Liquid exfoliation of molybdenum metallenes for non-inflammatory photothermal therapy of tumors.

Tissue damage and cell death occurring during photothermal therapy (PTT) for tumors can induce an inflammatory response that is detrimental to tumor therapy. Herein, ultrathin Mo metallene nanosheets with a thickness of <5 nm prepared by liquid phase exfoliation were explored as functional hyperthermia agents for non-inflammatory ablation of tumors. The obtained Mo metallene nanosheets exhibited good photothermal conversion properties and significant reactive oxygen species (ROS) scavenging ability, thus achieving superior cancer cell ablation and anti-inflammatory effects in vitro. For in vivo experiments, 4T1 tumors were ablated while the inflammation-related cytokine levels did not obviously increase, demonstrating that the inflammatory response induced by PTT was inhibited by the anti-inflammatory properties of Mo metallene nanosheets. Moreover, Mo metallene nanosheets depicted good dispersibility and biocompatibility, beneficial for biomedical applications. This work introduces Mo metallenes as promising hyperthermia agents for non-inflammatory PTT of tumors.

Rhodium-Rhenium Alloy Nanozymes for Non-inflammatory Photothermal Therapy.

Analogous to thermal ablation techniques in clinical settings, cell necrosis induced during tumor photothermal therapy (PTT) can provoke an inflammatory response that is detrimental to the treatment of tumors. In this study, we employed a straightforward one-step liquid-phase reduction process to synthesize uniform RhRe nanozymes with an average hydrodynamic size of 41.7 nm for non-inflammatory photothermal therapy. The obtained RhRe nanozymes showed efficient near-infrared (NIR) light absorption for effective PTT, coupled with a remarkable capability to scavenge reactive oxygen species (ROS) for anti-inflammatory treatment. After laser irradiation, the 4T1 tumors were effectively ablated without obvious tumor recurrence within 14 days, along with no obvious increase in pro-inflammatory cytokine levels. Notably, these RhRe nanozymes demonstrated high biocompatibility with normal cells and tissues, both in vitro and in vivo, as evidenced by the lack of significant toxicity in female BALB/c mice treated with 10 mg/kg of RhRe nanozymes over a 14 day period. This research highlights RhRe alloy nanoparticles as bioactive nanozymes for non-inflammatory PTT in tumor therapy.

2D Is Better: Engineering Polydopamine into Cationic Nanosheets to Enhance Anti-Inflammatory Capability.

Polydopamine nanomaterials have emerged as one of the most popular organic materials for the management of oxidative stress-mediated inflammatory diseases. However, their current anti-inflammatory ability is still unsatisfactory because of limited phenolic hydroxyl groups, and oxidation reaction-medicated reactive oxygen and nitrogen species (RONS) scavenging. Herein, via fusing dimension engineering and surface charge engineering, 2D cationic polydopamine nanosheets (PDA NSs) capable of scavenging multiple danger signals to enhance anti-inflammatory capability are reported. Compared with conventional spherical polydopamine nanoparticles, 2D PDA NSs exhibit three- to fourfold enhancement in RONS scavenging capability, which should be attributed to high specific surface area and abundant phenol groups of 2D ultrathin structure. To further enhance the anti-inflammatory ability, polylysine molecules are absorbed on the surface of PDA NSs to endow the scavenging capability of cell-free DNA (cfDNA), another typical inflammatory factor to exacerbate the pathogenesis of inflammation. Molecular mechanisms reveal that cationic PDA NSs can concurrently activate Keap1-Nrf2 and block TLR9 signaling pathway, achieving synergistical inflammation inhibition. As a proof of concept, cationic PDA NSs with RONS and cfDNA dual-scavenging capability effectively alleviate the inflammatory bowel disease in both delayed and prophylactic models, much better than the clinical drug 5-aminosalicylic acid.

Total Synthesis of Dynobactin A.

The first total synthesis of the potent antimicrobial agent dynobactin A is disclosed. This synthesis enlists a singular aziridine ring opening strategy to access the two disparate ß-aryl-branched amino acids present within this complex decapeptide. Featuring a number of unique maneuvers to navigate inherently sensitive and epimerizable functional groups, this convergent approach proceeds in only 16 steps (LLS) from commercial materials and should facilitate the synthesis of numerous analogues for medicinal chemistry studies.

Chiral Sulfur Nanosheets for Dual-Selective Inhibition of Gram-Positive Bacteria.

