DataSheet1_The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials.docx

Aims: Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have a potential cardiovascular and renal protective effect in type 2 diabetes. The aim of this meta-analysis was to quantify the effects of SGLT2 inhibitors on biomarkers of inflammation in randomized controlled trials (RCTs).Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were searched for eligible RCTs of adults with type 2 diabetes (T2D) with no time limit (updated to 12 October 2022). The biomarkers selected included C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, ferritin, plasminogen activator inhibitor (PAI)-1, and vascular cell adhesion molecule-1. Data were analyzed using a random-effect model in Review Manager 5.4.Results: Thirty-four studies with 6,261 patients (68.6% male) were eligible for this meta-analysis. The mean age of the participants was 62.57(±11.13) years old, and the median treatment duration length with follow-up was 24 weeks. Generally, the included trials were of good methodological quality. The meta-analysis revealed that ferritin levels were significantly reduced in SGLT2 inhibitor treatment groups versus placebo or standard diabetes therapies (SMD: −1.21; 95% CI: −1.91, −0.52, p Conclusion: This analysis provides strong evidence supporting anti-inflammatory effects of SGLT2 inhibitors in T2D subjects. The mechanisms and possible targets for the inflammation reducing and cardiorenal protective properties of SGLT2 inhibitors remain to be explored.</p

Table_5_A high-fat diet disrupts the hepatic and adipose circadian rhythms and modulates the diurnal rhythm of gut microbiota-derived short-chain fatty acids in gestational mice.XLSX

The prevalence of gestational obesity has reached epidemic proportions. Evidence supported that the interactions between the gut microbiota and circadian clocks far reached, affecting host metabolism. Our study aimed to investigate the effect of a high-fat diet (HF) on the hepatic and adipose circadian rhythms in gestational mice and to explore the role of gut microbiota-derived short-chain fatty acids (SCFAs) in mediating the effects. C57BL/6 female mice were randomly fed a standard chow diet (Ctr) or HF prior to and during pregnancy. Samples were collected every 4 h over 24 h (six time points), and 16S rRNA and metabonomics were carried out. Rhythmic patterns were identified and compared using CircaCompare. The results showed that the HF before and during pregnancy significantly induced obesity and worsen glucose tolerance, insulin sensitivity, and lipid metabolism in the gestational mice. Furthermore, the HF significantly disrupted the rhythmic pattern of hepatic and adipose circadian clock genes and downstream metabolic genes. Importantly, our results revealed that the HF altered the diurnal rhythm of the gut microbiota in a diverse manner, which was assessed across three categories: phase shift, loss rhythmicity, and gained rhythmicity. We report here, for the first time, a parallel alteration of the rhythmic phase of butyric acid and butyrate-producing Clostridiaceae_1, which was confirmed by a positive correlation between them. Overall, our research emphasized the importance of the rhythmicity of gut microbiota-derived SCFAs in mediating circadian disruption in response to the HF in gestational mice, which may provide novel insights into the prevention and treatment of gestational obesity.</p

Table_2_A high-fat diet disrupts the hepatic and adipose circadian rhythms and modulates the diurnal rhythm of gut microbiota-derived short-chain fatty acids in gestational mice.XLSX

The prevalence of gestational obesity has reached epidemic proportions. Evidence supported that the interactions between the gut microbiota and circadian clocks far reached, affecting host metabolism. Our study aimed to investigate the effect of a high-fat diet (HF) on the hepatic and adipose circadian rhythms in gestational mice and to explore the role of gut microbiota-derived short-chain fatty acids (SCFAs) in mediating the effects. C57BL/6 female mice were randomly fed a standard chow diet (Ctr) or HF prior to and during pregnancy. Samples were collected every 4 h over 24 h (six time points), and 16S rRNA and metabonomics were carried out. Rhythmic patterns were identified and compared using CircaCompare. The results showed that the HF before and during pregnancy significantly induced obesity and worsen glucose tolerance, insulin sensitivity, and lipid metabolism in the gestational mice. Furthermore, the HF significantly disrupted the rhythmic pattern of hepatic and adipose circadian clock genes and downstream metabolic genes. Importantly, our results revealed that the HF altered the diurnal rhythm of the gut microbiota in a diverse manner, which was assessed across three categories: phase shift, loss rhythmicity, and gained rhythmicity. We report here, for the first time, a parallel alteration of the rhythmic phase of butyric acid and butyrate-producing Clostridiaceae_1, which was confirmed by a positive correlation between them. Overall, our research emphasized the importance of the rhythmicity of gut microbiota-derived SCFAs in mediating circadian disruption in response to the HF in gestational mice, which may provide novel insights into the prevention and treatment of gestational obesity.</p

