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Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut microbiota, but relevant data are still lacking in humans, especially for the level below human safety threshold. We conducted a cross-sectional study in 4247 Chinese adults by measuring 34 parent antibiotics and their metabolites from six common categories (i.e., tetracyclines, qinolones, macrolides, sulfonamides, phenicols, and lincosamides) and ten representative bile acids in fasting morning urine using liquid chromatography coupled to mass spectrometry. Daily exposure dose of antibiotics was estimated from urinary concentrations of parent antibiotics and their metabolites. Urinary bile acids and their ratios were used to reflect bile acid homeostasis. The estimated daily exposure doses (EDED) of five antibiotic categories with a high detection frequency (i.e., tetracyclines, qinolones, macrolides, sulfonamides, and phenicols) were significantly associated with urinary concentrations of bile acids and decreased bile acid ratios in all adults and the subset of 3898 adults with a cumulative ratio of antibiotic EDED to human safety threshold of less than one. Compared to a negative detection of antibiotics, the lowest EDED quartiles of five antibiotic categories and four individual antibiotics with a high detection frequency (i.e., ciprofloxacin, ofloxacin, trimethoprim, and florfenicol) in the adults with a positive detection of antibiotics had a decrease of bile acid ratio between 6.6% and 76.6%. Except for macrolides (1.2×102 ng/kg/day), the medians of the lowest EDED quartile of antibiotic categories and individual antibiotics ranged from 0.32 ng/kg/day to 10 ng/kg/day, which were well below human safety thresholds. These results suggested that low-level antibiotic exposure could disrupt bile acid homeostasis in adults and existing human safety thresholds may be inadequate in safeguarding against the potential adverse health effects of low-level exposure to antibiotics. [Display omitted] • Daily exposure doses of antibiotic were estimated from urinary concentrations in 4247 adults. • Urinary bile acids and their ratios were used to reflect bile acid homeostasis. • A cumulative EDED of antibiotics below the safety threshold was observed in 91.8% of adults. • Antibiotic EDED was significantly associated with urinary bile acids and their ratios. • The lowest EDED disturbing bile acid homeostasis may be well below the safety threshold. [ABSTRACT FROM AUTHOR]

Previous studies have shown that early-life exposure to fine particulate matter (PM2.5) is associated with an increasing risk of autism spectrum disorder (ASD), however, the specific sensitive period of ASD is unknown. Here, a model of dynamic whole-body concentrated PM2.5 exposure in pre- and early-postnatal male offspring rats (MORs) was established. And we found that early postnatal PM2.5 exposed rats showed more typical ASD behavioral characteristics than maternal pregnancy exposure rats, including poor social interaction, novelty avoidance and anxiety disorder. And more severe oxidative stress and inflammatory responses were observed in early postnatal PM2.5 exposed rats. Moreover, the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) was down-regulated and the ratios of p-PI3K/PI3K and p-AKT/AKT were up-regulated in early postnatal PM2.5 exposed rats. This study suggests that early postnatal exposure to PM2.5 is more susceptible to ASD-like phenotype in offspring than maternal pregnancy exposure and the activation of PI3K-AKT signaling pathway may represent underlying mechanisms. • Early postnatal PM2.5 exposure induced more pronounced ASD-like phenotype in male offspring rats than maternal exposure. • Early postnatal period may be a sensitive window for PM2.5 to trigger autism spectrum disorder development. • PM2.5 exposure caused neuroinflammation and reduced anti-inflammatory melatonin levels in offspring rat brains. • PI3K-AKT pathway activation may link developmental PM2.5 exposure and autism spectrum disorder pathogenesis. [ABSTRACT FROM AUTHOR]

