SNP-based and haplotype-based genome-wide association on drug dependence in Han Chinese.

BACKGROUND: Drug addiction is a serious problem worldwide and is influenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese. METHODS: A total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping. RESULTS: Both single-SNP and haplotype tests revealed associations between illicit drug use and several immune-related genes in the major histocompatibility complex (MHC) region (SNP association: log10BF = 15.135, p = 1.054e-18; haplotype association: log10BF = 20.925, p = 2.065e-24). These genes may affect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide significant associations between rs3782886 (SNP association: log10BF = 8.726, p = 4.842e-11) in BRAP and rs671 (SNP association: log10BF = 7.406, p = 9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide significant association (haplotype association: log10BF = 7.607, p = 3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction. CONCLUSIONS: These findings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches.

Deep-learning architecture for PM2.5 concentration prediction: A review.

Accurately predicting the concentration of fine particulate matter (PM2.5) is crucial for evaluating air pollution levels and public exposure. Recent advancements have seen a significant rise in using deep learning (DL) models for forecasting PM2.5 concentrations. Nonetheless, there is a lack of unified and standardized frameworks for assessing the performance of DL-based PM2.5 prediction models. Here we extensively reviewed those DL-based hybrid models for forecasting PM2.5 levels according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We examined the similarities and differences among various DL models in predicting PM2.5 by comparing their complexity and effectiveness. We categorized PM2.5 DL methodologies into seven types based on performance and application conditions, including four types of DL-based models and three types of hybrid learning models. Our research indicates that established deep learning architectures are commonly used and respected for their efficiency. However, many of these models often fall short in terms of innovation and interpretability. Conversely, models hybrid with traditional approaches, like deterministic and statistical models, exhibit high interpretability but compromise on accuracy and speed. Besides, hybrid DL models, representing the pinnacle of innovation among the studied models, encounter issues with interpretability. We introduce a novel three-dimensional evaluation framework, i.e., Dataset-Method-Experiment Standard (DMES) to unify and standardize the evaluation for PM2.5 predictions using DL models. This review provides a framework for future evaluations of DL-based models, which could inspire researchers to standardize DL model usage in PM2.5 prediction and improve the quality of related studies.

Tissue accumulation of microplastics and potential health risks in human.

Microplastics have become ubiquitous throughout the environment. Humans constantly ingest and inhale microplastics, increasing concerns about the health risks of microplastic exposure. However, limited data impedes a full understanding of the internal exposure to microplastics. Herein, to evaluate microplastic exposure via the respiratory and digestive systems, we used laser direct infrared spectroscopy to identify microplastics >20 µm in size in different human tissues. Consequently, 20-100 µm microplastics were concentrated in all tissues, with polyvinyl chloride (PVC) being the dominant polymer. The highest abundance of microplastics was detected in lung tissue with an average of 14.19 ± 14.57 particles/g, followed by that in the small intestine, large intestine, and tonsil (9.45 ± 13.13, 7.91 ± 7.00, and 6.03 ± 7.37 particles/g, respectively). The abundance of microplastics was also significantly greater in females than in males (p < 0.05). Despite significant diversity, our estimation showed that the lungs accumulated the highest amounts of microplastic. Moreover, PVC particles may cause potential health risks because of their high polymer hazard index and maximal risk level. This study provides evidence regarding the occurrence of microplastics in humans and empirical data to support assessments of the health risks posed by microplastics.

[Research Progress on Characteristics of Human Microplastic Pollution and Health Risks].

Microplastic pollution is not only an environmental problem but also a social problem. Many studies have been conducted on the sources, abundance, and distribution of microplastics in the environment, but an understanding of human exposure levels and potential health risks remains very limited. Based on the bibliometric methods, the present review systematically summarized the exposure pathways of microplastics in humans, and then the characteristics and potential adverse impacts on human health were expounded upon. Available literature showed that microplastics in human bodies were mainly concentrated on sizes smaller than 50 µm, and polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET) were the main polymers. Microplastics in environments entered human bodies mainly through food and respiratory pathways, then accumulated in lung and gastrointestinal tissues. Most importantly, small-sized microplastics could distribute in tissues and organs via the circulatory system. The results from lab-based toxicological experiments showed that microplastics not only posed threats to cell membrane integrity, immune stress, gut microbiota, and energy metabolism but also had potentially adverse impacts on the reproductive system. To further understand the health risks of microplastic pollution, it is necessary to promote research on the toxicological effects of microplastics as well as the inner mechanisms and also to establish risk assessment frameworks for evaluating microplastic pollution. These works are crucial to preventing the risks of microplastic pollution with scientific evidence.

