Human transferrin receptor can mediate SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (KD ~2.95 nM) to mediate SARS-CoV-2 endocytosis. TfR knock-down (TfR-deficiency is lethal) and overexpression inhibit and promote SARS-CoV-2 infection, respectively. Humanized TfR expression enables SARS-CoV-2 infection in baby hamster kidney cells and C57 mice, which are known to be insusceptible to the virus infection. Soluble TfR, Tf, designed peptides blocking TfR-Spike interaction and anti-TfR antibody show significant anti-COVID-19 effects in cell and monkey models. Collectively, this report indicates that TfR is a receptor/co-receptor of SARS-CoV-2 mediating SARS-CoV-2 entry and infectivity by likely using the TfR trafficking pathway.

A novel bispecific T-cell engager using the ligand-target csGRP78 against acute myeloid leukemia.

Current medical therapies for treating acute myeloid leukemia (AML) remain unmet, and AML patients may benefit from targeted immunotherapy approaches that focus on specific tumor antigens. GRP78, which is upregulated in various malignant tumors such as AML, is partially expressed as cell surface GRP78 (csGRP78) on the cell membrane, making it an ideal target for redirecting T cells, including T-cell engagers. However, considering the conventional approach of using two scFv segments to construct a bispecific T-cell engager (BiTE), we have undertaken the development of a novel BiTE that utilizes a cyclic peptide ligand to specifically target csGRP78, which we refer to as GRP78-CD3/BiTE. We studied the effects of GRP78-CD3/BiTE on treatments for AML in vitro and in vivo and assessed the pharmacokinetics of this engager. Our findings demonstrated that GRP78-CD3/BiTE could not only effectively mediate the cytotoxicity of T cells against csGRP78-expressing AML cells but also specifically eliminate primary AML tumor cells in vitro. Furthermore, GRP78-CD3/BiTE exhibited a longer half-life despite having a lower molecular weight than CD19-CD3/BiTE. In a xenograft mouse model of AML, treatment with GRP78-CD3/BiTE prolonged the survival time of the mice. Our findings demonstrate that GRP78-CD3/BiTE is effective and selective for eliminating csGRP78-expressing AML cells and suggest that this approach to targeted immunotherapy could lead to effective new treatments for AML.

Electron Deficient Ir-O Bonds Promote Heterogeneous Ir-Catalyzed Anti-Markovnikov Hydroboration of Alkenes under Mild Neat Conditions.

Tuning electronic characteristics of metal-ligand bonds based on reaction pathways to achieve efficient catalytic processes has been widely studied and proven to be feasible in homogeneous catalysis, but it is scarcely investigated in heterogeneous catalysis. Herein, we demonstrate the regulation of the electronic configuration of Ir-O bonds in an Ir single-atom catalyst according to the borane activation mechanism. Ir-O bonds in Ir1/Ni(OH)x are found to be more electron-poor than those in Ir1/NiOx. Despite the mild solvent-free conditions and ambient temperature, Ir1/Ni(OH)x exhibits outstanding performance for the hydroboration of alkenes, furnishing the desired alkylboronic esters with a turnover frequency value of ≤3060 h-1 and 99% anti-Markovnikov selectivity, which is significantly better than that of Ir1/NiOx (42 h-1). It is further proven that the more electron-poor Ir-O bonds as active centers are more oxidative and so benefit the activation of the H-B bond in the reductive pinacolborane.

Novel CAR-T cells targeting TRKB for the treatment of solid cancer.

Chimeric antigen receptor (CAR) T-cell therapy is highly effective for treating blood cancers such as B-cell malignancies, however, its effectiveness as an approach to treat solid tumors remains to be further explored. Here, we focused on the development of CAR-T cell therapies targeting tropomyosin-related kinase receptor B (TRKB), a highly expressed protein that is significantly associated with tumor progression, malignancy, and drug resistance in multiple forms of aggressive solid tumors. To achieve this, we screened brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NTF4) ligand-based CAR-T cells for their efficiency in targeting the TRKB receptor in the context of solid tumors, particularly hepatocellular carcinoma and pancreatic cancer. We demonstrated that TRKB is overexpressed not only in hepatocellular carcinoma and pancreatic carcinoma cell lines but also in cancer stem-like cells (CSCs). Notably, BDNF-CAR T and NTF4-CAR T cells could not only effectively target and kill TRKB-expressing pan-cancer cell lines in a dose-dependent manner but also effectively kill CSCs. We also performed in vivo studies to show that NTF4-CAR T cells have a better potential to inhibit the tumor growth of hepatocellular carcinoma xenografts in mice, compared with BDNF-CAR T cells. Taken together, our findings suggest that CAR-T targeting TRKB may be a promising approach for developing novel therapies to treat solid cancers.

