Nanoparticle drug delivery systems for synergistic delivery of tumor therapy.

Nanoparticle drug delivery systems have proved anti-tumor effects; however, they are not widely used in tumor therapy due to insufficient ability to target specific sites, multidrug resistance to anti-tumor drugs, and the high toxicity of the drugs. With the development of RNAi technology, nucleic acids have been delivered to target sites to replace or correct defective genes or knock down specific genes. Also, synergistic therapeutic effects can be achieved for combined drug delivery, which is more effective for overcoming multidrug resistance of cancer cells. These combination therapies achieve better therapeutic effects than delivering nucleic acids or chemotherapeutic drugs alone, so the scope of combined drug delivery has also been expanded to three aspects: drug-drug, drug-gene, and gene-gene. This review summarizes the recent advances of nanocarriers to co-delivery agents, including i) the characterization and preparation of nanocarriers, such as lipid-based nanocarriers, polymer nanocarriers, and inorganic delivery carriers; ii) the advantages and disadvantages of synergistic delivery approaches; iii) the effectual delivery cases that are applied in the synergistic delivery systems; and iv) future perspectives in the design of nanoparticle drug delivery systems to co-deliver therapeutic agents.

Matching-Adjusted Indirect Comparisons of Filgotinib vs Vedolizumab, Tofacitinib, and Ustekinumab for Moderately to Severely Active Ulcerative Colitis.

BACKGROUND: Where head-to-head trials are lacking, indirect comparative effectiveness can aid treatment decisions. We conducted matching-adjusted indirect comparisons of clinical outcomes with filgotinib vs recently approved comparators (vedolizumab, tofacitinib, ustekinumab) in patients with moderately to severely active ulcerative colitis (UC). METHODS: Individual patient data from the SELECTION trial (NCT02914522) for filgotinib 200 mg were weighted to match average baseline characteristics of active treatment and placebo arms in comparator trials. Efficacy outcomes were compared for biologic-naive and biologic-experienced subgroups in induction and maintenance populations, if data were available. Safety and health-related quality of life outcomes were compared in the overall maintenance population. RESULTS: Filgotinib had a similar effect on efficacy outcomes compared with tofacitinib, ustekinumab, and subcutaneous vedolizumab in both the induction and maintenance populations. Filgotinib showed improved clinical response vs intravenous (IV) vedolizumab (odds ratio, 2.4; 95% confidence interval [CI], 1.0 to 5.5; P < .05) among the biologic-experienced induction population, and improved corticosteroid-free clinical remission (odds ratio, 15.2; 95% CI, 1.6 to 139.9; P < .05) among the biologic-naive maintenance population. Improved efficacy outcomes were reported with filgotinib compared with ustekinumab among the maintenance population. Higher estimates of serious adverse events were reported for filgotinib compared with vedolizumab IV 300 mg and tofacitinib 5 mg; however, imbalances were noted in their placebo groups. Health-related quality of life outcomes were similar between filgotinib and comparators. CONCLUSIONS: Matching-adjusted indirect comparison results suggest superiority of filgotinib 200 mg over vedolizumab IV in terms of clinical response and corticosteroid-free clinical remission in certain patient populations, noting small sample sizes and wide CIs, which may aid the selection of advanced therapies for moderately to severely active UC. A potential increased risk of serious adverse events was reported for filgotinib 200 mg vs vedolizumab IV and tofacitinib 5 mg, but findings should be interpreted with caution owing to underlying imbalances observed between the placebo groups of SELECTION and comparator trials.

Matching-adjusted indirect comparisons between filgotinib and subcutaneous vedolizumab, tofacitinib, and ustekinumab demonstrated similar effects on efficacy, safety, and health-related quality of life in patients with ulcerative colitis. Clinical response and corticosteroid-free remission were improved with filgotinib compared with intravenous vedolizumab.

Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity.

Doxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells. Epigallocatechin gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX. Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells. In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells. In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA. The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR). Additionally, we investigate the anti-drug resistant mechanism by Western Blot. The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay. In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX.

The Perspectives of Surrogates and Healthcare Providers Regarding SDM (Shared Decision-Making).

