Data_Sheet_1_Exercise-Generated β-Aminoisobutyric Acid (BAIBA) Reduces Cardiomyocyte Metabolic Stress and Apoptosis Caused by Mitochondrial Dysfunction Through the miR-208b/AMPK Pathway.docx

ObjectiveTo explore the cardioprotective effects of exercise-derived β-aminoisobutyric (BAIBA) on cardiomyocyte apoptosis and energy metabolism in a rat model of heart failure (HF).MethodsIn male Sprague-Dawley rats (8-week-old), myocardial infarction (MI) was used to induce HF by ligating the left anterior descending branch of the coronary artery. In the Sham group, the coronary artery was threaded but not ligated. After HF development, Sham and HF rats were exercised 60 min daily, 5 days/week on a treadmill for 8 weeks (50–60% maximal intensity) and exercise-induced cardiac remodeling after MI were assessed using echocardiography, hematoxylin and eosin (H&E), Masson's Trichrome, and TUNEL staining for the detection of apoptosis-associated factors in cardiac tissue. High-throughput sequencing and mass spectrometry were used to measure BAIBA production and to explore its cardioprotective effects and molecular actions. To further characterize the cardioprotective effects of BAIBA, an in vitro model of apoptosis was generated by applying H2O2 to H9C2 cells to induce mitochondrial dysfunction. In addition, cells were transfected with either a miR-208b analog or a miR-208b inhibitor. Apoptosis-related proteins were detected by Western Blotting (WB). ATP production was also assessed by luminometry. After administration of BAIBA and Compound C, the expression of proteins related to apoptosis, mitochondrial function, lipid uptake, and β-oxidative were determined. Changes in the levels of reactive oxygen species (ROS) were assessed by fluorescence microscopy. In addition, alterations in membrane potential (δψm) were obtained by confocal microscopy.ResultsRats with HF after MI are accompanied by mitochondrial dysfunction, metabolic stress and apoptosis. Reduced expression of apoptosis-related proteins was observed, together with increased ATP production and reduced mitochondrial dysfunction in the exercised compared with the Sham (non-exercised) HF group. Importantly, exercise increased the production of BAIBA, irrespective of the presence of HF. To assess whether BAIBA had similar effects to exercise in ameliorating HF-induced adverse cardiac remodeling, rats were treated with 75 mg/kg/ day of BAIBA and we found BAIBA had a similar cardioprotective effect. Transcriptomic analyses found that the expression of miR-208b was increased after BAIBA administration, and subsequent transfection with an miR-208b analog ameliorated both the expression of apoptosis-related proteins and energy metabolism in H2O2-treated H9C2 cells. In combining transcriptomic with metabolomic analyses, we identified AMPK as a downstream target for BAIBA in attenuating metabolic stress in HF. Further cell experiments confirmed that BAIBA increased AMPK phosphorylation and had a cardioprotective effect on downstream fatty acid uptake, oxidative efficiency, and mitochondrial function, which was prevented by the AMPK inhibitor Compound C.ConclusionExercise-generated BAIBA can reduce cardiomyocyte metabolic stress and apoptosis induced by mitochondrial dysfunction through the miR-208b/AMPK pathway.</p

Data_Sheet_3_Exercise-Generated β-Aminoisobutyric Acid (BAIBA) Reduces Cardiomyocyte Metabolic Stress and Apoptosis Caused by Mitochondrial Dysfunction Through the miR-208b/AMPK Pathway.docx

