Toxic effects of the insecticide tolfenpyrad on zebrafish embryos: Cardiac toxicity and mitochondrial damage.

Tolfenpyrad, a highly effective and broad-spectrum insecticide and acaricide extensively utilized in agriculture, presents a potential hazard to nontarget organisms. This study was designed to explore the toxic mechanisms of tolfenpyrad on zebrafish embryos. Between 24 and 96 h after exposure of the fertilized embryos to tolfenpyrad at concentrations ranging from 0.001 to 0.016 mg/L (96 h-LC50 = 0.017 mg/L), lethal effects were apparent, accompanied with notable anomalies including pericardial edema, increased pericardial area, diminished heart rate, and an elongated distance between the venous sinus and the arterial bulb. Tolfenpyrad elicited noteworthy alterations in the expression of genes pertinent to cardiac development and apoptosis, with the most pronounced changes observed in the cardiac development-related genes of bone morphogenetic protein 2b (bmp2b) and p53 upregulated modulator of apoptosis (puma). The findings underscore that tolfenpyrad induces severe cardiac toxicity and mitochondrial damage in zebrafish embryos. This data is imperative for a comprehensive assessment of tolfenpyrad risks to aquatic ecosystems, particularly considering the limited knowledge regarding its detrimental impact on aquatic vertebrates.

KLF13 overexpression protects sepsis-induced myocardial injury and LPS-induced inflammation and apoptosis.

Sepsis remains a worldwide public health problem. This study aims to explore the role and mechanism of transcriptional factors (TFs) in sepsis-induced myocardial injury. Firstly, TF KLF13 was selected to explore its role in sepsis-induced myocardial injury. The caecal ligation and puncture (CLP) -induced sepsis mouse model was established and the septic mice were examined using standard histopathological methods. KLF13 expression was detected in the septic mouse heart and was also seen in a lipoploysaccharide (LPS) -induced cellular inflammation model. To explore this further both pro-apoptotic cleaved-caspase3/caspase3 and Bax levels and anti-apoptotic Bcl2 levels were examined, also in both models, In addition inflammatory cytokine (IL-1ß, TNF-α, IL-8 and MCP-1) production and IκB-α protein level and p65 phosphorylation were examined in both septic mice and LPS-induced cells. Thus three parameters - cardiomyocyte apoptosis, inflammatory response and NF-κB pathway activation were evaluated under similar conditions. The septic mice showed significant oedema, disordered myofilament arrangement and degradation and necrosis to varying degrees in the myocardial cells. KLF13 was downregulated in both the septic mouse heart and the LPS-induced cellular inflammation model. Furthermore, both models showed abnormally increased cardiomyocyte apoptosis (increased cleaved-caspase3/caspase and Bax protein levels and decreased Bcl2 level), elevated inflammation (increased production of inflammatory cytokines) and the activated NF-κB pathway (increased p65 phosphorylation and decreased IκB-α protein level). KLF13 overexpression notably ameliorated sepsis-induced myocardial injury in vivo and in vitro. KLF13 overexpression protected against sepsis-induced myocardial injury and LPS-induced cellular inflammation and apoptosis via inhibiting the inflammatory pathways (especially NF-κB signalling) and cardiomyocyte apoptosis.

Alteration in brain functional connectivity in patients with post-stroke cognitive impairment during memory task: A fNIRS study.

OBJECTIVE: This study attempted to evaluate the functional connectivity (FC) in relevant cortex areas during three memory tasks using the functional near-infrared spectroscopy (fNIRS) method to expound the neural mechanisms in individuals with post-stroke cognitive impairment (PSCI). METHODS: Short-term memory and visuospatial abilities were assessed using the clock drawing test, digit span test, and Corsi Block-tapping tests with simultaneous fNIRS. The oxygenated hemoglobin concentration signals were recorded from the bilateral motor sense cortex (LMS/RMS) and prefrontal lobe (LPFT/PFT/RPFT) of 19 subjects with cognitive impairment (PSCI group), 27 stroke subjects (STR group) and 26 healthy subjects (HC group). RESULTS: MMSE scores were positively correlated with the clock drawing test and digit span test scores but not with Corsi Block-tapping scores. During each test, functional connectivity between the bilateral MS (LMS/RMS) was highest within each group, but the functional connectivity between motor sense cortex and frontal lobe was lowest. PSCI group showed decreased FC between bilateral motor sense cortex (P < 0.05) and between motor sense cortex and frontal lobe (P > 0.05) during clock drawing test and Corsi Block-tapping test while decreased FC between each region of interest during digit span test with no significant difference. Functional connectivity levels were closely related to MMSE scores. CONCLUSIONS: Decreased functional connectivity level may be a marker of impaired cognitive function in post-stroke cognitive impairment. The fNIRS-based functional connectivity provides a non-invasive method to recognize cognitive impairment post-stroke. Functional connectivity changes may help to further understand the neural mechanisms of cognitive impairment post stroke.

