Real world challenges and barriers for positive airway therapy use in acute ischemic stroke patients.

PURPOSE: Untreated obstructive sleep apnea (OSA) in patients with acute ischemic stroke (AIS) is associated with increased morbidity and mortality. However, diagnosing and treating OSA in AIS is challenging. We aimed to determine the feasibility of portable monitoring (PM) for diagnosis and positive airway pressure therapy for treatment of OSA in an inpatient stroke population. METHODS: We recruited inpatients with AIS from Cleveland Clinic. Those who consented underwent PM; participants with a respiratory event index (REI) ≥ 10 were offered auto-titrating positive airway pressure therapy (APAP). Ease-of-use questionnaires were completed. We summarized categorical variables using n(%) and continuous variables using mean ± SD or median [IQR]. RESULTS: 27 participants (age 59.8 ± 11.8, 51.9% female, 51.9% Black, BMI 33.4 ± 8.5) enrolled. The study ended early due to Medicare contracting that forced most patients to complete stroke rehabilitation outside the Cleveland Clinic health system. 59.3% had large vessel occlusions and 53.8% had moderate/severe disability (Modified Rankin score ≥ 2). PM was attempted in 21 participants, successful in 18. Nurses and patients rated the PM device as highly easy to use. 13 of 18 (72%) patients who had an REI ≥ 10 consented to APAP titration, but only eight (61.5%) of those 13 used APAP for more than one night, and only five (27.8%) used APAP up to 90 days with data captured for only one participant. Five required troubleshooting at titration, and only one had adherent APAP usage by objective assessment after discharge. CONCLUSIONS: This study demonstrates the real-world challenges of assessing and treating OSA in an AIS population, highlighting the necessity for further research into timely and feasible screening and treatment.

A convenient research strategy for functional verification of epigenetic regulators during spermatogenesis.

Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.

Phase 1 dose-escalation trial evaluating a group 2 influenza hemagglutinin stabilized stem nanoparticle vaccine.

The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (n = 3) or two 60 mcg doses 16 weeks apart (n = 22). Vaccination with H10ssF was safe and well tolerated with only mild systemic and local reactogenicity reported. No serious adverse events occurred. Vaccination significantly increased homologous H10 HA stem binding and neutralizing antibodies at 2 weeks after both first and second vaccinations, and these responses remained above baseline at 40 weeks. Heterologous H3 and H7 binding antibodies also significantly increased after each vaccination and remained elevated throughout the study. These data indicate that the group 2 HA stem nanoparticle vaccine is safe and induces stem-directed binding and neutralizing antibodies.

Lanthanum chloride exerts therapeutic potential for chronic kidney disease by suppressing nanohydroxyapatite-induced mitophagy and mitochondria-mediated apoptosis.

OBJECTIVE: To investigate the protective effect of lanthanum chloride on kidney injury in chronic kidney disease and its mechanism. METHODS: 1. Patients with CKD stage 2-5 were selected to analyze the effect of lanthanum-containing preparations on CKD. 2. Sixty healthy male Wistar rats were randomly divided into control group, model group, lanthanum chloride groups (0.03 ng/kg, 0.1 ng/kg, 0.3 ng/kg, q.3d., i.v.), and lanthanum carbonate group (0.3 g/kg, q.d., p.o.). The model group was given 2 % adenine suspension (200 mg/kg, q.d., p.o.) for the first two weeks, followed by adenine (200 mg/kg, b.i.d., p.o.) for 2 weeks, and all animals were sacrificed after eight weeks of administration. 3. The serum and kidneys of rats in each group were collected to detect the oxidative stress indicators and the expressions of LC3B-Ⅱ/Ⅰ, p62, Bcl-2, Bax, Caspase-3 and Cleaved Caspase-3. 4. Human renal tubular epithelial cells (HK-2 cells) were divided into control group, model group, lanthanum chloride group, pyrophosphate (PPI) group, chloroquine (CQ) group, rapamycin group, doxorubicin (DOX) group and N-acetyl-L-cysteine (NAC) group. The mitochondrial status, mitophagy and apoptosis levels were detected. RESULTS: 1.Lanthanum-containing preparations can significantly reduce the biochemical indexes of kidney injury in patients with CKD. 2. In the model group, the glomerular and renal tubular edema, the mitochondria were short and round, and the expression of LC3B-Ⅱ/Ⅰ and Bax increased, while the expression of P62, Bcl-2 and Caspase-3 decreased, and there was a significant improvement in the administration group, especially the 0.1 ng/kg group and lanthanum carbonate group. 3. In the HK-2 cell model group, mitochondrial membrane potential decreased, morphology changed and the results were reversed by lanthanum chloride. CONCLUSION: Lanthanum chloride may alter the morphology of nano-hydroxyapatite, thereby inhibiting its induced mitophagy and mitochondria-mediated apoptosis, and ultimately improve CKD renal injury effectively.

