ring structure is attributed to receding interfaces, the heterogeneity inside the droplet, and the self-assembly of polymer chains. This study contributes to the establishment of guidelines for designing deposition patterns of the linear diblock copolymer solution nanodroplet, which facilitates practical applications such as inkjet printing.

Interleukin-1 receptor 1 deficiency worsens hepatocellular carcinoma, while gemcitabine treatment alleviates the hepatocellular carcinoma-induced increase in intra-hepatic immune cells.

BACKGROUND AND AIM: Primary liver cancer, particularly hepatocellular carcinoma (HCC), represents a substantial global health challenge. Although immune checkpoint inhibitors are effective in HCC treatment, several patients still experience disease progression. Interleukin-1 (IL-1) regulates immunity and inflammation. We investigate the role of IL-1 in HCC development and progression and determine the potential therapeutic impact of gemcitabine in treating HCC. METHODS: Hydrodynamics-based transfection, employing the sleeping beauty transposase system, delivered surrogate tumor antigens, NRAS (NRAS proto-oncogene, GTPase), ShP53, and SB100 to C57BL/6 mice. A basic HCC mouse model was established. Pathogen-free animals were tested for serum and hepatotoxicity. The HCC prognosis was monitored using alanine aminotransferase and aspartate aminotransferase levels. Liver histology immunohistochemistry and mouse splenocyte/intra-hepatic immune cell flow cytometry were conducted. IL-1ß levels in human and mouse serum were assessed. RESULTS: Interleukin-1ß levels were elevated in patients with HCC compared with those in non-HCC controls. Hepatic IL-1ß levels were higher in HCC mouse models than those in non-HCC mice, suggesting localized hepatic inflammation. IL-1 receptor type 1 (IL-1R1) knockout (IL-1R1-/-) mice exhibited less severe HCC progression than that in wild-type mice, despite the high intra-hepatic IL-1ß concentration. IL-1R1-/- mice exhibited increased hepatic levels of myeloid-derived suppressor cells and regulatory T cells, which may exacerbate HCC. Gemcitabine significantly reduced the HCC tumor burden, improved liver conditions, and increased survival rates in HCC mouse models. Gemcitabine reduced the hepatic levels of myeloid-derived suppressor cells and regulatory T cells, potentially alleviating immune suppression in the liver. CONCLUSIONS: Targeting IL-1 or combining gemcitabine with immunotherapy is a promising approach for treating advanced-stage HCC.

NPRL2 is required for proliferation of oncogenic Ras-transformed bronchial epithelial cells.

Nitrogen permease regulator-like 2 (NPRL2/TUSC4) is known to exert both tumor-suppressing and oncogenic effects in different types of cancers, suggesting that its actions are context dependent. Here, we delineated the molecular and functional effects of NPRL2 in malignantly transformed bronchial epithelial cells. To do so, we depleted NPRL2 in oncogenic HRas-transduced and malignantly transformed human bronchial epithelial (BEAS2B), Ras-AI-T2 cells. Intriguingly, depletion of NPRL2 in these cells induced activation of mTORC1 downstream signaling, inhibited autophagy, and impaired Ras-AI-T2 cell proliferation both in vitro and in vivo. These results suggest that NPRL2 is required for oncogenic HRas-induced cell transformation. Depletion of NPRL2 increased levels of the DNA damage marker γH2AX, the cell cycle inhibitors p21 and p27, and the apoptosis marker cleaved-PARP. These NPRL2-depleted cells first accumulated at G1 and G2, and later exhibited signs of mitotic catastrophe, which implied that NPRL2 depletion may be detrimental to oncogenic HRas-transformed cells. Additionally, NPRL2 depletion reduced heat shock factor 1/heat shock element- and NRF2/antioxidant response element-directed luciferase reporter activities in Ras-AI-T2 cells, indicating that NPRL2 depletion led to the suppression of two key cytoprotective processes in oncogenic HRas-transformed cells. Overall, our data suggest that oncogenic HRas-transduced and malignantly transformed cells may depend on NPRL2 for survival and proliferation, and depletion of NPRL2 also induces a stressed state in these cells.

Different reference genomes determine different results: Comparing SNP calling in RAD-seq of Engelhardia roxburghiana using different reference genomes.