ObjectiveTo explore the cardioprotective effects of exercise-derived β-aminoisobutyric (BAIBA) on cardiomyocyte apoptosis and energy metabolism in a rat model of heart failure (HF).MethodsIn male Sprague-Dawley rats (8-week-old), myocardial infarction (MI) was used to induce HF by ligating the left anterior descending branch of the coronary artery. In the Sham group, the coronary artery was threaded but not ligated. After HF development, Sham and HF rats were exercised 60 min daily, 5 days/week on a treadmill for 8 weeks (50–60% maximal intensity) and exercise-induced cardiac remodeling after MI were assessed using echocardiography, hematoxylin and eosin (H&E), Masson's Trichrome, and TUNEL staining for the detection of apoptosis-associated factors in cardiac tissue. High-throughput sequencing and mass spectrometry were used to measure BAIBA production and to explore its cardioprotective effects and molecular actions. To further characterize the cardioprotective effects of BAIBA, an in vitro model of apoptosis was generated by applying H2O2 to H9C2 cells to induce mitochondrial dysfunction. In addition, cells were transfected with either a miR-208b analog or a miR-208b inhibitor. Apoptosis-related proteins were detected by Western Blotting (WB). ATP production was also assessed by luminometry. After administration of BAIBA and Compound C, the expression of proteins related to apoptosis, mitochondrial function, lipid uptake, and β-oxidative were determined. Changes in the levels of reactive oxygen species (ROS) were assessed by fluorescence microscopy. In addition, alterations in membrane potential (δψm) were obtained by confocal microscopy.ResultsRats with HF after MI are accompanied by mitochondrial dysfunction, metabolic stress and apoptosis. Reduced expression of apoptosis-related proteins was observed, together with increased ATP production and reduced mitochondrial dysfunction in the exercised compared with the Sham (non-exercised) HF group. Importantly, exercise increased the production of BAIBA, irrespective of the presence of HF. To assess whether BAIBA had similar effects to exercise in ameliorating HF-induced adverse cardiac remodeling, rats were treated with 75 mg/kg/ day of BAIBA and we found BAIBA had a similar cardioprotective effect. Transcriptomic analyses found that the expression of miR-208b was increased after BAIBA administration, and subsequent transfection with an miR-208b analog ameliorated both the expression of apoptosis-related proteins and energy metabolism in H2O2-treated H9C2 cells. In combining transcriptomic with metabolomic analyses, we identified AMPK as a downstream target for BAIBA in attenuating metabolic stress in HF. Further cell experiments confirmed that BAIBA increased AMPK phosphorylation and had a cardioprotective effect on downstream fatty acid uptake, oxidative efficiency, and mitochondrial function, which was prevented by the AMPK inhibitor Compound C.ConclusionExercise-generated BAIBA can reduce cardiomyocyte metabolic stress and apoptosis induced by mitochondrial dysfunction through the miR-208b/AMPK pathway.</p

Data_Sheet_2_Exercise-Generated β-Aminoisobutyric Acid (BAIBA) Reduces Cardiomyocyte Metabolic Stress and Apoptosis Caused by Mitochondrial Dysfunction Through the miR-208b/AMPK Pathway.docx

ObjectiveTo explore the cardioprotective effects of exercise-derived β-aminoisobutyric (BAIBA) on cardiomyocyte apoptosis and energy metabolism in a rat model of heart failure (HF).MethodsIn male Sprague-Dawley rats (8-week-old), myocardial infarction (MI) was used to induce HF by ligating the left anterior descending branch of the coronary artery. In the Sham group, the coronary artery was threaded but not ligated. After HF development, Sham and HF rats were exercised 60 min daily, 5 days/week on a treadmill for 8 weeks (50–60% maximal intensity) and exercise-induced cardiac remodeling after MI were assessed using echocardiography, hematoxylin and eosin (H&E), Masson's Trichrome, and TUNEL staining for the detection of apoptosis-associated factors in cardiac tissue. High-throughput sequencing and mass spectrometry were used to measure BAIBA production and to explore its cardioprotective effects and molecular actions. To further characterize the cardioprotective effects of BAIBA, an in vitro model of apoptosis was generated by applying H2O2 to H9C2 cells to induce mitochondrial dysfunction. In addition, cells were transfected with either a miR-208b analog or a miR-208b inhibitor. Apoptosis-related proteins were detected by Western Blotting (WB). ATP production was also assessed by luminometry. After administration of BAIBA and Compound C, the expression of proteins related to apoptosis, mitochondrial function, lipid uptake, and β-oxidative were determined. Changes in the levels of reactive oxygen species (ROS) were assessed by fluorescence microscopy. In addition, alterations in membrane potential (δψm) were obtained by confocal microscopy.ResultsRats with HF after MI are accompanied by mitochondrial dysfunction, metabolic stress and apoptosis. Reduced expression of apoptosis-related proteins was observed, together with increased ATP production and reduced mitochondrial dysfunction in the exercised compared with the Sham (non-exercised) HF group. Importantly, exercise increased the production of BAIBA, irrespective of the presence of HF. To assess whether BAIBA had similar effects to exercise in ameliorating HF-induced adverse cardiac remodeling, rats were treated with 75 mg/kg/ day of BAIBA and we found BAIBA had a similar cardioprotective effect. Transcriptomic analyses found that the expression of miR-208b was increased after BAIBA administration, and subsequent transfection with an miR-208b analog ameliorated both the expression of apoptosis-related proteins and energy metabolism in H2O2-treated H9C2 cells. In combining transcriptomic with metabolomic analyses, we identified AMPK as a downstream target for BAIBA in attenuating metabolic stress in HF. Further cell experiments confirmed that BAIBA increased AMPK phosphorylation and had a cardioprotective effect on downstream fatty acid uptake, oxidative efficiency, and mitochondrial function, which was prevented by the AMPK inhibitor Compound C.ConclusionExercise-generated BAIBA can reduce cardiomyocyte metabolic stress and apoptosis induced by mitochondrial dysfunction through the miR-208b/AMPK pathway.</p