Associations of oral health status and swallowing function with cognitive impairment in the aging population: a cross-sectional study.

BACKGROUND: The purpose of this study was to investigate the relationships of oral health status and swallowing function with cognitive impairment in community-dwelling older adults from Changsha, Hunan Province, China. METHODS: In this cross-sectional study, we analyzed the data of 215 participants aged ≥ 50 years which were retrieved from the Xiangya and Panasonic mild cognitive impairment (MCI) Study, a community-based study conducted among the residents of the urban areas of Hunan province in China. Demographic information of all participants was collected. We determined oral function by evaluating oral hygiene, oral dryness, occlusal force, tongue pressure, chewing function, swallowing function, remaining teeth number, and other indicators. The mini-mental state examination (MMSE) was used to screen for cognitive function. The relationship between each oral function evaluation item and cognitive function was investigated using correlation analysis. The associations between oral health status and swallowing function with cognitive impairment were inferred using multiple regression analysis. RESULTS: The general characteristics of participants showed statistically significant correlation coefficients in number of teeth remaining (p = 0.003) and number of teeth lost (p < 0.0001). Almost half of the 25 participants (48%) were aged from 70-80 years. Only 25 older adults (11.6% of the participants) were determined to have cognitive impairment by MMSE sores less than 24. Tongue pressure in male participants was the only significant independent variable that was associated with cognitive impairment (p = 0.01971). The results indicate that male participants with lower MMSE scores had a relative deficiency in tongue pressure. CONCLUSIONS: In this cross-sectional study, the oral health status and swallowing function of participants were in relatively good condition and showed low correlations with cognitive impairment. However, lower tongue pressures were associated with lower MMSE scores in males, indicating it could serve as a novel oral function index for evaluating cognitive impairment.

Ultrashort wave alleviates oxygen-glucose deprivation/reoxygenation injury via up-regulation of SPCA1 expression in N2a cells. / è¶ çŸ­æ³¢é€šè¿‡ä¸Šè°ƒSPCA1的表达减轻N2a细胞氧糖剥夺复氧后的损伤.

OBJECTIVES: Application of ultrashort wave (USW) to rats with cerebral ischemia and reperfusion injury could inhibit the decrease of expression of secretory pathway Ca2+-ATPase 1 (SPCA1), an important participant in Golgi stress, reduce the damage of Golgi apparatus and the apoptosis of neuronal cells, thereby alleviating cerebral ischemia-reperfusion injury. This study aims to investigate the effect of USW on oxygen-glucose deprivation/reperfusion (OGD/R) injury and the expression of SPCA1 at the cellular level. METHODS: N2a cells were randomly divided into a control (Con) group, an OGD/R group, and an USW group. The cells in the Con group were cultured without exposure to OGD. The cells in the OGD/R group were treated with OGD/R. The cells in the USW group were treated with USW after OGD/R. Cell morphology was observed under the inverted phase-contrast optical microscope, cell activity was detected by cell counting kit-8 (CCK-8), apoptosis was detected by flow cytometry, and SPCA1 expression was detected by Western blotting. RESULTS: Most of the cells in the Con group showed spindle shape with a clear outline and good adhesion. In the OGD/R group, cells were wrinkled, with blurred outline, poor adhesion, and lots of suspended dead cells appeared; compared with the OGD/R group, the cell morphology and adherence were improved, with clearer outlines and fewer dead cells in the USW group. Compared with the Con group, the OGD/R group showed decreased cell activity, increased apoptotic rate, and down-regulating SPCA1 expression with significant differences (all P<0.001); compared with the OGD/R group, the USW group showed increased cell activity, decreased apoptotic rate, and up-regulating SPCA1 expression with significant differences (P<0.01 or P<0.001). CONCLUSIONS: USW alleviates the injury of cellular OGD/R, and its protective effect may be related to its up-regulation of SPCA1 expression.

