Immune-related cardiovascular toxicities of PD-1/PD-L1 inhibitors in solid tumors: an updated systematic review and meta-analysis

PurposeThe objective of this study was to investigate the risk of cardiovascular toxicities related to PD-1/PD-L1 inhibitors in solid tumors.MethodsA literature search was performed following the participants, interventions, comparisons, outcomes, and study design (PICOS) principles, and the study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analysis was conducted using Review Manager version 5.4.ResultsThis meta-analysis included 69 randomized controlled trials (RCTs) divided into five groups based on the treatment regimens: PD-1/PD-L1 + chemotherapy versus chemotherapy, PD-1/PD-L1 versus chemotherapy, PD-1/PD-L1 versus placebo, PD-1/PD-L1 + CTLA-4 versus PD-1/PD-L1 and PD-1/PD-L1 + CTLA-4 versus chemotherapy. Compared to chemotherapy treatment alone, PD-1/PD-L1 +chemotherapy significantly increased the risk of hypertension [all-grade (OR = 1.27, 95% CI [1.05, 1.53], p = 0.01); grade 3–5 (OR = 1.36, 95% CI [1.04, 1.79], p = 0.03)], hypotension [all-grade (OR = 2.03, 95% CI [1.19, 3.45], p = 0.009); grade 3–5 (OR = 3.60, 95% CI [1.22, 10.60], p = 0.02)], arrhythmia [all-grade (OR = 1.53, 95% CI [1.02, 2.30], p = 0.04); grade 3–5 (OR = 2.91, 95% CI [1.33, 6.39], p = 0.008)] and myocarditis [all-grade (OR = 2.42, 95% CI [1.06, 5.54], p = 0.04)]. The risk of all-grade hypotension (OR = 2.87, 95% CI [1.26, 6.55], p = 0.01) and all-grade arrhythmia (OR = 2.03, 95% CI [1.13, 3.64], p = 0.02) significantly increased when treated with PD-1/PD-L1 inhibitors compared to the placebo. The risks of cardiovascular toxicities are significantly higher with PD-1+CTLA-4 compared to PD-1 alone (OR = 2.02, 95% CI [1.12, 3.66], p = 0.02).ConclusionPD-1/PD-L1 inhibitor leads to an increased risk of cardiovascular toxicities, especially hypertension, hypotension, arrhythmia, and myocarditis

Visible-light-driven coproduction of diesel precursors and hydrogen from lignocellulose-derived methylfurans

Photocatalytic hydrogen production from biomass is a promising alternative to water splitting thanks to the oxidation half-reaction being more facile and its ability to simultaneously produce solar fuels and value-added chemicals. Here, we demonstrate the coproduction of H2 and diesel fuel precursors from lignocellulose-derived methylfurans via acceptorless dehydrogenative C 12C coupling, using a Ru-doped ZnIn2S4 catalyst and driven by visible light. With this chemistry, up to 1.04\u2009g\u2009gcatalyst 121\u2009h 121 of diesel fuel precursors (~41% of which are precursors of branched-chain alkanes) are produced with selectivity higher than 96%, together with 6.0\u2009mmol\u2009gcatalyst 121\u2009h 121 of H2. Subsequent hydrodeoxygenation reactions yield the desired diesel fuels comprising straight- and branched-chain alkanes. We suggest that Ru dopants, substituted in the position of indium ions in the ZnIn2S4 matrix, improve charge separation efficiency, thereby accelerating C 12H activation for the coproduction of H2 and diesel fuel precursors

Effects of Hunger on Visual Perception in Binocular Rivalry

The effect of hunger on visual perception is largely absent from contemporary vision science. Using a well-established visual phenomenon termed binocular rivalry, this study was carried out to investigate the effects of hunger on visual perception. A within-subject design was applied in which participants attended two sessions before and after their lunch or dinner, i.e., a hunger state and a satiated state. In Experiment 1, we found that the mean dominance times to food-related pictures were larger in the hungry condition than that in the satiated condition, while the mean dominance time to the non-food stimuli were unaffected. In Experiment 2, we found the times to break through continuous flash suppression (b-CFS) for both food-related and non-food-related pictures were not affected by hunger. In Experiment 3, a probe-detection task was conducted to address possible response-biases. Our findings provide evidence that hunger biases the dynamic process of binocular rivalry to unsuppressed and visible food stimuli, while processing suppressed and invisible food-related was unaffected. Our results support the notion that the top-down modulation by hunger on food-related visual perception is limited to visible stimuli