Our study determined the toxic effects of zinc oxide (ZnO) particles with different diameters on dopaminergic (DA) neurons, the role of ubiquitin C-terminal hydrolase L1 (UCH-L1) for ZnO particles−induced neurotoxicity, and corresponding molecular mechanisms. We constructed an in vitro cell injury model for DA neurons to analyze the cytotoxicity of ZnO particles using SH-SY5Y cells. Following cell viability assays and flow cytometry, we found that the cytotoxicity of ZnO particles was affected by particle size, time, and dose of exposure. For example, the toxicity of ZnO particles with 50 nm or 100 nm diameter was stronger than that of ZnO particles with 1000 nm diameter. Furthermore, ZnO particles exposure resulted in a significant decrease in UCH-L1 expression in SH-SY5Y; whereas UCH-L1 overexpression led to a significant increase in cell viability and a sharp decrease in ROS level. Western blotting and adenovirus transfection found that exposure to ZnO particles with different diameters all activate the NF-κB signaling in SH-SY5Y cells; whereas UCH-L1 over-expression resulted in increased levels of IκBα, an endogenous inhibitor of NF-κB signaling pathway. ZnO particles with different diameters all induced cytotoxicity in DA neurons, which may be related to the free Zn2+ in the suspension. Regarding the neurotoxic effect of ZnO particles, UCH-L1 protects against and/or alleviates neuronal damage, possibly by deubiquitination of the endogenous inhibitor, IκBα, which leads to activation of NF-κB signaling. Therefore, one possible mechanism for ZnO particle−induced neurotoxicity may be mediated via the down-regulation of UCH-L1 expression in DA cells. • The cytotoxicity of micron and nanometer diameter ZnO NP in neurons was compared. • ZnO particle exposure down-regulates the abundance of UCH-L1 in DA neurons. • UCH-L1 plays a protective role against neurotoxic effect of ZnO particles. • UCH-L1 inhibits the activation of the NF- B pathway through IκBα. [ABSTRACT FROM AUTHOR]

Ru(II) complexes [Ru(phen) 2 (PIP)]2+ (Ru 1), [Ru(phen) 2 (p-HPIP)]2+ (Ru 2), and [Ru(phen) 2 (m-HPIP)]2+ (Ru 3) have been synthesized and characterized in this work. Their binding properties of the RNA duplex poly(A)•poly(U) have been investigated. The obtained results show that the three Ru(Ⅱ) complexes bind to the RNA duplex poly(A)•poly(U) by intercalation, and destabilize the RNA duplex. [Display omitted] • Complexes [Ru(phen) 2 L]2+ (Ru 1 , L = PIP; Ru 2 , L = p-HPIP; Ru 3 , L = m-HPIP) were synthesized. • Binding of the three complexes with RNA poly(A)•poly(U) were investigated. • The three complexes destabilize RNA poly(A)•poly(U). • This work reports for the first time small molecules capable of destabilizing an RNA duplex. To further explore the binding properties of Ru(Ⅱ) polypyridine complexes with RNA, three Ru(Ⅱ) complexes [Ru(phen) 2 (PIP)]2+ (Ru 1), [Ru(phen) 2 (p-HPIP)]2+ (Ru 2), and [Ru(phen) 2 (m- HPIP)]2+ (Ru 3) have been synthesized and characterized in this work. The binding properties of three Ru(Ⅱ) complexes with RNA duplex poly(A)•poly(U) have been investigated by spectral and viscosity experiments. These studies all support that these three Ru(Ⅱ) complexes bind to poly RNA duplex poly(A)•poly(U) by intercalation, and Ru 1 without substituents has a stronger binding affinity for poly(A)•poly(U). Interestingly, the thermal melting experiments show that these three Ru(Ⅱ) complexes all destabilize RNA duplex poly(A)•poly(U), and the destabilizing effect can be explained by the conformational changes of duplex structure induced by intercalating agents. To the best of our knowledge, this work report for the first time a small molecule capable of destabilizing an RNA duplex, which reflects that the substitution effect of intercalated ligands has an important influence on the affinity of Ru(Ⅱ) complexes to RNA duplex, and that not all Ru(Ⅱ) complexes show thermal stability effects on an RNA duplex. [ABSTRACT FROM AUTHOR]