DataSheet2_Comparative Analysis of the Efficacy and Safety of Different Traditional Chinese Medicine Injections in the Treatment of Cancer-Related Pain: A Bayesian Network Meta-Analysis.docx

Background: Given the limitations of three-step analgesic therapy and the extensive use of traditional Chinese medicine injections (TCMIs) for cancer-related pain (CRP), this network meta-analysis (NMA) aims to compare the efficacy and safety of different regimens of TCMIs for CRP.Methods: A literature search was conducted in seven electronic databases for all related articles published before 12 April 2021. Randomized controlled trials (RCTs) were screened by a prior eligible criteria. The quality of literature was evaluated by the Cochrane risk of bias tool. We used Stata 16.0 software to analyze data including total pain relief rate, quality of life, and the incidence of adverse reactions. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the interventions. Radar map was used to exhibit the most outstanding regimen for a certain outcome. Synthetic sorting bubble diagram was performed to show the relatively better regimen by integrating two or three outcomes.Results: A total of 84 RCTs involving 8,044 patients were included. The results indicated that YDZYR + AN (Yadanziyouru injection plus analgesic) ranked first for pain relief rate, closely followed by KLT + AN (Kanglaite injection plus analgesic). AD + AN (Aidi injection plus analgesic) ranked first for quality of life, KLT + AN following closely. The total adverse reaction rate of FFKS + AN (Fufangkushen injection plus analgesic) was the lowest, and the constipation rate of FFKS was the lowest. In terms of the incidence of nausea and vomiting, KLT + AN was the best choice. In the plots analysis, the results of integrated total incidence of adverse reactions and pain relief rate analysis indicated that FFKS + AN was the most appropriate regimen. Meanwhile, it had the lowest incidence of integrated constipation, nausea and vomiting, and total adverse reactions. KLT + AN was the best in alleviating pain and improving quality of life integrated outcomes.Conclusion: In conclusion, FFKS + AN was the best treatment regimen for the pain relief rate and total adverse reaction rate, and it was also the safest regimen for CRP treatment. KLT + AN was the most effective choice. Further, compared with analgesic treatment alone for patients with CRP, TCMIs + AN combination treatment strategies are significantly more effective. However, more high-quality RCTs are required to support these conclusions.Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/#recordDetails, https://www.crd.york.ac.uk/prospero/export_details_pdf.php), identifier (ChiCTR-ONC-CRD42021267829)</p

Fabrication of Coral-like Pd based Porous MnO₂ Nanosheet Arrays on Nickel Foam for Methanol Electrooxidation

Direct methanol fuel cells (DMFCs) have been seen as one of the desirable power sources, and the performance always depends on the ability of electrode materials to oxidize methanol. In this work, we report a novel electrode composed of coral-like Pd and porous MnO₂ nanosheet arrays on nickel foam (Pd–MnO₂/NF). MnO₂ and Pd are successively electrodeposited on NF with different concentrations of PdCl₂, which decides the shape of Pd and catalytic properties. Compared with Pd/NF, Pd–MnO₂/NF exhibits excellent catalytic performance and good stability for methanol oxidation in alkaline solution. The mass activity of Pd–MnO₂/NF with low Pd loading is 197.7 mA mg^–1, which is 2.3-fold higher than that of Pd/NF. The improvement of performance mainly comes from MnO₂, which supplies a number of oxygen atoms to reduce intermediates and enhance antipoisoning ability

Supplementary document for Ultracompact Vernier-effect-improved sensor by a single microfiber-knot resonator - 6263535.pdf

supplement materia

DataSheet1_Comparative Analysis of the Efficacy and Safety of Different Traditional Chinese Medicine Injections in the Treatment of Cancer-Related Pain: A Bayesian Network Meta-Analysis.docx