Functional near-infrared spectroscopy during motor imagery and motor execution in healthy adults. / 健康成人运动想象与运动执行期间的近红外脑功能成像.

OBJECTIVES: Studies on the influence of motor imagery (MI) on brain structure and function are limited to traditional imaging techniques and the mechanism for MI therapy is not clear. By observing the brain activation mode during MI and motor execution (ME) in healthy adults, this study aims to use near-infrared brain imaging technology to provide theoretical basis for the treatment of MI. METHODS: A total of 30 healthy adults recruited to the public from June 2021 to August 2021. The MI and ME of the right knee movement served as the task mode. Block design was repeated 5 times alternately in a 20 s task period and a 30 s resting period. The activation patterns of brain regions were compared between the 2 tasks, and the regression coefficient was calculated to reflect the activation intensity of each brain region by Nirspark and SPSS 23.0 softwares. RESULTS: Lane 2, 3, 4, 5, 7, 9, 19, 20, 21, 24, 25, 26, 27, 32, 33, and 34 were significantly activated during the ME task (P<0.05, corrected by FDR) and lane 2, 5, 9, 16, 27, 29, 33, 34, and 35 were significantly activated during the MI task (P<0.05, corrected by FDR). According to the channel brain region registration information, the brain region activation pattern was similar during both MI and ME tasks in healthy adults, including left primary motor cortex (LM1), left primary sensory cortex (LS1), prefrontal pole, Broca area, and right supramarginal gyrus. Both LM1 and left pre-motor cortex (LPMC) were activated during MI in healthy adults, whereas dorsolateral prefrontal cortex (DLPFC) and only LM1 of the motor region were activated during ME. Compared to MI, the activation intensity of left sensory and left motor cortex was significantly enhanced in ME, and that of left and right prefrontal cortex especially left and right pars triangularis Broca's area (P<0.001, corrected by FDR) were significantly enhanced. CONCLUSIONS: The rationality of MI therapy is proved by functional near-infrared spectroscopy. The involvement of DLPFC in motor decision-making may regulate the two-way feedback of premoter cortex-M1 during ME; and Broca area, closely related to the motor program understanding, participates in MI and ME.

Dual-logarithmic demodulation method application in a wide gas optical thickness range.

Direct absorption spectroscopy (DAS) is an extremely practical and effective technology to detect gas concentration in site applications. Dual-beam subtraction is one of the most common demodulation methods in DAS, yet this method cannot solve the problem of absolute absorption curve nonlinearization in a wide optical thickness range. A real-time and practical dual-logarithmic demodulation method is proposed and proved to be robust when the optical thickness is much greater than linear region. Moreover, the error of optical thickness peak is only 1.18% between the dual-logarithmic demodulation system and simulation after correcting the dual-beam subtraction demodulation system under a 300 K, 1 atm, and 3 m absorption path. When the range of optical thickness peak of acetylene is from 0.0252 to 2.5335 at 1532.83 nm, the peak voltages always maintain satisfactory linearity (R-square=0.9989).

Dual-beam antiphase method to improve the WMS measurement limit in long-distance methane detection.

Wavelength modulation spectroscopy (WMS) with second harmonic detection is an extremely effective technique to detect gases in site applications. However, the significant levels of nonlinear effects in a system give rise to high background signals that either limit detection sensitivity or distort the harmonic signals. This paper outlines the theory of WMS-involved background signals and focuses on the elimination of undesirable effects in the background. A real-time, long-distance methane sensor using a tunable diode laser near 1653.7 nm is developed to continuously monitor methane by using a variable optical attenuator to suppress the background. Trace methane detection experiments verify that the minimum detection limit of the system can be increased by 47.5 times compared to the traditional WMS method.

Effects of non-caloric ultrashort wave on the expression of CoQ10 and C1GALT1C1 in rats with cerebral ischemia reperfusion injury. / æ— çƒ­é‡è¶ çŸ­æ³¢å¯¹è„‘ç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ æ—©æœŸCoQ10和C1GALT1C1表达的影响.

