Association between low-density lipoprotein cholesterol levels and serum uric acid to serum creatinine ratio in Chinese male gout patients.

This study aimed to evaluate the association between low-density lipoprotein cholesterol (LDL-C) and serum uric acid to serum creatinine (SUA/SCr) ratio in male gout patients at different BMIs. This real-world study included 956 male gout patients aged 18-83 years. We retrospectively analyzed the medical records of Chinese male gout patients from 2017 to 2019. The correlation between LDL-C and SUA/SCr was tested after adjusting for confounding factors. We found a nonlinear relationship between LDL-C and SUA/SCr in the whole study population. Stratification analysis showed that there was actually a nonlinear relationship between LDL-C and SUA/SCr in men with a BMI of 24-28, the inflection point of LDL-C was 1.8 mmol/L, when LDL-C was greater than 1.8 mmol/L, there was a positive correlation between LDL-C levels and SUA/SCr (ß = 0.67, 95% CI 0.35-0.98, P < 0.001). Moreover, LDL-C showed a significant positive correlation with SUA/SCr with a BMI of 28 or greater (ß = 0.30, 95% CI 0.05-0.55, P = 0.019). However, no association was found between LDL-C and SUA/SCr with a BMI of less than 24 (ß = 0.42, 95% CI - 0.03-0.86, P = 0.070). LDL-C levels were associated with SUA/SCr in Chinese male gout patients, but this correlation appeared inconsistent among different BMIs. Our findings suggest that LDL-C levels may be more noteworthy in overweight and/or obese male gout patients.

Continuous microalgal culture module and method of culturing microalgae containing macular pigment.

This study established and investigated continuous macular pigment (MP) production with a lutein (L):zeaxanthin (Z) ratio of 4-5:1 by an MP-rich Chlorella sp. CN6 mutant strain in a continuous microalgal culture module. Chlorella sp. CN6 was cultured in a four-stage module for 10 days. The microalgal culture volume increased to 200 L in the first stage (6 days). Biomass productivity increased to 0.931 g/L/day with continuous indoor white light irradiation during the second stage (3 days). MP content effectively increased to 8.29 mg/g upon continuous, indoor white light and blue light-emitting diode irradiation in the third stage (1 day), and the microalgal biomass and MP concentrations were 8.88 g/L and 73.6 mg/L in the fourth stage, respectively. Using a two-step MP extraction process, 80 % of the MP was recovered with a high purity of 93 %, and its L:Z ratio was 4-5:1.

Case Report: Perianal infection in children caused by ingested jujube pits: a report of two cases.

Background: The ingestion of jujube pits by children is a rare cause of perianal infection.This article aimed to report two cases of perianal infection in children resulting from the ingestion of jujube pits. Methods: We reviewed the clinical records of perianal infection caused by jujube pits at our hospital. Details of the patients' presentation, imaging studies, complications and treatment were recorded. Results: Both pediatric patients presented with perianal swelling and pain. The caregivers of both patients denied a history of jujube consumption. Magnetic resonance imaging (MRI) indicated the presence of jujube pits, which were subsequently removed during surgery. Postoperatively, both patients recovered well, and follow-up showed no recurrence or the formation of anal fistulas. Conclusion: The ingestion of jujube pits leading to perianal infection is rare and inconspicuous. Early diagnosis and treatment are beneficial in preventing the occurrence of serious complications.

[Application strategy of artificial intelligence technology in feed-based development of medicinal and edible homologous traditional Chinese medicine(TCM)resources in era of the "antibiotic ban"].

In the context of the "antibiotic ban" era, the feed conversion of medicinal and edible traditional Chinese medicine(TCM) resources is a research hotspot in the field of antibiotic alternatives development. How to develop feed products that are beneficial to agriculture and livestock while ensuring nutrient balance and precision using medicinal and edible TCM resources as raw materials has become a challenge. Artificial intelligence(AI) technology has unique advantages in feed production and improving the efficiency of intelligent breeding. If AI technology is applied to the feed development of medicinal and edible TCM resources, it is possible to realize feeding and antibiotic-replacement value while ensuring precise nutrition. In order to better apply AI technology in the field of feed development of medicinal and edible TCM resources, this article used CiteSpace software to carry out literature visualization analysis and found that AI technology had a good application in the field of feed formulation optimization in recent years. However, there is still a gap in the research on the intelligent utilization of medicinal and edible TCM resources. Nonetheless, it is feasible for AI technology to be applied to the feed conversion of medicinal and edible TCM resources. Therefore, this article proposed for the first time an intelligent formulation system framework for feed materials derived from medicinal and edible TCM resources to provide new ideas for research in the field of feed development of medicinal and edible TCM resources and the research on the development of antibiotic alternatives. At the same time, it can pave the way for a new green industry chain for contemporary animal husbandry and the TCM industry.