Cell-free adipose tissue extracts as a novel treatment for rosacea by downregulating TRPV1.

Rosacea is a chronic inflammatory skin disease that typically affects the central facial area. Its main clinical symptoms include paroxysmal flushing, telangiectasia, and non-temporary erythema. Cell-free adipose tissue extracts (ATEs) are liquid components extracted from human adipose tissue that contain large amounts of growth factors. Despite the scar-reducing, anti-aging, and wound-healing effects of ATEs, the efficacy of ATEs in rosacea remains unknown. Therefore, the anti-rosacea effects of ATEs were investigated in human cathelicidin peptide (LL-37) induced rosacea mice and capsaicin (CAP)-stimulated HaCaT keratinocytes. In vitro, ATEs significantly reduced TRPV1 expression, intracellular calcium ions influx and the release of inflammatory factors (such as KLK5, IL-6, IL-8 and TNF-α) after intervening in CAP-stimulated cells. The in vivo results revealed that ATEs alleviated rosacea symptoms, such as erythema score, erythema area, transepidermal water loss, abnormal epidermal thickness, mast cell infiltration and telangiectasia upon downregulating TRPV1 and CD31 expression. Moreover, the up-regulated TRPV1 protein expression was also recovered by ATEs administration in vivo and in vitro. Meanwhile, ATEs demonstrated good biocompatibility. In summary, ATEs could be a potential therapeutic agent for rosacea by regulating inflammation and alleviating telangiectasia.

Systematic bibliometric and visualized analysis of research hotspots and trends on the application of artificial intelligence in glaucoma from 2013 to 2022.

AIM: To conduct a bibliometric analysis of research on artificial intelligence (AI) in the field of glaucoma to gain a comprehensive understanding of the current state of research and identify potential new directions for future studies. METHODS: Relevant articles on the application of AI in the field of glaucoma from the Web of Science Core Collection were retrieved, covering the period from January 1, 2013, to December 31, 2022. In order to assess the contributions and co-occurrence relationships among different countries/regions, institutions, authors, and journals, CiteSpace and VOSviewer software were employed and the research hotspots and future trends within the field were identified. RESULTS: A total of 750 English articles published between 2013 and 2022 were collected, and the number of publications exhibited an overall increasing trend. The majority of the articles were from China, followed by the United States and India. National University of Singapore, Chinese Academy of Sciences, and Sun Yat-sen University made significant contributions to the published works. Weinreb RN and Fu HZ ranked first among authors and cited authors. American Journal of Ophthalmology is the most impactful academic journal in the field of AI application in glaucoma. The disciplinary scope of this field includes ophthalmology, computer science, mathematics, molecular biology, genetics, and other related disciplines. The clustering and identification of keyword nodes in the co-occurrence network reveal the evolving landscape of AI application in the field of glaucoma. Initially, the hot topics in this field were primarily "segmentation", "classification" and "diagnosis". However, in recent years, the focus has shifted to "deep learning", "convolutional neural network" and "artificial intelligence". CONCLUSION: With the rapid development of AI technology, scholars have shown increasing interest in its application in the field of glaucoma. Moreover, the application of AI in assisting treatment and predicting prognosis in glaucoma may become a future research hotspot. However, the reliability and interpretability of AI data remain pressing issues that require resolution.