Centrifugo-Pneumatic Reciprocating Flowing Coupled with a Spatial Confinement Strategy for an Ultrafast Multiplexed Immunoassay.

Immunoassays serve as powerful diagnostic tools for early disease screening, process monitoring, and precision treatment. However, the current methods are limited by high costs, prolonged processing times (>2 h), and operational complexities that hinder their widespread application in point-of-care testing. Here, we propose a novel centrifugo-pneumatic reciprocating flowing coupled with spatial confinement strategy, termed PRCM, for ultrafast multiplexed immunoassay of pathogens on a centrifugal microfluidic platform. Each chip consists of four replicated units; each unit allows simultaneous detection of three targets, thereby facilitating high-throughput parallel analysis of multiple targets. The PRCM platform enables sequential execution of critical steps such as solution mixing, reaction, and drainage by coordinating inherent parameters, including motor rotation speed, rotation direction, and acceleration/deceleration. By integrating centrifugal-mediated pneumatic reciprocating flow with spatial confinement strategies, we significantly reduce the duration of immune binding from 30 to 5 min, enabling completion of the entire testing process within 20 min. As proof of concept, we conducted a simultaneous comparative test on- and off-the-microfluidics using 12 negative and positive clinical samples. The outcomes yielded 100% accuracy in detecting the presence or absence of the SARS-CoV-2 virus, thus highlighting the potential of our PRCM system for multiplexed point-of-care immunoassays.

A Universal In-Situ Interfacial Growth Strategy for Various MXene-Based van der Waals Heterostructures with Uniform Heterointerfaces: The Efficient Conversion from 3D Composite to 2D Heterostructures.

Two-dimensional (2D) van der Waals heterostructures endow individual 2D material with the novel functional structures, intriguing compositions, and fantastic interfaces, which efficiently provide a feasible route to overcome the intrinsic limitations of single 2D components and embrace the distinct features of different materials. However, the construction of 2D heterostructures with uniform heterointerfaces still poses significant challenges. Herein, a universal in-situ interfacial growth strategy is designed to controllably prepare a series of MXene-based tin selenides/sulfides with 2D van der Waals homogeneous heterostructures. Molten salt etching by-products that are usually recognized as undesirable impurities, are reasonably utilized by us to efficiently transform into different 2D nanostructures via in-situ interfacial growth. The obtained MXene-based 2D heterostructures present sandwiched structures and lamellar interlacing networks with uniform heterointerfaces, which demonstrate the efficient conversion from 3D composite to 2D heterostructures. Such 2D heterostructures significantly enhance charge transfer efficiency, chemical reversibility, and overall structural stability in the electrochemical process. Taking 2D-SnSe2/MXene anode as a representative, it delivers outstanding lithium storage performance with large reversible capacities and ultrahigh capacity retention of over 97% after numerous cycles at 0.2, 1.0, and 10.0 A g-1 current density, which suggests its tremendous application potential in lithium-ion batteries.

Ensemble classification based signature discovery for cancer diagnosis in RNA expression profiles across different platforms.

Molecular signatures have been excessively reported for diagnosis of many cancers during the last 20 years. However, false-positive signatures are always found using statistical methods or machine learning approaches, and that makes subsequent biological experiments fail. Therefore, signature discovery has gradually become a non-mainstream work in bioinformatics. Actually, there are three critical weaknesses that make the identified signature unreliable. First of all, a signature is wrongly thought to be a gene set, each component of which keeps differential expressions between or among sample groups. Second, there may be many false-positive genes expressed differentially found, even if samples derived from cancer or normal group can be separated in one-dimensional space. Third, cross-platform validation results of a discovered signature are always poor. In order to solve these problems, we propose a new feature selection framework based on ensemble classification to discover signatures for cancer diagnosis. Meanwhile, a procedure for data transform among different expression profiles across different platforms is also designed. Signatures are found on simulation and real data representing different carcinomas across different platforms. Besides, false positives are suppressed. The experimental results demonstrate the effectiveness of our method.