Dynamic changes in cardiac biomarkers in radiotherapy for oesophageal cancer and their correlations with cardiac radiation dosimetry.

Background and purpose: To investigate the dynamic changes in cardiac enzymes, high-sensitivity troponin T (hs-TnT), pro-brain natriuretic peptide (pro-BNP) and left ventricular ejection fraction (LVEF) during radiotherapy (RT) and 6 months after RT for oesophageal squamous cell carcinoma (ESCC) in the middle and lower locations and to analyse the correlations between these indicators and cardiac radiation dosimetry parameters. Methods: For 35 patients with ESCC in the middle and lower locations receiving radical concurrent chemoradiotherapy (cCRT), intensity-modulated RT was performed at 1.8 Gy or 2.0 Gy per day, and the totle dose was 50.4 Gy or 60 Gy. Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (α-HBDH), hs-TnT, pro-BNP and LVEF were measured before, during, and at the end of RT and 1, 3 and 6 months after RT, and correlations of these indicators with mean heart dose (MHD) and heart V5-V50 were analysed. Results: hs-TnT during, at the end and 6 months after RT for oesophageal cancer showed increasing trends, however, LVEF showed a downward trend. pro-BNP showed an increasing trend during RT and gradually returned to normal after RT. CK and CK-MB showed decreasing trends during RT and continued until one month after RT and then gradually returned to normal. Compared with the low-dose group (MHD < 2000 cGy), the high-dose group (MHD ≥ 2000 cGy) had larger increases in hs-TnT and pro-BNP, a more significant decrease in LVEF, and a longer recovery time for these indicators. MHD and V35 were positively correlated with dynamic changes in hs-TnT. Conclusions: Cardiac injury caused by cCRT for ESCC in the middle and lower locations led to increased hs-TnT and pro-BNP levels and a decrease in LVEF in the early stage of treatment, effects that were more pronounced in the high-dose group. MHD and V35 may be potential indicators to predict the degree of cardiac damage. hs-TnT and pro-BNP are sensitive indicators reflecting cardiac injury in RT for oesophageal cancer. Continuous dynamic monitoring of these markers can provide a reference for cardiac protection in clinical RT.

A long-term study comparing the quality of life and psychological status of patients with highly suspicious thyroid nodules ≤ 1 cm undergoing active surveillance with those undergoing immediate surgery.

BACKGROUND: Limited information is available on the long-term impact of active surveillance (AS) and immediate surgery (IS) on the quality of life (QoL) and psychological status of patients with highly suspicious sub-centimeter thyroid nodules. METHODS: A prospective study was conducted on 752 patients showing highly suspicious sub-centimeter thyroid nodules, among whom 584 chose AS and 168 chose IS. All patients underwent at least two assessments regarding their QoL and psychological status, using three questionnaires: THYCA-QoL, HADS and EORTC QLQ-C30. Propensity-score matching (PSM) at a ratio of 3:1 was utilized on patients in the AS and IS groups to mitigate selection bias (504 patients in the AS group and 168 in the IS group). Subsequently, the mixed linear model was used to analyze the QoL data. RESULTS: The median time from the initial evaluation to the last follow-up in the AS and IS groups was 24.0 months and 14.2 months, respectively. The AS group showed superior QoL outcomes compared to the IS group, mainly manifested in voice (p < 0.001), sympathetic (p = 0.008), throat/mouth (p < 0.001), and problems with scar (p < 0.001) domains, as per the THYCA-QoL questionnaire. Further, the EORTC QLQ-C30 questionnaire highlighted better outcomes in physical function (p = 0.029), role function (p < 0.001), social function (p < 0.001), global health status (p < 0.001), fatigue (p = 0.012), pain (p = 0.028), appetite loss (p = 0.017), and financial difficulties (p < 0.001). Compared to the initial assessment (one week after surgery), the IS group showed progressive improvements in QoL, especially in voice (p = 0.024), throat/mouth (p < 0.001), physical function (p = 0.004), social function (p = 0.014), nausea & vomiting (p < 0.001), pain (p = 0.006), and appetite loss (p = 0.048) domains as per both questionnaires. CONCLUSION: Patients with highly suspicious sub-centimeter thyroid nodules who choose IS tend to experience a poorer long-term QoL compared to those who choose AS. Although the situation may improve over time, certain issues might persist, making AS a favorable option for these patients.

