Evaluation of aconitine cardiotoxicity with a heart-on-a-particle prepared by a microfluidic device.

A heart-on-a-particle model based on multicompartmental microgel is proposed to simulate the heart microenvironment and study the cardiotoxicity of drugs. The relevant microgel was fabricated by a biocompatible microfluidic-based approach, where heart function-related HL-1 and HUVEC cells were arranged in separate compartments. Finally, the mechanism of aconitine-induced heart toxicity was elucidated using mass spectrometry and molecular biotechnology.

Traditional Chinese medicine in regulating macrophage polarization in immune response of inflammatory diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Numerous studies have demonstrated that various traditional Chinese medicines (TCMs) exhibit potent anti-inflammatory effects against inflammatory diseases mediated through macrophage polarization and metabolic reprogramming. AIM OF THE STUDY: The objective of this review was to assess and consolidate the current understanding regarding the pathogenic mechanisms governing macrophage polarization in the context of regulating inflammatory diseases. We also summarize the mechanism action of various TCMs on the regulation of macrophage polarization, which may contribute to facilitate the development of natural anti-inflammatory drugs based on reshaping macrophage polarization. MATERIALS AND METHODS: We conducted a comprehensive review of recently published articles, utilizing keywords such as "macrophage polarization" and "traditional Chinese medicines" in combination with "inflammation," as well as "macrophage polarization" and "inflammation" in conjunction with "natural products," and similar combinations, to search within PubMed and Google Scholar databases. RESULTS: A total of 113 kinds of TCMs (including 62 components of TCMs, 27 TCMs as well as various types of extracts of TCMs and 24 Chinese prescriptions) was reported to exert anti-inflammatory effects through the regulation of key pathways of macrophage polarization and metabolic reprogramming. CONCLUSIONS: In this review, we have analyzed studies concerning the involvement of macrophage polarization and metabolic reprogramming in inflammation therapy. TCMs has great advantages in regulating macrophage polarization in treating inflammatory diseases due to its multi-pathway and multi-target pharmacological action. This review may contribute to facilitate the development of natural anti-inflammatory drugs based on reshaping macrophage polarization.

Potassium-Promoted Limestone for Preferential Direct Hydrogenation of Carbonates in Integrated CO2 Capture and Utilization.

Integrated CO2 capture and utilization (ICCU) via the reverse water-gas shift (RWGS) reaction offers a particularly promising route for converting diluted CO2 into CO using renewable H2. Current ICCU-RWGS processes typically involve a gas-gas catalytic reaction whose efficiency is inherently limited by the Le Chatelier principle and side reactions. Here, we show a highly efficient ICCU process based on gas-solid carbonate hydrogenation using K promoted CaO (K-CaO) as a dual functional sorbent and catalyst. Importantly, this material allows ∼100% CO2 capture efficiency during carbonation and bypasses the thermodynamic limitations of conventional gas-phase catalytic processes in hydrogenation of ICCU, achieving >95% CO2-to-CO conversion with ∼100% selectivity. We showed that the excellent functionalities of the K-CaO materials arose from the formation of K2Ca(CO3)2 bicarbonates with septal K2CO3 and CaCO3 layers, which preferentially undergo a direct gas-solid phase carbonates hydrogenation leading to the formation of CO, K2CO3 CaO and H2O. This work highlights the immediate potential of K-CaO as a class of dual-functional material for highly efficient ICCU and provides a new rationale for designing functional materials that could benefit the real-life application of ICCU processes.

The Application of Biochar for CO2 Capture: Influence of Biochar Preparation and CO2 Capture Reactors.

This work investigates three types of biochar (bamboo charcoal, wood pellet, and coconut shell) for postcombustion carbon capture. Each biochar is structurally modified through physical (H2O, CO2) and chemical (ZnCl2, KOH, H3PO4) activation to improve carbon capture performance. Three methods (CO2 adsorption isotherms, CO2 fixed-bed adsorption, and thermogravimetric analysis) are used to determine the CO2 adsorption capacity. The results show that a more than 2.35 mmol·g-1 (1 bar, 298 K) CO2 capture capacity was achieved using the activated biochar samples. It is also demonstrated that the CO2 capture performance by biochar depends on multiple surface and textural properties. A high surface area and pore volume of biochar resulted in an enhanced CO2 capture capacity. Furthermore, the O*/C ratio and pore width show a negative correlation with the CO2 capture capacity of biochars.