Ensemble classification based feature selection: a case of identification on plant pentatricopeptide repeat proteins.

In order to identify plant pentatricopeptide repeat (PPR) proteins, a framework of variable selection has been proposed. In fact, it is an effective feature selection strategy that focuses on the performance of classification. Random forest has been used as the classifier with certain variables automatically selected for discrimination between PPR functional and non-functional proteins. However, it is found that samples regarded as PPR functional proteins are wrongly classified in a high rate. In this paper, we plan to improve the framework in order to achieve better classification results. Modifications are made on the framework for better identifying PPR functional proteins. Instead of random forest, a hybrid ensemble classifier is built with its base classifiers derived from six different classification methods. Besides, an incremental strategy and a clustering by search in descending order are alternatively used for feature selection, which can effectively select the most representative variables for identification on PPR proteins. In addition, it can be found that different base classifiers alternately play an important role in the ensemble classifier with feature dimension increasing. The experimental results demonstrate the effectiveness of our improvements.

Mesothelin-based CAR-T cells exhibit potent antitumor activity against ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is characterized by its rapid growth and spread which, accompanied by a low 5-year survival rate, necessitates the development of improved treatments. In ovarian cancer, the selective overexpression of Mucin-16 (MUC16, CA125) in tumor cells highlights its potential as a promising target for developing anti-tumor therapies. However, the potential effectiveness of CAR-T cell therapy that targets MUC16 in ovarian cancer cells is unknown. METHODS: The expression of MUC16 in viable OC cells was detected using immunofluorescence and flow cytometry techniques. A MSLN-CAR construct, comprising the MUC16-binding polypeptide region of mesothelin (MSLN), a CD8 hinge spacer and transmembrane domain, 4-1BB, and CD3ζ endo-domains; was synthesized and introduced into T cells using lentiviral particles. The cytotoxicity of the resultant CAR-T cells was evaluated in vitro using luciferase assays. Cytokine release by CAR-T cells was measured using enzyme-linked immunosorbent assays. The anti-tumor efficacy of the CAR-T cells was subsequently assessed in mice through both systemic and local administration protocols. RESULTS: MSLN-CAR T cells exhibited potent cytotoxicity towards OVCAR3 cells and their stem-like cells that express high levels of MUC16. Also, MSLN-CAR T cells were inefficient at killing SKOV3 cells that express low levels of MUC16, but were potently cytotoxic to such cells overexpressing MUC16. Moreover, MSLN-CAR T cells delivered via tail vein or peritoneal injection could shrink OVCAR3 xenograft tumors in vivo, with sustained remission observed following peritoneal delivery of MSLN-CAR T cells. CONCLUSIONS: Collectively, these results suggested that MSLN-CAR T cells could potently eliminate MUC16- positive ovarian cancer tumor cells both in vitro and in vivo, thereby providing a promising therapeutic intervention for MUC16-positive patients.

High Verdet constant of Tb2O3-doped TiO-B2O3-Al2O3-Na2O magneto-optical glass.

Tb-doped magneto-optical (MO) glass is widely used in fiber optics, optical isolators, and modulators. However, only the paramagnetic Tb3+ ions exhibit significant MO effects, whereas the diamagnetism Tb4+ ions suppress the MO effects. Therefore, the valence state control of Tb ions is very critical to optimize MO performance. Here, a reduction strategy was introduced to adjust the Tb valence in glass to achieve the high MO effect. The TiO, which has low valence Ti2+ ions and good reducibility, was used to suppress the oxidation of Tb3+ to Tb4+ ions. In the TiO-B2O3-Al2O3-Na2O glass, 10 mol% TiO can increase the Verdet constant at 650 nm by 19%. With the further increase in Tb2O3 concentration, the Verdet constant reaches a high value of 117 rad/(T·m) at 650 nm, which is close to the Verdet constant of TGG crystal (121 rad/(T·m)). This work provides a new approach to increase the Verdet constant of MO glass.