Construction of Six-Membered Lactam and Lactone Structures via Ligand-Free Pd-Catalyzed C-H Activation/[5 + 1] Cyclization Carbonylation.

An approach for the ligand-free Pd-catalyzed C-H activation/[5 + 1] cyclization carbonylation by employing readily available ClCF2COONa as a carbonyl source via difluorocarbene transfer and hydrolysis has been developed. The current protocol enables us to obtain a series of carbonylation cyclization product benzopyranone and phenanthridinone derivatives in up to 91% yield with excellent functional group compatibility. This protocol has the advantages of mild reaction conditions, wide applicable substrates, and simple and safe operation and provides a new method for the synthesis of complex lactam and lactone compounds.

Atomic Scale Responses of High Entropy Oxides to Redox Environments.

The potential of high entropy oxides (HEOs) as high-performance energy storage materials and catalysts has been mainly understood through their bulk structures. However, the importance of their surfaces, which may play an even more critical role, remains largely unknown. In this study, we employed advanced scanning transmission electron microscopy to investigate the atomic-scale structural and chemical responses of CeYLaHfTiZrOx HEOs to high-temperature redox environments. Our observations reveal dynamic elemental and structural reconstructions in the surface of HEOs under different gas environments, contrasting with the high stability of the bulk structure. Notably, the surfaces of HEO particles consistently exhibit abundant oxygen vacancies, regardless of the redox environment. These findings indicate that HEOs offer distinct advantages in facilitating chemical and electrochemical reactions, relying on oxygen vacancies. Our results also suggest that the exceptional performance of HEOs in energy storage applications arises from surface structural and chemical adaptability.

Nanoporous Polystyrene Inverse Opal Materials with Optical Interference Properties for Label-Free Biosensing.

Colloidal crystal nanomaterials have been proven to be valuable substrates for optical-based biosensing due to their ordered macroporous nanostructure and brilliant optical properties. In this work, silica colloidal crystal (SCC) thin films, as well as polystyrene-SCC composite films and inverse opal (IO) polystyrene films fabricated using SCC as templates, are investigated for their application as substrate materials in optical interferometric biosensors. The SCC films formed by the self-assembly of silica colloidal crystals have the most densely packed nano-3D structure, also known as the opal structure. IO films are fabricated by filling the opal pores of SCC with polystyrene and then removing the template, resulting in an interconnected nano-3D ordered macroporous structure, as indicated by the name inverse opal. The performance of the three materials was compared and discussed based on an ordered porous layer interferometry optical platform, focusing on refractive index response, protein adsorption response, and biomolecular interaction response. These results could potentially offer innovative material support for the advancement of label-free optical biosensors, which can be used for more biological/biochemical/biomolecular reaction monitoring studies.

Metalloproteomics Reveals Multi-Level Stress Response in Escherichia coli When Exposed to Arsenite.

The arsRBC operon encodes a three-protein arsenic resistance system. ArsR regulates the transcription of the operon, while ArsB and ArsC are involved in exporting trivalent arsenic and reducing pentavalent arsenic, respectively. Previous research into Agrobacterium tumefaciens 5A has demonstrated that ArsR has regulatory control over a wide range of metal-related proteins and metabolic pathways. We hypothesized that ArsR has broad regulatory control in other Gram-negative bacteria and set out to test this. Here, we use differential proteomics to investigate changes caused by the presence of the arsR gene in human microbiome-relevant Escherichia coli during arsenite (AsIII) exposure. We show that ArsR has broad-ranging impacts such as the expression of TCA cycle enzymes during AsIII stress. Additionally, we found that the Isc [Fe-S] cluster and molybdenum cofactor assembly proteins are upregulated regardless of the presence of ArsR under these same conditions. An important finding from this differential proteomics analysis was the identification of response mechanisms that were strain-, ArsR-, and arsenic-specific, providing new clarity to this complex regulon. Given the widespread occurrence of the arsRBC operon, these findings should have broad applicability across microbial genera, including sensitive environments such as the human gastrointestinal tract.