Combining surface-accessible Ag and Au colloidal nanomaterials with SERS for in situ analysis of molecule-metal interactions in complex solution environments.

The interactions between molecules and noble metal nanosurfaces play a central role in many areas of nanotechnology. The surface chemistry of noble metal surfaces under ideal, clean conditions has been extensively studied; however, clean conditions are seldom met in real-world applications. We developed a sensitive and robust characterization technique for probing the surface chemistry of nanomaterials in the complex environments that are directly relevant to their applications. Surface-enhanced Raman spectroscopy (SERS) can be used to probe the interaction of plasmonic nanoparticles with light to enhance the Raman signals of molecules near the surface of nanoparticles. Here, we explain how to couple SERS with surface-accessible plasmonic-enhancing substrates, which are capped with weakly adsorbing capping ligands such as citrate and chloride ions, to allow molecule-metal interactions to be probed in situ and in real time, thus providing information on the surface orientation and the formation and breaking of chemical bonds. The procedure covers the synthesis and characterization of surface-accessible colloids, the preliminary SERS screening with agglomerated colloids, the synthesis and characterization of interfacial nanoparticle assemblies, termed metal liquid-like films, and the in situ biphasic SERS analysis with metal liquid-like films. The applications of the approach are illustrated using two examples: the probing of π-metal interactions and that of target/ligand-particle interactions on hollow bimetallic nanostars. This protocol, from the initial synthesis of the surface-accessible plasmonic nanoparticles to the final in situ biphasic SERS analysis, requires ~14 h and is ideally suited to users with basic knowledge in performing Raman spectroscopy and wet synthesis of metal nanoparticles.

SERS as a Probe of Surface Chemistry Enabled by Surface-Accessible Plasmonic Nanomaterials.

ConspectusWhen the size of materials is reduced, their volume decreases much faster than their surface area, which in the most extreme case leads to 2D nanomaterials which are "all surface". Since atoms at the surface have free energies, electronic states, and mobility which are very different from bulk atoms, nanomaterials that have large surface-to-volume ratios can display remarkable new properties compared to their bulk counterparts. More generally, the surface is where nanomaterials interact with their environment, which in turn places surface chemistry at the heart of catalysis, nanotechnology, and sensing applications. Understanding and utilizing nanosurfaces are not possible without appropriate spectroscopic and microscopic characterization techniques. An emerging technique in this area is surface-enhanced Raman spectroscopy (SERS), which utilizes the interaction between plasmonic nanoparticles and light to enhance the Raman signals of molecules near the nanoparticles' surfaces. SERS has the great advantage that it can provide detailed in situ information on surface orientation and binding between molecules and the nanosurface. A long-standing dilemma that has limited the applications of SERS in surface chemistry studies is the choice between surface-accessibility and plasmonic activity. More specifically, the synthesis of metal nanomaterials with strong plasmonic and SERS-enhancing properties typically involves the use of strongly adsorbing modifier molecules, but these modifiers also passivate the surface of the product material, which prevents the general application of SERS in the analysis of weaker molecule-metal interactions.In this Account, we discuss our efforts in the development of modifier-free synthetic approaches to synthesize surface-accessible, plasmonic nanomaterials for SERS. We start by discussing the definition of "modifiers" and "surface-accessibility", especially in the context of surface chemistry studies in SERS. As a general rule of thumb, the chemical ligands on surface-accessible nanomaterials should be easily displaceable by a wide range of target molecules relevant to potential applications. We then introduce modifier-free approaches for the bottom-up synthesis of colloidal nanoparticles, which are the basic building blocks for nanotechnology. Following this, we introduce modifier-free interfacial self-assembly approaches developed by our group that allow the creation of multidimensional plasmonic nanoparticle arrays from different types of nanoparticle-building blocks. These multidimensional arrays can be further combined with different types of functional materials to form surface-accessible multifunctional hybrid plasmonic materials. Finally, we demonstrate applications for surface-accessible nanomaterials as plasmonic substrates for SERS studies of surface chemistry. Importantly, our studies revealed that the removal of modifiers led to not only significantly enhanced properties but also the observation of new surface chemistry phenomena that had been previously overlooked or misunderstood in the literature. Realizing the current limitations of modifier-based approaches provides new perspectives in manipulating molecule-metal interactions in nanotechnology and can have significant implications in the design and synthesis of the next generation of nanomaterials.

