Elucidating the Reactivity of Oxygenates on Single-Atom Alloy Catalysts.

Doping isolated transition metal atoms into the surface of coinage-metal hosts to form single-atom alloys (SAAs) can significantly improve the catalytic activity and selectivity of their monometallic counterparts. These atomically dispersed dopant metals on the SAA surface act as highly active sites for various bond coupling and activation reactions. In this study, we investigate the catalytic properties of SAAs with different bimetallic combinations [Ni-, Pd-, Pt-, and Rh-doped Cu(111), Ag(111), and Au(111)] for chemistries involving oxygenates relevant to biomass reforming. Density functional theory is employed to calculate and compare the formation energies of species such as methoxy (CH3O), methanol (CH3OH), and hydroxymethyl (CH2OH), thereby understanding the stability of these adsorbates on SAAs. Activation energies and reaction energies of C-O coupling, C-H activation, and O-H activation on these oxygenates are then computed. Analysis of the data in terms of thermochemical linear scaling and BroÌ·nsted-Evans-Polanyi relationship shows that some SAAs have the potential to combine weak binding with low activation energies, thereby exhibiting enhanced catalytic behavior over their monometallic counterparts for key elementary steps of oxygenate conversion. This work contributes to the discovery and development of SAA catalysts toward greener technologies, having potential applications in the transition from fossil to renewable fuels and chemicals.

Melatonin improves skin barrier damage caused by sleep restriction through gut microbiota.

It is widely known that lack of sleep damages the skin. Therefore, it is necessary to explore the relationship between sleep deprivation and skin damage and to find effective treatments. We established a 28-day sleep restriction (SR) mice model simulating continuous long-term sleep loss. We found that SR would damage the barrier function of mice's skin, cause oxidative stress damage to the skin, weaken the oscillations of the skin's biological clock, and make the circadian rhythm of Bacteroides disappear. The circadian rhythm of short-chain fatty acids (SCFA) receptors in the skin was disordered. After melatonin supplementation, the skin damage caused by SR was improved, the oscillations of the biological clock were enhanced, the circadian rhythm of Bacteroides was restored, and the rhythm of the receptor GPR43 of propionic acid was restored. We speculated that the improving effect of melatonin may be mediated by propionic acid produced by the gut microbiota. We verified in vitro that propionic acid could improve the keratinocytes barrier function of oxidative damage. We then consumed the gut microbiota of mice through antibiotics and found that oral melatonin could not improve skin damage. Moreover, supplementing mice with propionic acid could improve skin damage. Our research showed that lack of sleep impaired skin barrier function. Oral melatonin could improve skin damage by restoring the circadian rhythm of Bacteroides and its propionic acid metabolite.

Melatonin improves the homeostasis of mice gut microbiota rhythm caused by sleep restriction.

Insufficient sleep is regarded as a disruptor of circadian rhythm, and it also contributes to the occurrence of intestinal diseases. The physiological functions of the gut depend on the normal circadian rhythm of the intestinal microbiota. However, how lack of sleep affects intestinal circadian homeostasis is unclear. Therefore, we subjected mice to sleep restriction and found that chronic sleep loss disrupts the pattern of colonic microbial communities and reduces the proportion of gut microbiota with a circadian rhythm, with concomitant changes in the peak phase of the KEGG pathway. We then found that exogenous melatonin supplementation restored the proportion of gut microbiota with a circadian rhythm and increased the KEGG pathway with a circadian rhythm. And we screened for possible circadian oscillation families, Muribaculaceae and Lachnospiraceae, that are sensitive to sleep restriction and can be rescued by melatonin. Our results suggest that sleep restriction disrupts the circadian rhythm of the colonic microbiota. In contrast, melatonin ameliorates disturbances in the circadian rhythm homeostasis of the gut microbiota due to sleep restriction.

Perfecting the Life Clock: The Journey from PTO to TTFL.