The purpose of this paper is to explore the attitudes of surrogacy and medical service providers toward SDM and to identify the barriers and promoters of SDM in this population. To this end, we conducted a qualitative study of surrogacy and medical service providers in the First Affiliated Hospital of Soochow University using semistructured interviews. Thirty participants (11 agents, 12 ICU physicians, and 7 ICU nurses) were interviewed. The three stakeholders showed different attitudes toward SDM. They reported barriers to SDM, including insufficient cognition of decision-makers, high expectations, negative psychological experiences, previous decision-making experiences, excessive workload, heavy financial burden, and lack of decision AIDS. They reported facilitators of SDM, including trust, effective communication, decision support, value clarification, outcome commitment, and continuous service. This study explored the different attitudes of the three stakeholders and identified various barriers and facilitators of SDM. It highlights the need to develop localised decision AIDS and to involve agents and nurses more in the decision-making process. Therefore, this paper identifies barriers and facilitators of SDM in this population. In addition, the study identified various barriers and facilitators to SDM and highlighted the need to develop localised decision AIDS and involve agents and nurses more in the decision-making process. Finally, the barriers and facilitators of SDM are established. The paper also shows that the development of localized decision AIDS and greater involvement of agents and nurses in the decision-making process are integral to good treatment outcomes.

Effects of exercise or tai chi on Internet addiction in college students and the potential role of gut microbiota: A randomized controlled trial.

OBJECTIVE: This study aimed to explore the effect of exercise or tai chi on Internet addiction disorder (IAD) among college students and clarified the abundance and population changes of gut microbiota in different groups. Thus explore the potential role of gut microbiota between exercise and IAD. METHODS: A total of 93 subjects diagnosed with mild IAD were randomly assigned to the exercise group, the tai chi group, and the control group. The intervention groups received exercise or tai chi for 8 weeks and the control group was evaluated without any intervention. Fecal samples were collected after the intervention. RESULTS: 1) Analysis found a significant intervention effect with the exercise group showing an average decrease of 8.84 points on the Internet addiction test (IAT) compared with the control group (95%CI -15.41 to-2.27, P = 0.004). But there was no significant difference between the control group and the tai chi group. 2) Both exercise (P = 0.018) and tai chi (P = 0.026) could significantly relieve fatigue symptoms. 3) The relative abundance of the Betaproteobacteria, Porphyromonadaceae, Sutterellaceae, and Alistipes were significantly decreased in the exercise group compared with the control group, and the relative abundance of Escherichia was significantly increased in the exercise group. 4) The relative abundance of Betaproteobacteria, Sutterellaceae, and Escherichia had significant differences between the improved group and the no-improved group. CONCLUSION: Exercise intervention has a considerable effect on treating IAD. Exercise and tai chi might have effectiveness in relieving the symptoms of fatigue. Exercise intervention regulates the gut microflora and changes the abundance of microflora to improve IAD. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05529368.

Tumor microenvironment-responsive micelles assembled from a prodrug of mitoxantrone and 1-methyl tryptophan for enhanced chemo-immunotherapy.

Mitoxantrone (MX) can induce the immunogenic-cell death (ICD) of tumor cells and activate anti-tumor immune responses. However, it can also cause high expression of indole amine 2, 3-dioxygenase (IDO) during ICD, leading to T-cell apoptosis and a weakened immune response. An IDO inhibitor, 1-methyl tryptophan (1-MT), can inhibit the activity of IDO caused by MX, resulting in enhanced chemo-immunotherapy. Here, MX-1-MT was connected by ester bond which could be broken in an acidic tumor microenvironment. MX-1-MT was combined with polyethylene glycol (PEG) via a disulfide bond which could be reduced by glutathione overexpressed in tumors, thereby accelerating drug release at target sites. Folic acid-modified distearoyl phosphoethanolamine-polyethylene glycol (DSPE-PEG-FA) was introduced to form targeting micelles. The micelles were of uniform particle size, high stability, and high responsiveness. They could be taken-up by drug-resistant MCF-7/ADR cells, displayed high targeting ability, and induced enhanced cytotoxicity and ICD. Due to 1-MT addition, micelles could inhibit IDO. In vivo studies demonstrated that micelles could accumulate in the tumor tissues of nude mice, resulting in an enhanced antitumor effect and few side-effects.

A bidirectional association between smartphone addiction and depression among college students: A cross-lagged panel model.