Advances in next-generation sequencing (NGS) have significantly reduced the cost and improved the efficiency of obtaining single nucleotide polymorphism (SNP) markers, particularly through restriction site-associated DNA sequencing (RAD-seq). Meanwhile, the progression in whole genome sequencing has led to the utilization of an increasing number of reference genomes in SNP calling processes. This study utilized RAD-seq data from 242 individuals of Engelhardia roxburghiana, a tropical tree of the walnut family (Juglandaceae), with SNP calling conducted using the STACKS pipeline. We aimed to compare both reference-based approaches, namely, employing a closely related species as the reference genome versus the species itself as the reference genome, to evaluate their respective merits and limitations. Our findings indicate a substantial discrepancy in the number of obtained SNPs between using a closely related species as opposed to the species itself as reference genomes, the former yielded approximately an order of magnitude fewer SNPs compared to the latter. While the missing rate of individuals and sites of the final SNPs obtained in the two scenarios showed no significant difference. The results showed that using the reference genome of the species itself tends to be prioritized in RAD-seq studies. However, if this is unavailable, considering closely related genomes is feasible due to their wide applicability and low missing rate as alternatives. This study contributes to enrich the understanding of the impact of SNP acquisition when utilizing different reference genomes.

Asiatic acid inhibits osteosarcoma cell migration and invasion via the AKT/Sp1/MMP1 axis.

Osteosarcoma is a malignant bone tumor affecting adolescents and children. No effective treatment is currently available. Asiatic acid (AA), a triterpenoid compound found in Centella asiatica, possesses anti-tumor, anti-inflammatory, and anti-oxidant properties in various types of tumor cells. This study aims to determine whether AA exerts antitumor effects in human osteosarcoma cells. Our results indicate that AA does not influence the viability, proliferative rate, or cell cycle phase of human osteosarcoma cells under non-toxic conditions. AA suppressed osteosarcoma cell migration and invasion by down-regulating matrix metalloproteinase 1 (MMP1) expression. Data in the TNMplot database suggested MMP1 expression was higher in osteosarcoma than in normal tissues, with associated clinical significance observed in osteosarcoma patients. Overexpression of MMP1 in osteosarcoma cells reversed the AA-induced suppression of cell migration and invasion. AA treatment decreased the expression of specificity protein 1 (Sp1), while Sp1 overexpression abolished the effect of AA on MMP1 expression and cell migration and invasion. AA inhibited AKT phosphorylation, and treatment with a PI3K inhibitor (wortmannin) increased the anti-invasive effect of AA on osteosarcoma cells via the p-AKT/Sp1/MMP1 axis. Thus, AA exhibits the potential for use as an anticancer drug against human osteosarcoma.

Prediction of early postoperative pain using sleep quality and heart rate variability.

PURPOSE: Accurate predictions of postoperative pain intensity are necessary for customizing analgesia plans. Insomnia is a risk factor for severe postoperative pain. Moreover, heart rate variability (HRV) can provide information on the sympathetic-parasympathetic balance in response to noxious stimuli. We developed a prediction model that uses the insomnia severity index (ISI), HRV, and other demographic factors to predict the odds of higher postoperative pain. METHODS: We recruited gynecological surgery patients classified as American Society of Anesthesiologists class 1-3. An ISI questionnaire was completed 1 day before surgery. HRV was calculated offline using intraoperative electrocardiogram data. Pain severity at the postanesthesia care unit (PACU) was assessed with the 0-10 numerical rating scale (NRS). The primary outcome was the model's predictive ability for moderate-to-severe postoperative pain. The secondary outcome was the relationship between individual risk factors and opioid consumption in the PACU. RESULTS: Our study enrolled 169 women. Higher ISI scores (p = 0.001), higher parasympathetic activity (rMSSD, pNN50, HF; p < 0.001, p < 0.001, p < 0.001), loss of fractal dynamics (SD2, alpha 1; p = 0.012, p = 0.039) in HRV analysis before the end of surgery were associated with higher NRS scores, while laparoscopic surgery (p = 0.031) was associated with lower NRS scores. We constructed a multiple logistic model (area under the curve = 0.852) to predict higher NRS scores at PACU arrival. The five selected predictors were age (OR: 0.94; p = 0.020), ISI score (OR: 1.14; p = 0.002), surgery type (laparoscopic or open; OR: 0.12; p < 0.001), total power (OR: 2.02; p < 0.001), and alpha 1 (OR: 0.03; p < 0.001). CONCLUSION: We employed a multiple logistic regression model to determine the likelihood of moderate-to-severe postoperative pain upon arrival at the PACU. Physicians could personalize analgesic regimens based on a deeper comprehension of the factors that contribute to postoperative pain.

