Gut microbiota dysbiosis is associated with sepsis-induced cardiomyopathy in patients: A case-control study.

BACKGROUND: Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis-induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM. METHODS: A case-control and single-center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis-uninduced cardiomyopathy patients (SNICM, n = 16). RESULTS: Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28-day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM. CONCLUSIONS: SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.

Relationship between red blood cell distribution width-to-albumin ratio and outcome of septic patients with atrial fibrillation: a retrospective cohort study.

BACKGROUND: This retrospective cohort study aimed to investigate the association between red blood cell distribution width-to-albumin ratio (RAR) and in-hospital mortality in patients with sepsis and atrial fibrillation (AF). METHODS: Data were obtained from the Medical Information Mart for the Intensive Care Database IV database version 1.0. Multivariate Cox regression models, curve-fitting, and Kaplan-Meier analyses were performed to determine the correlation between RAR and in-hospital mortality in patients with sepsis and AF. RESULTS: This study included 3042 patients with sepsis and AF. Confounding variables were adjusted for in the Multivariable Cox regression analysis models. RAR was independently associated with in-hospital mortality (hazard ratio 1.06; 95% confidence interval 1.03-1.08; p < 0.001). A linear relationship was found between the RAR and in-hospital mortality in patients with sepsis and AF. CONCLUSION: Elevated RAR levels are associated with increased in-hospital mortality in patients with sepsis and AF. Further research is required to confirm this association.

The role of the cd99l2 gene on leukocyte interstitial migration in zebrafish.

Leukocytes play an essential role in ontogeny, tissue regeneration, and innate and adaptive immunity. The migration of leukocytes to the infected or traumatized areas is necessary for their immune response function. As an adhesion molecule, CD99L2 is crucial in the extravasation of leukocytes, however, its role in the interstitial migration of leukocytes remains unclear. In this study, the cd99l2 gene was knock-out by TALEN (transcription activator-like effector nuclease) in zebrafish and discovered that the deletion had no effect on zebrafish development. The number of granulocytes and macrophages recruited to the wounded tissue was significantly reduced in the cd99l2 mutants following caudal fin damage. Further research revealed that the expression of mfap4 was drastically decreased in the cd99l2 mutants, which may be one of the reasons that affect the migration of macrophages to the wound site. Moreover,transgenic lines with labeled vasculature, neutrophils and macrophages demonstrated that neutrophils and macrophages migrate throughout the interstitial space to the wound tissue in both wild-type and mutant zebrafish at 60 hours post-fertilization, indicating that the cd99l2 gene is involved in the interstitial migration of leukocytes. Finally, RNA transcription, protein folding, and the P450 pathway were enriched in cd99l2 mutants by RNA-seq analysis. Previous research had demonstrated that the regulation of transcription and signal transduction could be affected by adhesion molecules, which may suggest that the cd99l2 gene is involved in the cascade signaling pathway of leukocyte migration as an adhesion molecule. In conclusion, this study uncovered a novel function of the cd99l2 gene in the process of leukocyte migration in zebrafish, which is expected to provide a theoretical foundation for inflammatory and immune-related diseases.

Single-walled carbon nanotubes as delivery vehicles enhance the immunoprotective effect of an immersion DNA vaccine against infectious spleen and kidney necrosis virus in mandarin fish.

As a high mortality disease, Infectious spleen and kidney necrosis virus (ISKNV) can cause massive economic damage on mandarin fish farming industry in China, which seriously hindered the development of mandarin fish farming industry. In this research, SWCNTs (single-walled carbon nanotubes) as a candidate for DNA vaccine carrier was vaccinated by immersion (1, 2, 5, 10, 20 mg/L) in juvenile mandarin fish. In muscle, spleen and kidney tissues, the results showed that transcription and expression of MCP gene can be detected in pcDNA-MCP and SWCNTs-pcDNA-MCP groups after bath immunization. The immune response (immune-related genes expression, serum antibody production, enzyme activities and C3 content) was significantly enhanced in fish which vaccinated with SWCNTs-pcDNA-MCP in comparison with those vaccinated with pcDNA-MCP alone. After 14 d challenge, the RPS (relative percentage survival) can be enhanced which using SWCNTs as a carrier in SWCNTs-pcDNA-MCP (82.4%) group at 20 mg/L (the highest vaccine dose) than the naked pcDNA-MCP (54.2%) group. This study reveals that functionalized SWCNTs could be a promising immersion DNA vaccine carrier in aquaculture.