The crucial feature of chicken is real-time microbial growth detection along the supply chain. Hyperspectral imaging (HSI) is an online and nondestructive technique that is well suited to microorganism analysis applications. In this study, visible and near-infrared (Vis/NIR, 400–1000 nm) HSI were utilized to establish prediction models of the total viable count (TVC) of chicken breasts stored in vacuum, pallet, and combined packaging using partial least squares regression (PLSR) and support vector machine (SVM) after spectral pretreatments and optimal wavelength selection. The SVM algorithm was used to develop the best TVC prediction models for storage, with the following outcome: vacuum (R2 p = 0.91, RMSE p = 0.47, RPD = 2.44), pallet (R2 p = 0.90, RMSE p = 0.54, RPD = 2.32), and combined (R2 p = 0.89, RMSE p = 0.58, RPD = 2.21) packs. Successively, HSI combined with fluorescence (F–HSI) was used to predict the TVC and coliforms of chicken breasts in combined packaging. Compared to HSI, F–HSI achieved the best-predicted results for TVC (R2 p = 0.93, RMSE p = 0.44, RPD = 2.74) and coliforms (R2 p = 0.92, RMSE p = 0.46, RPD = 2.57). These results indicated that fluorescence, as a complementary technique for HSI, will be widely used in the chicken supply chain to predict microbial growth. • HSI combined with fluorescence was used to predict microbial growth of chickens. • TVC and coliforms as critical biological parameters were predicted by HSI and F–HSI. • Samples were stored in different packs and temperatures to detect microbial growth. • Comparing the effects of pretreatments and modelling methods on model performance. [ABSTRACT FROM AUTHOR]

Ambient ozone (O 3) pollution can induce respiratory and cardiovascular toxicity. However, its impact on the metabolome and the underlying mechanisms remain unclear. This study first investigated the serum metabolite changes in rats exposed to 0.5 ppm O 3 for 3 months using untargeted metabolomic approach. Results showed chronic ozone exposure significantly altered the serum levels of 34 metabolites with potential increased risk of digestive, respiratory and cardiovascular disease. Moreover, bile acid synthesis and secretion, and arachidonic acid (AA) metabolism became the most prominent affected metabolic pathways after O 3 exposure. Further studies on the mechanisms found that the elevated serum toxic bile acid was not due to the increased biosynthesis in the liver, but the reduced reuptake from the portal vein to hepatocytes owing to repressed Ntcp and Oatp1a1 , and the decreased bile acid efflux in hepatocytes as a results of inhibited Bsep , Ostalpha and Ostbeta. Meanwhile, decreased expressions of detoxification enzyme of SULT2A1 and the important regulators of FXR, PXR and HNF4α also contributed to the abnormal bile acids. In addition, O 3 promoted the conversion of AA into thromboxane A2 (TXA2) and 20-hydroxyarachidonic acid (20-HETE) in the liver by up-regulation of Fads2 , Cyp4a and Tbxas1 which resulting in decreased AA and linoleic acid (LA), and increased thromboxane B2 (TXB2) and 20-HETE in the serum. Furthermore, apparent hepatic chronic inflammation, fibrosis and abnormal function were found in ozone-exposed rats. These results indicated chronic ozone exposure could alter serum metabolites by interfering their metabolism in the liver, and inducing liver injury to aggravate metabolic disorders. [Display omitted] • Subchronic O 3 induces characteristic changes in serum metabolites of rats especially bile acids and arachidonic acid. • O 3 reduces reuptake of bile acids from the portal vein to hepatocytes by repressing Ntcp and Oatp1a1. • O 3 decreases bile acid efflux in hepatocytes by inhibiting Bsep, Ostalpha and Ostbeta. • O 3 promotes the conversion of AA into TXA2 and 20-HETE by up-regulating Fads2 , Cyp4a and Tbxas1 in liver. • O 3 induces hepatic inflammation, fibrosis and function disturbance which may mutually reinforce with abnormal metabolites. [ABSTRACT FROM AUTHOR]