The ubiquity of biological rhythms in life implies that it results from selection in the evolutionary process. The origin of the biological clock has two possible hypotheses: the selective pressure hypothesis of the oxidative stress cycle and the light evasion hypothesis. Moreover, the biological clock gives life higher adaptability. Two biological clock mechanisms have been discovered: the negative feedback loop of transcription-translation (TTFL) and the post-translational oscillation mechanism (PTO). The TTFL mechanism is the most classic and relatively conservative circadian clock oscillation mechanism, commonly found in eukaryotes. We have introduced the TTFL mechanism of the classical model organisms. However, the biological clock of prokaryotes is based on the PTO mechanism. The Peroxiredoxin (PRX or PRDX) protein-based PTO mechanism circadian clock widely existing in eukaryotic and prokaryotic life is considered a more conservative oscillation mechanism. The coexistence of the PTO and TTFL mechanisms in eukaryotes prompted us to explain the relationship between the two. Finally, we speculated that there might be a driving force for the evolution of the biological clock. The biological clock may have an evolutionary trend from the PTO mechanism to the TTFL mechanism, resulting from the evolution of organisms adapting to the environment.

Synthesis and antibacterial activity evaluation of N (7) position-modified balofloxacins.

A series of small-molecule fluoroquinolones were synthesized, characterized by HRMS and NMR spectroscopy, and screened for their antibacterial activity against MRSA, P. aeruginosa, and E. coli as model G+/G- pathogens. Compounds 2-e, 3-e, and 4-e were more potent than the reference drug balofloxacin against MRSA and P. aeruginosa (MIC values of 0.0195 and 0.039 µg/ml for 2-e, 0.039 and 0.078 µg/ml for each of 3-e and 4-e, respectively). Analysis of the time-dependent antibacterial effect of compound 2-e toward MRSA showed that in the early logarithmic growth phase, bactericidal effects occurred, while in the late logarithmic growth phase, bacterial inhibition occurred because of concentration effects and possibly the development of drug resistance. Compound 2-e exhibited low toxicity toward normal mammalian cell lines 3T3 and L-02 and tumor cell lines A549, H520, BEL-7402, and MCF-7. The compound was not hemolytic. Atomic force microscopy (AFM) revealed that compound 2-e could effectively destroy the membrane and wall of MRSA cells, resulting in the outflow of the cellular contents. Docking studies indicated the good binding profile of these compounds toward DNA gyrase and topoisomerase IV. ADMET's prediction showed that most of the synthesized compounds followed Lipinski's "rule of five" and possessed good drug-like properties. Our data suggested that compound 2-e exhibited potent anti-MRSA activity and is worthy of further investigation.

Role of Sleep Restriction in Daily Rhythms of Expression of Hypothalamic Core Clock Genes in Mice.

Lack of sleep time is a menace to modern people, and it leads to chronic diseases and mental illnesses. Circadian processes control sleep, but little is known about how sleep affects the circadian system. Therefore, we performed a 28-day sleep restriction (SR) treatment in mice. Sleep restriction disrupted the clock genes' circadian rhythm. The circadian rhythms of the Cry1 and Per1/2/3 genes disappeared. The acrophase of the clock genes (Bmal1, Clock, Rev-erbα, and Rorß) that still had a circadian rhythm was advanced, while the acrophase of negative clock gene Cry2 was delayed. Clock genes' upstream signals ERK and EIFs also had circadian rhythm disorders. Accompanied by changes in the central oscillator, the plasma output signal (melatonin, corticosterone, IL-6, and TNF-α) had an advanced acrophase. While the melatonin mesor was decreased, the corticosterone, IL-6, and TNF-α mesor was increased. Our results indicated that chronic sleep loss could disrupt the circadian rhythm of the central clock through ERK and EIFs and affect the output signal downstream of the core biological clock.

Evaluation of Short-Chain Antimicrobial Peptides With Combined Antimicrobial and Anti-inflammatory Bioactivities for the Treatment of Zoonotic Skin Pathogens From Canines.