Asymptomatic multicentric Castleman disease: A potential early stage of idiopathic MCD.

According to the diagnostic criteria for HHV-8 (human herpesvirus-8) negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network (CDCN) in 2017, there is a group of HHV-8 negative multicentric Castleman disease (MCD) patients who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000-2021. With a median follow-up time of 46.5 months (range: 4-279 months), 6 patients (5.3%) transformed to iMCD. The median time between diagnosis of aMCD and iMCD in these 6 patients was 28.5 months (range: 3-60 months). During follow-up, 7 patients died; three of them died from progression of MCD. Despite that 37.7% patients received systemic treatment targeting MCD, this strategy was neither associated with a lower probability of iMCD transformation nor a lower death rate. The 5-year estimated survival of all aMCD patients was 94.1% (95% CI 88.8-99.6%). Transformation to iMCD was an important predictor of death (log-rank p=0.01) (5-year estimated survival 83.3%). This study suggests that aMCD patients may represent a potential early stage of iMCD, who may not require immediate treatment but should be closely monitored.

Triphenylamine-Based Covalent Organic Framework Films for Dopamine-Responsive Electrofluorochromism.

Covalent organic framework (COF) film with electrofluorochromic (EFC) and electrochromic (EC) properties has been synthesized by using triphenylamine-based monomers. The film exhibited a high maximum fluorescence contrast of 151 when subjected to a drive voltage of 0.75 V vs the Ag/AgCl electrode, causing the fluorescence to be quenched, which resulted in the EFC process's "fluorescence off" state. The switching times for the fluorescence on and off states were 0.51 and 7.79 s, respectively. Over the same voltage range, the COF film also displayed EC properties, achieving a contrast of 50.23% and a coloration efficiency of 297.4 cm2 C-1 at 532 nm, with switching times of 18.6 s for coloration and 0.7 s for bleaching. Notably, the quenched fluorescence of the COF film could be restored by adding dopamine as a reductant. This phenomenon enabled the implementation of a NAND logic gate using the applied potential as a physical input and dopamine addition as a chemical input. This study demonstrates the successful development of COF films with bifunctional EFC and EC properties, showcasing their potential for use in constructing advanced optoelectronic devices.

Coating Dormant Collagenase-Producing Bacteria with Metal-Anesthetic Networks for Precision Tumor Therapy.

Tumor malignancy highly depends on the stiffness of tumor matrix, which mainly consists of collagen. Despite the destruction of tumor matrix is conducive to tumor therapy, it causes the risk of tumor metastasis. Here, metal-anesthetic network-coated dormant collagenase-producing Clostridium is constructed to simultaneously destruct tumor matrix and inhibit tumor metastasis. By metal-phenolic complexation and π-π stacking interactions, a Fe3+-propofol network is formed on bacterial surface. Coated dormant Clostridium can selectively germinate and rapidly proliferate in tumor sites due to the ability of carried Fe3+ ions to promote bacterial multiplication. Intratumoral colonization of Clostridium produces sufficient collagenases to degrade tumor collagen mesh and the loaded propofol restrains tumor metastasis by inhibiting tumor cell migration and invasion. Meanwhile, the delivered Fe3+ ions are reduced to the Fe2+ form by intracellular glutathione, thereby inducing potent Fenton reaction to trigger lipid peroxidation and ultimate ferroptosis of tumor cells. In addition to a satisfactory safety, a single intratumoral injection of coated dormant Clostridium not only effectively retards the growth of established large primary tumors, but also significantly suppresses distal lung metastasis in two different orthotopic tumor models. This work proposes a strategy to develop advanced therapeutics for malignant tumor treatment and metastasis prevention.

Flexible and high-strength bioactive glass fiber membrane for bone regeneration with the aid of alkoxysilane sol spinnability.