Background: Smartphone addiction (SA) is associated with adverse consequences, especially for freshmen. Evidence indicates that SA is associated with depression, and it is necessary to conduct a longitudinal study to explore the association further. Methods: SA (measured by the Smartphone Addiction Scale-Short Version) and depression (measured by the Zung's Self-Rating Depression Scale) among 1,186 freshmen were surveyed at baseline and a respective 12-month follow-up for each participant. The application of a cross-lagged panel model approach (CLPM) revealed an association between SA and depression after adjusting for demographic variables. Results: The CLPM results showed a significant path from baseline SA to follow-up depression (ß = 0.08, P < 0.001) and a significant path from baseline depression to follow-up SA (ß = 0.08, P < 0.001). Compared with the overall cross-lagged model, the cross-lagged coefficient of the path from baseline SA to follow-up depression increased in the female group (ß = 0.10, P = 0.015), and the cross-lagged coefficient of the path from baseline depression to follow-up SA also increased significantly (ß = 0.15, P < 0.001). In contrast, the cross-lagged model in the male group showed no predictive effect between SA and depression (P > 0.05). Conclusions: The current study showed a significant bidirectional association between smartphone addiction and depression among freshmen, but only in the female population.

RNAsmc: A integrated tool for comparing RNA secondary structure and evaluating allosteric effects.

RNA structure plays a crucial role in gene regulation, in RNA stability and the essential biological processes. RNA secondary structure (RSS) motifs are the basic building blocks for investigating the biological mechanisms of structure. Here, we present a strategy for structural motif-based dynamic alignment, namely, RNA secondary-structural motif-comparing (RNAsmc), to identify structural motifs and quantitatively evaluate their underlying molecular functions. RNAsmc also has strong robustness to sequence length, folding protocol and RNA structural profile by chemical probing. Notably, it is also applicable to quantify structural variation in special RNA editing events (SNVs or SNPs, fragment insertion or deletion, etc.). The findings indicate that RNAsmc can uncover the heterogeneity of RNA secondary structure and score for similarities among components, which provides an impetus to cluster RNA families and evaluate allosteric effects. We find that RNAsmc exhibits remarkable detection efficiency for experimentally-derived RiboSNitches. Finally, the pipeline was assembled into an R software package to serve as an automated toolkit to explore, align, and cluster RSS. It is freely available for download at https://CRAN.R-project.org/package=RNAsmc.

FCKDNet: A Feature Condensation Knowledge Distillation Network for Semantic Segmentation.

As a popular research subject in the field of computer vision, knowledge distillation (KD) is widely used in semantic segmentation (SS). However, based on the learning paradigm of the teacher-student model, the poor quality of teacher network feature knowledge still hinders the development of KD technology. In this paper, we investigate the output features of the teacher-student network and propose a feature condensation-based KD network (FCKDNet), which reduces pseudo-knowledge transfer in the teacher-student network. First, combined with the pixel information entropy calculation rule, we design a feature condensation method to separate the foreground feature knowledge from the background noise of the teacher network outputs. Then, the obtained feature condensation matrix is applied to the original outputs of the teacher and student networks to improve the feature representation capability. In addition, after performing feature condensation on the teacher network, we propose a soft enhancement method of features based on spatial and channel dimensions to improve the dependency of pixels in the feature maps. Finally, we divide the outputs of the teacher network into spatial condensation features and channel condensation features and perform distillation loss calculation with the student network separately to assist the student network to converge faster. Extensive experiments on the public datasets Pascal VOC and Cityscapes demonstrate that our proposed method improves the baseline by 3.16% and 2.98% in terms of mAcc, and 2.03% and 2.30% in terms of mIoU, respectively, and has better segmentation performance and robustness than the mainstream methods.

ST6GAL1 inhibits metastasis of hepatocellular carcinoma via modulating sialylation of MCAM on cell surface.

