Identification and validation of a signature based on myofibroblastic cancer-associated fibroblast marker genes for predicting prognosis, immune infiltration, and therapeutic response in bladder cancer.

PURPOSE: Myofibroblastic cancer-associated fibroblasts (myCAFs) are important components of the tumor microenvironment closely associated with tumor stromal remodeling and immunosuppression. This study aimed to explore myCAFs marker gene biomarkers for clinical diagnosis and therapy for patients with bladder cancer (BC). MATERIALS AND METHODS: BC single-cell RNA sequencing (scRNA-seq) data were obtained from the National Center for Biotechnology Information Sequence Read Archive. Transcriptome and clinical data were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Subsequently, univariate Cox and LASSO (Least Absolute Shrinkage and Selection Operator regression) regression analyses were performed to construct a prognostic signature. Immune cell activity was estimated using single-sample gene set enrichment analysis whilst the TIDE (tumor immune dysfunction and exclusion) method was employed to assess patient response to immunotherapy. The chemotherapy response of patients with BC was evaluated using genomics of drug sensitivity in cancer. Furthermore, Immunohistochemistry was used to verify the correlation between MAP1B expression and immunotherapy efficacy. The scRNA-seq data were analyzed to identify myCAFs marker genes. RESULTS: Combined with bulk RNA-sequencing data, we constructed a two-gene (COL6A1 and MAP1B) risk signature. In patients with BC, the signature demonstrated outstanding prognostic value, immune infiltration, and immunotherapy response. This signature served as a crucial guide for the selection of anti-tumor chemotherapy medications. Additionally, immunohistochemistry confirmed that MAP1B expression was significantly correlated with immunotherapy efficacy. CONCLUSIONS: Our findings revealed a typical prognostic signature based on myCAF marker genes, which offers patients with BC a novel treatment target alongside theoretical justification.

Scutellaria baicalensis Georgi alleviates Clostridium difficile associated diarrhea and its modulatory effects on the gut microbiota.

The growing incidence of Clostridium difficile associated diarrhea (CDAD) underscores the urgency for potent treatments. This research delves into the therapeutic potential of Scutellaria baicalensis Georgi (Lamiaceae) root (SR) in addressing CDAD and its influence on gut microbiota. Using a CDAD mouse model and fidaxomicin as a control, SR's impact was measured through diarrhea symptoms, colonic histopathology, and C. difficile toxin levels. Employing the PacBio platform, 16S rRNA full-length gene sequencing analyzed the gut microbial composition and the effect of SR. Results revealed SR considerably alleviated diarrhea during treatment and restoration phases, with a marked decrease in colonic inflammation. C. difficile toxin levels dropped significantly with SR treatment (P < 0.001). While SR didn't augment gut microbiota's overall abundance, it enhanced its diversity. It restored levels of Proteobacteria and Bacteroidetes, reduced Akkermansia spp. and Enterococcus spp. proportions, and modulated specific bacterial species' abundance. In essence, SR effectively mitigates CDAD symptoms, curtails inflammatory reactions, and beneficially restructures gut microbiota, suggesting its potential in advanced CDAD clinical intervention.

UPLC-MS based metabonomics revealed the protective effects of Buyang Huanwu decoction on ischemic stroke rats.

Objective: Storke is a leading cause of death and disability affecting million people worldwide, 80% of which is ischemic stroke (IS). Recently, traditional Chinese medicines (TCMs) have received great attentions in treating IS due to their low poisonous effects and high safety. Buyang Huanwu Decoction (BHD), a famous and classical Chinese prescription, has been used for treating stroke-induced disability for centuries. Yet, its underlying mechanism is still in fancy. Methods: We first constructed an IS model by middle cerebral artery occlusion (MCAO). Then, a metabonomics study on serum samples was performed using UHPLC-QTOF/MS, followed by multivariate data analysis including principal components analysis (PCA) and orthogonal partial least squares-discriminate analysis (OPLS-DA). Results: Metabolic profiling of PCA indicated metabolic perturbation caused by MCAO was regulated by BHD back to normal levels, which is in agreement with the neurobehavioral evaluations. In the OPLS-DA, 12 metabolites were screened as potential biomarkers involved in MCAO-induced IS. Three metabolic pathways were recognized as the most relevant pathways, involving one carbon pool by folate, sphingolipid metabolism and inositol phosphate metabolism. BHD significantly reversed the abnormality of 7 metabolites to normal levels. Conclusions: This is the first study to investigate the effect of BHD on IS at the metabolite level and to reveal the underlying mechanisms of BHD, which is complementary to neurobehavioral evaluation. In a broad sense, the current study brings novel and valuable insights to evaluate efficacy of TCMs, to interpret the action mechanisms, and to provide the theoretical basis for further research on the therapeutic mechanisms in clinical practice.