In this research, the spinnability of bioactive glass (BG) precursor solution was supplied by alkoxysilane sol with appropriate molar ratio of H2O/silicon (R) to prepare bioactive glass fiber membrane (BFM) using electrospinning (ES) technique. Alkoxysilane could form a linear or chain-like colloidal aggregation in hydrolysis-polycondensation with R = 2 or so, thereby exhibiting good spinnability. Therefore, the role of polymer binders could be largely replaced. Due to the significant decrease of polymer binder, the defects within the fibers are largely reduced and degree of fiber densification was improved after calcination, leading to BFM drastically enhanced strength and flexibility. The effect of R and calcination temperature on mechanical performance were investigated in detail. The tensile strength could reach the highest value 2.31 MPa with R = 2 and calcination at 700 °C. In addition, under this preparation condition, the BFM also possessed good flexibility with bending rigidity 37.7 mN. Furthermore, the great performance of promoting cell proliferation and osteogenesis could be observed from in vitro cellular experiment. The BFM calcined at 750 °C exhibited the best promoting osteogenic differentiation ability. The rat skull defect model revealed BFM could perform well in osteogenesis in vivo.

A disposable ultrasensitive immunosensor based on MXene/NH2-CNT modified screen-printed electrode for the detection of ovarian cancer antigen CA125.

Cancer antigen 125 (CA125) is the gold standard biomarker for clinical diagnosis of ovarian cancer, with a threshold value of 35 U/mL in serum. In this paper, a disposable ultrasensitive immunosensor based on Ti3C2Tx-MXene/amino-functionalized carbon nanotube (NH2-CNT) modified screen-printed carbon electrode (SPCE) was constructed for the detection of the ovarian cancer antigen CA125. By optimizing the mass ratio of Ti3C2Tx to NH2-CNT, Ti3C2Tx/NH2-CNT composite with excellent electrochemical properties was prepared, which is beneficial for amplifying the initial electrochemical signal. The positively charged NH2-CNT effectively alleviated the stacking problem of Ti3C2Tx, and its amino group also facilitated the covalent immobilization of the capture antibody. Meanwhile, chitosan (CS) with excellent film-forming ability was also used to successfully enhance the adsorption of electrode material, thus improving the stability of the sensor. In addition, CS could further enhance the current signal. The prepared immunosensor exhibited excellent performance in CA125 detection with a wide linear range from 1 mU/mL to 500 U/mL, and good selectivity, reproducibility and lomg-term stability. Furthermore, the immunosensor showed satisfactory results for the detection of CA125 in clinical serum samples, which is promising for the clinical screening, early diagnosis and prognostic examination of ovarian cancer.

Lnc557 promotes Bombyx mori nucleopolyhedrovirus replication by interacting with BmELAVL1 to enhance its stability and expression.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a major pathogen that threatens the growth and sustainability of the sericultural industry. Currently, accumulated studies showed that long non-coding RNAs (lncRNAs) play important roles in the genesis and progression of various viruses and host-pathogens interactions. However, the functions and regulatory mechanisms of lncRNAs in insect-virus interaction are still limited. In this study, transcriptome sequencing and ribosome profiling sequencing (Ribo-seq) were performed in the BmNPV-infected midgut and control tissue, and a total of 9 differentially expressed (DE) lncRNAs and 27 small ORFs (sORFs) with micropeptide coding potential were identified. Among them, lncRNA XR_001139971.3 (lnc557) is verified to be significantly up-regulated upon BmNPV infection and may have the potential to encode a small peptide (ORF-674). The subcellular localization experiment showed that lnc557 was expressed in the cytoplasm. Overexpression of lnc557 promotes BmNPV replication and vice versa. By combining RNA pull-down, mass spectrometry, protein truncation and RNA immunoprecipitation (RIP) assays, we confirmed that lnc557 can bind to the RRM-5 domain of BmELAVL1 protein. Subsequently, we found that lnc557 could promote the expression of BmELAVL1 by enhancing the stability of BmELAVL1. Further, enhancing the expression of BmELAVL1 can promote the proliferation of BmNPV, while knockdown shows the opposite effect. Our data suggest that lnc557-mediated BmELAVL1 expression enhancement could play a positive role in BmNPV replication, which will provide a new insight into the molecular mechanism of interaction between Bombyx mori and virus.