The role of immune and inflammatory-related indicators in cognitive dysfunction and disease severity in patients with parkinson's disease.

We aimed to explore the role of immune and inflammatory indicators in cognitive dysfunction and disease severity in patients with Parkinson's disease (PD). A total of 123 patients with Parkinson's disease were enrolled in the PD group and 49 healthy volunteers in the control group. The patients with PD were further divided into 2 subgroups by evaluating cognitive function using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE): the normal cognitive function (PD-NCI) group and the mild cognitive impairment (PD-MCI) group. Moreover, the PD patients were also divided into 2 subgroups using the defined scale of the Hoehn and Yahr (H-Y) stage: the early-stage group and the middle- and late-stage group. Immune and inflammatory indicators, including serum Aß1-42, Tau, CD4+, CD8+, CD3+, B lymphocytes cell, NK cell, Th17 cell, Treg cell, IL-6, IL-17, and TNF-α levels, were evaluated and analyzed to explore the potential correlation with the cognitive dysfunction and disease severity of PD. Among the 123 PD patients, 60 (48.8%) were diagnosed with mild cognitive impairment. Aß1-42, CD4+, CD8+, CD3+, and Treg levels observed in the PD-NCI group were lower than the control group (P < 0.001), while higher than the PD-MCI group (P < 0.001). The levels of Tau, Th17, IL-6, IL-17, and TNF-α observed in the PD-NCI group were higher than the control group (P < 0.001), while lower than in the PD-MCI group (P < 0.01). Using the same method, the results of the early-stage group and the middle- and the late-stage group were the same as above. Logistic regression analysis and ROC curve estimation were performed and indicated that the variation of Tau, CD8+, Treg, TNF-α levels was associated with cognitive decline in PD patients, and may serve as markers of PD onset. Furthermore, the variation of Aß1-42, IL-6, and TNF-α levels was found to correlate with the disease severity of PD. The immune and inflammatory-related indicators may represent an important factor in the pathogenesis of PD, cognitive dysfunction, and disease severity. The variation of Tau protein, CD8+, Treg, and TNF-α levels are associated with the cognitive dysfunction of PD, which may be considered as onset markers. Moreover, the variation of Aß1-42, IL-6, and TNF-α levels can predict the progression of PD.

Risk Factors Analysis of Severe Liver Injury Induced by Statins.

The aim of this study is to report the risk factors of severe statin induced liver injury (SILI). From the database of Shandong ADR Monitoring Center and Outpatients and inpatients in our hospital, SILI cases reported from 2013 to 2021 were extracted and screened. The diagnostic criteria of SILI, the inclusion and exclusion criteria of severe and general SILI were established separately. After the SILI cases were selected and confirmed, the socio-demographic and clinical characteristics were collected. Single factor chi-square test and multi-factor unconditional logistic regression analysis were used to analyze the influencing factors of severe SILI. From 1391 reported cases, 1211 met SILI diagnostic criteria, of which 157 were severe SILI and 964 were general SILI. Univariate analysis showed that age, drug combination, statin category were the influencing factors of severe SILI (p<0.1). Multivariate logistic analysis showed that drug combination and statin category were the influencing factors of severe SILI (p<0.05). Atorvastatin caused the most serious SILI, and its risk is 1.77 times higher than rosuvastatin. The serious SILI risk of drug combination was 2.08 times higher than statin alone. The patient with these factors should be monitored intensively during clinical treatment, to ensure their medication safety.

All-in-one detection of breast cancer-derived exosomal miRNA on a pen-based paper chip.

Exosomal microRNAs (miRNAs) play a pivotal role in intercellular communication, regulating gene expression in target cells, and hold significant promise as cancer biomarkers for early detection and screening. However, achieving precise and viable detection of exosomal miRNAs remains a challenge. This paper proposes an all-in-one detection strategy for breast cancer-derived exosomal miRNA-21 on a pen-based paper chip (PPC). The PPC is constructed using a modified automatic pen and lateral flow assay (LFA), which results in a cost-effective fabrication process. The user only needs to add the sample and trigger the top of the self-contained PPC after a period of time to complete the entire detection process. To enhance the sensitivity of exosomal miRNA testing, an enzyme-free catalyzed hairpin assembly (CHA) is further introduced, enabling highly sensitive detection of miRNA-21 with a limit of detection (LOD) of 25 fmol. Additionally, the detection of miRNAs in differentially-expressed cells and clinical samples has also been successfully achieved with high specificity. Overall, the proposed PPC provides an effective tool for detecting early cancer, monitoring diseases, and establishing point of care testing (POCT).