Elemental sulfur is the oldest known antimicrobial agent. However, conventional sulfur in the clinic suffers from poor aqueous solubility and limited antibacterial activity, greatly hindering its practical use. Herein, we report a reform strategy coupling dimension engineering with chirality transfer to convert conventional 3D sulfur particles into chiral 2D sulfur nanosheets (S-NSs), which exhibit 50-fold improvement of antibacterial capability and dual-selective inhibition against Gram-positive bacteria. Benefiting from the inherent selectivity of S-NSs and chirality selectivity from decorated d-histidine, the obtained chiral S-NSs are proven to precisely kill Gram-positive drug-resistant bacteria, while no obvious bacterial inhibition is observed for Gram-negative bacteria. Mechanism studies reveal that S-NSs produce numerous reactive oxygen specipoes and hydrogen sulfide after incubation with bacteria, thus causing bacterial membrane destruction, respiratory chain damage, and ATP production inhibition. Upon spraying chiral S-NSs dispersions onto MRSA-infected wounds, the skin healing process was greatly accelerated in 8 days due to metabolism inhibition and oxidative damage of bacteria, indicating the excellent treatment efficiency of MRSA-infected wounds. This work converts the traditional well-known sulfur into modern antibacterial agents with a superior Gram-selectivity bactericidal capability.

Emerging metallenes: synthesis strategies, biological effects and biomedical applications.

Metallenes, atomically thin-layered materials composed of coordination-deficient metal atoms, have emerged as a new category of two-dimensional materials. Metallenes exhibit exciting properties with a fusion of atom economy, ultrathin structure, photonic properties, and catalytic activity, which make them intriguing for a wide range of applications in biomedicine. The development of biomedical applications of metallenes is in its infancy yet fast-growing. In this review, after a brief introduction of the definition, structures, properties, and classification of metallenes, we outline two common synthesis strategies and identify their shortcomings. Then, we comprehensively discuss the biological effects of metallenes, such as nano-biointeractions and signaling pathway regulation. We also highlight their recent advances in biomedical applications, including antitumor, biosensing, bioimaging, antibacterial, and anti-inflammation. Finally, we provide personal perspectives on remaining challenges and future opportunities for the biomedical applications of metallenes.

Gut microbiota-derived indole 3-propionic acid partially activates aryl hydrocarbon receptor to promote macrophage phagocytosis and attenuate septic injury.

Sepsis is associated with a high risk of death, and the crosstalk between gut microbiota and sepsis is gradually revealed. Indole 3-propionic acid (IPA) is a gut microbiota-derived metabolite that exerts immune regulation and organ protective effects. However, the role of IPA in sepsis is not clear. In this study, the role of IPA in sepsis-related survival, clinical scores, bacterial burden, and organ injury was assessed in a murine model of cecal ligation and puncture-induced polymicrobial sepsis. Aryl hydrocarbon receptor (AhR) highly specific inhibitor (CH223191) was used to observe the role of AhR in the protection of IPA against sepsis. The effects of IPA on bacterial phagocytosis by macrophages were investigated in vivo and vitro. The levels of IPA in feces were measured and analyzed in human sepsis patients and patient controls. First, we found that gut microbiota-derived IPA was associated with the survival of septic mice. Then, in animal model, IPA administration protected against sepsis-related mortality and alleviated sepsis-induced bacterial burden and organ injury, which was blunted by AhR inhibitor. Next, in vivo and vitro, IPA enhanced the macrophage phagocytosis through AhR. Depletion of macrophages reversed the protective effects of IPA on sepsis. Finally, on the day of ICU admission (day 0), septic patients had significantly lower IPA level in feces than patient controls. Also, septic patients with bacteremia had significantly lower IPA levels in feces compared with those with non-bacteremia. Furthermore, in septic patients, reduced IPA was associated with worse clinical outcomes, and IPA in feces had similar prediction ability of 28-day mortality with SOFA score, and increased the predictive ability of SOFA score. These findings indicate that gut microbiota-derived IPA can protect against sepsis through host control of infection by promoting macrophages phagocytosis and suggest that IPA may be a new strategy for sepsis treatment.

Predicting prolonged postoperative length of stay risk in patients undergoing lumbar fusion surgery: Development and assessment of a novel predictive nomogram.

Objective: The purpose of this study was to develop and internally validate a prediction nomogram model in patients undergoing lumbar fusion surgery. Methods: A total of 310 patients undergoing lumbar fusion surgery were reviewed, and the median and quartile interval were used to describe postoperative length of stay (PLOS). Patients with PLOS > P75 were defined as prolonged PLOS. The least absolute shrinkage and selection operator (LASSO) regression was used to filter variables for building the prolonged PLOS risk model. Multivariable logistic regression analysis was applied to build a predictive model using the variables selected in the LASSO regression model. The area under the ROC curve (AUC) of the predicting model was calculated and significant test was performed. The Kappa consistency test between the predictive model and the actual diagnosis was performed. Discrimination, calibration, and the clinical usefulness of the predicting model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using the bootstrapping validation. Results: According to the interquartile range of PLOS in a total of 310 patients, the PLOS of 235 patients was ≤P75 (7 days) (normal PLOS), and the PLOS of 75 patients was > P75 (prolonged PLOS). The LASSO selected predictors that were used to build the prediction nomogram included BMI, diabetes, hypertension, duration of surgery, duration of anesthesia, anesthesia type, intraoperative blood loss, sufentanil for postoperative analgesia, and postoperative complication. The model displayed good discrimination with an AUC value of 0.807 (95% CI: 0.758-0.849, P < 0.001), a Kappa value of 0.5186 (cutoff value, 0.2445, P < 0.001), and good calibration. A high C-index value of 0.776 could still be reached in the interval validation. Decision curve analysis showed that the prolonged PLOS nomogram was clinically useful when intervention was decided at the prolonged PLOS possibility threshold of 3%. Conclusions: This study developed a novel nomogram with a relatively good accuracy to help clinicians access the risk of prolonged PLOS in lumbar fusion surgery patients. By an estimate of individual risk, surgeons and anesthesiologists may shorten PLOS and accelerate postoperative recovery of lumbar fusion surgery through more accurate individualized treatment.