Background: Given the limitations of three-step analgesic therapy and the extensive use of traditional Chinese medicine injections (TCMIs) for cancer-related pain (CRP), this network meta-analysis (NMA) aims to compare the efficacy and safety of different regimens of TCMIs for CRP.Methods: A literature search was conducted in seven electronic databases for all related articles published before 12 April 2021. Randomized controlled trials (RCTs) were screened by a prior eligible criteria. The quality of literature was evaluated by the Cochrane risk of bias tool. We used Stata 16.0 software to analyze data including total pain relief rate, quality of life, and the incidence of adverse reactions. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the interventions. Radar map was used to exhibit the most outstanding regimen for a certain outcome. Synthetic sorting bubble diagram was performed to show the relatively better regimen by integrating two or three outcomes.Results: A total of 84 RCTs involving 8,044 patients were included. The results indicated that YDZYR + AN (Yadanziyouru injection plus analgesic) ranked first for pain relief rate, closely followed by KLT + AN (Kanglaite injection plus analgesic). AD + AN (Aidi injection plus analgesic) ranked first for quality of life, KLT + AN following closely. The total adverse reaction rate of FFKS + AN (Fufangkushen injection plus analgesic) was the lowest, and the constipation rate of FFKS was the lowest. In terms of the incidence of nausea and vomiting, KLT + AN was the best choice. In the plots analysis, the results of integrated total incidence of adverse reactions and pain relief rate analysis indicated that FFKS + AN was the most appropriate regimen. Meanwhile, it had the lowest incidence of integrated constipation, nausea and vomiting, and total adverse reactions. KLT + AN was the best in alleviating pain and improving quality of life integrated outcomes.Conclusion: In conclusion, FFKS + AN was the best treatment regimen for the pain relief rate and total adverse reaction rate, and it was also the safest regimen for CRP treatment. KLT + AN was the most effective choice. Further, compared with analgesic treatment alone for patients with CRP, TCMIs + AN combination treatment strategies are significantly more effective. However, more high-quality RCTs are required to support these conclusions.Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/#recordDetails, https://www.crd.york.ac.uk/prospero/export_details_pdf.php), identifier (ChiCTR-ONC-CRD42021267829)</p

Supplementary document for Ultracompact Vernier-effect-improved sensor by a single microfiber-knot resonator - 6237197.pdf

supplemental material

Anti-gastric cancer effect of Salidroside through elevating miR-99a expression

Salidroside is an active ingredient extracted from Rhodiola rosea that has anti-tumor activities. The current paper attempted to assess the impact of Salidroside on gastric cancer (GC) and explore the potential mechanism. GC cell lines (SNU-216 and MGC803) and gastric epithelial cell line GES-1 were treated with Salidroside. CCK-8 assay, colony formation assay, flow cytometry and Transwell assay were respectively performed to evaluate GC cells phenotype. qRT-PCR and western blot were conducted to reveal the downstream genes and signaling of Salidroside. We found that 800 μM Salidroside was capable of reducing GC cells viability, while has no such impacts on GES-1 cells. Salidroside inhibited GC cells proliferation, migration, invasion and promoted apoptosis, which coupled with the down-regulation of p21, Bcl-2, MMP2, RhoA, p-ROCK1, Vimentin and the up-regulations of CyclinD1, Bax, cleaved caspases. miR-99a was found to be highly expressed in response to Salidroside treatment. Besides, the inhibition of MAPK/ERK and PI3K/AKT signaling induced by Salidroside was attenuated by miR-99a silence and in this process, IGF1R worked as a target of miR-99a. The anti-GC effect of Salidroside was also confirmed in a mouse model of GC. The promoting effect of Salidroside on miR-99a expression was also verified in vivo. Furthermore, Salidroside promoted the cisplatin-sensitivity of SGC7901/DDP cells. In conclusion, this study demonstrated that Salidroside possessed anti-GC effects through regulating miR-99a/IGF1R axis and inhibiting MAPK/ERK and PI3K/AKT pathways.</p

Thermodynamic Regulation of Dendrite-Free Li Plating on Li₃Bi for Stable Lithium Metal Batteries

Rechargeable batteries with metallic lithium (Li) anodes are attracting ever-increasing interests because of their high theoretical specific capacity and energy density. However, the dendrite growth of the Li anode during cycling leads to poor stability and severe safety issues. Here, Li3Bi alloy coated carbon cloth is rationally chosen as the substrate of the Li anode to suppress the dendrite growth from a thermodynamic aspect. The adsorption energy of a Li atom on Li3Bi is larger than the cohesive energy of bulk Li, enabling uniform Li nucleation and deposition, while the high diffusion barrier of the Li atom on Li3Bi blocks the migration of adatoms from adsorption sites to the regions of fast growth, which further ensures uniform Li deposition. With the dendrite-free Li deposition, the composite Li/Li3Bi anode enables over 250 cycles at an ultrahigh current density of 20 mA cm–2 in a symmetrical cell and delivers superior electrochemical performance in full batteries