Multiomics Analyses Reveal Microbiome-Gut-Brain Crosstalk Centered on Aberrant Gamma-Aminobutyric Acid and Tryptophan Metabolism in Drug-Naïve Patients with First-Episode Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia (SCZ) is associated with complex crosstalk between the gut microbiota and host metabolism, but the underlying mechanism remains elusive. Investigating the aberrant neurotransmitter processes reflected by alterations identified using multiomics analysis is valuable to fully explain the pathogenesis of SCZ. STUDY DESIGN: We conducted an integrative analysis of multiomics data, including the serum metabolome, fecal metagenome, single nucleotide polymorphism data, and neuroimaging data obtained from a cohort of 127 drug-naïve, first-episode SCZ patients and 92 healthy controls to characterize the microbiome-gut-brain axis in SCZ patients. We used pathway-based polygenic risk score (PRS) analyses to determine the biological pathways contributing to genetic risk and mediation effect analyses to determine the important neuroimaging features. Additionally, a random forest model was generated for effective SCZ diagnosis. STUDY RESULTS: We found that the altered metabolome and dysregulated microbiome were associated with neuroactive metabolites, including gamma-aminobutyric acid (GABA), tryptophan, and short-chain fatty acids. Further structural and functional magnetic resonance imaging analyses highlighted that gray matter volume and functional connectivity disturbances mediate the relationships between Ruminococcus_torgues and Collinsella_aerofaciens and symptom severity and the relationships between species Lactobacillus_ruminis and differential metabolites l-2,4-diaminobutyric acid and N-acetylserotonin and cognitive function. Moreover, analyses of the Polygenic Risk Score (PRS) support that alterations in GABA and tryptophan neurotransmitter pathways are associated with SCZ risk, and GABA might be a more dominant contributor. CONCLUSIONS: This study provides new insights into systematic relationships among genes, metabolism, and the gut microbiota that affect brain functional connectivity, thereby affecting SCZ pathogenesis.

Engineering antioxidant ceria-zirconia nanomedicines for alleviating podocyte injury in rats with adriamycin-induced nephrotic syndrome.

BACKGROUND: Primary nephrotic syndrome (PNS) is characterized by edema, heavy proteinuria, hypoalbuminemia and hyperlipidemia. Moreover, podocyte injury is the key pathological change of PNS. Even though the pathophysiological etiology of PNS has not been fully understood, the production of excessive reactive oxygen species (ROS) plays an important role in the development and progression of the disease. Glucocorticoids are the first-line medications for patients with PNS, but their clinical use is hampered by dose-dependent side effects. Herein, we accelerated the rate of conversion from Ce4+ to Ce3+ by doping Zr4+ in ceria-zirconia nanomedicines to treat the PNS rat model by removal of ROS. RESULTS: The engineered Ce0.7Zr0.3O2 (7CZ) nanomedicines significantly improved the ROS scavenging ability of podocytes at a very low dose, enabling effective inhibition of podocyte apoptosis and actin cytoskeleton depolymerization induced by adriamycin (ADR). Accordingly, podocyte injury was effectively alleviated in rat models of ADR-induced nephrotic syndrome, as confirmed by serum tests and renal tissue staining. Moreover, the mRNA sequencing assay revealed the protective molecular signaling pathways of 7CZ nanomedicines in podocytes. CONCLUSION: 7CZ nanomedicines were highly effective in protecting against ADR-induced podocyte injury in vitro and in vivo at a very low concentration.

The association between oral and gut microbiota in male patients with alcohol dependence.