Molecular diagnosis is an important indicator for response to growth hormone therapy in children with short stature.

BACKGROUND: Significant differences have been observed in the efficacy of recombinant human growth hormone (rhGH) treatment for short children. The present study aimed to identify the genetic etiology of short stature and to assess the role of molecular diagnosis in predicting responses to rhGH treatment. METHODS: A total of 407 short children were included in the present study, 226 of whom received rhGH treatment. Whole-exome sequencing (WES) was conducted on short children to identify the underlying genetic etiology. Correlations between molecular diagnosis and the efficacy of rhGH treatment were examined. RESULTS: Pathogenic or likely pathogenic mutations were identified in 86 of the 407 patients (21.1%), including 36 (41.9%) novel variants. Among the multiple pathways affecting short stature, genes involved in fundamental cellular processes (38.7%) play a larger role, especially the RAS-MAPK pathway. In general, patients without pathogenic mutations responded better to rhGH than those with mutations. Furthermore, patients with hormone signaling pathway mutations had a better response to rhGH, while those with paracrine factor mutations had a worse response to rhGH. CONCLUSIONS: This study highlights the utility of WES in identifying genetic etiology in children with short stature. Identifying likely causal mutations is an important factor in predicting rhGH response.

Human umbilical cord derived mesenchymal stem cells overexpressing HO-1 attenuate neural injury and enhance functional recovery by inhibiting inflammation in stroke mice.

AIMS: The current evidence demonstrates that mesenchymal stem cells (MSCs) hold therapeutic potential for ischemic stroke. However, it remains unclear how changes in the secretion of MSC cytokines following the overexpression of heme oxygenase-1 (HO-1) impact excessive inflammatory activation in a mouse ischemic stroke model. This study investigated this aspect and provided further insights. METHODS: The middle cerebral artery occlusion (MCAO) mouse model was established, and subsequent injections of MSC, MSCHO-1 , or PBS solutions of equal volume were administered via the mice's tail vein. Histopathological analysis was conducted on Days 3 and 28 post-MCAO to observe morphological changes in brain slices. mRNA expression levels of various factors, including IL-1ß, IL-6, IL-17, TNF-α, IL-1Ra, IL-4, IL-10, TGF-ß, were quantified. The effects of MSCHO-1 treatment on neurons, microglia, and astrocytes were observed using immunofluorescence after transplantation. The polarization direction of macrophages/microglia was also detected using flow cytometry. RESULTS: The results showed that the expression of anti-inflammatory factors in the MSCHO-1 group increased while that of pro-inflammatory factors decreased. Small animal fluorescence studies and immunofluorescence assays showed that the homing function of MSCsHO-1 was unaffected, leading to a substantial accumulation of MSCsHO-1 in the cerebral ischemic region within 24 h. Neurons were less damaged, activation and proliferation of microglia were reduced, and polarization of microglia to the M2 type increased after MSCHO-1 transplantation. Furthermore, after transplantation of MSCsHO-1 , the mortality of mice decreased, and motor function improved significantly. CONCLUSION: The findings indicate that MSCs overexpressing HO-1 exhibited significant therapeutic effects against hyper-inflammatory injury after stroke in mice, ultimately promoting recovery after ischemic stroke.

Case Report: CD19 and CD20 monoclonal antibodies with sequential chemotherapy for refractory acute B-lymphocytic leukemia in children.