To study the regulatory relationship between ozone-induced mitophagy and pyroptosis in lung epithelial cells. First, type I primary alveolar epithelial cells and male Wistar rats were treated with ozone at different dosages. The ATP content and mitochondrial membrane potential significantly decreased in type I primary alveolar epithelial cells. The mitophagy-related markers and PINK1/Parkin pathway-related proteins, and the co-localization of LC3, Parkin, and mitochondria in type I alveolar epithelial cells indicated that ozone exposure triggered mitophagy. On the other hand, the reactive oxygen species (ROS) inhibitor NAC could significantly alleviate mitophagy in epithelial cells. After treatment with the mitophagy inhibitor MDIVI-1, the levels of the NLRP3 inflammasome, cleaved caspase-1, and N-gasdermin D (N-GSDMD) significantly decreased in the cells. Altogether, these results indicated that mitophagy can be triggered by ozone exposure, and subsequently induces cell death mediated by the NLRP3 inflammasome. Finally, the overexpression and knockdown of NLRP3 confirmed this conclusion. Ozone exposure induced oxidative damage, leading to mitochondrial structural and functional damage. Ozone-induced ROS triggered mitophagy through the activation of the PINK1/Parkin signaling pathway, then pyroptosis through activation of the NLRP3 inflammasome. • Ozone exposure can lead to pulmonary mitochondrial dysfunction in vivo and in vitro. • Ozone exposure can lead to mitophagy in lung, and ROS is involved in this process. • ROS induce mitophagy through the activation of the PINK1/Parkin signaling pathway. • Mitophagy induced by ozone can induce pyroptosis through the activation of NLRP3 inflammasome in lung. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we consider the orbital stability of smooth solitary wave solutions of the generalized Camassa–Holm equation. By constructing the functional extremum problem and using the orbital stability theory presented by Grillakis, Shatah, Strauss and Bona, and Souganidis, we show that the solitary wave solutions of the generalized Camassa–Holm equation are orbitally stable or unstable as determined by the sign of a discriminant. The conclusions presented by the previous authors, such as Hakkaev and Kirchev, Constantin and Strauss, can be considered as a special case of our results. [Copyright &y& Elsevier]

In this study, a natural extract from the plant Radix hedysari (ER) was proven to be useful for the green synthesis of silver nanoparticles (AgNPs) and ER-AgNPs in particular. Considering the complexity of plant extracts, high-pressure liquid chromatography (HPLC) was effective at confirming the components of ER, surprisingly, formononetin was found to comprise more than 85% of the total contents. Since formononetin was confirmed to be the primary component of ER, this compound was also used as the basis to synthesize AgNPs designated FMT-AgNPs that was highly pure and of high quality. The FMT-AgNPs functionalized by formononetin were optimized for further study. A simple, fast and sensitive colorimetric method detect formothion was achieved using FMT-AgNPs. A wide linear range from 0.1 μM to 10 μM was established with a low limit of detection (LOD) of 14.6 nM. Since formononetin performed multiple roles during the synthesis, it was confirmed that the mechanism of detection was based on aldol condensation, intermolecular hydrogen bonds and electrostatic attraction between formononetin and formothion. Finally, the green synthesized FMT-AgNPs were further applied in typical fruit and vegetable samples, indicating that FMT-AgNPs were potentially highly useful. [Display omitted] • The plant extract (ER) and formononetin was utilized to green synthesize silver nanoparticles (ER-AgNPs/FMT-AgNPs). • FMT-AgNPs were proven to be pure and of high quality. • The relevant synthesis or mechanism of detection was clearly explained. • FMT-AgNPs were sensitive and selective for the detection of formothion. • FMT-AgNPs were applied to detect formothion in typical vegetable and fruit samples. [ABSTRACT FROM AUTHOR]

