XP-524 is a dual-BET/EP300 inhibitor that represses oncogenic KRAS and potentiates immune checkpoint inhibition in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is associated with extensive dysregulation of the epigenome and epigenetic regulators, such as bromodomain and extraterminal motif (BET) proteins, have been suggested as potential targets for therapy. However, single-agent BET inhibition has shown poor efficacy in clinical trials, and no epigenetic approaches are currently used in PDAC. To circumvent the limitations of the current generation of BET inhibitors, we developed the compound XP-524 as an inhibitor of the BET protein BRD4 and the histone acetyltransferase EP300/CBP, both of which are ubiquitously expressed in PDAC tissues and cooperate to enhance tumorigenesis. XP-524 showed increased potency and superior tumoricidal activity than the benchmark BET inhibitor JQ-1 in vitro, with comparable efficacy to higher-dose JQ-1 combined with the EP300/CBP inhibitor SGC-CBP30. We determined that this is in part due to the epigenetic silencing of KRAS in vitro, with similar results observed using ex vivo slice cultures of human PDAC tumors. Accordingly, XP-524 prevented KRAS-induced, neoplastic transformation in vivo and extended survival in two transgenic mouse models of aggressive PDAC. In addition to the inhibition of KRAS/MAPK signaling, XP-524 also enhanced the presentation of self-peptide and tumor recruitment of cytotoxic T lymphocytes, though these lymphocytes remained refractory from full activation. We, therefore, combined XP-524 with an anti-PD-1 antibody in vivo, which reactivated the cytotoxic immune program and extended survival well beyond XP-524 in monotherapy. Pending a comprehensive safety evaluation, these results suggest that XP-524 may benefit PDAC patients and warrant further exploration, particularly in combination with immune checkpoint inhibition.

Adaptive coded phase mask design and high-quality image reconstruction for interference-less coded aperture correlation holography.

The interference-less coded aperture correlation holography is a non-scanning, motionless, and incoherent technique for imaging three-dimensional objects without two-wave interference. Nevertheless, a challenge lies in that the coded phase mask encodes the system noise, while traditional reconstruction algorithms often introduce unwanted surplus background components during reconstruction. A deep learning-based method is proposed to mitigate system noise and background components simultaneously. Specifically, this method involves two sub-networks: a coded phase mask design sub-network and an image reconstruction sub-network. The former leverages the object's frequency distribution to generate an adaptive coded phase mask that encodes the object wave-front precisely without being affected by the superfluous system noise. The latter establishes a mapping between the autocorrelations of the hologram and the object, effectively suppresses the background components by embedding a prior physical knowledge and improves the neural network's adaptability and interpretability. Experimental results demonstrate the effectiveness of the proposed method in suppressing system noise and background components, thereby significantly improving the signal-to-noise ratio of the reconstructed images.

Novel insights and new therapeutic potentials for macrophages in pulmonary hypertension.

Inflammation and immune processes underlie pulmonary hypertension progression. Two main different activated phenotypes of macrophages, classically activated M1 macrophages and alternatively activated M2 macrophages, are both involved in inflammatory processes related to pulmonary hypertension. Recent advances suggest that macrophages coordinate interactions among different proinflammatory and anti-inflammatory mediators, and other cellular components such as smooth muscle cells and fibroblasts. In this review, we summarize the current literature on the role of macrophages in the pathogenesis of pulmonary hypertension, including the origin of pulmonary macrophages and their response to triggers of pulmonary hypertension. We then discuss the interactions among macrophages, cytokines, and vascular adventitial fibroblasts in pulmonary hypertension, as well as the potential therapeutic benefits of macrophages in this disease. Identifying the critical role of macrophages in pulmonary hypertension will contribute to a comprehensive understanding of this pathophysiological abnormality, and may provide new perspectives for pulmonary hypertension management.

Structural, Optical, and Mechanical Insights into Cellulose Nanocrystal Chiral Nematic Film Engineering by Two Assembly Techniques.