The poor prognosis of hepatocellular carcinoma (HCC) is mainly because of its high rate of metastasis. Thus, elucidation of the molecular mechanisms underlying HCC metastasis is of great significance. Glycosylation is an important post-translational modification that is closely associated with tumor progression. Altered glycosylation including the altered sialylation resulting from aberrant expression of ß-galactoside α2,6 sialyltransferase 1 (ST6GAL1) has long been considered as an important feature of cancer cells. However, there is limited information on the roles of ST6GAL1 and α2,6 sialylation in HCC metastasis. Here, we found that ST6GAL1 and α2,6 sialylation were negatively correlated with the metastatic potentials of HCC cells. Moreover, ST6GAL1 overexpression inhibited migration and invasion of HCC cells in vitro and suppressed HCC metastasis in vivo. Using a metabolic labeling-based glycoproteomic strategy, we identified a list of sialylated proteins that may be regulated by ST6GAL1. In particular, an increase in α2,6 sialylation of melanoma cell adhesion molecule (MCAM) inhibited its interaction with galectin-3 and decreased its expression on cell surface. In vitro and in vivo analysis showed that ST6GAL1 exerted its function in HCC metastasis by regulating MCAM expression. Finally, we found the relative intensity of sialylated MCAM was negatively correlated with tumor malignancy in HCC patients. Taken together, these results demonstrate that ST6GAL1 may be an HCC metastasis suppressor by affecting sialylation of MCAM on cell surface, which provides a novel insight into the roles of ST6GAL1 in HCC progression and supports the functional complexity of ST6GAL1 in a cancer type- and tissue type-specific manner.

Massively Parallel CRISPR-Based Genetic Perturbation Screening at Single-Cell Resolution.

The clustered regularly interspaced short palindromic repeats (CRISPR)-based genetic screening has been demonstrated as a powerful approach for unbiased functional genomics research. Single-cell CRISPR screening (scCRISPR) techniques, which result from the combination of single-cell toolkits and CRISPR screening, allow dissecting regulatory networks in complex biological systems at unprecedented resolution. These methods allow cells to be perturbed en masse using a pooled CRISPR library, followed by high-content phenotyping. This is technically accomplished by annotating cells with sgRNA-specific barcodes or directly detectable sgRNAs. According to the integration of distinct single-cell technologies, these methods principally fall into four categories: scCRISPR with RNA-seq, scCRISPR with ATAC-seq, scCRISPR with proteome probing, and imaging-based scCRISPR. scCRISPR has deciphered genotype-phenotype relationships, genetic regulations, tumor biological issues, and neuropathological mechanisms. This review provides insight into the technical breakthrough of scCRISPR by systematically summarizing the advancements of various scCRISPR methodologies and analyzing their merits and limitations. In addition, an application-oriented approach guide is offered to meet researchers' individualized demands.

Comparative efficacy of advanced treatments in biologic-naïve or biologic-experienced patients with ulcerative colitis: a systematic review and network meta-analysis.

BACKGROUND: Only one head-to-head comparison of advanced treatments in moderately to severely active ulcerative colitis (UC) has been published; therefore, there remains a need for further comparisons. AIM: The relative treatment effects of filgotinib and adalimumab, golimumab, infliximab, tofacitinib, ustekinumab and vedolizumab were estimated using a network meta-analysis (NMA). METHOD: Systematically identified studies (MEDLINE, Embase and Cochrane Library; searched: inception-May 2019, updated November 2020) investigating treatments for moderately to severely active UC were re-evaluated for inclusion in a Bayesian NMA (fixed-effects model). Relative treatment effects were estimated using different permutations of patient population (biologic-naïve or biologic-experienced), treatment phase (induction or maintenance) and outcomes (MCS response/remission or endoscopic mucosal healing). RESULTS: Seventeen trials (13 induction; 9 maintenance) were included in the NMA; 8 treatment networks were constructed. Most targeted therapies were superior to placebo in terms of MCS response/remission and endoscopic mucosal healing; filgotinib 200 mg was similar to most other treatments. Infliximab 5 mg/kg was superior to filgotinib 200 mg (biologic-naïve; induction) for MCS response/remission (mean relative effect, 0.34 [95% credible interval: 0.05, 0.62]). Filgotinib 200 mg was superior to adalimumab 160/80/40 mg for MCS response/remission (biologic-experienced; induction; - 0.75 [- 1.16, - 0.35]), and endoscopic mucosal healing (biologic-naïve; maintenance; - 0.90 [- 1.89, - 0.01]); and to golimumab 50 mg every 4 weeks (biologic-naïve; maintenance; - 0.46 [- 0.94, 0]) for MCS response/remission. CONCLUSION: The current treatment landscape benefits patients with moderately to severely active UC, improving key outcomes; filgotinib 200 mg was similar to current standard of care in most outcomes.