OBJECTIVES: To examine the changes of coenzyme Q10 (CoQ10) and ß1,3-galactosyl transferase specific chaperone 1 (C1GALT1C1) in brain of rats with ischemic injury at different time points and to explore the protective mechanism of ultrashort wave (USW) on ischemic brain injury. METHODS: Fifty SD rats were randomly divided into 5 groups (n=10 per group): a sham group (control group) and 4 experimental group (ischemia for 2 h). The 4 experimental groups were set as a model 1 d group, a USW 1 d group, a model 3 d group and a USW 3 d group, respectively. Five rats were randomly selected for 2,3,5-triphenyltetrazoliumchloride (TTC) staining in each experimental group, and the remaining 5 rats were subjected to Western blotting and real-time PCR. The percentage of cerebral infarction volume and the relative expression level of CoQ10 and C1GALT1C1 in the brain were examined and compared. RESULTS: The infarct volume percentage after TTC staining was zero in the sham group. With the progress of disease and USW therapy, the infarct volume percentage was decreased in the experimental groups (all P<0.05); Western blotting and real-time PCR showed that the relative expression level of CoQ10 in the sham group was the highest, while in the experimental groups, the content of CoQ10 showed a upward trend with the extension of disease and USW therapy, with significant difference (all P<0.05). The relative expression level of C1GALT1C1 in the sham group was the lowest, but in the experimental groups, they showed a downward trend with the extension of disease and USW therapy, with significant difference (all P<0.05). CONCLUSIONS: Non-caloric USW therapy may upregulate the expression of CoQ10 to suppress the expression of C1GALT1C1 in rats, leading to alleviating cerebral ischemic reperfusion injury.

A new cyclic lipopeptide isolated from Bacillus amyloliquefaciens HAB-2 and safety evaluation.

Bacillus is the most widely studied biocontrol agent and has been extensively used in the development of biopesticides and fungicides. In this study, a new cyclic lipopeptide was isolated from Bacillus amyloliquefaciens HAB-2 by column chromatography on silica gel and Sephadex LH-20, and its structures was elucidated on the basis of spectroscopic analysis. This compound is a bacillomycin d-like compound, named as bacillomycin DC. The activity of bacillomycin DC was evaluated against C. gloeosporioides Penz. The median inhibitory concentration of bacillomycin DC was 1.21µg/mL. In addition, bacillomycin DC may have low toxicity to aquatic species as indicated by its 96h half maximum lethal concentration of 22.20µg/mL to zebrafish (Danio rerio). Our current study further provides evidence that bacillomycin DC is a potent fungicide against C. gloeosporioides Penz.

Developmental toxicity and inhibition of the fungicide hymexazol to melanin biosynthesis in zebrafish embryos.

Hymexazol is an efficacious and widely used fungicide. However, its environmental toxicological assessment has not been well documented. It had no report of its toxicity to fish embryo. Fish embryo acute toxicity tests are highly predictive of aquatic embryotoxicity outcome. In this study, zebrafish (Danio rerio) embryos were exposed to hymexazol at varying concentrations for the study of the developmental toxicity, melanin biosynthesis, biochemical and transcriptional endpoints. The embryotoxicity tests indicated that the 96h LC50 value of hymexazol was 649mg/L with a 95% confidence interval range of 632-667mg/L. Hymexazol at concentrations of 417-738mg/L decreased the heart rate and increased the voluntary swing. Hymexazol inhibited normal development at concentrations above 554mg/L. the 96h EC50 was 411mg/L. Hymexazol in a concentration range of 417-738mg/L induced cardiac edema and yolk sac edema. Exposure of hymexazol at such concentrations to zebrafish embryos for 48h decreased the pigment area density compared with the no hymexazol control. Tyrosinase activity was inhibited by hymexazol relative to the untreated control. The P53 mRNA expression level in embryos upon exposure to 480mg/L or greater of hymexazol was significantly higher than that of the control. The results indicated that hymexazol has quite low acute toxicity and low embryotoxicity to zebrafish.

The allelopathic effect and safety evaluation of 3,4-Dihydroxybenzalacetone on Microcystis aeruginosa.

Harmful algal blooms (HABs) has been a serious problem in recent years, because of large quantities of cyanobacterial in eutrophic water. We studied the effects of 3,4-Dihydroxybenzalacetone (DBL) and other four compounds (vanillic acid, ferulic acid, 3,5-Dichlorophenol and cupric sulfate) on Microcystis aeruginosa. The results showed that the growth of M. aeruginosa was significantly inhibited by all tested compounds with a half maximal effect concentration (EC50) of 5.2, 22.8, 54.7, 1.5, 0.3µg/mL, respectively. Our data also demonstrated that DBL triggered the generation of superoxide anion radicals (O2-). The O2- might induce a lipid peroxidation which may change cell membrane penetrability, thereby leading to the eventual death of M. aeruginosa. In addition, DBL may has few toxic to aquatic species as indicated by its 96h half maximum lethal concentration value to zebrafish (Danio rerio) was far higher than 128µg/mL. Our current study further provides evidence that some phenolic acids such as DBL may be a potential effective solution for aquatic management.