Development of standardized nursing terminology for the process documentation of patients with chronic kidney disease.

Introduction: European Nursing care Pathways (ENP) is a professional care language that utilizes software to map care processes and utilize the data for research purposes, process control, and personnel requirement calculations. However, there is a lack of internationally developed terminology systems and subset specifically designed for the nutritional management of CKD. The aim of this study was to create a subset of the standardized nursing terminology for nutrition management in patients with chronic kidney disease (CKD). Materials and methods: According to the guidelines for subset development, four research steps were carried out: (i) Translation of version 3.2 of the ENP (chapter on kidney diseases) and understanding of the framework structure and coding rules of the ENP; (ii) Identification of relevant six-dimensional nursing terms; (iii) Creation of a framework for the subset; (iv) Review and validation by experts. Results: A subset for CKD nutritional care was created as part of this project, comprising 630 terms, with 17 causal relationships related to nursing diagnoses, 115 symptoms, 31 causes, 34 goals/outcomes, 420 intervention specifications and 13 resources, including newly developed care terms. All terms within the subset have been created using a six-step maintenance procedure and a clinical standard pathway for nutrition management in the SAPIM mode. Implications for nursing practice: This terminology subset can facilitate standardized care reports in CKD nutrition management, which is used to standardize nursing practice, quantify nursing, services, guidance on care decisions, promoting the exchange and use of CKD nutrition data and serve as a reference for the creation of standardized subset of nursing terminology in China.

Prevalence and risk factors of exposure keratopathy among critically ill patients: A systematic review and meta-analysis.

AIMS: To identify the incidence, prevalence and risk factors of exposure keratopathy (EK) among critically ill patients. DESIGN: Systematic review and meta-analysis, in accordance with the PRISMA 2020 Statement. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China Knowledge Resource Integrated Database (CNKI), Chinese Biomedical Database (CBM), Weipu Database (VIP) and WanFang Database were systematically searched from inception to June 2022. Observational studies that reported EK among paediatric and adult critically ill patients were screened and included original articles based on the inclusion criteria. Two reviewers independently completed data extraction and quality assessments. Subgroup analysis investigated potential causes of heterogeneity. RESULTS: Of the 4508 studies identified, 23 studies involving 3519 subjects were included. The pooled prevalence of EK was 34.0%, and the pooled incidence rate of EK was 23.0%. Risk factors associated with EK in critically ill patients included lagophthalmos, chemosis, eye blinks <5 times per minute, mechanical ventilation, sedation, lower Glasgow Coma Scale (GCS) score and higher Acute Physiology and Chronic Health Evaluation (APACHE) II score. CONCLUSION: This review shows that EK rates are high in critically ill patients and are influenced by multiple factors. Medical staff should pay more attention to EK in critically ill patients, conduct professional evaluations and implement targeted eye care protocols to reduce its occurrence. IMPLICATIONS FOR PRACTICE: This study shows the frequency of and multiple risk factors for EK in critically ill patients, which provides evidence-based guidance for nurses to evaluate the risk of EK in critically ill patients and take appropriate precautions to reduce the risk. PROTOCOL REGISTRATION: The protocol was registered in PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42022346964). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Development and validation of the patient-reported outcome scale for chronic kidney disease.

PURPOSE: The patient-reported outcomes (PROs) measuring patient's experience and perception of disease are important components of approach to care. However, no tools are available to assess the PROs of chronic kidney disease (CKD). This study aims to develop and verify a PROs scale to evaluate clinical outcomes in CKD patients. METHODS: The theoretical structure model and original item pool were formed through a literature review, patient interviews and references to relevant scales. The Delphi method, classical test theory methods and item response theory method were used to select items and adjust dimensions to form the final scale. Altogether 360 CKD patients were recruited through convenience sampling. CKD-PROs could be evaluated from four aspects, namely reliability, content validity, construct validity, responsibility, and feasibility. RESULTS: The CKD-PROs scale covers 4 domains, including the physiological, psychological, social, and therapeutic domain, and 12 dimensions, 54 items. The Cronbach's α is 0.939, the split reliability coefficient is 0.945, and the correlation of the scores each item and domain's coefficients range from 0.413 to 0.669. The results of structure validity, content validity and reactivity showed that the multidimensional measurement of the scale met professional expectations. The recovery rate and effective rate of the scale were over 99%. CONCLUSION: The CKD-PROs scale has great reliability, validity, reactivity, acceptability and is capable of being used as one of the evaluation tools for the clinical outcomes of CKD patients.