Iridescent cellulose nanocrystal (CNC) films with chiral nematic nanostructures exhibit great potential in optical devices, sensors, painting, and anticounterfeiting applications. CNCs can assemble into a chiral nematic liquid crystal structure by evaporation-assisted self-assembly (EISA) and vacuum-assisted self-assembly (VASA) techniques. However, there is a lack of comprehensive examinations of their structure-property correlations, which are essential for fabricating materials with unique properties. In this work, we gained insights into the optical, mechanical, and structural differences of CNC films engineered using the two techniques. In contrast to the random self-assembly at the liquid-air interface in EISA, the continuous external pressure in the VASA process forces CNCs to assemble at the filter-liquid interface. This results in fewer defects in the interfaces between tactoids and highly ordered cholesteric phases. Owing to the distinct CNC assembly behaviors, the films prepared by these two methods show great differences in the nanostructure, microstructure, and macroscopic morphology. Consequently, the highly ordered cholesteric structure gives VASA-CNC films a more uniform structural color and enhanced mechanical performance. These fundamental understandings of the relationship of structure-property nanoengineering through various assembly techniques are essential for designing and constructing high-performance chiral iridescent CNC materials.

Optimizing skyrmionium movement and stability via stray magnetic fields in trilayer nanowire constructs.

Skyrmioniums, known for their unique transport and regulatory properties, are emerging as potential cornerstones for future data storage systems. However, the stability of skyrmionium movement faces considerable challenges due to the skyrmion Hall effect, which is induced by deformation. In response, our research introduces an innovative solution: we utilized micro-magnetic simulations to create a sandwiched trilayer nanowire structure augmented with a stray magnetic field. This combination effectively guides the skyrmionium within the ferromagnetic (FM) layer. Our empirical investigations reveal that the use of a stray magnetic field not only reduces the size of the skyrmionium but also amplifies its stability. This dual-effect proficiently mitigates the deformation of skyrmionium movement and boosts their thermal stability. We find these positive outcomes are most pronounced at a particular intensity of the stray magnetic field. Importantly, the required stray magnetic field can be generated using a heavy metal (HM1) layer of suitable thickness, rendering the practical application of this approach plausible in real-world experiments. Additionally, we analyze the functioning mechanism based on the Landau-Lifshitz-Gilbert (LLG) equation and energy variation. We also develop a deep spiking neural network (DSNN), which achieves a remarkable recognition accuracy of 97%. This achievement is realized through supervised learning via the spike timing dependent plasticity rule (STDP), considering the nanostructure as an artificial synapse device that corresponds to the electrical properties of the nanostructure. In conclusion, our study provides invaluable insights for the design of innovative information storage devices utilizing skyrmionium technology. By tackling the issues presented by the skyrmion Hall effect, we outline a feasible route for the practical application of this advanced technology. Our research, therefore, serves as a robust platform for continued investigations in this field.

Efficient Production of Flavonoid Glucuronides in Escherichia coli Using Flavonoid O-Glucuronosyltransferases Characterized from Marchantia polymorpha.

As a model liverwort, Marchantia polymorpha contains various flavone glucuronides with cardiovascular-promoting effects and anti-inflammatory properties. However, the related glucuronosyltransferases have not yet been reported. In this study, two bifunctional UDP-glucuronic acid/UDP-glucose:flavonoid glucuronosyltransferases/glucosyltransferases, MpUGT742A1 and MpUGT736B1, were identified from M. polymorpha. Extensive enzymatic assays found that MpUGT742A1 and MpUGT736B1 exhibited efficient glucuronidation activity for flavones, flavonols, and flavanones and showed promiscuous regioselectivity at positions 3, 6, 7, 3', and 4'. These enzymes catalyzed the production of a variety of flavonoid glucuronides with medicinal value, including apigenin-7-O-glucuronide and scutellarein-7-O-glucuronide. With the use of MpUGT736B1, apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide were prepared by scaled-up enzymatic catalysis and structurally identified by NMR spectroscopy. MpUGT742A1 also displayed glucosyltransferase activity on the 7-OH position of the flavanones using UDP-glucose as the sugar donor. Furthermore, we constructed four recombinant strains by combining the pathway for increasing the UDP-glucuronic acid supply with the two novel UGTs MpUGT742A1 and MpUGT736B1. When apigenin was used as a substrate, the extracellular apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide production obtained from the Escherichia coli strain BB2 reached 598 and 81 mg/L, respectively. Our study provides new candidate genes and strategies for the biosynthesis of flavonoid glucuronides.

Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.

Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.

Impact of One-Lung Ventilation on Oxygenation and Ventilation Time in Thoracoscopic Heart Surgery: A Comparative Analysis with Median Thoracotomy.