Efficacy of propofol-based anesthesia against risk of brain swelling during craniotomy: A meta-analysis of randomized controlled studies.

STUDY OBJECTIVE: This meta-analysis aimed to compare the risk of brain swelling during craniotomy between propofol-based and volatile-based anesthesia. DESIGN: Meta-analysis of randomized controlled trials (RCTs). SETTING: Operating room. INTERVENTION: Propofol-based anesthesia. PATIENTS: Adult patients undergoing craniotomy. MEASUREMENTS: Databases, including EMBASE, MEDLINE, Google Scholar, and Cochrane Library, were searched from inception to April 2023. The primary outcome was the risk of brain swelling, while the secondary outcomes included the impact of anesthetic regimens on surgical and recovery outcomes, as well as the risk of hemodynamic instability. MAIN RESULTS: Our meta-analysis of 17 RCTs showed a significantly lower risk of brain swelling (risk ratio [RR]: 0.85, p = 0.03, I2 = 21%, n = 1976) in patients receiving propofol than in those using volatile agents, without significant differences in surgical time or blood loss between the two groups. Moreover, propofol was associated with a lower intracranial pressure (ICP) (mean difference: -4.06 mmHg, p < 0.00001, I2 = 44%, n = 409) as well as a lower risk of tachycardia (RR = 0.54, p = 0.005, I2 = 0%, n = 822) and postoperative nausea/vomiting (PONV) (RR = 0.59, p = 0.002, I2 = 19%, n = 1382). There were no significant differences in other recovery outcomes (e.g., extubation time), risk of bradycardia, hypertension, or hypotension between the two groups. Subgroup analysis indicated that propofol was not associated with a reduced risk of brain swelling when compared to individual volatile agents. Stratified by craniotomy indications, propofol reduced brain swelling in elective craniotomy, but not in emergency craniotomy (e.g., traumatic brain injury), when compared to volatile anesthetics. CONCLUSIONS: By reviewing the available evidence, our results demonstrate the beneficial effects of propofol on the risk of brain swelling, ICP, PONV, and intraoperative tachycardia. In emergency craniotomy for traumatic brain injury and subarachnoid hemorrhage, brain swelling showed no significant difference between propofol and volatile agents. Further large-scale studies are warranted for verification.

Exploring mechanical properties and failure mechanisms of aramid and PBO crystals through molecular dynamics simulations.

Molecular dynamics simulations were used to analyze the mechanical properties and failure processes of poly(p-phenylene-terephthalamide) (PPTA), poly(p-phenylene-benzimidazole-terephthalamide) (PBIA), PBIA-PPTA (formed by 1:1 copolymerization of PPTA and PBIA), and poly(p-phenylene-benzobisoxazole) (PBO) crystals at different strain rates and temperatures. The failure stress and strain were found to be linear with the temperature and logarithmic strain rate. Moreover, based on the kinetic theory of fracture and the comprehensive simulation results, we formulated a model that describes the failure stress of the aforementioned crystals under varying strain rates and temperatures. Through the analysis of the failure process, we found that in PPTA, PBIA, and PBIA-PPTA crystals, the bond failure probability is correlated with the strain rate and temperature. The examination of bond lengths and angles unveiled that bonds with larger initial aligning angles are more susceptible to failure during the strain process. Intriguingly, the stretching process induced a conformational change in the PBO molecular chain, leading to a deviation from the linear relation in its stress-strain curve.

Comparing 5G mobile stroke unit and emergency medical service in patients acute ischemic stroke eligible for t-PA treatment: A prospective, single-center clinical trial in Ya'an, China.