Carbon nanotubes production from real-world waste plastics and the pyrolysis behaviour.

The investigation of the pyrolysis behaviour of real-world waste plastics (RWWP) and using them as the feedstock to produce carbon nanotubes (CNTs) could serve as an effective solution to address the global waste plastics catastrophe. This research aimed to characterize the pyrolysis behaviour of RWWP via thermogravimetric analysis (TG) and fast pyrolysis-TG/mass spectrometry (Py-TG/MS) analyses. Activation energies (131.04 kJ mol-1 -171.04 kJ mol-1) for RWWP pyrolysis were calculated by three methods: Flynn-Wall-Ozawa (FWO) method, Kissinger-Akahira-Sunose (KAS) method, and Starink method. Py-TG/MS results indicated that the RWWP could be identified as polystyrene (RWWP-1), polyethylene (RWWP-2), polyethylene terephthalate (RWWP-3, 4), and polypropylene (RWWP-5, 6). In addition, RWWP-1, 2, 5, 6 outperform RWWP-3 and 4 as sources of carbon for producing CNTs. The results showed a high carbon yield of 32.21 wt% and a high degree of CNT purity at 93.04%.

Probing the interaction of ex situ biofilms with plasmonic metal nanoparticles using surface-enhanced Raman spectroscopy.

Biofilms are complex environments where matrix effects from components such as extracellular polymeric substances and proteins can strongly affect SERS performance. Here the interactions between SERS-enhancing Ag and Au particles were studied using ex situ biofilms (es-biofilms), which were more homogenous than in situ biofilm samples. This allowed systematic quantitative studies, where samples could be accurately diluted and analysed, to be carried out. Strong signals from intrinsic marker compounds were found for the Pseudomonas aeruginosa and Staphylococcus aureus extracted es-biofilms, which the standard addition method showed were due to 2 × 10-3 mol dm-3 pyocyanin or the equivalent of 1 × 10-4 mol dm-3 adenine, respectively. The es-biofilms hindered aggregation of Ag colloids more than Au but for both Au and Ag nanospheres the presence of es-biofilm reduced SERS signals through a combination of poorer aggregation and blocking of surface sites. For Ag, the effect of lower aggregation was to reduce the signals by a factor of ca. 2×, while site blocking gave a further 10× reduction for adenine. Similar results were found for Au nanospheres with adenine, although these particles gave low enhancement with pyocyanin. Nanostars were found to be unaffected by reduced aggregation and also showed lower site blocking effects, giving more reproducible signals than those from aggregated particles, which compensated for their lower enhancement factor. These results provide a rational basis for selecting enhancing substrates for use in in situ studies, where the further complexity means that it is important to begin with well-understood and controllable enhancing media.

General approach to surface-accessible plasmonic Pickering emulsions for SERS sensing and interfacial catalysis.

Pickering emulsions represent an important class of functional materials with potential applications in sustainability and healthcare. Currently, the synthesis of Pickering emulsions relies heavily on the use of strongly adsorbing molecular modifiers to tune the surface chemistry of the nanoparticle constituents. This approach is inconvenient and potentially a dead-end for many applications since the adsorbed modifiers prevent interactions between the functional nanosurface and its surroundings. Here, we demonstrate a general modifier-free approach to construct Pickering emulsions by using a combination of stabilizer particles, which stabilize the emulsion droplet, and a second population of unmodified functional particles that sit alongside the stabilizers at the interface. Freeing Pickering emulsions from chemical modifiers unlocks their potential across a range of applications including plasmonic sensing and interfacial catalysis that have previously been challenging to achieve. More broadly, this strategy provides an approach to the development of surface-accessible nanomaterials with enhanced and/or additional properties from a wide range of nano-building blocks including organic nanocrystals, carbonaceous materials, metals and oxides.

Metabolites from scutellarin alleviating deferoxamine-induced hypoxia injury in BV2 cells cultured on microfluidic chip combined with a mass spectrometer.