The incidence of zoonotic Staphylococcus pseudintermedius and Microsporum canis infections is rapidly growing worldwide in the context of an increasing frequency of close contact between animals and humans, presenting challenges in both human and veterinary medicine. Moreover, the development of microbial resistance and emergence of recalcitrant biofilms, accompanied by the insufficiency of new antimicrobial agents, have become major obstacles in treating superficial skin infections caused by various microbes including S. pseudintermedius and M. canis. Over recent years, the prospects of antimicrobial peptides as emerging antimicrobials to combat microbial infections have been demonstrated. In our study, two novel short-chain peptides, namely, allomyrinasin and andricin B, produced by Allomyrina dichotoma and Andrias davidianus, were revealed to exhibit potent antimicrobial efficacy against clinical isolates of S. pseudintermedius and M. canis with remarkable and rapid fungicidal and bactericidal effects, while allomyrinasin exhibited inhibition of biofilm formation and eradication of mature biofilm. These peptides displayed synergistic activity when combined with amoxicillin and terbinafine against S. pseudintermedius and M. canis. Cytoplasmic leakage via cytomembrane permeabilization serves as a mechanism of action. Extremely low hemolytic activity and serum stability in vitro, as well as superior anti-infective efficacy in reducing bacterial counts and relieving the inflammatory response in vivo, were detected. The potent antibacterial, antifungal, and anti-inflammatory activities of allomyrinasin and andricin B might indicate promising anti-infective alternatives for the treatment of S. pseudintermedius and M. canis infections in the context of human and veterinary medicine.

Effects of general versus subarachnoid anaesthesia on circadian melatonin rhythm and postoperative delirium in elderly patients undergoing hip fracture surgery: A prospective cohort clinical trial.

BACKGROUND: Circadian rhythm disturbance is common postoperatively in older patients with hip fractures, which may contribute to the development of postoperative delirium (POD). As a reliable biomarker of endogenous circadian rhythms, melatonin regulates the sleep-wake cycle and environmental adaptation, and its secretory rhythm may be modified by anaesthesia and surgery. This study compared the impact of subarachnoid anaesthesia (SA) and general anaesthesia (GA), on the peak of melatonin secretion (primary outcome), the circadian rhythm of melatonin, cortisol and sleep, and the POD incidence (secondary outcome). METHODS: In this prospective cohort observational study, hip fracture surgery patients were enrolled and assigned to receive either SA or GA. Postoperative plasma melatonin and cortisol levels were dynamically measured every six hours on seven time-points, and the circadian rhythm parameters including mesor, amplitude, and acrophase were calculated. Subjective and objective sleep assessments were performed by sleep diaries and sleep trackers, respectively. The Confusion Assessment Method was used twice daily by a specific geriatrician to screen for POD occurrence. FINDINGS: In a cohort of 138 patients who underwent hip fracture surgery, the circadian rhythm disruption of the patients in the GA group (n=69) was greater than the SA group (n=69). Compared with SA, GA provided the lower peak concentration, mesor, and amplitude of melatonin secretion on postoperative day 1 (p < 0.05). Patients in the GA group experienced higher awakenings, more sleep deprivation, and poor sleep quality on surgery day (p < 0.05). A proportion of 12 patients in the SA group (17.4%) and 24 patients in the GA group (34.8%) experienced POD (p = 0.020). INTERPRETATION: These results suggest that SA may be superior to GA in elderly patients undergoing hip fracture surgery as SA is associated with less impairment of the melatonin rhythm and sleep patterns, and fewer POD occurrences. FUNDING: The study was supported by the National Natural Science Foundation of China (81971012, 81873726, 81901095, 81701052, and 81801070), Key Clinical Projects of Peking University Third Hospital (BYSYZD2019027), and Peking University "Clinical Medicine plus X" Youth Project (PKU2020LCXQ016).

Receptor-interacting serine/threonine kinase 1- and 3-dependent inflammation induced in lungs of chicken infected with Pasteurella multocida.