Introduction: The relationship between oral and gut microbiota in alcohol dependence (AD) is not well understood, particularly the effects of oral microbiota on the intestinal microbiota. The current study aimed to explore the association between oral and gut microbiota in AD to clarify whether oral microbiota could ectopically colonize into the gut. Methods: 16S rRNA sequence libraries were used to compare oral and gut microbial profiles in persons with AD and healthy controls (HC). Source Tracker and NetShift were used to identify bacteria responsible for ectopic colonization and indicate the driver function of ectopic colonization bacteria. Results: The α-diversity of oral microbiota and intestinal microbiota was significantly decreased in persons with AD (all p < 0.05). Principal coordinate analysis indicated greater similarity between oral and gut microbiota in persons with AD than that in HC, and oral-gut overlaps in microbiota were found for 9 genera in persons with AD relative to only 3 genera in HC. The contribution ratio of oral microbiota to intestinal microbiota composition in AD is 5.26% based on Source Tracker，and the AD with ectopic colonization showed the daily maximum standard drinks, red blood cell counts, hemoglobin content, and PACS scores decreasing (all p < 0.05). Discussion: Results highlight the connection between oral-gut microbiota in AD and suggest novel potential mechanistic possibilities.

Metatranscriptomic analysis revealed Prevotella as a potential biomarker of oropharyngeal microbiomes in SARS-CoV-2 infection.

Background and objectives: Disease severity and prognosis of coronavirus disease 2019 (COVID-19) disease with other viral infections can be affected by the oropharyngeal microbiome. However, limited research had been carried out to uncover how these diseases are differentially affected by the oropharyngeal microbiome of the patient. Here, we aimed to explore the characteristics of the oropharyngeal microbiota of COVID-19 patients and compare them with those of patients with similar symptoms. Methods: COVID-19 was diagnosed in patients through the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Characterization of the oropharyngeal microbiome was performed by metatranscriptomic sequencing analyses of oropharyngeal swab specimens from 144 COVID-19 patients, 100 patients infected with other viruses, and 40 healthy volunteers. Results: The oropharyngeal microbiome diversity in patients with SARS-CoV-2 infection was different from that of patients with other infections. Prevotella and Aspergillus could play a role in the differentiation between patients with SARS-CoV-2 infection and patients with other infections. Prevotella could also influence the prognosis of COVID-19 through a mechanism that potentially involved the sphingolipid metabolism regulation pathway. Conclusion: The oropharyngeal microbiome characterization was different between SARS-CoV-2 infection and infections caused by other viruses. Prevotella could act as a biomarker for COVID-19 diagnosis and of host immune response evaluation in SARS-CoV-2 infection. In addition, the cross-talk among Prevotella, SARS-CoV-2, and sphingolipid metabolism pathways could provide a basis for the precise diagnosis, prevention, control, and treatment of COVID-19.

Long-term prednisone treatment causes fungal microbiota dysbiosis and alters the ecological interaction between gut mycobiome and bacteriome in rats.

Glucocorticoids (GCs) are widely used in the treatment of immune-mediated diseases due to their anti-inflammatory and immunosuppressive effects. Prednisone is one of the most commonly used GCs. However, it is still unknown whether prednisone affects gut fungi in rats. Herein we investigated whether prednisone changed the composition of gut fungi and the interactions between gut mycobiome and bacteriome/fecal metabolome in rats. Twelve male Sprague-Dawley rats were randomly assigned to a control group and a prednisone group which received prednisone daily by gavage for 6 weeks. ITS2 rRNA gene sequencing of fecal samples was performed to identify differentially abundant gut fungi. The associations between gut mycobiome and bacterial genera/fecal metabolites obtained from our previously published study were explored by using Spearman correlation analysis. Our data showed that there were no changes in the richness of gut mycobiome in rats after prednisone treatment, but the diversity increased significantly. The relative abundance of genera Triangularia and Ciliophora decreased significantly. At the species level, the relative abundance of Aspergillus glabripes increased significantly, while Triangularia mangenotii and Ciliophora sp. decreased. In addition, prednisone altered the gut fungi-bacteria interkingdom interactions in rats after prednisone treatment. Additionally, the genus Triangularia was negatively correlated with m-aminobenzoic acid, but positively correlated with hydrocinnamic acid and valeric acid. Ciliophora was negatively correlated with phenylalanine and homovanillic acid, but positively correlated with 2-Phenylpropionate, hydrocinnamic acid, propionic acid, valeric acid, isobutyric acid, and isovaleric acid. In conclusion, long-term prednisone treatment caused fungal microbiota dysbiosis and might alter the ecological interaction between gut mycobiome and bacteriome in rats.