BACKGROUND: This study aims to assess and compare the functional outcomes of patients with acute ischemic stroke (AIS) eligible for tissue plasminogen activator (t-PA) treatment who received care from either a fifth-generation(5G) mobile stroke unit (MSU) or traditional emergency medical service (EMS). METHOD: The study recruited patients between February 2020 and January 2022, with the final 90-day follow-up concluded in April 2022. Prior to enrollment, patients were assigned to either EMS or MSU care based on predetermined rules. The primary outcome measure was the Modified Rankin Scale (mRS) score at 90 days, with secondary outcome measures including time metrics, mRS and National Institutes of Health Stroke Scale scores at 7-day follow-up, and hospitalization costs. RESULTS: Of the 2281 enrolled patients, 207 were eligible for t-PA treatment, with 101 allocated to MSU care and 106 to EMS care. The percentage of patients achieving a favorable mRS score (0-2) at 90 days was 82.2% in the MSU group compared to 72.6% in the EMS group (p < .05). Median times from symptom onset to thrombolysis were 146 min in the MSU group and 204 min in the EMS group, while median times from ambulance alert to computed tomography (CT) completion were 53 and 128 min, respectively. Hospitalization charges averaged approximately $3592 in the MSU group and $4800 in the EMS group. CONCLUSIONS: Our findings indicate that 5G MSU care significantly reduces the time from symptom onset to stroke diagnosis and intravenous thrombolysis in patients with AIS, resulting in improved functional outcomes compared to EMS care. As China continues its deployment of 5G technology and other digital infrastructures, the adoption of 5G MSU care on a broader scale may eventually supplant traditional stroke treatment approaches.

miR-221/222 induce instability of p53 By downregulating deubiquitinase YOD1 in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a hematological malignancy characterized by the impaired differentiation and uncontrolled proliferation of myeloid blasts. Tumor suppressor p53 is often downregulated in AML cells via ubiquitination-mediated degradation. While the role of E3 ligase MDM2 in p53 ubiquitination is well-accepted, little is known about the involvement of deubiquitinases (DUBs). Herein, we found that the expression of YOD1, among several DUBs, is substantially reduced in blood cells from AML patients. We identified that YOD1 deubiqutinated and stabilized p53 through interaction via N-terminus of p53 and OTU domain of YOD1. In addition, expression levels of YOD1 were suppressed by elevated miR-221/222 in AML cells through binding to the 3' untranslated region of YOD1, as verified by reporter gene assays. Treatment of cells with miR-221/222 mimics and inhibitors yielded the expected effects on YOD1 expressions, in agreement with the negative correlation observed between the expression levels of miR-221/222 and YOD1 in AML cells. Finally, overexpression of YOD1 stabilized p53, upregulated pro-apoptotic p53 downstream genes, and increased the sensitivity of AML cells to FLT3 inhibitors remarkably. Collectively, our study identified a pathway connecting miR-221/222, YOD1, and p53 in AML. Targeting miR-221/222 and stimulating YOD1 activity may improve the therapeutic effects of FLT3 inhibitors in patients with AML.

Role of Mutations of Mitochondrial Aminoacyl-tRNA Synthetases Genes on Epileptogenesis.

Mitochondria are the structures in cells that are responsible for producing energy. They contain a specific translation unit for synthesizing mitochondria-encoded respiratory chain components: the mitochondrial DNA (mt DNA). Recently, a growing number of syndromes associated with the dysfunction of mt DNA translation have been reported. However, the functions of these diseases still need to be precise and thus attract much attention. Mitochondrial tRNAs (mt tRNAs) are encoded by mt DNA; they are the primary cause of mitochondrial dysfunction and are associated with a wide range of pathologies. Previous research has shown the role of mt tRNAs in the epileptic mechanism. This review will focus on the function of mt tRNA and the role of mitochondrial aminoacyl-tRNA synthetase (mt aaRS) in order to summarize some common relevant mutant genes of mt aaRS that cause epilepsy and the specific symptoms of the disease they cause.

The landscape of novel strategies for acute myeloid leukemia treatment: Therapeutic trends, challenges, and future directions.