Fowl cholera is a serious, highly contagious disease caused by the bacterium Pasteurella multocida (P. multocida) in a range of avian species and is characterized by an acute form of septicaemia. The pathogenic mechanism of chicken lung injury caused by the bacterium is unclear. Therefore, P. multocida Q (a reference standard strain isolated from chicken) and 1G1 (a clinic isolated strain from duck) were selected to infect chickens, establishing fowl cholera-induced laying hen models. Several important proteins involved in the process of lung injury were identified and quantified using immunohistochemistry and WB. The results showed that chicken lungs infected with bacteria for 24 h showed congestion and edema. The inflammatory factors HMGB1 and IL-6, intercellular matrix MMP, the cell apoptosis-associated caspase-3 and necrotic apoptosis signal molecules RIPK1 and RIPK3 were widely expressed in the lungs of group Q and were significantly different compared with those of 1G1 group and uninfected group (P < 0.05). The results indicated that RIPK1 and RIPK3 are involved in the injury process of chicken lungs after infection with P. multocida, and the mechanisms of lung injury induced by different strains are different.

Mutual Correlation Attentive Factors in Dyadic Fusion Networks for Speech Emotion Recognition.

Emotion recognition in dyadic communication is challenging because: 1. Extracting informative modality-specific representations requires disparate feature extractor designs due to the heterogenous input data formats. 2. How to effectively and efficiently fuse unimodal features and learn associations between dyadic utterances are critical to the model generalization in actual scenario. 3. Disagreeing annotations prevent previous approaches from precisely predicting emotions in context. To address the above issues, we propose an efficient dyadic fusion network that only relies on an attention mechanism to select representative vectors, fuse modality-specific features, and learn the sequence information. Our approach has three distinct characteristics: 1. Instead of using a recurrent neural network to extract temporal associations as in most previous research, we introduce multiple sub-view attention layers to compute the relevant dependencies among sequential utterances; this significantly improves model efficiency. 2. To improve fusion performance, we design a learnable mutual correlation factor inside each attention layer to compute associations across different modalities. 3. To overcome the label disagreement issue, we embed the labels from all annotators into a k-dimensional vector and transform the categorical problem into a regression problem; this method provides more accurate annotation information and fully uses the entire dataset. We evaluate the proposed model on two published multimodal emotion recognition datasets: IEMOCAP and MELD. Our model significantly outperforms previous state-of-the-art research by 3.8%-7.5% accuracy, using a more efficient model.

Immunogenicity and protective capacity of EF-Tu and FtsZ of Streptococcus suis serotype 2 against lethal infection.

Vaccine development efforts against Streptococcus suis serotype 2 (S. suis 2) are often constrained by strain/serotype antigen variability. Bioinformatics analyses revealed two highly conserved S. suis 2 factors, EF-Tu and FtsZ. Murine immunization with recombinant proteins emulsified in white oil adjuvant or eukaryotic DNA vaccine vectors provided significant protection against lethal S. suis 2 challenge. Immune responses elicited by recombinant protein immunization revealed the robust generation of humoral immune responses, with a mixed induction of Th1-type and Th2-type responses. Furthermore, the antiserum from mice immunized with recombinant proteins significantly inhibited the growth of S. suis 2 in healthy pig whole blood, suggesting the triggering of a strong opsonizing response. Histological examination found that immunizing mice with purified recombinant proteins reduced neutrophil and macrophage accumulation in brain and lung tissues after challenge with virulent S. suis. Taken together, these findings reveal that EF-Tu and FtsZ may be promising targets for subunit and DNA vaccine candidates against S. suis 2 infection.

The VraSR regulatory system contributes to virulence in Streptococcus suis via resistance to innate immune defenses.

Streptococcus suis is a highly invasive pathogen that can cause sepsis and meningitis in pigs and humans. However, we have limited understanding of the mechanisms S. suis uses to evade innate immunity. To investigate the involvement of the two-component signal transduction system of S. suis in host immune defense, we examined the expression of 15 response regulators of S. suis following stimulation with polymorphonuclear leukocytes (PMNs). We found that several response regulators were significantly up-regulated including vraR. Thus, we constructed an isogenic deletion mutant of vraSR genes in S. suis and demonstrated VraSR promotes both bacterial survival in human blood and resistance to human PMN-mediated killing. The VraSR mutant was more susceptible to phagocytosis by human PMNs and had greater sensitivity to oxidant and lysozyme than wild-type S. suis. Furthermore, in vitro findings and in vivo evidence from a mouse infection model together strongly demonstrate that ΔvraSR had greatly attenuated virulence compared with wild-type S. suis. Collectively, our data reveal that VraSR is a critical regulatory system that contributes to the survival of S. suis and its ability to defend against host innate immunity.