Microplastics transferring from abiotic to biotic in aquatic ecosystem: A mini review.

Microplastics have been detected in global aquatic ecosystems, so it is vital to understand the bioaccumulation and biomagnification of microplastics for ecological risk assessment. However, variability between studies, including sampling, pretreatment processes, and polymer identification methods have made it difficult to draw definitive conclusions. Alternatively, the compilation and statistical analysis of available experimental and investigation data provides insight into the fates of microplastics in an aquatic ecosystem. To reduce bias, we performed a systematic literature retrieval and compiled these reports on microplastic abundance in the natural aquatic environment. Our results indicate that microplastics are more abundant in sediments than in water, mussels, and fish. There is a significant correlation between mussels and sediments, but not between water and mussels or between water/sediment and fish. Bioaccumulation of microplastics appears to occur through water, but the route of biomagnification is unclear. More sound evidence is required to fully understand the biomagnification of microplastics in aquatic environments.

New insight in the cross-talk between microglia and schizophrenia: From the perspective of neurodevelopment.

Characterized by psychotic symptoms, negative symptoms and cognitive deficits, schizophrenia had a catastrophic effect on patients and their families. Multifaceted reliable evidence indicated that schizophrenia is a neurodevelopmental disorder. Microglia, the immune cells in central nervous system, related to many neurodevelopmental diseases. Microglia could affect neuronal survival, neuronal death and synaptic plasticity during neurodevelopment. Anomalous microglia during neurodevelopment may be associated with schizophrenia. Therefore, a hypothesis proposes that the abnormal function of microglia leads to the occurrence of schizophrenia. Nowadays, accumulating experiments between microglia and schizophrenia could afford unparalleled probability to assess this hypothesis. Herein, this review summarizes the latest supporting evidence in order to shed light on the mystery of microglia in schizophrenia.

Associations between Short-Term Air Pollution Exposure and the Peripheral Leukocyte Distribution in the Adult Male Population in Beijing, China.

The inflammatory effects of air pollution exposure may account for increased public health risk. However, evidence regarding the effects of air pollution on peripheral blood leukocytes in the population is inconsistent. We investigated the association between the short-term effects of ambient air pollution and the peripheral blood leukocyte distribution in adult men in Beijing, China. From January 2015 to December 2019, a total of 11,035 men aged 22-45 years in Beijing were included in the study. Their peripheral blood routine parameters were measured. The ambient pollution monitoring parameters (particulate matter ≤ 10 µm (PM10), PM2.5, nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3)) were collected daily. The potential association between ambient air pollution exposure and peripheral blood leukocyte count and classification was analyzed with generalized additive models (GAMs). After adjusting for confounding factors, PM2.5, PM10, SO2, NO2, O3, and CO were significantly correlated with changes to at least one peripheral leukocyte subtype. Short-term and cumulative air pollutant exposure dramatically increased the participants' peripheral blood neutrophil, lymphocyte, and monocyte numbers and decreased eosinophils and basophils. Our results demonstrated that air pollution induced inflammation in the participants. The peripheral leukocyte count and classification can be utilized to evaluate the inflammation induced by air pollution in the exposed male population.

Primary nephrotic syndrome relapse within 1 year after glucocorticoid therapy in children is associated with gut microbiota composition at syndrome onset.