BACKGROUND One-lung ventilation is the separation of the lungs by mechanical methods to allow ventilation of only one lung, particularly when there is pathology in the other lung. This retrospective study from a single center aimed to compare 49 patients undergoing thoracoscopic cardiac surgery using one-lung ventilation with 48 patients undergoing thoracoscopic cardiac surgery with median thoracotomy. MATERIAL AND METHODS This single-center retrospective study analyzed patients who underwent thoracoscopic cardiac surgery based on one-lung ventilation (experimental group, n=49). Other patients undergoing a median thoracotomy cardiac operation were defined as the comparison group (n=48). The oxygenation index and the mechanical ventilation time were also recorded. RESULTS There was no significant difference in the immediate oxygenation index between the experimental group and comparison group (P>0.05). There was no significant difference for the oxygenation index between men and women in both groups (P>0.05). The cardiopulmonary bypass time significantly affected the oxygenation index (F=7.200, P=0.009). Operation methods (one-lung ventilation thoracoscopy or median thoracotomy) affected postoperative ventilator use time (F=8.337, P=0.005). Cardiopulmonary bypass time (F=16.002, P<0.001) and age (F=4.384, P=0.039) had significant effects on ventilator use time. There was no significant effect of sex (F=0.75, P=0.389) on ventilator use time. CONCLUSIONS Our results indicated that one-lung ventilation thoracoscopic cardiac surgery did not affect the immediate postoperative oxygenation index; however, cardiopulmonary bypass time did significantly affect the immediate postoperative oxygenation index. Also, one-lung ventilation thoracoscopic cardiac surgery had a shorter postoperative mechanical ventilation use time than did traditional median thoracotomy cardiac surgery.

Mechanism of Allosteric Modulation of Nicotinamide Phosphoribosyltransferase to Elevate Cellular NAD.

In aging and disease, cellular nicotinamide adenine dinucleotide (NAD+) is depleted by catabolism to nicotinamide (NAM). NAD+ supplementation is being pursued to enhance human healthspan and lifespan. Activation of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ biosynthesis, has the potential to increase the salvage of NAM. Novel NAMPT-positive allosteric modulators (N-PAMs) were discovered in addition to the demonstration of NAMPT activation by biogenic phenols. The mechanism of activation was revealed through the synthesis of novel chemical probes, new NAMPT co-crystal structures, and enzyme kinetics. Binding to a rear channel in NAMPT regulates NAM binding and turnover, with biochemical observations being replicated by NAD+ measurements in human cells. The mechanism of action of N-PAMs identifies, for the first time, the role of the rear channel in the regulation of NAMPT turnover coupled to productive and nonproductive NAM binding. The tight regulation of cellular NAMPT via feedback inhibition by NAM, NAD+, and adenosine 5'-triphosphate (ATP) is differentially regulated by N-PAMs and other activators, indicating that different classes of pharmacological activators may be engineered to restore or enhance NAD+ levels in affected tissues.

Transcript-wide identification and expression pattern analysis to comprehend the roles of AP2/ERF genes under development and abiotic stress in Trichosanthes kirilowii.

BACKGROUND: The APETALA 2/ ethylene-responsive element binding factors (AP2/ERF), are thought to be associated with plant abiotic stress response, and involved in some plant hormone signaling pathways. Trichosanthes kirilowii is an important edible and medicinal crop, so far no research has been conducted on the TkAP2/ERF genes. RESULT: In this study, a total of 135 TkERFs were identified, these genes were divided into 4 subfamilies and clustered into 13 groups. Moreover, 37 paralogous pairs were identified, with only two having Ka/Ks values greater than 1, proving that most TkERF genes underwent purifying selection during evolution. Co-expression networks constructed using transcriptome data at various flowering stages revealed that 50, 64, and 67 AP2/ERF genes correlated with members of the ethylene, gibberellin, and abscisic acid signaling pathways, respectively. When tissue cultured seedlings were treated with ETH, GA3 and ABA, 11, 12 and 17 genes were found to be up-regulated, respectively, suggesting that some members of the TkERF gene family may be involved in plant hormone signaling pathways. And under 4 ℃, PEG and NaCl treatment, 15, 20 and 19 genes were up-regulated, respectively, this suggested that these selected genes might be involved in plant abiotic stresses. CONCLUSIONS: Overall, we identified 135 AP2/ERF family members, a comprehensive analysis of AP2/ERF gene expression patterns by RNA-seq and qRT-PCR showed that they played important roles in flower development and abiotic stress. This study provided a theoretical basis for the functional study of TkAP2/ERF genes and the genetic improvement of T. kirilowii.