Objective: This paper observes the efficacy of chemotherapy combined with CD19 and CD20 monoclonal antibodies in clearing minimal residual disease (MRD) and bridging transplantation for refractory acute B-lymphoblastic leukemia (B-ALL) in children and reviews the literature. Methods: A 4-year-old boy diagnosed with B-ALL in our hospital was treated with the SCCLG-ALL-2016 protocol. MRD and gene quantification decreased after induction but remained persistently positive, with poor efficacy. After this patient received three cycles of consolidation chemotherapy combined with blinatumomab and rituximab, MRD and fusion gene quantification became negative, and he received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: During the use of monoclonal antibodies, neurotoxicity, CRS, or other side effects did not occur. Before transplantation, MRD became negative, and the bone marrow had been in complete remission since transplantation (13 months). Conclusion: Chemotherapy combined with blinatumomab for refractory B-ALL in children can bring a better remission rate for patients and is a means of bridging transplantation. Nevertheless, sequential CD20 monoclonal antibody therapy is the first report , and no adverse effects were observed in our case. It is well tolerated and can be used as one of the treatments for refractory B-ALL.

Insights into the volatile flavor and quality profiles of loquat (Eriobotrya japonica Lindl.) during shelf-life via HS-GC-IMS, E-nose, and E-tongue.

Loquat fruits are among the most popular Chinese fruits because of their unique taste and aroma. The quality profiles of these fruits during 18 days of shelf-life at 20 °C were elucidated by headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS), E-nose, and E-tongue. During shelf-life period, the properties and variations of 43 (20 aldehydes, 7 esters, 6 ketones, 1 alcohol, and 1 furan) volatile flavored compounds were determined by GC-IMS, which showed that the contents of methyl 3-methyl butanoate, ethyl acetate, and dimethyl ketone gradually decrease with prolonged shelf-life time, while (E)-2-heptenal, heptanal, (E)-2-pentenal, 1-penten-3-one 3-pentanone and 2-pentylfuran increase. The PCA based on the signal intensity of GC-IMS and E-nose, revealed that loquat fruits are well distinguished at different shelf-life times. The taste profile alternates as the storage time increases, along with higher pH, and lower amounts of total soluble solids, vitamin C, and total phenolics. The visual plots of GC-IMS, E-nose, and E-tongue had good consistency, and they characterized the aroma characteristics of loquat fruits well during different shelf-life periods. The findings of this research provide a useful understanding of the flavors of loquat fruits during their prolonged shelf-life, and a potential research basis for advancements in the loquat industry.

Prevention of STAT3-related pathway in SK-N-SH cells by natural product astaxanthin.

PURPOSE: Neuroblastoma (NB) is the most common solid malignancy in children. Despite current intensive treatment, the long-term event-free survival rate is less than 50% in these patients. Thus, patients with NB urgently need more valid treatment strategies. Previous research has shown that STAT3 may be an effective target in high-risk NB patients. However, there are no effective inhibitors in clinical evaluation with low toxicity and few side effects. Astaxanthin is a safe and natural anticancer product. In this study, we investigated whether astaxanthin could exert antitumor effects in the SK-N-SH neuroblastoma cancer cell line. METHOD: MTT and colony formation assays were used to determine the effect of astaxanthin on the proliferation and colony formation of SK-N-SH cells. Flow cytometry assays were used to detect the apoptosis of SK-N-SH cells. The migration and invasion ability of SK-N-SH cells were detected by migration and invasion assays. Western blot and RT-PCR were used to detect the protein and mRNA levels. Animal experiments were carried out and cell apoptosis in tissues were assessed using a TUNEL assay. RESULT: We confirmed that astaxanthin repressed proliferation, clone formation ability, migration and invasion and induced apoptosis in SK-N-SH cells through the STAT3 pathway. Furthermore, the highest inhibitory effect was observed when astaxanthin was combined with si-STAT3. The reason for this may be that the combination of astaxanthin and si-STAT3 can lower STAT3 expression further than astaxanthin or si-STAT3 alone. CONCLUSION: Astaxanthin can exert anti-tumor effect on SK-N-SH cells. The inhibitory effect was the higher when astaxanthin was combined with si-STAT3.

Covalent 14-3-3 Molecular Glues and Heterobifunctional Molecules Against Nuclear Transcription Factors and Regulators.