The changes of metabolites of tricarboxylic acid (TCA) cycle in cells under hypoxia play a key role in drug screening. In order to dynamically monitor the drug metabolism changes of Scutellarin in the hypoxia environment induced by deferoxamine (DFO), a microfluidic-chip mass spectrometry method was used to study the real-time monitoring of drug metabolism changes under hypoxia conditions. This system has six drug-loading units, cell culture chamber, metabolite collection, filtration, HPLC separation and mass spectrometer. The cells in each microchannel were incubated with continuous flow of culture medium, metabolites will be collected by the fixed card slot, automatic sampling needle will be precise positioned and sampled. Through this new system combined with molecular biological methods, the changes of metabolites in TCA cycle of BV2 cells and drug metabolism of Scutellarin can be determined in real-time. In general, we illustrated a new mechanism of Scutellarin for reducing BV2 cell hypoxia injury and presented a novel analysis strategy that opened a way for real-time online monitoring of the energy metabolic mechanism of the effect of drugs on cells and further provided a superior strategy to screen natural drug candidates for hypoxia-related brain disease treatment.

Regulatory effect of dietary nitrate on blood pressure: a meta-analysis of randomized controlled trials.

Hypertension is the leading risk factor for global disease burden. Many clinical studies have reported that dietary inorganic nitrate can affect blood pressure. In this study, the PubMed, Embase, and Cochrane Library databases were searched for relevant literature published before December 2021 to explore the preventive and therapeutic effects of inorganic nitrate on hypertension. Two reviewers evaluated the randomized controlled trials of inorganic nitrates. This study included a total of 19 articles. The analyzed outcomes of the study were systolic, diastolic and mean arterial blood pressures as well as 24-hour ambulatory blood pressure. RevMan 5.4 was used to conduct meta-analysis. In the healthy population, inorganic nitrate lowered systolic blood pressure (-2.42 mmHg, 95% confidence intervals (CI) [-4.28, -0.57]; P = 0.01) but not diastolic blood pressure (-0.58 mmHg, 95% CI [-1.84, 0.68]; P = 0.36) or mean arterial pressure (-1.01 mmHg, 95% CI [-3.55, 1.54]; P = 0.44). However, in the hypertensive population, inorganic nitrates did not lower systolic blood pressure (-0.82 mmHg, 95% CI [-2.53, 0.90]; P = 0.35), diastolic blood pressure (-0.03 mmHg, 95% CI [-1.35, 1.30]; P = 0.97), 24-hour ambulatory systolic blood pressure (-0.22 mmHg, 95% CI [-1.50, 1.94]; P = 0.8), or 24-hour ambulatory diastolic blood pressure (-0.33 mmHg, 95% CI [-2.03, 1.37]; P = 0.7). In conclusion, inorganic nitrate can mildly reduce systolic blood pressure in healthy people, but does not have a lowering effect on blood pressure in patients with hypertension. Further research is required to obtain more definitive data and prove the link between inorganic nitrate and blood pressure.

Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry.

Aconitine, a common and main toxic component of Aconitum, is toxic to the central nervous system. However, the mechanism of aconitine neurotoxicity is not yet clear. In this work, we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine. HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system. Meanwhile, to confirm the metabolic mechanism of aconitine toxicity on HT22 cells, the levels of lactate dehydrogenase, intracellular Ca2+, reactive oxygen species, glutathione and superoxide dismutase, and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology. Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid, which was followed by the accumulation of lactic acid and reduction of glucose. The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca2+ overload and oxidative stress, and eventually result in cell apoptosis. In general, we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.

Effect of celecoxib plus standard chemotherapy on cancer prognosis: A systematic review and meta-analysis.

BACKGROUND: Inflammation is closely related to cancer prognosis. The effect of celecoxib, a nonsteroidal anti-inflammatory drug, on the prognosis of patients with cancer remains uncertain. To assess the association between celecoxib plus standard chemotherapy and cancer prognosis, we conducted a systematic review and meta-analysis of published studies. METHODS: PubMed, EMBASE, and the Cochrane Library were searched from inception until July 2022 for randomized controlled trials reporting the prognosis of patients with cancer treated with celecoxib plus standard chemotherapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Meta-analysis was performed using Review Manager software version 5.4. The following search terms were used in the databases: ((((celecoxib)) AND ((((((((cancer) OR (carcinoma)) OR (sarcoma)) OR (neoplasms)) OR (tumor)) OR (tumour)) OR (tumors)) OR (tumours))) AND ((survival) OR (mortality))) AND (((Clinical Trials, Randomized) OR (Trials, Randomized Clinical)) OR (Controlled Clinical Trials, Randomized)). RESULTS: Overall, 13 randomized controlled trials, including 8957 patients with cancer, were included in the analysis. Compared to conventional chemotherapy alone, 1-year OS and 1-year PFS rates were not significantly improved with celecoxib adjuvant therapy (OS: p = .38; PFS: p = .65). In addition, no differences were observed between the celecoxib and placebo groups in 3-year overall (p = .98), 3-year progression-free (p = .40), 5-year overall (p = .59), or 5-year progression-free (p = .56) survival rates. An increase in the risk ratio of leukopenia (p = .02) and thrombocytopenia (p = .05) was also observed, suggesting that celecoxib promotes hematologic toxicity. No increased risk of cardiovascular (p = .96) and gastrointestinal (p = .10-.91) events was observed. CONCLUSIONS: The addition of celecoxib to standard chemotherapy did not improve OS or PFS rates of patients with cancer. Additionally, celecoxib can increase hematologic toxicity without increasing the risk of gastrointestinal or cardiovascular reactions. Further randomized controlled trials are necessary to clarify its effects and applications.