Investigation of Novel Pesticides with Insecticidal and Antifungal Activities: Design, Synthesis and SAR Studies of Benzoylpyrimidinylurea Derivatives.

In order to find pesticides with insecticidal and antifungal activities, a series of novel benzoyl pyrimidinylurea derivatives were designed and synthesized. All target compounds were identified by ¹H-NMR spectroscopy and HRMS. Insecticidal and antifungal activity of these compounds were evaluated and the structure-activity relationships (SAR) were clearly and comprehensively illustrated. Compound 7, with low toxicity to zebrafish (LC50 = 378.387 µg mL-1) showed 100% inhibition against mosquito (Culex pipiens pallens) at 0.25 µg mL-1. Both compounds 19 and 25 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 13 phytopathogenic fungi), which were better than those of the commercial pesticide pyrimethanil (>50% inhibitory activities against eight phytopathogenic fungi). Furthermore, compounds 19 and 25 exhibited protective activity against Sclerotinia sclerotiorum on leaves of Brassica oleracea L. during in vivo experiments.

Toxic effects of indoxacarb enantiomers on the embryonic development and induction of apoptosis in zebrafish larvae (Danio rerio).

Indoxacarb is a highly potent insecticide widely used to control Lepidoptera insects in vegetable, tea, cotton, and rice fields. It can run off into aquatic environments. It is consisted of two enantiomers. Environmental risks and aquatic toxicity of indoxacarb enantiomers have not been fully investigated. In this study, zebrafish (Danio rerio) embryos were exposed to varying concentrations of (-)-R-indoxacarb and (+)-S-indoxacarb until 96-h post-fertilization (hpf) to assess the embryonic toxicity. (-)-R-indoxacarb was 1.3-fold more toxic than (+)-S-isomer to zebrafish embryos at 96 hpf. (-)-R-indoxacarb exhibited reduction in body length and pericardial edema compared with (+)-S-indoxacarb. (-)-R-indoxacarb decreased the hatching rate sixfold greater than (+)-S-indoxacarb. The rate of pericardial edema induced by (-)-R-indoxacarb was 2.5 times greater than that by (+)-S-indoxacarb. The heart rate of the larvae exposed to (-)-R-indoxacarb was 30% lower than that to (+)-S-indoxacarb. In addition, exposure to the chiral isomers resulted in significant increases in apoptosis; interestingly (-)-R-indoxacarb induced apoptosis in the heart area, whereas (+)-S-indoxacarb induced apoptosis in the head area. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 7-16, 2017.

[Effect of high frequency electrotherapy on caspase-3 and ultra microstructure of hippocampus in rats following cerebral ischemia/reperfusion].

OBJECTIVE: To investigate the effect of high frequency electrotherapy (HFE) on rat hippocampus after cerebral ischemia/reperfusion (I/R).
 Methods: A rat model of cerebral I/R injury was established. The rats were randomly divided into a sham group, an I/R group and an HFE group. The HFE group received thearapy daily for different sessions for 1, 3, 7 d. Neuronal deficit score,neuron ultra microstructure in the hippocampus and caspase-3 protein expression were measured on 1 st, 3 th and 7th d.
 Results: Compared with the I/R group, the HFE group showed the decreased neurological deficit scores, with significant differences between the 2 groups (P<0.05). The injury in HFE group was reduced compared with that in the I/R group based on the electron microscope test, with significant difference. Caspase-3 protein in brain tissue in the HFE group also downregulated compared with that in the I/R group (P<0.05).
 Conclusion: High frequency electrotherapy can improve neural function, suppress caspase-3 expression and apoptosis in nerve cells and improve the ultra microstructure of neurons, displaying a protective effect on cerebral I/R injury in rats.

A New Approach of Short Wave Protection against Middle Cerebral Artery Occlusion/Reperfusion Injury via Attenuation of Golgi Apparatus Stress by Inhibition of Downregulation of Secretory Pathway Ca(2+)-ATPase Isoform 1 in Rats.