Development of macrophage-associated genes prognostic signature predicts clinical outcome and immune infiltration for sepsis

Abstract Sepsis is a major global health problem, causing a significant burden of disease and death worldwide. Risk stratification of sepsis patients, identification of severe patients and timely initiation of treatment can effectively improve the prognosis of sepsis patients. We procured gene expression datasets for sepsis (GSE54514, GSE65682, GSE95233) from the Gene Expression Omnibus and performed normalization to mitigate batch effects. Subsequently, we applied weighted gene co-expression network analysis to categorize genes into modules that exhibit correlation with macrophage activity. To pinpoint macrophage-associated genes (MAAGs), we executed differential expression analysis and single sample gene set enrichment analysis. We then established a prognostic model derived from four MAAGs that were significantly differentially expressed. Functional enrichment analysis and immune infiltration assessments were instrumental in deciphering the biological mechanisms involved. Furthermore, we employed principal component analysis and conducted survival outcome analyses to delineate molecular subgroups within sepsis. Four novel MAAGs—CD160, CX3CR1, DENND2D, and FAM43A—were validated and used to create a prognostic model. Subgroup classification revealed distinct molecular profiles and a correlation with 28-day survival outcomes. The MAAGs risk score was developed through univariate Cox, LASSO, and multivariate Cox analyses to predict patient prognosis. Validation of the risk score upheld its prognostic significance. Functional enrichment implicated ribonucleoprotein complex biogenesis, mitochondrial matrix, and transcription coregulator activity in sepsis, with an immune infiltration analysis indicating an association between MAAGs risk score and immune cell populations. The four MAAGs exhibited strong diagnostic capabilities for sepsis. The research successfully developed a MAAG-based prognostic model for sepsis, demonstrating that such genes can significantly stratify risk and reflect immune status. Although in-depth mechanistic studies are needed, these findings propose novel targets for therapy and provide a foundation for future precise clinical sepsis management

Plasma metabolic profiling reveals that chromium yeast alleviates the negative effects of heat stress in mid-lactation dairy cows

Chromium yeast (CY) supplementation has the potential to alleviate the negative effects of heat stress in dairy cows, but the mechanism remains elusive. We aimed to identify the metabolic mechanisms whereby CY supplementation alleviates the negative effects of heat stress in mid-lactation dairy cows. Twelve Holstein dairy cows with similar milk yield (24.6 ± 1.5 kg/d), parity (2 or 3) and days in milk (125 ± 8 d) were fed the same basal diet containing 0.09 mg of Cr/kg DM. They were allocated randomly to 2 groups: a control group (CON, without CY supplementation) and a CY group (CY, administered 0.36 mg Cr/kg DM). The experiment was performed over 8 weeks during a hot summer, in which the mean temperature-humidity index was 79.0 ± 3.13 (>72), indicating that the dairy cows were exposed to heat stress. Chromium yeast supplementation reduced rectal temperature (P = 0.032), and increased the lactation performance by increasing the yield of milk (+2.6 kg/d), protein, lactose and total solid, and protein and lactose percentages in the milk of the heat-stressed dairy cows (P 1.0, P < 0.05), and found to be involved in 6 Kyoto Encyclopedia of Genes and Genomes pathways, including those involved in nicotinate and nicotinamide metabolism. Specifically, plasma concentration of nicotinamide was higher after CY supplementation, which might also contribute to the reduction of rectal temperature, the regulation of glucose homeostasis, and an improvement in the lactation performance of heat-stressed dairy cows. In conclusion, CY supplementation reduces rectal temperature, influences metabolism by reducing serum insulin concentration and increasing serum glucose and plasma nicotinamide concentrations, and finally increases lactation performance of heat-stressed dairy cows

Surface Assistant Charge Separation in PEC Cu2S-Ni/Cu2O Cathode

Fabrication of a high efficiency photocathode is a challenging issue in photoelectrocatalysis (PEC). In this work, a Cu2S-Ni/Cu2O photocathode was constructed via electrodeposition followed by a two-step overlayer deposition procedure including direct-current magnetron sputtering (DCMS) and ion exchange reaction. We found that the presence of Ni in the inner-layer could not only affect the morphology but also enhance the formation rate of the outerlayer Cu2S. The XPS results indicate that the Ni exist as NiOx instead of Ni-0. The photocurrent of Cu2S-Ni/Cu2O achieved 2 times of it on the pristine Cu2O. The charge dynamic characterizations, including electrochemical impedance spectroscopy (EIS), Tafel slopes, and photoluminescence (PL) spectra, demonstrated that the Ni can promote the hydrogen evolution reaction follow the Heyrovsky reaction, while Cu2S shows a crucial role on the surface charge separation. At last, surface photovoltage microscopy (SPVM) technology was used to reveal the function of each overlayer. It gives direct evidence for the charge transportation pathway in the system and explains the function of each component