Resveratrol augments paclitaxel sensitivity by modulating miR-671-5p/STOML2/PINK1/Parkin-mediated autophagy signaling in A549 cell.

BACKGROUND: Paclitaxel (PTX) resistance has become a notable clinical concern of Non-small cell lung cancer (NSCLC). Our study aim is to investigate the effects of Resveratrol (RES) on NSCLC cells that have developed resistance to PTX. The NSCLC cell line A549 was employed in this investigation to establish a PTX-resistant NSCLC cell line, denoted as A549/PTX, and established tumor transplantaton model. The presence of miR-671-5p, Stomatin-like protein 2 (STOML2), and mitophagy biomarkers was evaluated using quantitative teal-time PCR (qRT-PCR) and western blot, The assessment of cell proliferation and apoptosis was conducted through the utilisation of colony formation and flow cytometry assays. The investigation of mitochondrial autolysosomes was conducted using transmission electron microscopy (TEM). Our results showed that the application of RES therapy resulted in a substantial improvement in the sansitivity of A549/PTX cells. RES exhibited an augmentation of apoptosis and a suppression of mitophagy in A549/PTX cells. RES induced an upregulation in the expression of miR-671-5p. This, in turn, leaded to the inhibition of STOML2, a protein that directly interacts with PINK1. In summary, our research indicates that RES improved the susceptibility of A549/PTX cells to PTX through miR-671-5p-mediated STOML2 inhibition.

Unraveling the link between childhood maltreatment and depression: Insights from the role of ventral striatum and middle cingulate cortex in hedonic experience and emotion regulation.

Childhood maltreatment is an established risk factor for psychopathology. However, it remains unclear how childhood traumatic events relate to mental health problems and how the brain is involved. This study examined the serial mediation effect of brain morphological alterations and emotion-/reward-related functions on linking the relationship from maltreatment to depression. We recruited 156 healthy adolescents and young adults and an additional sample of 31 adolescents with major depressive disorder for assessment of childhood maltreatment, depressive symptoms, cognitive reappraisal and anticipatory/consummatory pleasure. Structural MRI data were acquired to identify maltreatment-related cortical and subcortical morphological differences. The mediation models suggested that emotional maltreatment of abuse and neglect, was respectively associated with increased gray matter volume in the ventral striatum and greater thickness in the middle cingulate cortex. These structural alterations were further related to reduced anticipatory pleasure and disrupted cognitive reappraisal, which contributed to more severe depressive symptoms among healthy individuals. The above mediating effects were not replicated in our clinical group partly due to the small sample size. Preventative interventions can target emotional and reward systems to foster resilience and reduce the likelihood of future psychiatric disorders among individuals with a history of maltreatment.

Clinical characteristics and prognoses in pediatric neuroblastoma with bone or liver metastasis: data from the SEER 2010-2019.