BACKGROUND: Children with primary nephrotic syndrome (PNS) who relapse after glucocorticoid therapy are shown to have a decreased total proportion of butyrate-producing bacteria in the gut at onset. Glucocorticoid treatment changes the gut microbiota composition. It is unclear whether gut microbiota at remission right after therapy and gut bacteria other than butyrate-producing bacteria are associated with PNS relapse. METHODS: PNS relapse of paediatric patients within 1 year after glucocorticoid therapy was recorded. The gut microbiota composition, profiled with 16S rRNA gene V3-V4 region sequencing, was compared between relapsing and non-relapsing PNS children at onset before glucocorticoid treatment (preT group) and in PNS children at remission right after treatment (postT group), respectively. RESULTS: The gut microbiota composition of postT children significantly differed from that of preT children by having lower levels of Bacteroides, Lachnoclostridium, Flavonifractor, Ruminococcaceae UBA1819, Oscillibacter, Hungatella and Coprobacillus and higher levels of Ruminococcaceae UCG-013 and Clostridium sensu stricto 1 group. In the preT group, compared with non-relapsing patients, relapsing patients showed decreased Blautia, Dialister and total proportion of butyrate-producing bacteria and increased Oscillibacter, Anaerotruncus and Ruminococcaceae UBA1819. However, relapsing and non-relapsing postT children showed no difference in gut microbiota composition. CONCLUSIONS: PNS relapse-associated gut microbiota dysbiosis at onset, which includes alterations of both butyrate-producing and non-butyrate-producing bacteria, disappeared right after glucocorticoid therapy. It is necessary to study the association of the longitudinal changes in the complete profiles of gut microbiota after glucocorticoid treatment with later PNS relapse.

Vancomycin Induced Ferroptosis in Renal Injury Through the Inactivation of Recombinant Glutathione Peroxidase 4 and the Accumulation of Peroxides.

Background: Vancomycin (VCM) has long been used clinically to fight against Gram-positive bacterial infections. In recent decades, an increased number of kidney injury cases caused by VCM overdose have been reported. In this study, we further investigated the mechanism of VCM-overdose-induced kidney injury. Methods: Immunohistochemistry (IHC) staining, RT-qPCR and Western blot assays were used to determine ki67, DDX5, PTGS2, GPX4 and SLC7A11 expressions in the kidney tissues of mice. CCK-8 and flow cytometry assays were used to determine HK2 cell viability and apoptosis. In addition, RT-qPCR and Western blot assays was applied to evaluate the expressions of ACSL4, PTGS2, GPX4, SLC7A11, DDX5 and Ki67 in HK2 cells. Results: We found that VCM induced ferroptosis in vitro and in vivo. Ferrostatin-1 (Fer-1) is a potent inhibitor of ferroptosis, Fer-1 rescued cell viability and renal function renal morphology in VCM-treated cells and mice, respectively. Further, GPX4, which plays an essential role in reducing lipid hydroperoxides and preventing ferroptosis, was observed to be downregulated by VCM treatment. Interestingly, we found that GPX4-knockdown HK-2 cells exhibited a similar phenotype and gene expression level of ACSL4, PTGS2, DDX5 and Ki67 compared with VCM-treated cells, which suggested that VCM could induce ferroptosis in HK2 cells by down-regulating GPX4. Conclusion: In conclusion, VCM induced renal injury in the kidney tissues of mice. In addition, VCM induced ferroptosis cell death in HK-2 cells and in the kidney tissues of mice by down-regulating GPX4 and causing the accumulation of peroxides. These data suggested that VCM could induce renal injury in vitro and in vivo via triggering ferroptosis. This study further elucidates the mechanism of VCM-induced renal injury and provides additional references for clinical use of VCM.

Comparison between the stem and leaf photosynthetic productivity in Eucalyptus urophylla plantations with different age.

MAIN CONCLUSION: We developed a more realistic modeling framework by integrating stem photosynthesis into the canopy carbon assimilation model to compare the photosynthetic productivity between the stem and leaf of Eucalyptus urophylla plantations. Stems of Eucalyptus species with smooth outer bark have photosynthetic green tissue that can recycle internal stem CO2. However, the potential contribution of stem photosynthesis to forest productivity has not previously been adequately quantified, and we also do not know how it compares to leaf photosynthetic productivity. To assist in addressing this knowledge gap, we conducted field surveys in Eucalyptus urophylla plantations of different ages and developed a more realistic modeling framework by integrating stem photosynthesis into the existing canopy carbon assimilation model. We calculated the proportion of tree stems shaded by neighboring tree trunks based on Poisson spatial point process. Under the stand density of 2000 trees per hectare, the light absorption area of tree trunks of 2-year-old and 7-year-old E. urophylla plantations were 0.11 (± 0.15) and 0.35 (± 0.12) m2 stem m-2 land, the stem photosynthetic productivity (GPPstem) was 0.72 (± 0.45) and 1.81 (± 1.12) mol C m-2 month-1, and the ratios of GPPstem to leaf photosynthetic productivity (GPPleaf) were 5.10 and 8.17% for 2- and 7-year-old plantations, respectively. Overall, this study presents the feasibility of incorporating stem photosynthesis into the productivity prediction of E. urophylla plantations by developing the stem light absorption model.