The roles of temperamental inhibition in affective and cognitive empathy in Chinese toddlers.

Empathy, crucial to harmonious interpersonal relationships and moral development, has both affective and cognitive components. Previous studies found that toddlers' temperamental inhibition may influence their empathy, but mainly focused on emotional response to others' distress. Little is known about whether inhibited children's poor empathy is due to high reactivity and social withdrawal when sharing others' affective states, such as distress (affective empathy), or to a difficulty in comprehending and inferring others' perspective (cognitive empathy). The current study investigated the role of behavioral inhibition (BI) in affective empathy (response to pain simulation) and cognitive empathy (performance in perspective-taking task) among 163 Chinese toddlers and tested in both only and non-only children. Correlation analyses showed that BI was only negatively associated with affective empathy. The relation between BI and cognitive empathy was moderated by self-regulation and inhibited children who were low in self-regulation presented low cognitive empathy. Additionally, only children presented advanced cognitive empathy but poorer affective empathy than non-only children. These findings imply different roles of BI in affective versus cognitive empathy in early childhood. Although highly inhibited children rarely show positive social expression toward others' distress, caution is needed in inferring that they lack a capacity for cognitive empathy.

[Apoptosis mechanism of taxol combined with resveratrol on human laryngeal carcinoma Hep-2 cells].

Laryngeal cancer is one of the most common malignant tumors in the respiratory tumors, and its incidence ranks second highest in the respiratory tumors. Resveratrol (Res) is a kind of polyphenols, which can inhibit nucleotides can inhibit the growth of liver cancer cells, gastric cancer cells, pancreatic cells and other tumor cells by inhibiting ribonucleotide reductase in the cells. Taxol (Tax) is a kind of secondary metabolites of Taxus chinensis, which has anti-tumor activity for breast cancer, cervical cancer, ovarian cancer and other tumors by inhibiting cellular microtubule depolymerization. But at present the effects of resveratrol combined with taxol on human laryngeal carcinoma cell strain Hep-2 and their underlying molecular mechanisms are rarely reported. After human laryngeal cancer cell Hep-2 cells were processed with resveratrol (Res) and taxol (Tax), CCK-8 assay was used to evaluate the effect of these two herbs on the proliferation of cancer cells; AO/PI staining and JC-1 were used to detect Hep-1 cells apoptosis; the expression of Bax, Bcl-2, PARP, TRIB3, and XIAP genes was detected by real time quantitative PCR; the activity of caspase-3 and caspase-8 was determined with quantitative fluorescence method. The experimental results showed that compared with Tax, Res medication alone, joint group significantly enhanced inhibition of Hep-2 cells activity, decreased the dosage of Tax, increased the expression of Bax and PARP, TRIB3, reduced the expression of the Bcl-2 and XIAP, and promoted the activity of caspase-3 and caspase-8. The test results showed that compared with the single medication, combined group could significantly increase the inhibitory effect on Hep-2 cells, significantly reduce Tax dosage, increase expressions of Bax, PARP, TRIB3, reduce expressions of Bcl-2, XIAP, and promote activity of caspase-3, caspase-8. This indicated apoptosis of human laryngeal carcinoma cell strain Hep-2 may be induced with Res, Tax, and the combination of these two herbs by mitochondria pathway. It provides valuable clue for further research on combination of Res and Tax for the treatment of laryngeal cancer, and expanding the combined application of Res and Tax.

A mussel-inspired chitooligosaccharide based multidentate ligand for highly stabilized nanoparticles.

Inspired by the adhesion behaviors of mussels, we synthesized a chitooligosaccharide (COS) based multidentate ligand (ML) for preparing robust biocompatible magnetic iron oxide nanoparticles (IONPs). The COS was modified with mussel adhesive protein (MAP) mimetic multiple catechol groups and branched poly(ethylene glycol) moieties, which can not only strongly bind to IONPs through multiple catechol groups, but also afford IONPs with good colloidal stability and biocompatibility due to PEG integrated into the COS coating. The resultant ML-stabilized IONPs consist of single nanoparticles coated with ML shells and exhibited high dispersion stability in aqueous solution for a wide range of pH and concentrated salt solutions. The potential of ML-stabilized IONPs as contrast agents for T2-weighted magnetic resonance imaging was demonstrated by conducting in vivo imaging and relaxivity measurements. The ML-stabilized IONPs are therefore expected to be useful for magnetic resonance imaging under physiological conditions.