14-3-3 proteins have the unique ability to bind and sequester a multitude of diverse phosphorylated signaling proteins and transcription factors. Many previous studies have shown that 14-3-3 interactions with specific phosphorylated substrate proteins can be enhanced through small-molecule natural product or fully synthetic molecular glue interactions. However, enhancing 14-3-3 interactions with both therapeutically intractable transcription factor substrates as well as potential neo-substrates to sequester and inhibit their function has remained elusive. One of the 14-3-3 proteins, 14-3-3σ or SFN, has a cysteine C38 at the substrate binding interface near sites where previous 14-3-3 molecular glues have been found to bind. In this study, we screened a fully synthetic cysteine-reactive covalent ligand library to identify molecular glues that enhance interaction of 14-3-3σ with not only druggable transcription factors such as estrogen receptor (ERα), but also challenging oncogenic transcription factors such as YAP and TAZ that are part of the Hippo transducer pathway. We identified a hit EN171 that covalently targets 14-3-3 to enhance 14-3-3 interactions with ERα, YAP, and TAZ leading to impaired estrogen receptor and Hippo pathway transcriptional activity. We further demonstrate that EN171 could not only be used as a molecular glue to enhance native protein interactions, but also could be used as a covalent 14-3-3 recruiter in heterobifunctional molecules to sequester nuclear neo-substrates such as BRD4 into the cytosol. Overall, our study reveals a covalent ligand that acts as a novel 14-3-3 molecular glue for challenging transcription factors such as YAP and TAZ and also demonstrates that these glues can be potentially utilized in heterobifunctional molecules to sequester nuclear neo-substrates out of the nucleus and into the cytosol to enable targeted protein localization.

Covalent Targeting of Glutamate Cysteine Ligase to Inhibit Glutathione Synthesis.

Dysregulated oxidative stress plays a major role in cancer pathogenesis and some types of cancer cells are particularly vulnerable to inhibition of their cellular antioxidant capacity. Glutamate-cysteine ligase (GCL) is the first and rate-limiting step in the synthesis of the major cellular antioxidant glutathione (GSH). Developing a GCL inhibitor may be an attractive therapeutic strategy for certain cancer types that are particularly sensitive to oxidative stress. In this study, we reveal a cysteine-reactive ligand, EN25, that covalently targets an allosteric cysteine C114 on GCLM, the modifier subunit of GCL, and leads to inhibition of GCL activity. This interaction also leads to reduced cellular GSH levels and impaired cell viability in ARID1A-deficient cancer cells, which are particularly vulnerable to glutathione depletion, but not in ARID1A-positive cancer cells. Our studies uncover a novel potential ligandable site within GCLM that can be targeted to inhibit GSH synthesis in vulnerable cancer cell types.

Clinical and genetic evaluation of children with short stature of unknown origin.

BACKGROUND: Short stature is a common human trait. More severe and/or associated short stature is usually part of the presentation of a syndrome and may be a monogenic disease. The present study aimed to identify the genetic etiology of children with short stature of unknown origin. METHODS: A total of 232 children with short stature of unknown origin from March 2013 to May 2020 were enrolled in this study. Whole exome sequencing (WES) was performed for the enrolled patients to determine the underlying genetic etiology. RESULTS: We identified pathogenic or likely pathogenic genetic variants in 18 (7.8%) patients. All of these variants were located in genes known to be associated with growth disorders. Five of the genes are associated with paracrine signaling or cartilage extracellular matrix in the growth plate, including NPR2 (N = 1), ACAN (N = 1), CASR (N = 1), COMP (N = 1) and FBN1 (N = 1). Two of the genes are involved in the RAS/MAPK pathway, namely, PTPN11 (N = 6) and NF1 (N = 1). Two genes are associated with the abnormal growth hormone-insulin-like growth factor 1 (GH-IGF1) axis, including GH1 (N = 1) and IGF1R (N = 1). Two mutations are located in PROKR2, which is associated with gonadotropin-releasing hormone deficiency. Mutations were found in the remaining two patients in genes with miscellaneous mechanisms: ANKRD11 (N = 1) and ARID1A (N = 1). CONCLUSIONS: The present study identified pathogenic or likely pathogenic genetic variants in eighteen of the 232 patients (7.8%) with short stature of unknown origin. Our findings suggest that in the absence of prominent malformation, genetic defects in hormones, paracrine factors, and matrix molecules may be the causal factors for this group of patients. Early genetic testing is necessary for accurate diagnosis and precision treatment.

Discovery of Potent Pyrazoline-Based Covalent SARS-CoV-2 Main Protease Inhibitors.