Table_1_A high-fat diet disrupts the hepatic and adipose circadian rhythms and modulates the diurnal rhythm of gut microbiota-derived short-chain fatty acids in gestational mice.DOCX

The prevalence of gestational obesity has reached epidemic proportions. Evidence supported that the interactions between the gut microbiota and circadian clocks far reached, affecting host metabolism. Our study aimed to investigate the effect of a high-fat diet (HF) on the hepatic and adipose circadian rhythms in gestational mice and to explore the role of gut microbiota-derived short-chain fatty acids (SCFAs) in mediating the effects. C57BL/6 female mice were randomly fed a standard chow diet (Ctr) or HF prior to and during pregnancy. Samples were collected every 4 h over 24 h (six time points), and 16S rRNA and metabonomics were carried out. Rhythmic patterns were identified and compared using CircaCompare. The results showed that the HF before and during pregnancy significantly induced obesity and worsen glucose tolerance, insulin sensitivity, and lipid metabolism in the gestational mice. Furthermore, the HF significantly disrupted the rhythmic pattern of hepatic and adipose circadian clock genes and downstream metabolic genes. Importantly, our results revealed that the HF altered the diurnal rhythm of the gut microbiota in a diverse manner, which was assessed across three categories: phase shift, loss rhythmicity, and gained rhythmicity. We report here, for the first time, a parallel alteration of the rhythmic phase of butyric acid and butyrate-producing Clostridiaceae_1, which was confirmed by a positive correlation between them. Overall, our research emphasized the importance of the rhythmicity of gut microbiota-derived SCFAs in mediating circadian disruption in response to the HF in gestational mice, which may provide novel insights into the prevention and treatment of gestational obesity.</p

Table_4_A high-fat diet disrupts the hepatic and adipose circadian rhythms and modulates the diurnal rhythm of gut microbiota-derived short-chain fatty acids in gestational mice.XLSX

The prevalence of gestational obesity has reached epidemic proportions. Evidence supported that the interactions between the gut microbiota and circadian clocks far reached, affecting host metabolism. Our study aimed to investigate the effect of a high-fat diet (HF) on the hepatic and adipose circadian rhythms in gestational mice and to explore the role of gut microbiota-derived short-chain fatty acids (SCFAs) in mediating the effects. C57BL/6 female mice were randomly fed a standard chow diet (Ctr) or HF prior to and during pregnancy. Samples were collected every 4 h over 24 h (six time points), and 16S rRNA and metabonomics were carried out. Rhythmic patterns were identified and compared using CircaCompare. The results showed that the HF before and during pregnancy significantly induced obesity and worsen glucose tolerance, insulin sensitivity, and lipid metabolism in the gestational mice. Furthermore, the HF significantly disrupted the rhythmic pattern of hepatic and adipose circadian clock genes and downstream metabolic genes. Importantly, our results revealed that the HF altered the diurnal rhythm of the gut microbiota in a diverse manner, which was assessed across three categories: phase shift, loss rhythmicity, and gained rhythmicity. We report here, for the first time, a parallel alteration of the rhythmic phase of butyric acid and butyrate-producing Clostridiaceae_1, which was confirmed by a positive correlation between them. Overall, our research emphasized the importance of the rhythmicity of gut microbiota-derived SCFAs in mediating circadian disruption in response to the HF in gestational mice, which may provide novel insights into the prevention and treatment of gestational obesity.</p

Table_3_A high-fat diet disrupts the hepatic and adipose circadian rhythms and modulates the diurnal rhythm of gut microbiota-derived short-chain fatty acids in gestational mice.XLSX