Performance of Noninvasive Airway Occlusion Maneuvers to Assess Lung Stress and Diaphragm Effort in Mechanically Ventilated Critically Ill Patients.

BACKGROUND: Monitoring and controlling lung stress and diaphragm effort has been hypothesized to limit lung injury and diaphragm injury. The occluded inspiratory airway pressure (Pocc) and the airway occlusion pressure at 100 ms (P0.1) have been used as noninvasive methods to assess lung stress and respiratory muscle effort, but comparative performance of these measures and their correlation to diaphragm effort is unknown. The authors hypothesized that Pocc and P0.1 correlate with diaphragm effort and lung stress and would have strong discriminative performance in identifying extremes of lung stress and diaphragm effort. METHODS: Change in transdiaphragmatic pressure and transpulmonary pressure was obtained with double-balloon nasogastric catheters in critically ill patients (n = 38). Pocc and P0.1 were measured every 1 to 3 h. Correlations between Pocc and P0.1 with change in transdiaphragmatic pressure and transpulmonary pressure were computed from patients from the first cohort. Accuracy of Pocc and P0.1 to identify patients with extremes of lung stress (change in transpulmonary pressure > 20 cm H2O) and diaphragm effort (change in transdiaphragmatic pressure < 3 cm H2O and >12 cm H2O) in the preceding hour was assessed with area under receiver operating characteristic curves. Cutoffs were validated in patients from the second cohort (n = 13). RESULTS: Pocc and P0.1 correlate with change in transpulmonary pressure (R2 = 0.62 and 0.51, respectively) and change in transdiaphragmatic pressure (R2 = 0.53 and 0.22, respectively). Area under receiver operating characteristic curves to detect high lung stress is 0.90 (0.86 to 0.94) for Pocc and 0.88 (0.84 to 0.92) for P0.1. Area under receiver operating characteristic curves to detect low diaphragm effort is 0.97 (0.87 to 1.00) for Pocc and 0.93 (0.81 to 0.99) for P0.1. Area under receiver operating characteristic curves to detect high diaphragm effort is 0.86 (0.81 to 0.91) for Pocc and 0.73 (0.66 to 0.79) for P0.1. Performance was similar in the external dataset. CONCLUSIONS: Pocc and P0.1 correlate with lung stress and diaphragm effort in the preceding hour. Diagnostic performance of Pocc and P0.1 to detect extremes in these parameters is reasonable to excellent. Pocc is more accurate in detecting high diaphragm effort.

Application of carbon nanotube prepared from waste plastic to phase change materials: The potential for battery thermal management.

Carbon nanotube (CNT), has been demonstrated as a promising high-value product from thermal chemical conversion of waste plastics and securing new applications is an important prerequisite for large-scale production of CNT from waste-plastic recycling. In this study, CNT, produced from waste plastic through chemical vapor deposition (pCNT), was applied as a nanofiller in phase change material (PCM), affording pCNT-PCM composites. Compared with pure PCM, the addition of 5.0 wt% pCNT rendered the peak melting temperature increase by 1.3 ℃, latent heat retain by 90.7%, and thermal conductivity increase by 104%. The results of morphological analysis and leakage testing confirmed that pCNT has similar PCM encapsulation performance and shape stability to those of commercial CNT. The formation of uniform pCNT cluster networks allowed for a large CNT loading into the PCM on the premise of free phase change, responsible for the high thermal conductivity inside the homogeneous phase. Thus, the resulting capillary forces retained a high latent heat capacity and suitable melting temperature and prohibited PCM leakage from the matrix to the outside during re-melting as the pCNT loading ratio increased. Therefore, the as-prepared pCNT-PCM composite is believed to have similar potential to cCNT and shows prominent performance as a flowable conductive filler for battery thermal management systems.