BACKGROUND: Short wave (SW), a pattern of electromagnetic therapy, achieves an oscillating electromagnetic field. It has been reported that it may have a potential effect on cerebral injury. The present study was designed to investigate the potential role and possible mechanism of SW in focal cerebral ischemia/reperfusion (I/R) injury in rats. Secretory pathway Ca(2+)/Mn(2+) ATPase isoform 1 is a major component of Golgi apparatus stress. It has been reported as representative of Golgi apparatus stress. METHODS: Up to 120 minutes of middle cerebral artery occlusion (MCAO) and reperfusion injury was induced in male Sprague-Dawley rats. Different sessions of SW daily were administered over head after reperfusion from day 1 to day 7. Functional recovery scores, survival rates, infarct volume analysis, electron microscope test, and western blotting studies were used to analyze the therapy. RESULTS: SW protected against neuronal death and apoptosis in cornu ammon 1 region of hippocampus by reducing neuronal deficit, infarct volume, and ultrastructure. SW partly inhibited upregulation of caspase3. In addition, the expression of secretory pathway Ca(2+)-ATPase isoform 1 (SPCA1) was upregulated by SW. CONCLUSIONS: Our data indicate that SW can be protected against focal cerebral I/R injury, and the influence on Golgi apparatus stress might provide us a new perspective in further study. To the authors' knowledge, this is the first report using SW to increase expression of SPCA1 indicating modulate Golgi apparatus stress in MCAO and reperfusion model.

[Reliability and validity of the Chinese Eating Assessment Tool (EAT-10) in evaluation of acute stroke patients with dysphagia].

OBJECTIVE: To study the reliability and validity of the Chinese Eating Assessment Tool (EAT-10) in evaluation of acute stroke patients with dysphagia.
 METHODS: The inpatients of stroke were assessed with Chinese EAT-10. As a golden standard for evaluation of dysphagia, videofluoroscopic swallow study (VFSS) test was used to judge the reliability and validity of EAT-10.
 RESULTS: A total of 130 qualified questionnaires were collected. The Cronbach's alpha coefficient for Chinese EAT-10 scale was 0.845. The total score of each item was related. The lowest or highest correlation coefficient for the item 2 or 3 was 0.271 or 0.772. The retest reliability was greater than 0.7, which met the requirements. According to the investigator consistency reliability test, the value collected from the investigator in the item 2 kept constant. The consistent correlation coefficient of the remaining nine items was more than 0.7. The consistency between each item and the mean score was high. The EAT-10 with the cut-off point at 1 was an optimal cut-off point. With the cut-off value of 1 (EAT-10 score ≥ 1), the sensitivity and specificity for EAT-10 was 77.9% and 66.1%, respectively. The positive predictive value (PPV) and negative value (NPV) was 71.6% and 73.2%, respectively, with 2.30 LHR+ and 0.33 LHR- for dysphagia. 
 CONCLUSION: The Chinese EAT-10 has a good reliability and validity in evaluation of the acute stroke patients with dysphagia. The sensitivity and negative value are the best with the cut-off value of 1 (EAT-10 score ≥ 1). It offers a good way to discriminate dysphagia, impaired efficacy, penetrations, and aspirations in acute stroke patients.

Golden bifid treatment regulates gut microbiota and serum metabolites to improve myocardial dysfunction in cecal ligation and puncture-induced sepsis mice.

Myocardial damage is a major consequence and a significant contributor to death in cases of sepsis, a severe infection characterized by a distinct inflammatory response and a potential threat to the patient's life. Recently, the effects of intestinal microbiota and serum metabolites on sepsis have garnered increasing attention. Herein, the effects of golden bifid treatment upon cecal ligation and puncture (CLP)-induced sepsis in mice as a model for myocardial dysfunction were explored. Our results demonstrated that golden bifid treatment partially improved myocardial dysfunction and apoptosis, cardiac inflammation and oxidative stress, and intestinal mucosal permeability and barrier dysfunction in CLP-induced sepsis mice. The intestinal microbiota diversity and abundance were also altered within sepsis mice and improved by golden bifid treatment. Mucispirillum schaedleri, Acinetobacter baumannii and Lactobacullus intestinalis were significantly correlated with heart damage markers, inflammatory factors, or oxidative stress indicators. Serum differential metabolite levels were also significantly correlated with these parameters. Altogether, golden bifid treatment might be an underlying approach for treating sepsis-induced myocardial dysfunction and highlight the underlying effect of intestinal microbiota and serum metabolites on the pathogenesis and treatment of sepsis-triggered myocardial dysfunction.