Carbohydrates and ginsenosides in shenmai injection jointly improve hematopoietic function during chemotherapy-induced myelosuppression in mice.

BACKGROUND: Shenmai injection (SMI), a traditional Chinese medicine (TCM) injection prepared from Red ginseng and Ophiopogon japonicus, is widely used in clinics to treat chemotherapy-induced myelosuppression. Similar to other TCM injections, SMI contains a high amount of carbohydrates (fructose, sucrose, and maltose) in addition to the bioactive substances, specifically ginsenosides (Rg1, Re, and Rb1). To date, the role of these carbohydrates in the hematopoietic function of SMI remains unclear. PURPOSE: We aimed to investigate the hematopoietic effects and potential mechanisms of SMI and its components, focusing on the carbohydrates present in SMI. EXPERIMENTAL DESIGN/METHODS: First, we evaluated the hematopoietic effect of SMI on 5-fluorouracil (5-FU)-induced myelotoxicity in a tumor-bearing mouse model. Then we prepared mixtures of ginsenosides and carbohydrates according to their proportions in SMI and evaluated their hematopoietic function in mice with 5-FU-induced myelosuppression. Finally, hematopoiesis-related molecular networks were built based on RNA sequencing (RNA-seq) of the bone marrow stromal cells (BMSCs), and the potential mechanisms of carbohydrates and ginsenosides were evaluated. RESULTS: SMI attenuated 5-FU-induced myelotoxicity in tumor-bearing mice. Both ginsenosides and carbohydrates increased the bone marrow nucleated cell (BMNC) count and improved the bone marrow morphology in myelosuppressive mice; they promoted the proliferation of BMSCs derived from those myelosuppressive mice. Bioinformatics analyses revealed ECM-receptor interaction, Hippo signaling, and Wnt signaling are common pathways regulated by both ginsenosides and carbohydrates; Gstt1, Gstp2, Gsta4 and Oplah in Glutathione metabolism pathway and Cd19, Cd79a, and Cd79b in B cell receptor pathway are uniquely regulated genes related to carbohydrates but not ginsenosides. CONCLUSIONS: Carbohydrates may collaborate with ginsenosides and contribute to the hematopoietic function of SMI. Carbohydrates could be considered as a bioactive component in this TCM injection.

Multimodal integrated strategy for the discovery and identification of quality markers in traditional Chinese medicine.

With the modernization and internationalization of traditional Chinese medicine (TCM), the requirement for quality control has increased. The quality marker (Q-marker) is an important standard in this field and has been implemented with remarkable success in recent years. However, the establishment of Q-markers remains fragmented and the process lacks systematicity, resulting in inconsistent quality control and insufficient correlation with clinical efficacy and safety of TCM. This review introduces four multimodal integrated approaches that contribute to the discovery of more comprehensive and accurate Q-markers, thus aiding in the establishment of new quality control patterns based on the characteristics and principles of TCM. These include the whole-process quality control strategy, chemical-activity-based screening method, efficacy, safety, and consistent combination strategy, and TCM theory-guided approach. Furthermore, methodologies and representative examples of these strategies are described, and important future directions and questions in this field are also proposed.

Comparison of percutaneous transluminal angioplasty and surgical revision after intraoperative dilatation with biliary tract probes for arteriovenous fistula stenosis at juxta-anastomosis.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) is widely used for stenosis of vascular access (VA) for hemodialysis. We aimed to evaluate the effectiveness of both PTA and surgical revision after intraoperative dilatation with biliary tract probes for juxta-anastomotic stenosis in autogenous radiocephalic arteriovenous fistulas (RCAVFs). METHODS: We performed a retrospective analysis of PTA and surgical revision after intraoperative dilatation with biliary tract probes; these were the first interventions after RCAVF establishment in 112 patients with juxta-anastomotic stenosis. Anatomical (number of stenoses) and clinical variables (age and gender of the patient, time of hemodialysis, AVF age, presence of diabetes mellitus, and cause of end-stage renal disease) were reviewed. Technical success, clinical success, and post-intervention primary patency were evaluated. RESULTS: Our study enrolled 35 patients in the PTA group and 77 patients in the surgical revision group. Clinical and technical success rates of both groups were 100%. There were no complications, such as bleeding or hematomas. Using the Kaplan-Meier method, the post-intervention primary patency rates at 3, 6, 9, 12, 18, and 24 months in the PTA group were 100%, 94.28%, 77.1%, 60%, 54.29%, and 45.71%, respectively, and those in the surgical revision group were 100%, 94.81%, 92.2%, 90.91%, 81.82%, and 76.62%, respectively. The post-intervention primary patency rates at 9-24 months in the surgical revision group were significantly higher than those in the PTA group (χ2 = 19.04, p < 0.0001). CONCLUSION: The post-intervention long-term primary patency rate of surgical revision after intraoperative dilatation with biliary tract probes is higher than that of PTA for the first intervention of patients with juxta-anastomotic stenosis in RCAVFs. The surgical revision method is safe and effective, especially in hospitals that have not yet carried out PTA.