Screening and Properties of Functional Probiotics for Apple Fermentation

[Objectives] To screen functional probiotics for apple fermentation and study their probiotic properties. [Methods] A total of 35 strains were screened from traditional fermented foods in different regions. After primary screening, re-screening and research on growth characteristics, two characteristic strains, CTCF-LC1 (LC1, with strong acid production ability) and CTCF-LT1 (LT1, with strong adaptability), were obtained. [Results] The results of physiological and biochemical identification and 16sDNA-based identification show that LC1 is Lactobacillus casei and LT1 is Lactobacillus reuteri. Their fermentation performance in apple juice was tested, and it was found that the two strains grew well in the fermentation broth, and the total number of colonies could reach 109 cfu/mL. The final pH value of LC1 fermentation broth dropped below 3.5, and the total acid content exceeded 12 g/L. The pH of LT1 fermentation broth dropped to 3.9, and the total acid content also exceeded 6 g/L. In the study on the antioxidation property of apple juice, it was found that after high temperature and high pressure steam sterilization, the DPPH free radical scavenging rate of apple juice extract increased by 35.8%, and potassium ferricyanide reduction capability increased by 68%. After fermentation by LC1 and LT1, the potassium ferricyanide reducing power of apple juice was increased by 42.9%. [Conclusions] This has a good application prospect in the development of fruit and vegetable juice fermented beverages

Novel concentration gradient LiNi0.815Co0.15Al0.035O2 microspheres as cathode material for lithium ion batteries

A novel concentration gradient LiNi0.815Co0.15Al0.035O2 microsphere is synthesized successfully based on hydrothermal method combined with solid-state sintering process. Compared with traditional coprecipitation method, the prepared microspheres are only about 6 mu m in diameter, which is beneficial to shorten the paths of ion/electron diffusion. As demonstrated by cyclic voltammetry (CV) and galvanostatic intermittent titration technique (GITT) tests, the positive electrodes show a remarkable ion diffusion kinetics, which resulted in a superb rate capability. Besides, highly agglomerated primary particles and concentration gradient distribution of element can promote the structure stability of the material, which is beneficial to its cycle performance. As the cathode material, it possesses a capacity up to 196.2 mAh g(-1) at 0.1 C with capacity retention of 93% circulated for 100 times at 1 C and capacity retention of 88% circulated for 330 times at 2 C. What's more, a high capacity up to 165.6 mAh g(-1) could be achieved even at 5 C. In addition, a reusable lithium-ion full cell is assembled with cathode LiNi0.815Co0.15Al0.035O2 and anode graphite to explore its potential for practical application and it's found to deliver an excellent electrochemical property. This research provides a possible and feasible reference strategy to accelerate the application of Ni-rich cathodes

Efficacy and safety of umbilical cord mesenchymal stem cells for the treatment of patients with COVID-19

OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted

Suppressed androgen receptor expression promotes M2 macrophage reprogramming through the STAT3/SOCS3 pathway

Macrophages are important mediators of inflammatory cardiovascular diseases, and various macrophage phenotypes exert opposite effects during inflammation. In our previous study, we proved that suppressed androgen receptor (AR) alleviated inflammation during experimental autoimmune myocarditis (EAM). As anti-inflammatory cells, whether M2 macrophages are involved in this process remains unclear. Here, we showed that anti-inflammatory cytokines and M2 macrophages were elevated when AR was suppressed during EAM. In IL-4 stimulationinduced M2 macrophages, impaired AR with ASC-J9 increased the expression of M2 macrophage-related factors. Moreover, suppressed AR expression resulted in macrophage M2 polarization by reducing SOCS3 production and enhancing STAT3 activation. Taken together, our data suggest that AR plays a critical role in macrophage polarization and suppressed redundant AR expression promotes anti-inflammatory M2 macrophages reprogramming. This study suggests a potential therapeutic agent for inflammatory cardiomyopathy through the use of ASC-J9