Structural Elucidation and Cytotoxic Activity of New Monoterpenoid Indoles from Gelsemium elegans.

Two new monoterpenoid indole alkaloids, gelselegandines F (1) and G (2), were isolated from the aerial parts of Gelsemium elegans. Their structures were elucidated by means of spectroscopic techniques and quantum chemical calculations. The ECD calculations were conducted at the B3LYP/6-311G(d,p) level and NMR calculations were carried out using the Gauge-Including Atomic Orbitals (GIAO) method. Structurally, the two new compounds possessed rare, cage-like, monoterpenoid indole skeletons. All isolated compounds and the total alkaloids extract were tested for cytotoxicity against four different tumor cell lines. The total alkaloids extract of G. elegans exhibited significant antitumor activity with IC50 values ranging from 32.63 to 82.24 ug/mL. In order to discover anticancer leads from the active extraction, both new indole compounds (1-2) were then screened for cytotoxicity. Interestingly, compound 2 showed moderate cytotoxicity against K562 leukemia cells with an IC50 value of 57.02 uM.

Patellar Resurfacing in Primary Total Knee Arthroplasty: A Meta-analysis and Trial Sequential Analysis of 50 Randomized Controlled Trials.

OBJECTIVE: During total knee arthroplasty, femur and tibia parts are regularly replaced, while resurfacing the patellar or not is an ongoing discussion. To compare revision rate, anterior knee pain rate, patient-reported outcome measures, complication, radiographic, and clinical outcomes after patellar resurfacing versus non-resurfacing in total knee arthroplasty. METHODS: PubMed, Medline, EMBASE, CENTRAL, and CINAHL databases were searched on 25 April 2021 to enroll randomized controlled trials that compared patellar resurfacing versus non-resurfacing. We used the grading of recommendations assessment, development and evaluation (GRADE) framework to assess the certainty of evidence. Our primary outcome was revision rate and secondary outcomes was anterior knee pain rate. Outcomes were pooled using the random-effect model and presented as risk ratio (RR), or mean difference (MD), with 95% confidence interval (CI). RESULTS: Fifty studies (5586 knees) were included. Significant reductions in patellar revision rate (RR 0.41, 95% CI [0.19, 0.88]; P = 0.02; I2  = 24.20%) and non-patellar revision rate (RR 0.64, 95% CI [0.55, 0.75]; P < 0.001; I2  = 0%) were seen after patellar resurfacing. Patellar resurfacing significantly reduced the anterior knee pain rate than nonresurfacing (RR 0.72, 95% CI [0.57, 0.91]; P = 0.006; I2  = 69.5%). Significant differences in patient-reported outcome measures were found. However, these differences were inconsistent and lacked clinical importance. Patellar resurfacing resulted in a significant lower rate of patellar clunk (RR 0.58, 95% CI [0.38, 0.88]; P = 0.01; I2  = 0%), a higher patellar score (MD 1.24, 95% CI [0.67, 0.81]; P < 0.001; I2  = 73.8%), but prolonged surgical time (MD 8.59, 95% CI [5.27, 11.91]; P < 0.001; I2  = 88.8%). CONCLUSIONS: The clear relationship is that patellar resurfacing reduces revisions, anterior knee pain, and patellar clunk. It will be interesting to compare the initial cost with the revision cost when required and cost-utility analysis with long-term results in future studies.

Daily Walking Dose and Health-related Quality of Life in Patients With Chronic Kidney Disease.