Acute myeloid leukemia (AML) is a highly heterogeneous subtype of hematological malignancies with a wide spectrum of cytogenetic and molecular abnormalities, which makes it difficult to manage and cure. Along with the deeper understanding of the molecular mechanisms underlying AML pathogenesis, a large cohort of novel targeted therapeutic approaches has emerged, which considerably expands the medical options and changes the therapeutic landscape of AML. Despite that, resistant and refractory cases caused by genomic mutations or bypass signalling activation remain a great challenge. Therefore, discovery of novel treatment targets, optimization of combination strategies, and development of efficient therapeutics are urgently required. This review provides a detailed and comprehensive discussion on the advantages and limitations of targeted therapies as a single agent or in combination with others. Furthermore, the innovative therapeutic approaches including hyperthermia, monoclonal antibody-based therapy, and CAR-T cell therapy are also introduced, which may provide safe and viable options for the treatment of patients with AML.

Factors Impacting Advance Decision Making and Health Care Agent Appointment among Taiwanese Urban Residents after the Passage of Patient Right to Autonomy Act.

In recent years, advance care planning (ACP) promotion in Taiwan has expanded beyond clinical practice to the broader population. This study aims to investigate people's attitudes toward ACP and to identify factors influencing their signing of advance directives (ADs) and appointment of health care agents (HCAs). METHODS: We identified 2337 ACP participants from consultation records between 2019 and 2020. The relationships among the participants' characteristics, AD completion, and HCA appointment were investigated. RESULTS: Of 2337 cases, 94.1% completed ADs and 87.8% were appointed HCAs. Welfare entitlement (OR = 0.47, p < 0.001), the place ACP progressed (OR = 0.08, p < 0.001), the participation of second-degree relatives (OR = 2.50, p < 0.001), and the intention of not being a family burden (OR = 1.65, p = 0.010) were significantly correlated with AD completion. The probability of appointing HCAs was higher in participants with family caregiving experience (OR = 1.42, p < 0.05), who were single (OR = 1.49, p < 0.05), and who expected a good death with dignity (OR = 1.65, p < 0.01). CONCLUSIONS: Our research shows that adopting ACP discussion in Taiwan is feasible, which encourages ACP conversation and facilitates AD completion. IMPLICATIONS: Male and younger adults may need extra encouragement to discuss ACP matters with their families. LIMITATIONS: due to sampling restrictions, our data were chosen from an urban district to ensure the integrity of the results. Furthermore, interview data could be collected in future research to supplement the quantitative results.

Targeting the elevated IFN-γ in vitiligo patients by human anti- IFN-γ monoclonal antibody hampers direct cytotoxicity in melanocyte.

BACKGROUND: Vitiligo is an autoimmune disease that progressively destroys melanocytes in the skin, resulting in patchy disfiguring depigmentation. The direct pathological effect of IFN-γ, CXCL10 to the melanocytes in vitiligo has been reported, but there are contradictory results to which cytokine exerts the critical cytotoxic effect on melanocytes. OBJECTIVE: The overarching goal was to study the direct toxicity of highly expressed cytokine in vitiligo skin lesions to melanocytes. METHODS: We obtained the interstitial fluid analyte from lesion and non-lesion skin of vitiligo patients and healthy control and sent for high sensitivity multiplex cytokine panel. We further performed functional study to identify the direct toxicity effect of the highly expressed cytokines. RESULTS: We found a significant elevation of IFN-γ, CXCL9, CXCL10, CXCL11 in the vitiligo skin. Ex vivo melanocyte studies support the direct role of IFN-γ per se in melanocyte cell loss, increased oxidative stress and melanogenesis disruption. Interestingly, we found that IFN-γ regulated cell death through oxidative stress-related ferroptosis cell death, which may initiate autoimmunity in vitiligo. In contrast to blocking selected cell death pathway, our in vitro study supports the rescue effect of human anti-IFN-γ monoclonal antibody 2A6Q to IFN-γ induced cell death, oxidative stress, and loss of function in melanocytes by interrupting IFN-γ signaling, which may be a potential therapeutic option for vitiligo. CONCLUSION: This study further confirms the direct of toxicity effect of IFN-γ per se towards melanocyte in vitiligo skin and the potential utility of human anti-IFN-γ monoclonal antibody in treating vitiligo.

Automatic Multiscale Method of Building up a Cross-linked Polymer Reaction System: Bridging SMILES to the Multiscale Molecular Dynamics Simulation.