The mouse WD repeat and FYVE domain containing 1 (Wdfy1) gene is located in chromosome 1qC4 and spans over 73.7 kilobases. It encodes a protein of 410-amino acid protein that shares 97.8% amino acid sequence identity with the human WDFY1 protein. However, the expression pattern of WDFY1 in reproductive organs and its function in male fertility remain unknown. In this study, we generated transgenic mice expressing FLAG-Wdfy1-mCherry cDNA driven by the Wdfy1 promoter to clarify the expression of WDFY1. The results showed that WDFY1 is highly expressed in mouse testes and located in the cytoplasm of late pachytene spermatocytes to elongated spermatids. Interestingly, the global Wdfy1 knockout (KO) male mice displayed normal growth, development, and fertility. Further histological analysis of Wdfy1 knockout mouse testes revealed that all spermatogenic cells are present in Wdfy1 KO seminiferous tubules. Together, our data demonstrate that WDFY1 is dispensable for mouse spermatogenesis and male fertility. • WDFY1 is preferentially expressed in mouse testes. • WDFY1 is located in the cytoplasm of late pachytene spermatocytes to elongated spermatids. • The global Wdfy1 knockout (KO) male mice displayed normal growth, development, and fertility. [ABSTRACT FROM AUTHOR]

Abstract: This paper aims to investigate the problem of state-feedback stabilization for stochastic high-order nonlinear systems with Markovian switching. By using the generalized Itô formula and Dynkin formula for Markovian switching systems, a state-feedback controller is constructed to ensure that the closed-loop system has a unique solution and the solution of the closed-loop systems is almost surely asymptotically stable. Finally, the effectiveness of the controller is demonstrated by a simulation example. [Copyright &y& Elsevier]

Abstract: Emerging evidence suggests that a high level of circulating heat shock protein 70 (HSP70) correlates with a lower risk of vascular disease; however, the biological significance of this inverse relationship has not been explored. Herein, we report that oxidative low density lipoprotein (Ox-LDL) and homocysteine (Hcy) induce HSP70 release from endothelial cells. In rat endothelial cells, Ox-LDL and Hcy induced robust release of HSP70, independent of the classical route of endoplasmic reticulum/Golgi protein trafficking or the formation of lipid rafts. In contrast, Ox-LDL and Hcy significantly enhanced the exosomal secretory rate and increased the HSP70 content of exosomes. Exogenous HSP70 had no impact on LPS-, Ox-LDL- and Hcy-induced activation of endothelial cells, whereas HSP70 did activate monocytes alone, resulting in monocyte adhesion to endothelial cells. These results indicate that exosome-dependent secretion of HSP70 from endothelial cells provides a novel paracrine mechanism to regulate vascular endothelial functional integrity. [Copyright &y& Elsevier]

• Considerable portion of COVID-19 patients presented depression and anxiety symptoms. • CRP levels correlated with the scores of PHQ-9 in patients with depression features. • The more improvement of CRP level resulted in lower level of depression. • Stigma and uncertainty of the disease were two main concerns among COVID-19 patients. Since the end of 2019, Corona Virus Disease 2019 (COVID-19) has been the cause of a worldwide pandemic. The mental status of patients with COVID-19 who have been quarantined and the interactions between their psychological distress and physiological levels of inflammation have yet to be analyzed. Using a mixed-method triangulation design (QUAN + QUAL), this study investigated and compared the mental status and inflammatory markers of 103 patients who, while hospitalized with mild symptoms, tested positive with COVID-19 and 103 matched controls that were COVID-19 negative. The severity of depression, anxiety, and post-traumatic stress symptoms (PTSS) was measured via an on-line survey. Using a convenience sampling technique, qualitative data were collected until the point of data saturation. In addition, a semi-structured interview was conducted among five patients with COVID-19. Peripheral inflammatory markers were also collected in patients, both at baseline and within ± three days of completing the on-line survey. Results revealed that COVID-19 patients, when compared to non-COVID controls, manifested higher levels of depression (P < 0.001), anxiety (P < 0.001), and post-traumatic stress symptoms (P < 0.001). A gender effect was observed in the score of "Perceived Helplessness", the subscale of PSS-10, with female patients showing higher scores compared to male patients (Z = 2.56, P = 0.010), female (Z = 2.37, P = 0.018) and male controls (Z = 2.87, P = 0.004). Levels of CRP, a peripheral inflammatory indicator, correlated positively with the PHQ-9 total score (R = 0.37, P = 0.003, Spearman's correlation) of patients who presented symptoms of depression. Moreover, the change of CRP level from baseline inversely correlated with the PHQ-9 total score (R = -0.31, P = 0.002), indicative of improvement of depression symptoms. Qualitative analysis revealed similar results with respect to patient reports of negative feelings, including fear, guilt, and helplessness. Stigma and uncertainty of viral disease progression were two main concerns expressed by COVID-19 patients. Our results indicate that significant psychological distress was experienced by hospitalized COVID-19 patients and that levels of depressive features may be related to the inflammation markers in these patients. Thus, we recommend that necessary measures should be provided to address depression and other psychiatric symptoms for COVID-19 patients and attention should be paid to patient perceived stigma and coping strategies when delivering psychological interventions. [ABSTRACT FROM AUTHOR]