OBJECTIVE: Exercise, like daily walking, may improve overall health and impede progression of chronic kidney disease (CKD); however, no specific walking dose has been recommended for patients with CKD. We aimed to investigate the association between daily walking steps and health-related quality of life (HRQOL) in adults with CKD. DESIGN AND METHODS: The walking steps of patients with CKD were extracted from the We Run mobile application. Their average daily walking steps were calculated and subdivided into the low-, middle-, and high-level groups. HRQOL was assessed using the physical component summary (PCS) and mental component summary (MCS) of the MOS 36 Short Form Health Survey (SF-36). RESULTS: A total of 558 adults (50.5%, men) with an average age of 40.2 (±13.8) years were enrolled. The median daily step count was 7,404 steps. The daily walking step count demonstrated an inverse U-shaped relationship with the SF-36 and subscale scores. Participants with daily walking steps between 7,000 and 12,000 have the highest PCS (68.1 ± 12.2) and MCS scores (70.0 ± 19.5). The multiple linear regression model showed that compared with patients with a daily step count of 7,000 to 12,000, patients with a daily step count >12,000 had a significantly lower MCS score (P < .001), while patients with a daily step count <7,000 had significantly lower PCS (P < .001) and MCS scores (P = .034). Moreover, the multivariable logistic regression model showed that patients with a daily step count >12,000 had significantly lower mental health-related quality (odds ratio [OR], 2.188; 95% confidence interval [CI], 1.079-1.439 for low MCS), while those with a daily step count <7,000 had a significantly lower HRQOL than the 7,000 to 12,000 daily step count group (OR, 2.113; 95% CI, 1.203-3.711 for low PCS; OR, 2.099; 95% CI, 1.210-3.643 for low MCS). CONCLUSIONS: These findings suggest that daily walking steps between 7,000 and 12,000 are associated with high HRQOL in adults with CKD.

Factors promoting shared decision-making in renal replacement therapy for patients with end-stage kidney disease: systematic review and qualitative meta-synthesis.

PURPOSE: Shared decision-making (SDM) about the type of renal replacement therapy to use is a matter of great importance involving patients, their families, and health treatment teams. This review aims to synthesize the volume of qualitative work explaining the factors influencing SDM regarding renal replacement therapy. METHODS: A systematic review and qualitative meta-synthesis approach recommended by JBI was used, six databases were searched. Studies were qualitative or mixed research published since 2000, with a primary focus on patient experiences, perceptions and practices regarding which method to choose for renal replacement therapy in End-Stage Kidney Disease (ESKD) patients. All themes were analyzed and compared to the established connectedness. RESULTS: A total of 1313 patients were enrolled in 32 studies focusing on factors associated with SDM regarding renal replacement therapy were included. All quality evaluations of the literature were medium to high. Four common themes were identified in our synthesis: (1) patient personal reasons, (2) family-related factors, (3) health care professional-related factors, and (4) social factors influence. CONCLUSION: The model proposes pathways that could be explored further in future qualitative and quantitative studies and suggests that patients' beliefs, emotions, and awareness should be targeted alongside patients' decision-making practices to increase the efficacy of interventions. The majority of studies included in this review focus on older patients, and all report patients' perspectives. Further research is required to understand the family member perspectives on SMD of renal replacement therapy.

Protective Effect of Fresh/Dry Dandelion Extracts on APAP-Overdose-Induced Acute Liver Injury.