BACKGROUND: To investigate clinical characteristics, prognoses, and impacts of treatments on prognoses of neuroblastoma patients with bone or liver metastasis. METHODS: This retrospective cohort study extracted data from the Surveillance, Epidemiology, and End Results (SEER) database 2010-2019. The outcomes were 3-year cancer-specific survival (CSS) and 5-year CSS. Multivariable COX risk proportional models were established to assess the association between metastasis types and CSS. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. RESULTS: Totally 425 patients with metastatic neuroblastoma were eligible for 3-year CSS analysis and 320 for 5-year CSS analysis. For 3-year follow-up, 62 (14.59%) patients had liver metastasis alone, 289 (0.68%) had bone metastasis alone, and 74 (17.41%) had both liver and bone metastasis. For 5-year follow-up, 44 (13.75%) patients had liver metastasis alone, 223 (69.69%) had bone metastasis alone, and 53 (16.56%) had both liver and bone metastasis. Significant differences were observed in age, tumor size, surgery for the primary site, chemotherapy, radiation, brain metastasis, lung metastasis, and vital status between patients with liver metastasis alone, bone metastasis alone, and both liver and bone metastasis (all P < 0.05). Compared with patients with liver metastasis alone, patients with bone metastasis alone (HR = 2.30, 95%CI: 1.10-4.82, P = 0.028) or both (HR = 2.35, 95%CI: 1.06-5.20, P = 0.035) had significantly poorer 3-year CSS; patients with bone metastasis alone (HR = 2.32, 95%CI: 1.14-4.70, P = 0.020) or both liver and bone metastasis (HR = 2.33, 95%CI: 1.07-5.07, P = 0.032) exhibited significantly worse 5-year CSS than those with liver metastasis alone. In patients with bone metastasis, those with chemotherapy had significantly better 3-year CSS than those without (HR = 0.24, 95%CI: 0.07-0.75, P = 0.014). Among patients with liver metastasis, receiving radiation was associated with significantly worse 3-year CSS (HR = 2.00, 95%CI: 1.05-3.81, P = 0.035). CONCLUSION: Compared with patients with liver metastasis alone, those with bone metastasis alone or both had poorer 3- and 5-year CSS. For patients with bone metastasis, undergoing chemotherapy was associated with better 3-year CSS. For patients with liver metastasis, receiving radiation was associated with worse 3-year CSS.

Surgical outcomes after reoperation for patients with recurrent presacral tumors: a retrospective study.

BACKGROUND: Relevant reports on the surgical resection and prognosis of recurrent presacral tumors are limited. The objective of this study was to explore the outcomes associated with surgical resection of recurrent presacral tumors. METHODS: The data of patients with recurrent presacral tumors who received surgical resection in our hospital between June 2009 and November 2018 were retrospectively analyzed. RESULTS: Thirty-one patients, comprising 22 females and 9 males, with recurrent presacral lesions were included in our study. A posterior approach was utilized in 27 patients, an anterior approach in 1 patient, and a combined approach in 3 patients. Intraoperative complications occurred in 13 patients (41.9%), while postoperative complications occurred in 6 patients (19.4%). The length of hospital stay was significantly shorter in patients who underwent the posterior approach compared to those who underwent the anterior and combined approaches (P = 0.002). The operative time for the posterior approach was significantly shorter compared to both the anterior and combined approaches (P = 0.006). Temporary tamponade was performed for hemostasis in 4 patients, while staged resection was performed in 2 patients during the surgical treatment process. After a median follow-up period of 115.5 months, 5 patients with recurrent malignant presacral tumors succumbed to tumor recurrence after reoperation in our hospital. CONCLUSIONS: Surgical resection remains the mainstream treatment for recurrent presacral tumors. The outcomes for recurrent benign presacral tumors after surgery demonstrate favorable results, whereas further enhancements are required to improve the outcomes for recurrent malignant presacral tumors after surgery.

Identification of predictors for short-term recurrence: comprehensive analysis of 296 retroperitoneal liposarcoma cases.

BACKGROUND: The short-term (≤ 1 year) recurrence (STR) is the primary determinant impacting both the life quality and survival duration in patients who have undergone surgical resection for retroperitoneal liposarcoma (RPLS), a condition with intricate and ambiguous pathogenesis. The purpose of this study was to analyze the risk factors associated with STR in cases of RPLS and primary retroperitoneal liposarcoma (PRPLS). METHODS: For this retrospective observational study, a total of 296 RPLS cases were selected as research subjects, who experienced tumor recurrence during the follow-up period. The Local recurrence-free survival (LRFS) rates were estimated using the Kaplan-Meier method and subsequently compared between groups utilizing the log-rank test. The subsequent analyses involved univariate and multivariate logistic regression to identify predictors of STR in RPLS cases. Additionally, a logistic regression model was constructed for PRPLS. RESULTS: The 1-, 3-, and 5-year LRFS rates of the 296 RPLS cases were 51.7%, 16.9%, and 7.1%, respectively. In the univariate analysis, several factors were found to be associated with STR, including preoperative neutrophil/lymphocyte ratio (NLR), smoking history, surgical frequency, combined organ excision, operative time, intraoperative bleeding, transfer to the intensive care unit (ICU), multiple primary tumors, tumor shape and capsule characteristics, histological subtype, and presence of tumor necrosis. The elevated preoperative NLR, surgical frequency of ≥ 3 times, transfer to the ICU, presence of multiple primary tumors, and tumor necrosis were identified as independent risk factors for STR in surgically resected RPLS. Conversely, diabetes, intact tumor capsule, and well-differentiated histological subtype appeared to be independent protective factors. Analysis for PRPLS revealed that tumor capsule and tumor necrosis were independent predictors of STR. CONCLUSIONS: The elevated preoperative NLR, surgical frequency of ≥ 3 times, transfer to the ICU, presence of multiple primary tumors, tumor necrosis, and tumor capsule were expected to serve as predictive factors of STR for surgical resected RPLS and PRPLS.