Chiroptical Nanocellulose Bio-Labels for Independent Multi-Channel Optical Encryption.

Advanced multiplexing optical labels with multiple information channels provide a powerful strategy for large-capacity and high-security information encryption. However, current optical labels face challenges of difficulty to realize independent multi-channel encryption, cumbersome design, and environmental pollution. Herein, multiplexing chiroptical bio-labels integrating with multiple optical elements, including structural color, photoluminescence (PL), circular polarized light activity, humidity-responsible color, and micro/nano physical patterns, are constructed in complex design based on host-guest self-assembly of cellulose nanocrystals and bio-gold nanoclusters. The thin nanocellulose labels exhibit tunable circular polarized structural color crossover the entire visible wavelength and circularly polarized PL with the highest-recorded dissymmetry factor up to 1.05 due to the well-ordered chiral organization of templated gold nanoclusters. Most importantly, these elements can independently encode customized anti-counterfeiting information to achieve five independent channels of high-level anti-counterfeiting, which are rarely achieved in traditional materials and design counterparts. Considering the exceptional seamless integration of five independent encryption channels and the recyclable features of labels, the bio-labels have great potential for the next generation anti-counterfeiting materials technology.

Evidence for distinct mechanisms of small molecule inhibitors of filovirus entry.

Many small molecules have been identified as entry inhibitors of filoviruses. However, a lack of understanding of the mechanism of action for these molecules limits further their development as anti-filoviral agents. Here we provide evidence that toremifene and other small molecule entry inhibitors have at least three distinctive mechanisms of action and lay the groundwork for future development of anti-filoviral agents. The three mechanisms identified here include: (1) direct binding to the internal fusion loop region of Ebola virus glycoprotein (GP); (2) the HR2 domain is likely the main binding site for Marburg virus GP inhibitors and a secondary binding site for some EBOV GP inhibitors; (3) lysosome trapping of GP inhibitors increases drug exposure in the lysosome and further improves the viral inhibition. Importantly, small molecules targeting different domains on GP are synergistic in inhibiting EBOV entry suggesting these two mechanisms of action are distinct. Our findings provide important mechanistic insights into filovirus entry and rational drug design for future antiviral development.

Correction: Histone demethylase LSD1 restricts influenza A virus infection by erasing IFITM3-K88 monomethylation.

[This corrects the article DOI: 10.1371/journal.ppat.1006773.].

Gut microbiome, metabolome, host immunity associated with inflammatory bowel disease and intervention of fecal microbiota transplantation.

Gut dysbiosis has been associated with inflammatory bowel disease (IBD), one of the most common gastrointestinal diseases. The microbial communities play essential roles in host physiology, with profound effects on immune homeostasis, directly or via their metabolites and/or components. There are increasing clinical trials applying fecal microbiota transplantation (FMT) with Crohn's disease (CD) and ulcerative colitis (UC). The restoration of dysbiotic gut microbiome is considered as one of the mechanisms of FMT therapy. In this work, latest advances in the alterations in gut microbiome and metabolome features in IBD patients and experimental mechanistic understanding on their contribution to the immune dysfunction were reviewed. Then, the therapeutic outcomes of FMT on IBD were summarized based on clinical remission, endoscopic remission and histological remission of 27 clinical trials retrieved from PubMed which have been registered on ClinicalTrials.gov with the results been published in the past 10 years. Although FMT is established as an effective therapy for both subtypes of IBD, the promising outcomes are not always achieved. Among the 27 studies, only 11 studies performed gut microbiome profiling, 5 reported immune response alterations and 3 carried out metabolome analysis. Generally, FMT partially restored typical changes in IBD, resulted in increased α-diversity and species richness in responders and similar but less pronounced shifts of patient microbial and metabolomics profiles toward donor profiles. Measurements of immune responses to FMT mainly focused on T cells and revealed divergent effects on pro-/anti-inflammatory functions. The very limited information and the extremely confounding factors in the designs of the FMT trials significantly hindered a reasonable conclusion on the mechanistic involvement of gut microbiota and metabolites in clinical outcomes and an analysis of the inconsistencies.