OBJECITVIE: To compare the liver protective activity of fresh/dried dandelion extracts against acetaminophen (APAP)-induced hepatotoxicity. METHODS: Totally 90 Kunming mice were randomly divided into 10 groups according to body weight (9 mice for each group). The mice in the normal control and model (vehicle control) groups were administered sodium carboxymethyl cellulose (CMC-Na, 0.5%) only. Administration groups were pretreated with high and low-dose dry dandelion extract (1,000 or 500 g fresh herb dried and then decocted into 120 mL solution, DDE-H and DDE-L); low-, medium- and high-dose dandelion juice (250, 500, 1,000 g/120 mL, DJ-L, DJ-M, and DJ-H); fresh dandelions evaporation juice water (120 mL, DEJW); dry dandelion extract dissolved by pure water (1 kg/120 mL, DDED-PW); dry dandelion extract dissolved by DEJW (120 g/120 mL, DDED-DEJW) by oral gavage for 7 days at the dosage of 0.5 mL solution/10 g body weight; after that, except normal control group, all other groups were intraperitonealy injected with 350 mg/kg APAP to induce liver injury. Twenty hours after APAP administration, serum and liver tissue were collected and serum alanine aminotransferase (AST), aspartate transaminase (ALT), alkaline phosphatase (AKP), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) activities were quantified by biochemical kits; tumor necrosis factor (TNF-α), interleukin (IL)-2, and IL-1 ß contents in liver tissue were determined by enzyme linked immunosorbent assay kits. Histopathological changes in liver tissues were observed by hematoxylin and eosin staining; TUNEL Assay and Hoechst 33258 staining were applied for cell apoptosis evaluation. The expressions of heme oxygenase-1 (HO-1), nuclear factor erythroid-2-related factor 2 (Nrf-2), caspase-9, B-cell leukemia/lymphoma 2 (Bcl-2), Bax and p-JNK were determined by Western blot analysis. RESULTS: Pretreatment with fresh dandelion juice (FDJ, including DJ-L, DJ-M, DJ-H, DEJW and DDED-DEJW) significantly decreased the levels of serum ALT, AST, AKP, TNF-α and IL-1ß compared with vehicle control group (P<0.05 or P<0.01). Additionally, compared with the vehicle control group, FDJ decreased the levels of hepatic MDA and restored GSH levels and SOD activity in livers (P<0.05 or P<0.01). FDJ inhibited the overexpression of pro-inflammatory factors including cyclooxygenase-2 and inducible nitric oxide synthase in the liver tissues (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that FDJ pretreatment inhibited activation of apoptotic signaling pathways via decreasing of Bax, and caspase-9 and JNK protein expression, and inhibited activation of JNK pathway (P<0.05 or P<0.01). Liver histopathological observation provided further evidence that FDJ pretreatment significantly inhibited APAP-induced hepatocyte necrosis, inflammatory cell infiltration and congestion. CONCLUSIONS: FDJ pretreatment protects against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway, and the effect of fresh dandelion extracts was superior to dried dandelion extracts in APAP hepatotoxicity model mice.

A Sharp Estimate on the Transient Time of Distributed Stochastic Gradient Descent.

This paper is concerned with minimizing the average of n cost functions over a network in which agents may communicate and exchange information with each other. We consider the setting where only noisy gradient information is available. To solve the problem, we study the distributed stochastic gradient descent (DSGD) method and perform a non-asymptotic convergence analysis. For strongly convex and smooth objective functions, in expectation, DSGD asymptotically achieves the optimal network independent convergence rate compared to centralized stochastic gradient descent (SGD). Our main contribution is to characterize the transient time needed for DSGD to approach the asymptotic convergence rate. Moreover, we construct a "hard" optimization problem that proves the sharpness of the obtained result. Numerical experiments demonstrate the tightness of the theoretical results.

Loss of mpv17 affected early embryonic development via mitochondria dysfunction in zebrafish.

MVP17 encodes a mitochondrial inner-membrane protein, and mutation of human MVP17 can cause mitochondria DNA depletion syndrome (MDDS). However, the underlying function of mpv17 is still elusive. Here, we developed a new mutant with mpv17 knockout by using the CRISPR/Cas9 system. The mpv17-/- zebrafish showed developmental defects in muscles, liver, and energy supply. The mpv17-/- larvae hardly survived beyond a month, and they showed abnormal growth during the development stage. Abnormal swimming ability was also found in the mpv17-/- zebrafish. The transmission electron microscope (TEM) observation indicated that the mpv17-/- zebrafish underwent severe mitochondria dysfunction and the disorder of mitochondrial cristae. As an energy producer, the defects of mitochondria significantly reduced ATP content in mpv17-/- zebrafish, compared to wild-type zebrafish. We hypothesized that the disorder of mitochondria cristae was contributed to the dysfunction of muscle and liver in the mpv17-/- zebrafish. Moreover, the content of major energy depot triglycerides (TAG) was decreased dramatically. Interestingly, after rescued with normal exogenous mitochondria by microinjection, the genes involved in the TAG metabolism pathway were recovered to a normal level. Taken together, this is the first report of developmental defects in muscles, liver, and energy supply via mitochondria dysfunction, and reveals the functional mechanism of mpv17 in zebrafish.

Array Design of 300 GHz Dual-Band Microstrip Antenna Based on Dual-Surfaced Multiple Split-Ring Resonators.