Cancer Stem Cell Biomarkers in the Nervous System.

Cancer stem cells (CSCs) have been increasingly recognized in recent years. CSCs from human neural tumors are one of the root causes of metastatic tumor progression, therapeutic resistance and recurrence. However, there is a lack of comprehensive literature that systematically consolidates the biomarkers specific to CSCs in neurological cancers. Therefore, this review provides a comprehensive summary of cancer stem cell (CSC) biomarkers for neurological tumors such as glioma, meningioma, medulloblastoma and neurofibroma. It also points out the possible functions of these biomarkers in diagnosis, treatment and prognosis, providing a broader perspective. First, we quantitatively screened key words such as CSCs, biomarkers, and expression by bibliometric analysis and clarified the intrinsic connections between the key words. Then, we describe the CSC biomarkers of major neurological tumors and their pathway mechanisms, and provide an in-depth analysis of the commonalities and differences with the biomarkers of non-CSCs. In addition, many studies have shown that antipsychotic drugs can inhibit tumor growth and reduce the expression of CSC biomarkers, which facilitates targeted therapy against tumors in the nervous system. Therefore, this study will focus on the biomarkers of CSCs in the nervous system, hoping to provide guidance for future in-depth exploration and monitoring of neurological tumors for clinical applications.

Gut mycobiota dysbiosis in drug-naïve, first-episode schizophrenia.

Bacterial dysbiosis has been demonstrated in patients with schizophrenia (SCH). The aim of the present study was to investigate alterations in mycobiota composition and fungi-bacteria correlation network in drug-naïve, first episode SCH. We recruited 205 SCH patients and 125 healthy controls (HCs), whose gut bacterial and fungal compositions were characterized by 16S and 18S ribosomal RNA gene amplicon sequencing, respectively. Fungal-bacterial relative correlation network analysis was performed using the Spearman's test and distance correlation. We also computed relative networks connectedness, which represents the ratio of significant interactions (edges) and taxa (nodes) in the network. SCH patients showed lower fungal α-diversity compared with that of HCs. Furthermore, we identified 29 differential fungal markers at multiple taxonomies between SCH patients and HCs. SCH patients also showed a significantly lower fungi-to-bacteria α-diversity ratio compared with that of HCs (p = 1.81 × 10-8). In risk prediction models, we observed that combining bacterial and fungal markers achieved higher accuracy than that of bacterial markers alone (AUC = 0.847 vs AUC = 0.739; p = 0.043). Fungal-bacterial correlation network was denser in HCs than in SCH patients and was characterized by a high number of neighbors (p < 0.05). In addition, an increased abundance of Purpureocillium was associated with more severe psychiatric symptoms and poorer cognitive function in SCH patients (p < 0.05). Our study demonstrated a disrupted and weakened fungi-bacteria network in SCH patients, which might be associated with their clinical manifestations. Future research on fungal-bacterial correlation network is warranted to advance our understanding about the role of mycobiota in the etiology of SCH and to explore novel intervention approaches.

FBXO39 predicts poor prognosis and correlates with tumor progression in cervical squamous cell carcinoma.