The prevalence of gestational obesity has reached epidemic proportions. Evidence supported that the interactions between the gut microbiota and circadian clocks far reached, affecting host metabolism. Our study aimed to investigate the effect of a high-fat diet (HF) on the hepatic and adipose circadian rhythms in gestational mice and to explore the role of gut microbiota-derived short-chain fatty acids (SCFAs) in mediating the effects. C57BL/6 female mice were randomly fed a standard chow diet (Ctr) or HF prior to and during pregnancy. Samples were collected every 4 h over 24 h (six time points), and 16S rRNA and metabonomics were carried out. Rhythmic patterns were identified and compared using CircaCompare. The results showed that the HF before and during pregnancy significantly induced obesity and worsen glucose tolerance, insulin sensitivity, and lipid metabolism in the gestational mice. Furthermore, the HF significantly disrupted the rhythmic pattern of hepatic and adipose circadian clock genes and downstream metabolic genes. Importantly, our results revealed that the HF altered the diurnal rhythm of the gut microbiota in a diverse manner, which was assessed across three categories: phase shift, loss rhythmicity, and gained rhythmicity. We report here, for the first time, a parallel alteration of the rhythmic phase of butyric acid and butyrate-producing Clostridiaceae_1, which was confirmed by a positive correlation between them. Overall, our research emphasized the importance of the rhythmicity of gut microbiota-derived SCFAs in mediating circadian disruption in response to the HF in gestational mice, which may provide novel insights into the prevention and treatment of gestational obesity.</p

Sequential Construction Strategy for Rational Design of Luminescent Iridacycles

A convenient and general strategy has been developed to synthesize stable iridapolycycles <b>5</b>–<b>8</b>. Reaction of arylacetylenes with iridium-hydride complex [IrH­(CO)­Cl­(PPh₃)₃]­BF₄ via nucleophilic addition, oxidative decarbonylation, and C–H bond activation results in the formation of a series of iridacyclopentadiene derivatives, including benzo-iridacyclopentadiene <b>5</b>, naphtho-iridacyclopentadiene <b>6</b>, pyreno-iridacyclopentadiene <b>7</b>, and thieno-iridacyclopentadiene <b>8</b>. These iridapolycycles display high thermal and air stability yet can be further functionalized via facile ligand substitution reactions. As an example, complex <b>5</b> was used as a metallosynthon to react with 2,2′-dipyridyl to give intensely luminescent Ir­(III) complex <b>9</b> bearing one C^∧C and one N^∧N ligands. Density functional theory (DFT) calculations reveal that the lowest unoccupied molecular orbitals (LUMOs) of iridapolycycles <b>5</b>–<b>8</b> are located on the phosphonium groups while the highest occupied molecular orbitals (HOMOs) are mainly located on the metal-embedded C^∧C frameworks. Our method offers a sequential construction strategy for constructing luminescent iridacycles, which potentially allows facile tuning of the photoluminescence properties by modulating the C^∧C and N^∧N moieties independently

Sequential Construction Strategy for Rational Design of Luminescent Iridacycles

A convenient and general strategy has been developed to synthesize stable iridapolycycles <b>5</b>–<b>8</b>. Reaction of arylacetylenes with iridium-hydride complex [IrH­(CO)­Cl­(PPh₃)₃]­BF₄ via nucleophilic addition, oxidative decarbonylation, and C–H bond activation results in the formation of a series of iridacyclopentadiene derivatives, including benzo-iridacyclopentadiene <b>5</b>, naphtho-iridacyclopentadiene <b>6</b>, pyreno-iridacyclopentadiene <b>7</b>, and thieno-iridacyclopentadiene <b>8</b>. These iridapolycycles display high thermal and air stability yet can be further functionalized via facile ligand substitution reactions. As an example, complex <b>5</b> was used as a metallosynthon to react with 2,2′-dipyridyl to give intensely luminescent Ir­(III) complex <b>9</b> bearing one C^∧C and one N^∧N ligands. Density functional theory (DFT) calculations reveal that the lowest unoccupied molecular orbitals (LUMOs) of iridapolycycles <b>5</b>–<b>8</b> are located on the phosphonium groups while the highest occupied molecular orbitals (HOMOs) are mainly located on the metal-embedded C^∧C frameworks. Our method offers a sequential construction strategy for constructing luminescent iridacycles, which potentially allows facile tuning of the photoluminescence properties by modulating the C^∧C and N^∧N moieties independently