Phosphorylation of enteroviral 2Apro at Ser/Thr125 benefits its proteolytic activity and viral pathogenesis.

Enteroviral 2A proteinase (2Apro ), a well-established and important viral functional protein, plays a key role in shutting down cellular cap-dependent translation, mainly via its proteolytic activity, and creating optimal conditions for Enterovirus survival. Accumulated data show that viruses take advantage of various signaling cascades for their life cycle; studies performed by us and others have demonstrated that the extracellular signal-regulated kinase (ERK) pathway is essential for enterovirus A71 (EV-A71) and other viruses replication. We recently showed that ERK1/2 is required for the proteolytic activity of viral 2Apro ; however, the mechanism underlying the regulation of 2Apro remains unknown. Here, we demonstrated that the 125th residue Ser125 of EV-A71 2Apro or Thr125 of coxsackievirus B3 2Apro , which is highly conserved in the Enterovirus, was phosphorylated by ERK1/2. Importantly, 2Apro with phosphor-Ser/Thr125 had much stronger proteolytic activity toward eukaryotic initiation factor 4GI and rendered the virus more efficient for multiplication and pathogenesis in hSCARB2 knock-in mice than that in nonphospho-Ser/Thr125A (S/T125A) mutants. Notably, phosphorylation-mimic mutations caused deleterious changes in 2Apro catalytic function (S/T125D/E) and in viral propagation (S125D). Crystal structure simulation analysis showed that Ser125 phosphorylation in EV-A71 2Apro enabled catalytic Cys to adopt an optimal conformation in the catalytic triad His-Asp-Cys, which enhances 2Apro proteolysis. Therefore, we are the first to report Ser/Thr125 phosphorylation of 2Apro increases enteroviral adaptation to the host to ensure enteroviral multiplication, causing pathogenicity. Additionally, weakened viruses containing a S/T125A mutation could be a general strategy to develop attenuated Enterovirus vaccines.

Unraveling the Emerging Photocatalytic, Thermoelectric, and Topological Properties of Intercalated Architecture MZX (M = Ga and In; Z = Si, Ge and Sn; X = S, Se, and Te) Monolayers.

The continuous advancements in studying two-dimensional (2D) materials pave the way for groundbreaking innovations across various industries. In this study, by employing density functional theory calculations, we comprehensively elucidate the electronic structures of MZX (M = Ga and In; Z = Si, Ge, and Sn; X = S, Se, and Te) monolayers for their applications in photocatalytic, thermoelectric, and spintronic fields. Interestingly, GaSiS, GaSiSe, InSiS, and InSiSe monolayers are identified to be efficient photocatalysts for overall water splitting with band gaps close to 2.0 eV, suitable band edge positions, and excellent optical harvest ability. In addition, the InSiTe monolayer exhibits a ZT value of 1.87 at 700 K, making it highly appealing for applications in thermoelectric devices. It is further highlighted that GaSnTe, InSnS, and InSnSe monolayers are predicted to be 2D topological insulators (TIs) with bulk band gaps of 115, 54, and 152 meV, respectively. Current research expands the family of 2D GaGeTe materials and establishes a path toward the practical utilization of MZX monolayers in energy conversion and spintronic devices.

Design, synthesis and biological evaluation of 2,4,6- trisubstituted triazine derivatives as new nonpeptide small-molecule SIRT5 inhibitors.

Human sirtuin 5 (SIRT5) participates in a variety of metabolic disorder-associated diseases, including cancer. Inhibition of SIRT5 has been confirmed to provide a new strategy for treatment of related diseases. Previously, we discovered a pyrimidine skeleton inhibitor XIV, which showed low micromolar inhibitory activity against SIRT5. Herein, we utilized the scaffold-hopping strategy to design and synthesize a series of 2,4,6- trisubstituted triazine derivatives. The SAR analysis led to the discovery of several new SIRT5 inhibitors with low micromolar inhibition levels. The most potent compounds 10 (IC50 = 5.38 µM), and 14 (IC50 = 4.07 µM) were further confirmed to be the substrate-competitive SIRT5 inhibitors through enzyme kinetic assays, which is consistent with the molecular docking analyses. Fluorescence-based thermal shift assays proved that these compounds may stabilize SIRT5 by binding withprotein.. In addition, compounds 10 and 14 were also revealed to have moderate selectivity to SIRT5 over SIRT1-3. This study will aid further efforts to develop highly potent and selective SIRT5 inhibitors for the treatment of cancer and other related diseases.