Immersion vaccination of Mandarin fish Siniperca chuatsi against infectious spleen and kidney necrosis virus with a SWCNTs-based subunit vaccine.

Infectious spleen and kidney necrosis virus (ISKNV) cause a high mortality disease which lead to significant economic loss on mandarin fish in China. There is no effective drug or vaccine against this fatal disease at present. Meanwhile, many drugs and vaccines had no effect in many cases account of several impenetrable barriers (cell, skin and gastrointestinal tract). Here we reported an immersion subunit vaccine system (SWCNTs-MCP) encoding MCP gene of ISKNV based on single-walled carbon nanotubes (SWCNTs). To evaluate its efficacy against ISKNV, we found a stronger and longer duration immune response (serum antibody production, enzyme activities and immune-related genes expression) can be induced in fish vaccinated with SWCNTs-MCP in comparison with those vaccinated with MCP alone. Importantly, SWCNTs can increase the immune protective effect of naked subunit vaccine by ca. 23.8%. Thereby, this study demonstrates that SWCNTs as a promising carrier for subunit vaccine might be used to vaccinate large-scale juvenile mandarin fish by bath administration approach.

Ruthenium-Catalyzed Carbonylation of Oxalyl Amide-Protected Benzylamines with Isocyanate as the Carbonyl Source.

An efficient synthesis of isoindolin-1-ones from oxalyl amide-protected benzylamines, through ruthenium-catalyzed intramolecular C(sp2)-H carbonylation, has been developed. Variously substituted benzylamines could be well tolerated in this new protocol, affording the corresponding products in moderate to excellent yields. This approach constitutes the first example of Ru(II)-catalyzed C(sp2)-H carbonylation with isocyanate as a novel commercially available carbonyl source.

Pd-Catalyzed regioselective sequential meta-, ortho-C-H functionalization of arenes: a predictable approach to the synthesis of polysubstituted ß-arylethylamines.

With the assistance of the same bidentate directing group, the first example of sequential, controllable C-H functionalization of ß-arylethylamines at different positions for the construction of polysubstituted arenes is reported. Pd-Catalyzed highly regioselective ortho-C-H functionalization reactions of meta-aryl substituted arylethylamines are performed, including alkynylation, iodination, acetoxylation and amination, which led to a concise approach to the synthesis of polysubstituted ß-arylethylamine derivatives.

An efficient one-pot synthesis of functionalized chromeno[4,3-b]pyridine derivatives under catalyst-free conditions.

A concise, efficient one-pot synthesis of functionalized chromeno[4,3-b]pyridine derivatives via a three-component reaction of 4-oxo-4H-chromene-3-carbaldehydes, malononitrile or cyanoacetates, and aromatic amines under catalyst-free conditions in an environmentally friendly medium (ethanol-water, 3:1 v/v) is described. This synthesis involves a group-assisted purification process, which avoids traditional recrystallization and chromatographic purification methods.

Palladium-Catalyzed Carbonylation of ß-Arylethylamide Directed by Oxalyl Amide in the Presence of Carbon Monoxide.

Pd-catalyzed regioselective coupling of ß-C(sp(2))-H bonds in aromatic amines protected by oxalyl amide with carbon monoxide is reported. The reaction could tolerate various functional groups and could afford good to excellent yields of the corresponding 3,4-dihydroisoquinolinone derivatives. Remarkably, it could also tolerate ß-arylethylamino acid and thiopheneethylamine derivatives, thus showing their potential for producing several important units for bioactive compound synthesis.

Pd-Catalyzed Coupling of γ-C(sp(3))-H Bonds of Oxalyl Amide-Protected Amino Acids with Heteroaryl and Aryl Iodides.

Pd-catalyzed regioselective coupling of γ-C(sp(3))-H bonds of oxalyl amide-protected amino acids with heteroaryl and aryl iodides is reported. A wide variety of iodides are tolerated, giving the corresponding products in moderate to good yields. Various oxalyl amide-protected amino acids were compatible in this C-H transformation, thus representing a practical method for constructing non-natural amino acid derivatives.

Multicomponent Strategy to Pyrazolo[3,4-e]indolizine Derivatives under Microwave Irradiation.