Iron Porphyrin as a Cytochrome P450 Model for the Degradation of Dye.

Organic dyes are widely used in the textile, biological, medical and other fields. However, a serious environmental problem has appeared because of the presence of organic dyes in industrial aqueous effluents. Thus, the efficient treatment of organic dyes in industrial wastewaters is currently in real demand. The current study investigated the oxidative degradation of the organic dye gentian violet by meso-tetra(carboxyphenyl) porphyriniron(III), [FeIII(TCPP)] as a cytochrome P450 model and iodosylbenzene (PhIO) as an oxidant at room temperature. The degradation reaction was monitored by UV-vis absorption spectroscopy via the observation of UV-vis spectral changes of the gentian violet. The results showed that the efficiency of catalyzed degradation reached more than 90% in 1 h, indicating the remarkable oxidative degradation capacity of the [FeIII(TCPP)]/PhIO system, which provided an efficient approach for the treatment of dyeing wastewater.

Angong Niuhuang Pill ameliorates cerebral ischemia/reperfusion injury in mice partly by restoring gut microbiota dysbiosis.

Angong Niuhuang Pill (ANP) is a famous traditional Chinese patent medicine and is used for treating ischemic or hemorrhagic stroke for centuries. However, the mechanism of action of ANP in stroke treatment has rarely been reported. With increasing evidence for a mechanistic link between acute ischemic stroke and gut microbiota alterations, this study aimed to determine the mechanism of action of ANP in treating acute ischemic stroke from the perspective of the gut microbiota. A mouse model of acute ischemic stroke by middle cerebral artery occlusion (MCAO) was established, and 16S ribosomal RNA (rRNA) gene sequencing and metabolomic analysis were performed on the cecal content samples collected from the sham, model, and ANP-treated MCAO mice. The results showed that ANP significantly ameliorated cerebral infarct volume, improved neurological deficits, and reduced histopathological injuries in the ipsilateral ischemic cortex, hippocampus, and striatum. The latter effects included inhibition of neuronal death, increased Nissl bodies, and decreased cell apoptosis. Moreover, ANP reversed gut microbiota dysbiosis by modulating the abundance of bacteria whose effects may mitigate MCAO damage, such as the phyla Bacteroidetes and Firmicutes, the families Lachnospiraceae and Prevotellaceae, and the genera Alloprevotella and Roseburia. Microbial metabolites related to inflammation and neuroprotection, such as prostaglandin I2 and uridine, were also regulated by ANP treatment. Uridine, guanosine, and inosine might be potential neuromodulators produced by the gut microbiota in the ANP-treated group. Spearman correlation analysis revealed that these metabolites were intimately related to certain genera, including Alloprevotella, Lachnoclostridium, Enterorhabdus, Roseburia, Lachnospiraceae_UCG-006, and Colidextribacter. Our results demonstrated that alleviating gut microbiota dysbiosis is one of the mechanisms by which ANP protects against ischemic stroke and suggest that targeting Alloprevotella, Lachnoclostridium, Enterorhabdus, Roseburia, Lachnospiraceae_UCG-006, and Colidextribacter might be a potential anti-stroke therapy.

Optimizing phenyl selenide-based BODIPYs as fluorescent probes for diagnosing cancer and drug-induced liver injury via cysteine.

Herein, by optimizing phenyl selenide-based BODIPYs, BDP-Se-MOS was obtained, which possessed resistance to ROS and could selectively detect Cys. BDP-Se-MOS could not only discriminate between normal and cancer cells, but also image Cys levels in tumor-bearing mice in real time as well as image the fluctuations of Cys levels in an APAP-induced DILI model.