Vibrational non-Boltzmann effects on the dissociation rate of oxygen.

Both the internal energy nonequilibrium and the NB effects of the vibrational state distribution influence the calculation of the dissociation rate coefficient. The state-to-state (STS) method gives the exact dissociation rate coefficients under the influence of two nonequilibrium effects, while the single group linear maximum-entropy (SGLM) model only considers the internal energy nonequilibrium effects. Therefore, the ratio ζ of the dissociation rate coefficient calculated by the STS method and the SGLM model is used in this paper to describe the NB effects on the dissociation rate coefficient. The zero-dimensional (0D) heating adiabatic thermochemical nonequilibrium process of oxygen was simulated by the STS method with a post-surge temperature of 7000-11 000 K. The variation regularity of the NB effects in the relaxation process were investigated using ζ, and it was found that the NB effects were mainly affected by temperature. And then the relaxation process after the normal shock with the same post-surge temperature of 7000-11 000 K was simulated. The NB effects in the two non-equilibrium processes were compared, and it was found that although there is a conversion between internal energy and fluid kinetic energy in the latter, the NB effects in both processes have similar change rules with similar temperature change rules. If the specific internal energy is the same, the NB effects in both processes are also quantitatively consistent. This finding provides a basis for the improvement of the nonequilibrium model considering the NB effects.

Identifying the protonation site and the scope of non-proline cis-peptide bond conformations: a first-principles study on protonated oligopeptides.

The existence of non-proline cis-peptide bond conformations of protonated triglycine proposed by us has been verified through a recent IR-IR double resonance experiment. However, the scope of such unique structures in protonated oligopeptides and whether protonation at amide oxygen is more stable than that at traditional amino nitrogen remain unsolved. In this study, the most stable conformers of a series of protonated oligopeptides were fully searched. Our findings reveal that the special cis-peptide bond structure appears with high energies for diglycine and is energetically less favored for tetra- and pentapeptides, while it acts as the global minimum only for tripeptides. To explore the formation mechanism of the cis-peptide bond, electrostatic potential analysis, and intramolecular interactions were analyzed. Advanced theoretical calculations confirmed that amino nitrogen is still preferred as the protonated site in most cases except glycylalanylglycine(GAG). The energy difference between the two protonated isomers of GAG is only 0.03 kcal mol-1, indicating that the tripeptide is most likely to be protonated on the amide oxygen first. We also conducted chemical (infrared (IR)) and electronic (X-ray photoelectron spectra (XPS) and near-edge X-ray absorption fine structure spectra (NEXAFS)) structure calculations of these peptides to identify their notable differences unambiguously. This study thus provides valuable information for exploring the scope of cis-peptide bond conformation and the competition between two different protonated ways.

Anharmonic phonon renormalization and thermoelectric properties of CsPbX3 (X = Cl, Br, and I): first-principles calculations.

Halide perovskites with ultralow thermal conductivity have emerged as promising candidates for thermoelectric materials. We study the lattice dynamics and thermoelectric properties of cubic all-inorganic lead halide perovskites CsPbX3 (X = Cl, Br, and I) through first-principles calculations. Combined with self-consistent phonon theory, we have successfully renormalized the phonon frequency using a quartic anharmonic term, allowing us to accurately reproduce the phonon dispersion of the high-temperature cubic phase of CsPbX3 without any imaginary frequencies. Cubic CsPbX3 exhibit ultralow lattice thermal conductivities (0.61-1.71 Wm-1 K-1) at room temperature. Because of the strong quartic anharmonic renormalization and hardening of the soft modes, the lattice thermal conductivities of cubic CsPbX3 all exhibit weak temperature dependence. Notably, CsPbCl3 exhibits remarkably high thermal conductivity and a long phonon lifetime. This can be attributed to the smallest atomic mean square displacement and the weakest tilting and distortions of PbCl6 octahedra, resulting from the strongest Pb-Cl covalent bonding. Furthermore, the maximum ZT value of 0.63 at 900 K is obtained for the n-type CsPbBr3.