Network analysis combined with pharmacological evaluation strategy to reveal the mechanism of Tibetan medicine Wuwei Shexiang pills in treating rheumatoid arthritis.

Tibetan medicine is an important part of traditional Chinese medicine and a significant representative of ethnic medicine in China. Tibetan medicine is gradually recognized by the world for its unique curative effects. Wuwei Shexiang pills (WPW) has been widely used to treat "Zhenbu" disease (Also known as rheumatoid arthritis) in Tibetan medicine, however, its potential bioactive ingredients and mechanism for RA treatment remain unclear. In this study, we used a combination of gas chromatography-mass spectrometry (GC-MS), ultra-performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry (UPLC-Q-TOF/MS), network analysis and experimental validation to elucidate the potential pharmacodynamic substances and mechanisms of WPW in the treatment of rheumatoid arthritis (RA). The results showed that songoramine, cheilanthifoline, saussureanine C, acoric acid, arjunolic acid, peraksine, ellagic acid, arjungenin and other 11 components may be the main activities of WPW in the treatment of RA. PIK3CA, AKT, MAPK, IL-6, TNF, MMP1, MMP3, and CDK1 are considered as core targets. PI3K-AKT, MAPK, apoptosis, cell cycle, and other signaling pathways may be the key pathways for WPW to play a role in the treatment of RA. Furthermore, we validated the underlying molecular mechanism of WPW predicted by network analysis and demonstrated its possible mechanism through in vivo animal experiments. It was found that WPW could significantly improve the degree of paw swelling, and reduce ankle joint diameter and arthritis index. Further histomorphological analysis showed that WPW could reduce the degree of synovial tissue inflammation and ankle joint cartilage damage. Meanwhile, WPW could down-regulate the levels of IL-6, IL-1ß, and IL-17, and increase the levels of IL-10 and IL-4 in the serum of AA rats. TUNEL staining confirmed that WPW could significantly promote the apoptosis of synovial cells. Moreover, the immunohistochemical results showed that WPW decreased the expression of PI3K, AKT, MAPK, MMP1, MMP3, CDK1, and Bcl-2, as well as increased the expression of Bax protein. In conclusion, we successfully combined GC-MS, UPLC-Q-TOF/MS, network analysis, and experimental validation strategies to elucidate the inhibition of inflammation by WPW in AA model rats via PI3K/AKT, MAPK, cell cycle and apoptotic pathways process. This not only provides new evidence for the study of potential pharmacodynamic substances and the mechanism of WPW in the treatment of RA, but also provides ideas for the study of other Tibetan medicine compound preparations.

Analysis of hypervirulent Klebsiella pneumoniae and classic Klebsiella pneumoniae infections in a Chinese hospital.

AIMS: To evaluate the clinical and genetic virulence characteristics of critically ill patients with hypervirulent Klebsiella pneumoniae (hvKP) and classic KP (cKP) infection. METHODS AND RESULTS: The patients included in this retrospective study (n = 225) were grouped according to their hvKP (n = 114) or cKP (n = 111) status, and their clinical characteristics were analysed and compared. Cox multivariate analysis was conducted to determine the risk factors for hvKP infection. Length of hospital stay, length of intensive care unit stay, duration of mechanical ventilation and 28-day survival rate were similar between the groups. However, the incidence of septic shock was higher in the hvKP group (16.7%) than in the cKP group (8.1%). CONCLUSIONS: There was a high rate of hvKP infection in this population. Compared to patients with cKP infection, those with hvKP infection showed a higher probability of having septic shock; nevertheless, survival and length of hospital stay were similar between the groups. Risk factors for hvKP infection included hospital-acquired infection and renal insufficiency. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents relevant information on the characteristics of hvKP infection in a Chinese population, and this promotes early diagnosis and supports the view that the prevalence of hvKP is high in China.

Lung- and Diaphragm-Protective Ventilation by Titrating Inspiratory Support to Diaphragm Effort: A Randomized Clinical Trial.