A simple and efficient one-pot construction of pyrazolo[3,4-e]indolizine derivatives via a diethylamine-catalyzed three-component domino reaction of arylglyoxals, cyclic 1,3-diones, and 5-aminopyrazoles under microwave irradiation is described. In this one-pot transformation, seven bonds and two new rings are efficiently formed. This synthesis was confirmed to follow the group-assisted-purification (GAP) chemistry process, which can avoid traditional recrystallization or chromatography purification methods.

Multicomponent strategy to indeno[2,1-c]pyridine and hydroisoquinoline derivatives through cleavage of carbon­carbon bond.

A concise and efficient three-component domino reaction has been developed for the synthesis of polyfunctionalized indenopyridine and hydroisoquinoline derivatives via the cleavage of a C­C bond under transition-metal-free conditions. This reaction provides facile access to complex nitrogen-containing heterocycles by simply mixing three common starting materials in EtOH in the presence of 20 mol % NaOH under microwave irradiation conditions.

Palladium-Catalyzed Oxalyl Amide-Directed γ-Arylation of Aliphatic Amines.

A method for palladium-catalyzed oxalyl amide-directed arylation of α-unsubstituted aliphatic amines with aryl iodides has been developed. A wide variety of aryl iodides are tolerated in this transformation, affording various γ-arylpropylamine derivatives. Heterocyclic iodides can also be competent reagents in this γ-C(sp(3))-H bonds transformation.

Palladium-Catalyzed ortho-Olefination of Phenyl Acetic and Phenyl Propylacetic Esters via C-H Bond Activation.

A highly regioselective palladium-catalyzed ester-directed ortho-olefination of phenyl acetic and propionic esters with olefins via C-H bond activation has been developed. A wide variety of phenyl acetic and propionic esters were tolerated in this transformation, affording the corresponding olefinated aromatic compounds. The ortho-olefination of heterocyclic acetic and propionic esters also took place smoothly giving the products in good yields, thus proving the potential utility of this protocol in synthetic chemistry.

Selective synthesis of polyfunctionalized pyrido[2,3-b]indoles by multicomponent domino reactions.

A series of novel polyfunctionalized pyrido[2,3-b]indoles were synthesized by three- or four-component domino reactions under microwave irradiation. This protocol has the advantages of readily available starting materials, short reaction times, high yields, easy workup, and high chemo- and regioselectivities.

An efficient three-component synthesis of highly functionalized tetrahydroacenaphtho[1,2-b]indolone derivatives catalyzed by L-proline.

An efficient and diastereoselective synthetic procedure for highly functionalized tetrahydroacenaphtho[1,2-b]indolone derivatives was successfully developed by the three-component reaction of acenaphthequinone, enaminones, and barbituric acid in the presence of a catalytic amount of L-proline. This method has the advantages of convenient operation, excellent yields, mild reaction conditions, and environmental friendliness.

Incidence of chemotherapy-related cardiac dysfunction in cancer patients.

BACKGROUND: Cancer patients are increasingly affected by chemotherapy-related cardiac dysfunction. The reported incidence of this condition vary significantly across different studies. HYPOTHESIS: A better comprehensive understanding of chemotherapy-related cardiac dysfunction incidence in cancer patients is imperative. Therefore, we performed a meta-analysis to establish the overall incidence of chemotherapy-related cardiac dysfunction in cancer patients. METHODS: We searched articles in PubMed and EMBASE from database inception to May 1, 2023. Studies that reported the incidence of chemotherapy-related cardiac dysfunction in cancer patients were included. RESULTS: A total of 53 studies involving 35 651 individuals were finally included in the meta-analysis. The overall pooled incidence of chemotherapy-related cardiac dysfunction in cancer patients was 63.21 per 1000 person-years (95% CI: 57.28-69.14). The chemotherapy-related cardiac dysfunction incidence increased steeply within half a year of cancer chemotherapy. Also, the trend of chemotherapy-related cardiac dysfunction incidence appeared to have plateaued after a longer duration of follow-up. In addition, chemotherapy-related cardiac dysfunction incidence rates are significantly higher among patients with age ≥50 years versus patients with age <50 years (99.96 vs. 34.48 per 1000 person-years). The incidence rate of cardiac dysfunction was higher among breast cancer patients (72.97 per 1000 person-years), leukemia patients (65.21 per 1000 person-years), and lymphoma patients (55.43 per 1000 person-years). CONCLUSION: Our meta-analysis unveiled a definitive overall incidence rate of chemotherapy-related cardiac dysfunction in cancer patients. In addition, it was found that the risk of developing this condition escalates within the initial 6 months postchemotherapy, subsequently tapering off to become statistically insignificant after a duration of 6 years.