To meet the increasing need of high-data-rate and broadband wireless communication systems, the devices and its circuits R&D under Millimeter, Sub-Millimeter, or even Terahertz (THz) frequency bands are attracting more and more attention from not only academic, but also industrial areas. Most of the former research on the THz waveband (0.1-10 THz) antenna design is mainly focused on realizing high directional gain, such as horn antennas, even though the coverage area is very limited when comparing with the current Wi-Fi system. One solution for the horizontally omnidirectional communication antenna is using the structure of multiple split-ring resonators (MSRRs). Aiming at this point, a novel 300 GHz microstrip antenna array based on the dual-surfaced multiple split-ring resonators (DSMSRRs) is proposed in this paper. By employing the two parallel microstrip transmission lines, different MSRRs are fed and connected on two surfaces of the PCB with a centrally symmetric way about them. The feeding port of the whole antenna is in between the centers of the two microstrip lines. Thus, this kind of structure is a so-called DSMSRR. Based on the different size of the MSRRs, different or multiple working wavebands can be achieved on the whole antenna. Firstly, in this paper, the quasi-static model is used to analyze the factors affecting the resonance frequency of MSRRs. Simulation and measured results demonstrate that the resonant frequency of the proposed array antenna is 300 GHz, which meets the design requirements of the expected frequency point and exhibits good radiation characteristics. Then, a dual-band antenna is designed on the above methods, and it is proved by simulation that the working frequency bands of the proposed dual-band antenna with reflection coefficient below -10 dB are 274.1-295.6 GHz and 306.3-313.4 GHz.

Compact Design of Annular-Microstrip-Fed mmW Antenna Arrays.

In this paper, a series of four novel microstrip antenna array designs based on different annular-microstrip feeding lines at 60-GHz millimeter wave (mmW) band are proposed, aiming at the potential usage of the mmW coverage antenna with multi-directional property. As the feeding network, the annular contour microstrip lines are employed to connect the patch units so as to form a more compact array. Our first design is to use an outer contour annular microstrip line to connect four-direction linear arrays composed of 1 × 3 rectangular patches, thus the gain of 8.4 dBi and bandwidth of over 300 MHz are obtained. Our second design is to apply the two-direction pitchfork-shaped array each made up of two same linear arrays as the above, therefore the gain of 9.65 dBi and bandwidth of around 250 MHz are achieved. Our third design is to employ dual (inner and outer contour) annular-microstrip feeding lines to interconnect the above four-direction linear arrays, while our fourth design is to bring bridged annular-microstrip feeding lines, both of which can realize the goal of multi-directional radiation characteristic and higher gain of over 10 dBi.

Complete chloroplast genome sequences of Lagotis brevituba (Plantaginaceae): a famous Tibetan medicine plant.

Lagotis brevituba is a famous Tibetan medicine plant and its complete chloroplast genome is determined in this study. The complete chloroplast genome is 152,967 bp in length, with a large single-copy (LSC) region of 83,740 bp, a small single copy (SSC) region of 17,845 bp, and a pair of inverted repeats (IRs) of 25,691 bp. The whole genome contained 131 genes, including 86 protein-coding genes, 37 tRNA genes and 8 rRNA genes. The phylogenetic tree showed that L. brevituba clustered with L. yunnanensis in family Plantaginaceae.

Chronic exposure to PPCPs mixture at environmentally relevant concentrations (ERCs) altered carbohydrate and lipid metabolism through gut and liver toxicity in zebrafish.

Pharmaceuticals and personal care products (PPCPs) have been widely distributed and posed ecotoxicological risks in the aquatic environment. This study aims to evaluate the toxic effects after chronic exposure to PPCPs mixture at the environment relevant concentrations (ERCs). Our results indicated that PPCPs induced serious metabolic effects by disturbing the carbohydrate and lipid metabolism pathways. Chronic exposure caused a significant reduction in the hepatosomatic index (HSI), the gut weight ratios, and histological alterations in liver and gut tissues. Further, exposure to the combined PPCPs disrupted the carbohydrate metabolism via significant upregulation of hk1, gk, pck1, and insr genes. The lipid metabolism was affected with higher ppars expression levels that increased the fatty acid ß-oxidation and ultimately decreased the lipidogenesis. Moreover, the altered responses of the insulin growth factor (IGF) pathway more in male gut tissue than that of female revealed sex-dependent disturbance in the gut homeostasis induced by PPCPs mixture. In conclusion, chronic exposure to PPCPs mixtures at ERCs can induce developmental effects and metabolic dysfunction in both male and female fish. The consumption and environmental disposal of these PPCPs should be regulated to ensure ecological health and environmental safety.

Role of manganese superoxide dismutase (Mn-SOD) against Cr(III)-induced toxicity in bacteria.