An automatic method is introduced to generate the initial configuration and input file from SMILES for multiscale molecular dynamics (MD) simulation of cross-linked polymer reaction systems. Inputs are a modified version of SMILES of all the components and conditions of coarse-grained (CG) and all-atom (AA) simulations. The overall process comprises the following steps: (1) Modified SMILES inputs of all the components are converted to 3-dimensional coordinates of molecular structures. (2) Molecular structures are mapped to the coarse-grained scale, followed by a CG reaction simulation. (3) CG beads are backmapped to the atomic scale after the CG reaction. (4) An AA productive run is finally performed to analyze volume shrinkage, glass transition, and atomic detail of network structure. The method is applied to two common epoxy resin reactions, that is, the cross-linking process of DGEVA (diglycidyl ether of vanillyl alcohol) and DHAVA (dihydroxyaminopropane of vanillyl alcohol) and that of DGEBA (diglycidyl ether of bisphenol A) and DETA (diethylenetriamine). These components form network structures after the CG cross-linking reaction and are then backmapped to calculate properties in the atomic scale. The result demonstrates that the method can accurately predict volume shrinkage, glass transition, and all-atom structure of cross-linked polymers. The method bridges from SMILES to MD simulation trajectories in an automatic way, which shortens the time of building up cross-linked polymer reaction model and suitable for high-throughput computations.

Defect transition of smectic liquid crystals confined in spherical cavities.

The formation and transformation of defects in confined liquid crystals are fascinating fundamental problems in soft matter. Here, we use molecular dynamics (MD) simulations to study ellipsoidal liquid crystals (LCs) confined in a spherical cavity, which significantly affects the orientation and translation of LC molecules near the surface. The liquid-crystal droplet can present the isotropic to smectic-B phase transition through the smectic-A phase, as the number density of the LC molecules increases. We further find the change of LC structure from bipolar to watermelon-striped during the phase transition from smectic-A (SmA) to smectic-B (SmB) phases. Our results reveal the transition from bipolar defects to the inhomogeneous structures with the coexistence of nematic and smectic phases in smectic liquid-crystal droplets. We also study the influence of the sphere size in the range of 10σ0 ≤ Rsphere ≤ 50σ0 on the structural inhomogeneities. It shows a weak dependence on the sphere size. We further focus on how the structures can be affected by the interaction strength εGB-LJ. Interestingly, we find the watermelon-striped structure can be changed into a configuration with four defects at the vertices of a tetrahedron upon increasing the interaction strength. The liquid crystals at a strong interaction strength of εGB-LJ = 10.0ε0 show the two-dimensional nematic phase at the surface. We further present an explanation for the origin of the striped-pattern formation. Our results highlight the potential for using confinement to control these defects and their associated nanostructural heterogeneity.

Mitophagy Effects of Protodioscin on Human Osteosarcoma Cells by Inhibition of p38MAPK Targeting NIX/LC3 Axis.

Protodioscin (PD) is a steroidal saponin with various pharmacological activities, including neuro-protective, anti-inflammatory, and anti-tumor activities. However, the effect of PD on human osteosarcoma (OS) cells is unclear. In this study, we found that PD significantly inhibits the growth of human HOS and 143B OS cells through the upregulation of apoptotic-related proteins (cleaved caspase-3, cleaved caspase-9, and cleaved PARP) and mitophagy-related proteins (LC3B and NIX), which contribute to the induction of apoptosis, and MMP (mitochondrial membrane potential) dysfunction and mitophagy. The inhibition of LC3 or NIX was shown to decrease apoptosis and mitophagy in PD-treated OS cells. The knockdown of p38MAPK by siRNA decreased mitochondrial dysfunction, autophagy, mitophagy, and the NIX/LC3B expression in the PD-treated OS cells. A binding affinity analysis revealed that the smaller the KD value (-7.6 Kcal/mol and -8.9 Kcal/mol, respectively), the greater the binding affinity in the PD-NIX and PD-LC3 complexes. These findings show the inhibitory effects of PD-induced mitophagy in human OS cells and may represent a novel therapeutic strategy for human OS, by targeting the NIX/LC3 pathways.