The clove extract showed the best inhibitory effect on all the five spoilage bacteria of dry-cured ducks among eight commonly used spices. The proliferation of Staphylococcus simulans 2 was inhibited significantly with no logarithmic phase following the treatment of the clove extract. The MIC of clove extract against Staphylococcus simulans 2 was 9 mg/mL. The clove extract had remarkable effects on inhibiting proteins synthesis and enhancing the permeability of the cell membrane, which induced the inactivation of the spoilage bacteria and the irregular, pitted, and shriveled bacterial morphology. Besides, the clove extract showed the strongest antioxidant capacity in vitro than the other seven spices. The clove extract had the highest scavenging activity on DPPH·, OH· and O2−·, which were 95.28%, 95.88% and 62.63%, respectively. It had the unique antioxidant capacity in duck grease, which was almost equivalent to TBHQ. As the clove extract was applied in the manufacture of dry-cured duck, the peroxide value, acid value, and total bacterial colony count declined significantly, and the shelf-life extended from 3 months to 6 months. It confirmed that the clove extract had distinguished antibacterial and antioxidant properties in the manufacture of traditional dry-cured duck. • The clove extract had distinguished antibacterial effect and the mechanism was also elucidated preliminary. • The clove extract also showed distinguished antioxidant activity in vitro and in practical application. • The clove could inhibit microbial growth, decline lipid oxidation, and prolong the shelf-life of dry-cured duck effectively. • In contrast to chemical preservatives, natural plant extracts are more acceptable to consumers. [ABSTRACT FROM AUTHOR]

Hypoxic injury of cardiac microvascular endothelial cells (CMECs) is an important pathophysiological event in myocardial infarction, whereas, the underlying mechanism is still poorly understood. Autophagy, a highly conserved process of cellular degradation, is required for normal cardiac function and also has been implicated in various cardiovascular diseases. Here we investigated the potential role of autophagy in CMEC dysfunction under hypoxia. CMECs were isolated from SD rats. Hypoxia (6–24 h, 1% O 2 ) induced autophagy in CMECs as evidenced by formation of punctate LC3, increased conversion of LC3-I to LC3-II and increased p62 degradation. Importantly, hypoxia-induced apoptosis in CMECs was attenuated by 3-Methyladenine (5 mM), an autophagy inhibitor, and aggravated by rapamycin (1.0 μg/L), an autophagy inducer. Meanwhile, hypoxia increased the nuclear localization of FoxO3α, accompanying with the decreased phosphorylation of FoxO3α and Akt. FoxO3α silencing decreased hypoxia-induced autophagy and the resultant apoptosis. Furthermore, treatment with 3-Methyladenine (10 mg/kg/day) improved the endothelial-dependent diastolic function of coronary artery in rats with myocardial infarction. These results indicated that hypoxia-induced autophagy formation in CMECs is mediated by FoxO3α and contributes to hypoxic injury of hearts. [ABSTRACT FROM AUTHOR]

Highlights: [•] FXR up-regulates apoF. [•] It binds to ER1 element. [•] It activates apoF gene promoter. [ABSTRACT FROM AUTHOR]