OBJECTIVES: Lung- and diaphragm-protective ventilation is a novel concept that aims to limit the detrimental effects of mechanical ventilation on the diaphragm while remaining within limits of lung-protective ventilation. The premise is that low breathing effort under mechanical ventilation causes diaphragm atrophy, whereas excessive breathing effort induces diaphragm and lung injury. In a proof-of-concept study, we aimed to assess whether titration of inspiratory support based on diaphragm effort increases the time that patients have effort in a predefined "diaphragm-protective" range, without compromising lung-protective ventilation. DESIGN: Randomized clinical trial. SETTING: Mixed medical-surgical ICU in a tertiary academic hospital in the Netherlands. PATIENTS: Patients (n = 40) with respiratory failure ventilated in a partially-supported mode. INTERVENTIONS: In the intervention group, inspiratory support was titrated hourly to obtain transdiaphragmatic pressure swings in the predefined "diaphragm-protective" range (3-12 cm H2O). The control group received standard-of-care. MEASUREMENTS AND MAIN RESULTS: Transdiaphragmatic pressure, transpulmonary pressure, and tidal volume were monitored continuously for 24 hours in both groups. In the intervention group, more breaths were within "diaphragm-protective" range compared with the control group (median 81%; interquartile range [64-86%] vs 35% [16-60%], respectively; p < 0.001). Dynamic transpulmonary pressures (20.5 ± 7.1 vs 18.5 ± 7.0 cm H2O; p = 0.321) and tidal volumes (7.56 ± 1.47 vs 7.54 ± 1.22 mL/kg; p = 0.961) were not different in the intervention and control group, respectively. CONCLUSIONS: Titration of inspiratory support based on patient breathing effort greatly increased the time that patients had diaphragm effort in the predefined "diaphragm-protective" range without compromising tidal volumes and transpulmonary pressures. This study provides a strong rationale for further studies powered on patient-centered outcomes.

Chlorogenic acid, a natural product as potential inhibitor of COVID-19: virtual screening experiment based on network pharmacology and molecular docking.

Chlorogenic acid (CGA) is a potential inhibitor of Coronavirus Disease 2019 (COVID-19). ACE2 and its co-expressed proteins are SARS-CoV-2 receptors, which have been linked to SARS-CoV-2 infection and considered as the key target of SARS-CoV-2 in entering target cells. Here, network pharmacology was used to investigate the mechanism by which CGA affected COVID-19. A total of 70 potential targets related to the treatment of COVID-19 were obtained, among which NFE2L2, PPARG, ESR1, ACE, IL6, and HMOX1 might be the main potential targets. Finally, CGA and potential target proteins were scored by molecular docking, and the prediction results of network pharmacology were preliminarily verified. Moreover, CGA had potential anti-SARS-CoV-2 activity via integrating three common receptors in clinical practice compared with clinical trial drugs registered for the treatment of COVID-19, as shown by molecular docking. The mechanism of CGA against COVID-19 was initially investigated using network pharmacology, followed by molecular docking.

Inorganic nitrate alleviates irradiation-induced salivary gland damage by inhibiting pyroptosis.

Over 80% of patients undergoing radiotherapy (RT) for head and neck cancer (HNC) suffer reduced saliva secretion and dry mouth symptoms due to salivary gland damage. Although therapeutic interventions to alleviate such RT-induced damage are available, long-term hypofunction remains a significant issue. Therefore, novel therapeutic solutions to prevent irradiation (IR)-induced salivary gland damage are required. This study explored the protective effect of inorganic nitrate in preventing IR-induced salivary gland injury via pyroptosis suppression, both in vivo and in vitro. In the treatment group, C57BL/6 mice were pretreated with 2 mmol/L NaNO3 supplied in drinking water one week before a single-dose of 15 Gy IR in the submandibular gland (SMG) region. Human vein endothelial cells (HUVECs) and mice SMG cells were treated with 10 µmol/L or 100 µmol/L NaNO3 2 h before a single-dose of 8 Gy IR. In vivo, IR-induced decreased saliva flow rate and body weight loss could be alleviated by nitrate supplementation. Nitrate prevented acinar and microvascular endothelial cell loss. Moreover, nitrate improved mitochondrial function and significantly decreased pyroptosis-related indexes. In vitro, nitrate supplementation reduced reactive oxygen species (ROS) generation by preserving mitochondrial homeostasis to inhibit NLPR3 inflammasome-mediated pyroptosis both in HUVECs and SMG cells. Nitrate showed potential as an oral protective agent to prevent IR-induced salivary gland damage; prospective insight into the underlying molecular mechanisms is presented.