BACKGROUND: Cancer/testis antigen (CTA) is a class of antigen molecules mainly expressed in the germinal epithelium of testis and some tumor tissues. FBXO39, also known as F-box protein 39, is a crucial CTA molecule. F-box protein 39 (FBXO39) is overexpressed in cervical squamous cell carcinomas (CESCs), however its function in cancer development and clinical significance are still unknown. METHODS: We used paraffin-embedded tumor tissues from 124 patients and fresh-harvested and paired adjacent normal esophageal tissues from 15 CESC patients who underwent primary surgical resection in Xijing Hospital between 2015 and 2020. The expression level of FBXO39 was evaluated through immunohistochemistry, Western Blot and q-PCR. Prognostic and survival analyses were conducted using univariate/multivariate analysis and log-rank analysis with SPSS 23.0. CCK-8, wound-healing and Transwell assays were applied to demonstrate that FBXO39 promoted the proliferation, migration and invasion. Finally, we constructed a xenografts model of the C-33A cell lines to observe the effect of FBXO39 on tumorigenesis in vivo. RESULTS: Immunohistochemical results showed that FBXO39 was highly expressed in cancer tissues than in corresponding non-cancer tissues. Similarly, we proved this result at protein and mRNA level by Western-Blotting and q-PCR. Prognostic and OS analyses showed that the FBXO39 expression level was an individual prognostic factor in CESC patients. CCK-8, wound-healing and Transwell assays proved that the overexpression of FBXO39 in Si-Ha cells promoted the proliferation, migration and invasion of the cells. Knocking down FBXO39 in C-33A cells inhibited the proliferation, migration and invasion of cells. The experimental results of xenografts model in nude mice showed that the knockdown of FBXO39 in C-33A cells slowed down the growth of tumor. CONCLUSION: FBXO39 is a poor prognostic factor of cervical squamous cell carcinoma, which may provide a novel therapeutic target for CESC.

A Hybrid Imaging Platform(CT/PET/FMI) for Evaluating Tumor Necrosis and Apoptosis in Real-Time.

Multimodality imaging is an advanced imaging tool for monitoring tumor behavior and therapy in vivo. In this study, we have developed a novel hybrid tri-modality system that includes two molecular imaging methods: positron emission computed tomography (PET) and fluorescence molecular imaging (FMI) and the anatomic imaging modality X-ray computed tomography (CT). The following paper describes the system development. Also, its imaging performance was tested in vitro (phantom) and in vivo, in Balb/c nude mice bearing a head and neck tumor xenograft treated with novel gene therapy [a new approach to the delivery of recombinant bacterial gene (IL-24-expressing strain)]. Using the tri-modality imaging system, we simultaneously monitored the therapeutic effect, including the apoptotic and necrotic induction within the tumor in vivo. The apoptotic induction was examined in real-time using an 18F-ML-10 tracer; the cell death was detected using ICG. A CT was used to evaluate the anatomical situation. An increased tumor inhibition (including tumor growth and tumor cell apoptosis) was observed in the treatment group compared to the control groups, which further confirmed the therapeutic effect of a new IL-24-expressing strain gene therapy on the tumor in vivo. By being able to offer concurrent morphological and functional information, our system is able to characterize malignant tissues more accurately. Therefore, this new tri-modality system (PET/CT/FMI) is an effective imaging tool for simultaneously investigating and monitoring tumor progression and therapy outcomes in vivo.

Association between ambient air pollution and blood sex hormones levels in men.

Concerns are growing over time on the adverse health effects of air pollution. However, the association between ambient air pollution and blood sex hormones in men is poorly understood. We included 72,917 men aged 20-55 years from February 2014 to December 2019 in Beijing, China in this study. Blood testosterone, follicle stimulating hormone, luteinizing hormone, estradiol, and prolactin levels of each participant were measured. We collected exposure data of daily ambient levels of particulate matter ≤10 µm (PM10) and ≤2.5 µm (PM2.5), nitrogen dioxide, sulfur dioxide (SO2), carbon monoxide, and ozone. Generalized linear mixed models were used to analyze the potential association between ambient air pollution exposure and blood sex hormone levels. The results showed that both immediate and short-term cumulative PM2.5, PM10, and SO2 exposure was related to altered serum sex hormone levels in men, especially testosterone. An increase of 10 µg/m3 in PM2.5 and PM10 in the current day was related to a 1.6% (95% confidence interval [CI]: 0.9%-2.3%) and 1.1% (95% CI: 0.5%-1.6%) decrease in testosterone, respectively, and a decreasing tendency of accumulated effects persisted within lag 0-30 days. The present study demonstrated that it is important to control ambient air pollution exposure to reduce effects on the reproductive health of men.