Abstract: To study the apoptosis of lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients and the possible role of IL-10 in this apoptosis involved in the pathogenesis of SLE, three color fluorescence and flow cytometry were used to investigate the early apoptosis of lymphocyte subsets from freshly separated or cultured peripheral blood mononuclear cells (PBMCs). ELISA was employed to detect the levels of IL-10 in serum and the levels of sFas and sFasL in cultured PBMC supernatants, and the results of sFas and sFasL were confirmed by real-time PCR of Fas and FasL mRNA. The results showed that in cells from SLE patients, the apoptosis of CD3+, CD4+, and CD8+ T cells was distinctly increased, and the percentage of CD4+ cells and the CD4/CD8 ratio was significantly decreased, as compared with normal controls. The apoptosis of T lymphocytes cultured with SLE serum was markedly higher than that of cells cultured with control’s serum. Blockade of interleukin-10 (IL-10) activation by an anti-IL-10 antibody reduced the SLE serum induced apoptosis of CD4+ and CD8+ T cells. The levels of sFas and sFasL in the culture supernatant and Fas and FasL mRNA expressions in cultured cells were significantly higher in the SLE serum-cultured groups, but decreased evidently in the presence of the anti-IL-10 antibody. Above findings suggested that SLE cells showed abnormally high apoptosis of T lymphocytes, especially of the CD4+ subpopulation, resulting in a decreased CD4/CD8 ratio. The high percentage of apoptotic T cells in SLE patients may be related to the high levels of IL-10 in SLE serum, as IL-10 may induce the abnormally activated T cells to trigger apoptosis via the Fas–FasL pathway. [Copyright &y& Elsevier]

The epidemic of pneumonia (COVID-19) caused by novel coronavirus (SARS-CoV-2) infection has been listed as a public health emergency of international concern by the World Health Organization (WHO), and its harm degree is defined as a global "pandemic". At present, the efforts of various countries focus on the rapid diagnosis and isolation of patients, as well as to find a treatment that can combat the most serious impact of the disease. The number of reported COVID-19 virus infections is still increasing. Unfortunately, no drugs or vaccines have been approved for the treatment of human coronaviruses, but there is an urgent need for in-depth research on emerging human infectious coronaviruses. Clarification transmission routes and pathogenic mechanisms, and identification of potential drug treatment targets will promote the development of effective prevention and treatment measures. In the absence of confirmed effective treatments, due to public health emergencies, it is essential to study the possible effects of existing approved antivirals drugs or Chinese herbal medicines for SARS-CoV-2. This review summarizes the epidemiological characteristics, pathogenesis, virus structure and targeting strategies of COVID-19. Meanwhile, this review also focus on the re-purposing of clinically approved drugs and Chinese herbal medicines that may be used to treat COVID-19 and provide new ideas for the discovery of small molecular compounds with potential therapeutic effects on novel COVID-19. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most common cancers among women in both developed and developing countries with a rising incidence. Using the MMTV-PyMT transgenic mouse model and xenografted breast cancer model, we found that R5, a neutralizing antibody to Robo1, significantly inhibited BC growth and metastasis. Angiogenesis is involved in the growth and metastasis of BC. Interestingly, R5 significantly decreases microvessel density in BC tissues, and inhibits blood vessel formation and development in in vivo chick embryo chorioallantoic membrane (CAM), yolk sac membrane (YSM) and Matrigel plug models. To investigate whether its anti-breast cancer efficacy is ascribed to its direct antiangiogenic properties, xenografted breast cancer model on CAM was established. Furthermore, R5 significantly reduces the tube formation of the vascular plexus on xenografted breast tumor on CAM. R5 also suppresses the migration and the tubular structure formation of human umbilical vein endothelial cells (HUVECs) by down-regulating the expression of filamin A (FLNA). These findings show that R5 has the potential to be a promising agent for the treatment of BC by suppressing the tumor-induced angiogenesis. [ABSTRACT FROM AUTHOR]