The Role of Osteopontin (OPN) in Regulating Microglia Phagocytosis in Nervous System Diseases.

Phagocytosis is the process by which certain cells or organelles internalise foreign substances by engulfing them and then digesting or disposing of them. Microglia are the main resident phagocytic cells in the brain. It is generally believed that microglia/macrophages play a role in guiding the brain's repair and functional recovery processes. However, the resident and invading immune cells of the central nervous system can also exacerbate tissue damage by stimulating inflammation and engulfing viable neurons. The functional consequences of microglial phagocytosis remain largely unexplored. Overall, phagocytosis is considered a beneficial phenomenon in acute brain injury because it eliminates dead cells and induces an anti-inflammatory response. Osteopontin (OPN) is a phosphorylated glycoprotein induced by injury in various tissues, including brain tissue. In acute brain injuries such as hemorrhagic stroke and ischemic stroke, OPN is generally believed to have anti-inflammatory effects. OPN can promote the reconstruction of the blood-brain barrier and up-regulate the scavenger receptor CD36. But in chronic diseases such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), OPN can cause microglia to engulf neurons and worsen disease progression. We explored the role of OPN in promoting microglial phagocytosis in nervous system disorders.

The correlation of inflammation, tryptophan-kynurenine pathway, and suicide risk in adolescent depression.

Accumulating evidence suggests a role for the tryptophan-kynurenine pathway (TKP) in the psychopathology of major depressive disorder (MDD). Abnormal inflammatory profile and production of TKP neurotoxic metabolites appear more pronounced in MDD with suicidality. Progress in understanding the neurobiology of MDD in adolescents lags significantly behind that in adults due to limited empirical evidence. Aims of this study was to investigate the association between inflammation, TKP, and suicidality in adolescent depression. Seventy-three adolescents with MDD were assessed for serum levels of interleukin (IL)-1ß, IL-6, IL-18, IL-10, tumor necrosis factor-α (TNF-α), tryptophan (TRP), kynurenine (KYN), 3-hydroxykynurenine (3-HK), and kynurenine acid (KA). Correlations between cytokines and TKP measures were examined. Patients were divided into high- (n = 42) and non-high-suicide-risk groups (n = 31), and serum levels of cytokines and TKP metabolites were compared. Significant negative correlations were found between TRP and IL-8 (r = - 0.27, P < 0.05) and IL-10 (r = - 0.23, P < 0.05), while a significant positive correlation was observed between 3-HK and IL-8 (r = 0.39, P < 0.01) in depressed adolescents. The KYN/TPR (index of indoleamine 2,3-dioxygenase, IDO) was positively correlated with IL-1ß (r = 0.34), IL-6 (r = 0.32), IL-10 (r = 0.38) and TNF-α (r = 0.35) levels (P < 0.01); and 3-HK/KYN (index of kynurenine3-monooxidase, KMO) was positively correlated with IL-8 level (r = 0.31, P < 0.01). Depressed adolescents at high suicide risk exhibited significantly higher levels of IL-1ß (Z = 2.726, P < 0.05), IL-10 (Z = 2.444, P < 0.05), and TNF-α (Z = 2.167, P < 0.05) and lower levels of 3-HK (Z = 2.126, P < 0.05) compared to their non-high suicide risk counterparts. Our findings indicated that serum inflammatory cytokines were robustly associated with IDO and KMO activity, along with significantly decreased serum level of TRP, increased level of 3-HK, and higher suicide risk in adolescent depression.