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Territorial ecological restoration planning is a carrier process for carrying out territorial space regulation and ecological restoration. However, current urban planning efforts only focus on ecological processes, and fail to coordinate the development of both ecology and society. Taking Shantou, a city in Guangdong Province, as an example, we focused on the identification of ecological restoration nodes and the development of differentiated planning strategies from a comprehensive ecological-social perspective. By considering ecosystem integrity, we extracted the ecological corridors and key points by identifying ecological sources and constructing resistance surfaces, constructed an ecological recreation service evaluation system from the social perspective in terms of recreational allocation and recreational value to identify key areas for recreation services, and obtained different types of ecological restoration strategies by synthesizing the results of ecology and recreation. The results showed that there were 136 ecological corridors and 77 ecological nodes in Shantou, with a total length of 380.58 km. The most important recreation areas were the coastline, several inland bays, and wetland tidal flats, with an area of 33.78 km2 and accounting for 1.6% of the total area. Low-level recreation areas was the largest, accounting for 57.3% of the total area. We proposed the composite strategy of "recreation expansion & fishery development", the connectivity strategy of "ecological construction & corridor connection", and the protection strategy of "vegetation restoration & development restriction". This study would provide a comprehensive analysis path for the ecological protection and restoration planning of coastal cities, and would help promote the practicality and maximizing the comprehensive benefits of territorial ecological restoration planning.

The role of glucocorticoids in increasing cardiovascular risk.

Introduction: Different studies provide conflicting evidence regarding the potential for glucocorticoids (GCs) to increase the risk of cardiovascular diseases. This study performed a systematic review and meta-analysis to determine the correlation between GCs and cardiovascular risk, including major adverse cardiovascular events (MACE), death from any cause, coronary heart disease (CHD), heart failure (HF), and stroke. Methods: We performed a comprehensive search in PubMed and Embase (from inception to June 1, 2022). Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Results: A total of 43 studies with 15,572,512 subjects were included. Patients taking GCs had a higher risk of MACE (RR = 1.27, 95% CI: 1.15-1.40), CHD (RR = 1.25, 95% CI: 1.11-1.41), and HF (RR = 1.92, 95% CI: 1.51-2.45). The MACE risk increased by 10% (95% CI: 6%-15%) for each additional gram of GCs cumulative dose or by 63% (95% CI: 46%-83%) for an additional 10 µg daily dose. The subgroup analysis suggested that not inhaled GCs and current GCs use were associated with increasing MACE risk. Similarly, GCs were linked to an increase in absolute MACE risk of 13.94 (95% CI: 10.29-17.58) cases per 1,000 person-years. Conclusions: Administration of GCs is possibly related with increased risk for MACE, CHD, and HF but not increased all-cause death or stroke. Furthermore, it seems that the risk of MACE increased with increasing cumulative or daily dose of GCs.

Gut microbe-derived milnacipran enhances tolerance to gut ischemia/reperfusion injury.

There are significant differences in the susceptibility of populations to intestinal ischemia/reperfusion (I/R), but the underlying mechanisms remain elusive. Here, we show that mice exhibit significant differences in susceptibility to I/R-induced enterogenic sepsis. Notably, the milnacipran (MC) content in the enterogenic-sepsis-tolerant mice is significantly higher. We also reveal that the pre-operative fecal MC content in cardiopulmonary bypass patients, including those with intestinal I/R injury, is associated with susceptibility to post-operative gastrointestinal injury. We reveal that MC attenuates mouse I/R injury in wild-type mice but not in intestinal epithelial aryl hydrocarbon receptor (AHR) gene conditional knockout mice (AHRflox/flox) or IL-22 gene deletion mice (IL-22-/-). Collectively, our results suggest that gut microbiota affects susceptibility to I/R-induced enterogenic sepsis and that gut microbiota-derived MC plays a pivotal role in tolerance to intestinal I/R in an AHR/ILC3/IL-22 signaling-dependent manner, revealing the pathological mechanism, potential prevention and treatment drugs, and treatment strategies for intestinal I/R.