ZnO nanotubes supported molecularly imprinted polymers arrays as sensing materials for electrochemical detection of dopamine.

In this study, ZnO nanotubes (ZNTs) were prepared onto fluorine-doped tin oxide (FTO) glass and used as supports for MIPs arrays fabrication. Due to the imprinted cavities are always located at both inner and outer surface of ZNTs, these ZNTs supported MIPs arrays have good accessibility towards template and can be used as sensing materials for chemical sensors with high sensitivity, excellent selectivity and fast response. Using K3[Fe(CN)6] as electron probe, the fabricated electrochemical sensor shows two linear dynamic ranges (0.02-5µM and 10-800µM) towards dopamine. This proposed electrochemical sensor has been applied for dopamine determination with satisfied recoveries and precision. More complex human urine samples also confirmed that the proposed method has good accuracy for dopamine determination in real biological samples. These results suggest potential applicability of the proposed method and sensor in important molecule analysis.

The Role of Necroptosis, Apoptosis, and Inflammation in Fowl Cholera-Associated Liver Injury in a Chicken Model.

Fowl cholera resulting from infection with Pasteurella multocida causes huge economic losses in the poultry industry. Necrotic hepatitis is reported to be a significant lesion associated with fowl cholera in chickens. Clarifying the underlying molecular mechanism of hepatic injury caused by P. multocida infection is needed to develop new strategies to control fowl cholera. Pasteurella multocida Q (the standard reference strain) and P. multocida 1G1 (a clinical strain) were used to infect healthy laying hens. Clinical signs were observed and gross lesions in livers were observed postmortem. Histologic lesions and the localization and expression of protein molecules associated with necroptosis, apoptosis, and inflammation in hepatic tissues were examined by hematoxylin and eosin staining and immunohistochemistry. Western blot analysis was used to determine the expression of liver injury-related genes. Necroptotic molecules such as RIPK1 (receptor interaction protein kinases 1), RIPK3 (receptor interaction protein kinases 3), and MLKL (mixed lineage kinase domain-like protein) were observed by immunostaining primarily in the cytoplasm of hepatocytes within or around necrotic foci, and inflammatory mediators HMGB1 (high-mobility group box 1) and IL-6 (interleukin-6) were found in the cytoplasm of heterophils, monocytes/macrophages, and hepatic sinusoids. In addition, MMP9 (matrix metalloproteinase 9) and TIMP1 (tissue inhibitor of metalloproteinase 1) were observed in hepatic parenchymal cells, inflammatory cells, and interstitial spaces, whereas the apoptotic effector molecule caspase-3 (cysteine-containing aspartic proteolytic enzymes 3) was mainly found in hepatocytes. The expression of RIPK1, RIPK3, and MLKL was significantly higher in the infected chickens than in the controls. HMGB1 and IL-6 protein levels were also increased in infected chickens relative to those in controls. Both MMP9 and TIMP1 were highly expressed in infected chickens. In addition, caspase-3 protein levels were significantly elevated in infected chickens. Necroptosis, apoptosis, and inflammation played a significant role in hepatic injury caused by P. multocida.

Draft genome sequence of Gordonia neofelifaecis NRRL B-59395, a cholesterol-degrading actinomycete.

We report a draft sequence of the genome of Gordonia neofelifaecis NRRL B-59395, a cholesterol-degrading actinomycete isolated from fresh feces of a clouded leopard (Neofelis nebulosa). As predicted, the reported genome contains several gene clusters for cholesterol degradation. This is the second available genome sequence of the family Gordoniaceae.