While vaccines and antivirals are now being deployed for the current SARS-CoV-2 pandemic, we require additional antiviral therapeutics to not only effectively combat SARS-CoV-2 and its variants, but also future coronaviruses. All coronaviruses have relatively similar genomes that provide a potential exploitable opening to develop antiviral therapies that will be effective against all coronaviruses. Among the various genes and proteins encoded by all coronaviruses, one particularly "druggable" or relatively easy-to-drug target is the coronavirus Main Protease (3CLpro or Mpro), an enzyme that is involved in cleaving a long peptide translated by the viral genome into its individual protein components that are then assembled into the virus to enable viral replication in the cell. Inhibiting Mpro with a small-molecule antiviral would effectively stop the ability of the virus to replicate, providing therapeutic benefit. In this study, we have utilized activity-based protein profiling (ABPP)-based chemoproteomic approaches to discover and further optimize cysteine-reactive pyrazoline-based covalent inhibitors for the SARS-CoV-2 Mpro. Structure-guided medicinal chemistry and modular synthesis of di- and tri-substituted pyrazolines bearing either chloroacetamide or vinyl sulfonamide cysteine-reactive warheads enabled the expedient exploration of structure-activity relationships (SAR), yielding nanomolar potency inhibitors against Mpro from not only SARS-CoV-2, but across many other coronaviruses. Our studies highlight promising chemical scaffolds that may contribute to future pan-coronavirus inhibitors.

[Clinical Features and Prognosis of Multiple Myeloma Patients with Secondary Primary Malignancies].

OBJECTIVE: To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies. METHODS: The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated. RESULTS: A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the ß2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027). CONCLUSION: The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.

Daphnia magna uptake and excretion of luminescence-labelled polystyrene nanoparticle as visualized by high sensitivity real-time optical imaging.

The environmental and ecological consequences of nanoplastics (NPs) draw increasing research interests and social concerns. However, the in situ and real-time detection of NPs from living organisms and transferring media remains as a major technical obstacle for scientific investigation. Herein we report a novel time-gated imaging (TGI) strategy capable of real-time visualizing the intake of NPs by an individual living organism, which is based on the polystyrene NPs labelled with lanthanide up-conversion luminescence. The limit of detection (LOD) of the TGI apparatus was 600 pg (SNR = 3) in a field of view of 2.4 × 3.8 mm. Taking Daphnia magna as the aquatic model, we investigated the dynamics of uptake and accumulation of NPs (500 µg/L) for 24 h, and the subsequent excretion process (in clean medium) for 48 h, and quantitively analyzed the distribution and the overall mass of NPs deposited in D. magna. The uptake of NPs via filter-feeding occurred in a few minutes, whereas a longer accumulation was found, in a timescale of several hours. And similar behaviors (bi-phase elimination) were also seen in the excretion, indicating the migration of NPs into the circulatory system. The average mass of NPs accumulated in an individual D. magna was ∼12 ng after 24 h exposure, indicating that D. magna as a filter feeder tends to retain NPs. The observed NPs accumulation in D. magna exemplifies the potential risk of aquatic ecosystem on exposure to NP contamination.

Gap junction is essential for the antidepressant effects of fluoxetine.

OBJECTIVES: Fluoxetine has been used as the first line for the therapy of depression. However, lack of therapeutic efficacy and time lag still limit the application of fluoxetine. Gap junction dysfunction is a potentially novel pathogenic mechanism for depression. To clarify the mechanism underlying these limitations, we investigated whether gap junction was related to the antidepressant effects of fluoxetine. METHODS AND KEY FINDINGS: After chronic unpredictable stress (CUS), animals showed decreases in gap junction intracellular communication (GJIC). Treatment with fluoxetine 10 mg/kg significantly improved GJIC and anhedonia of rats until six days. These results indicated that fluoxetine improved gap junction indirectly. Furthermore, to test the role of gap junction on antidepressant effects of fluoxetine, we blocked gap junction using carbenoxolone (CBX) infusion in the prefrontal cortex. CBX dampened fluoxetine-induced decrease in immobility time of mice in tail suspension test (TST). CONCLUSIONS: Our study suggested that gap junction dysfunction blocks antidepressant effects of fluoxetine, contributing to understanding the mechanism underlying the time lag of fluoxetine.