Combined toxicity of trifloxystrobin and fluopyram to zebrafish embryos and the effect on bone development.

Trifloxystrobin (TRI) is a methacrylate fungicide, and fluopyram (FLU) is a new pyridylethylbenzamide fungicide and nematicide. Both are often detected in water bodies and may be highly toxic to many aquatic organisms. Unfortunately, the aquatic biological risks of single FLU or a mixture of trifloxystrobin and fluopyram have not been reported. In this study, zebrafish was selected as the test organism to investigate the combined toxicity of trifloxystrobin and fluopyram to zebrafish. After zebrafish embryos exposed to three pesticide solutions, Alcian-blue staining, Alizarin-red staining and quantitative PCR (qPCR) were performed. The results indicated that 96h-LC50 of TRI was 0.159 mg·L-1 to zebrafish embryo, which was highly toxic. The 96h-LC50 of FLU to zebrafish embryos was 4.375 mg·L-1, being moderately toxic. The joint toxicity to zebrafish embryos(FLU at 96h-LC50 and TRI at 96h-LC50 in a 1:1 weight ratio to form a series of concentration treatment groups) was antagonistic. Both trifloxystrobin and fluopyram also inhibited the skeletal development of zebrafish and showed to be antagonistic. The results of qPCR indicated upregulations of different genes upon three different treatments. TRI mainly induced Smads up-expression, which may affect the BMP-smads pathway. FLU mainly induced an up-expression of extracellular BMP ligands and type I receptor (Bmpr-1a), which may affect the BMP ligand receptor pathway. The 1:1 mixture (weight ratio) of trifloxystrobin and fluopyram induced a reduction of the genes of extracellular BMP ligand (Smads) and type I receptor (Bmpr1ba), which may down-regulate BMP signaling and thus attenuating cartilage hyperproliferation, hypertrophy and mineralization. The results warren an interest in further studying the effect of the two fungicides in a mixture on zebrafish.

mTOR/ULK1 signaling axis mediated ultrashort wave regulation of autophagy to alleviate diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is closely related to autophagy and inflammation. The mTOR/unc-51 like autophagy activating kinase 1 (ULK1) signaling axis is involved in the regulation of autophagy. Ultrashort wave (USW) therapy has been extensively studied in inflammatory diseases. However, the therapeutic effect of USW on DKD and the role of the mTOR/ULK1 signaling axis in USW interventions remain uncertain. OBJECTIVES: This study aimed to explore the therapeutic effects of USW on DKD rats and the role of the mTOR/ULK1 signaling axis in USW interventions. MATERIAL AND METHODS: A DKD rat model was established using a high-fat diet (HFD)/sugar diet and streptozocin (STZ) induction. The optimal duration of USW intervention was determined using different USW treatments. The levels of metabolism, inflammation and fibrosis associated with kidney injury in rats were measured. Western blot analysis was performed on the related indexes of autophagy and the mTOR/ULK1 signaling axis. RESULTS: In DKD rats, microalbuminuria (MAU), glucose (GLU), creatinine (CRE), and blood urea nitrogen (BUN) levels decreased after the USW intervention. Levels of interleukin (IL)-1ß, inducible nitric oxide synthase (iNOS), immunoglobulin M (IgM), immunoglobulin G (IgG), IL-18, tumor necrosis factor alpha (TNF-α), and IL-6 decreased in the USW group compared to the model group. The IL-10 and arginase (Arg-1) levels were increased in the USW group. The content of fibrosis-related indexes (vascular endothelial growth factor (VEGF), fibronectin (FN), type IV collagen, and type I collagen) decreased in the urine of the DKD rats. After USW treatment, LC3B and Beclin1 levels increased, while the level of p62 decreased. The levels of nephrin, podocin and synaptopodin increased. Ultrashort wave could reduce p-mTOR/mTOR ratios and increase ULK1 expression. After the overexpression of ULK1, the levels of LC3B and Beclin1 were higher in the overexpression (oe)-ULK1 group than in the oe-negative control (NC) group, while the level of p62 decreased. After mTOR activation, LC3B and ULK1 expression decreased, while CRE, BUN, MAU, and GLU levels increased. CONCLUSIONS: Ultrashort wave alleviated kidney injury induced by the HFD/sugar diet and STZ. The USW intervention reversed the decreased autophagy levels in the DKD rats. The mTOR/ULK1 signaling axis mediated USW to promote autophagy.