Longitudinal antinuclear antibody titers in systemic lupus erythematosus and other rheumatic diseases.

Introduction: Antinuclear antibodies (ANAs) are a key feature of systemic lupus erythematosus (SLE) and marker of subclinical autoimmunity. Little is known about longitudinal ANA titers in individuals from the general population or in predicting clinical disease course in persons with rheumatic diseases. Methods: We performed an exploratory analysis from an academic health system between 1999 and 2020 to assess intra-individual variation in ANAs longitudinally in persons with SLE, other ANA-associated rheumatic diseases, and ANA+ controls without rheumatic disease. Results: Persons with SLE had a higher odds of positive ANA compared to those with other ANA-associated rheumatic diseases [OR 2.10, 95% CI (1.82, 2.43)] controlling for time and demographics (age, sex, race, ethnicity). Compared to ANA+ controls, the ANA titer strength was significantly higher for both the ANA-associated rheumatic disease (0.33 log units higher) and SLE groups (0.42 log units higher) controlling for demographics and time (p < 0.001 for both). Over time from the first positive ANA, titer strength significantly decreased for all three groups, with average monthly decreases ranging between 0.001 to 0.004 log titer units (p ≤ 0.001 for all). Conclusion: Based on this analysis of electronic health data spanning two decades, ANA titers may be more dynamic than previously accepted in patients with SLE and ANA-associated rheumatic diseases, with average titers tending to be higher in early disease and decreasing over time.

Camrelizumab combined with chemotherapy for stage IV pulmonary sarcomatoid cancer with pancreatic metastases.

The pancreas is a rare metastatic site for lung cancer. We report the case of a 66-year-old male with pulmonary sarcomatoid carcinoma (PSC) with pancreatic and right posterior renal fascia metastases treated with immunotherapy and platinum-based chemotherapy. A pathological biopsy of the right posterior fascial mass showed lung invasive adenocarcinoma and sarcomatoid carcinoma metastasis. Immunohistochemistry staining showed that PD- L1 expression was high and next-generation sequencing revealed KRAS and TP53 mutations. Camrelizumab and chemotherapy were administered, and the metastasis disappeared. Immunotherapy combined with platinum-based chemotherapy is effective in treating PSC with pancreatic metastases.

VPS34 Governs Oocyte Developmental Competence by Regulating Mito/Autophagy: A Novel Insight into the Significance of RAB7 Activity and Its Subcellular Location.

Asynchronous nuclear and cytoplasmic maturation in human oocytes is believed to cause morphological anomalies after controlled ovarian hyperstimulation. Vacuolar protein sorting 34 (VPS34) is renowned for its pivotal role in regulating autophagy and endocytic trafficking. To investigate its impact on oocyte development, oocyte-specific knockout mice (ZcKO) are generated, and these mice are completely found infertile, with embryonic development halted at 2- to 4-cell stage. This infertility is related with a disruption on autophagic/mitophagic flux in ZcKO oocytes, leading to subsequent failure of zygotic genome activation (ZGA) in derived 2-cell embryos. The findings further elucidated the regulation of VPS34 on the activity and subcellular translocation of RAS-related GTP-binding protein 7 (RAB7), which is critical not only for the maturation of late endosomes and lysosomes, but also for initiating mitophagy via retrograde trafficking. VPS34 binds directly with RAB7 and facilitates its activity conversion through TBC1 domain family member 5 (TBC1D5). Consistent with the cytoplasmic vacuolation observed in ZcKO oocytes, defects in multiple vesicle trafficking systems are also identified in vacuolated human oocytes. Furthermore, activating VPS34 with corynoxin B (CB) treatment improved oocyte quality in aged mice. Hence, VPS34 activation may represent a novel approach to enhance oocyte quality in human artificial reproduction.

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.