The toxicity of Cr(VI) was widely investigated, but the defense mechanism against Cr(III) in bacteria are seldom reported. Here, we found that Cr(III) inhibited bacterial growth and induced reactive oxygen species (ROS). After exposure to Cr(III), loss of sodA not only led to the excessive generation of ROS, but also enhanced the level of lipid peroxidation and reduced the GSH level, indicating that the deficiency of Mn-SOD decreased the bacterial resistance ability against Cr(III). The adverse effects of oxidative stress caused by Cr(III) could be recovered by the rescue of Mn-SOD in the sodA-deficient strain. Besides the oxidative stress, Cr(III) could cause the bacterial morphology variation, which was distinct between the wild-type and the sodA-deficient strains due to the differential expressions of Z-ring division genes. Moreover, Mn-SOD might prevent Cr(III) from oxidation on the bacterial surface by combining with Cr(III). Taken together, our results indicated that the Mn-SOD played a vital role in regulating the stress resistance, expression of cell division-related genes, bacterial morphology, and chemistry valence state of Cr. Our findings firstly provided a more in-depth understanding of Cr(III) toxicity and bacterial defense mechanism against Cr(III).

Target verification of allyl isothiocyanate on the core subunits of cytochrome c oxidase in Sitophilus zeamais by RNAi.

BACKGROUND: Allyl isothiocyanate (AITC) is a volatile organic compound with a potent insecticidal activity to the stored-grain pest Sitophilus zeamais Motschulsky, which severely damages grain storage and container transport worldwide. Our previous study showed that mitochondrial complex IV was the primary target of AITC in adult Sitophilus zeamais. To further verify the targets of AITC, we employed RNA interference (RNAi) by using double-stranded RNA (dsRNA) to knockdown three core subunits of cytochrome c oxidase (COX)-I, -II and -III in 18-day-old larvae prior to their exposure to AITC to detect susceptibility changes. RESULTS: The susceptibility of dsRNACOX-I and -II injection treatments to AITC significantly increased at 72 h while the mortality reached up to 85.56% and 67.78%, respectively, and dsRNACOX-I and dsRNACOX-II injection showed the same subcellular structural characteristics showing vacuolization and vague mitochondrial cristae and decrease of COX activity during AITC fumigation treatment, suggesting the potential of COX-I and COX-II as the targets of AITC. High mortality reached up to 75.55%, 71.88% and 82.22%, respectively, and the phenotype of larvae turning from milky white to dark brown in the thorax and death eventually was confirmed after dsRNACOX-I, -II and -III injection. CONCLUSION: COX-I and -II were elucidated as the potential targets of AITC and dsRNACOX-I, -II and -III have the potential to be developed into nucleic acid pesticides for their robust lethal effects and are worth pursuing for improving AITC fumigation activity in Sitophilus zeamais control. © 2020 Society of Chemical Industry.

Pharmacological effects of indole alkaloids from Alstonia scholaris (L.) R. Br. on pulmonary fibrosis in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Alstonia scholaris (L.) R. Br. (Apocynaceae) is a Dai folk medicine for the treatment of lung diseases in China. AIM OF THE STUDY: The present study investigated the anti-pulmonary fibrosis effects of total alkaloids (TA) and the potential active ingredients and its possible mechanism. MATERIALS AND METHODS: After intratracheal instillation of bleomycin (BLM, 5 mg/kg), mice were divided into ten groups, and orally treated with the corresponding samples once daily for 28 days. The effect of indole alkaloids was determined through analysis of cytokines, as well as histopathological examinations and gene expressions. RESULTS: Severe lung fibrosis was observed in the BLM-treated mice on day 28. However, the administration of TA significantly ameliorated the pathological changes in the lungs, decreased the content of Krebs von den Lungen-6, lactate dehydrogenase, transforming growth factor-ß (TGF-ß), hydroxyproline, type I collagen, and malonaldehyde, and enhanced the activity of superoxide dismutase in the serum and lung tissues. In addition, the enhanced TGF-ß and matrix metalloproteinase-1 (MMP-1) expressions in BLM-induced mice were obviously weakened by indole alkaloids, as well as the ratio of matrix metalloproteinase-1 to tissue inhibitor of metalloproteinase-1 was decreased. Moreover, picrinine and scholaricine yielded markedly better values in the aforementioned indices than those in other samples, indicating that they may be the active ingredients of alkaloids. CONCLUSIONS: TA exerted protective effects against BLM-induced pulmonary fibrosis by reducing collagen deposition through TGF-ß/MMP-1 pathway.