Sluggish and Chemically-Biased Interstitial Diffusion in Concentrated Solid Solution Alloys: Mechanisms and Methods

Interstitial diffusion is a pivotal process that governs the phase stability and irradiation response of materials in non-equilibrium conditions. In this work, we study sluggish and chemically-biased interstitial diffusion in Fe-Ni concentrated solid solution alloys (CSAs) by combining machine learning (ML) and kinetic Monte Carlo (kMC), where ML is used to accurately and efficiently predict the migration energy barriers on-the-fly. The ML-kMC reproduces the diffusivity that was reported by molecular dynamics results at high temperatures. With this powerful tool, we find that the observed sluggish diffusion and the "Ni-Ni-Ni"-biased diffusion in Fe-Ni alloys are ascribed to a unique "Barrier Lock" mechanism, whereas the "Fe-Fe-Fe"-biased diffusion is influenced by a "Component Dominance" mechanism. Inspired by the mentioned mechanisms, a practical AvgS-kMC method is proposed for conveniently and swiftly determining interstitial-mediated diffusivity by only relying on the mean energy barriers of migration patterns. Combining the AvgS-kMC with the differential evolutionary algorithm, an inverse design strategy for optimizing sluggish diffusion properties is applied to emphasize the crucial role of favorable migration patterns.Comment: 30 pages,9 figure

The global/local (limited to some regions) effect of cesarean delivery on the risk of pediatric allergic rhinitis: a systematic review and meta-analysis

BackgroundAllergic rhinitis is a chronic and refractory disease that can be affected by a variety of factors. Studies have shown an association between cesarean section and the risk of pediatric allergic rhinitis.MethodsThe PubMed, Springer, Embase, Cochrane Library, and Web of Science databases were searched to retrieve all studies published from January 2000 to November 2022, focusing on the relationship between cesarean section and the risk of pediatric allergic rhinitis. A meta-analysis was conducted to find a correlation between cesarean section and the risk of pediatric allergic rhinitis. A subgroup analysis was performed, considering the region and family history of allergy, after adjusting for confounding factors. Pooled odds ratios (ORs) were calculated, publication bias was assessed using a funnel plot, and heterogeneity between study-specific relative risks was taken into account.ResultsThe results showed that cesarean section was significantly associated with an increased risk of pediatric allergic rhinitis (OR: 1.27, 95% CI: 1.20–1.35). Subgroup analysis stratified by region indicated that cesarean section increased the risk of pediatric allergic rhinitis, with the highest increase in South America (OR: 1.67, 95% CI: 1.10–2.52) and the lowest in Europe (OR: 1.13, 95% CI: 1.02–1.25). The results of the subgroup analysis stratified by family history of allergy indicate that family history of allergy was not associated with the risk of pediatric allergic rhinitis.ConclusionAn association exists between cesarean section as the mode of delivery and the increased risk of pediatric allergic rhinitis, and cesarean section is a risk factor for allergic rhinitis

Identification and treatment of intestinal malrotation with midgut volvulus in childhood: a multicenter retrospective study

BackgroundIntestinal malrotation is a rare condition, and its delayed diagnosis can lead to fatal consequences. This study aimed to investigate the identification and treatment of malrotation in children.MethodsClinical data, imaging, operative findings, and early postoperative outcomes of 75 children with malrotation were retrospectively analyzed.ResultsThe mean age was 6.18 ± 4.93 days and 51.26 ± 70.13 months in the neonatal group (56 patients) and non-neonatal group (19 patients), respectively. Sixty-seven patients were under the age of 1 year at the time of diagnosis. The occurrence of bilious vomiting and jaundice was significantly higher in the neonatal group (89.29%) than that in the non-neonatal group (37.5%), p < 0.05 and p < 0.01, respectively. The incidence of abnormal ultrasound (US) findings was 97.30% and 100%, respectively, and the sensitivities of the upper gastrointestinal series were 84.21% and 87.5%, respectively. Sixty-six (88%) patients had midgut volvulus, including in utero volvulus (two patients) and irreversible intestinal ischemia (four patients). Most neonates (89.29%) underwent open Ladd's procedure with a shorter operative time (p < 0.01). Reoperation was performed for postoperative complications (four patients) or missed comorbidities (two patients).ConclusionsNon-bilious vomiting was the initial symptom in >10% of neonates and nearly 40% of non-neonates. This highlights the importance for emergency physicians and surgeons to be cautious about ruling out malrotation in patients with non-bilious vomiting. Utilizing US can obviate the need for contrast examinations owing to its higher diagnostic accuracy and rapid diagnosis and can be recommended as a first-line imaging technique. Additionally, open surgery is still an option for neonatal patients

Comprehensive succinylome analyses reveal that hyperthermia upregulates lysine succinylation of annexin A2 by downregulating sirtuin7 in human keratinocytes

Background and Objectives: Local hyperthermia at 44°C can clear multiple human papillomavirus (HPV)-infected skin lesions (warts) by targeting a single lesion, which is considered as a success of inducing antiviral immunity in the human body. However, approximately 30% of the patients had a lower response to this intervention. To identify novel molecular targets for anti-HPV immunity induction to improve local hyperthermia efficacy, we conducted a lysine succinylome assay in HaCaT cells (subjected to 44°C and 37°C water baths for 30 min). Methods: The succinylome analysis was conducted on HaCaT subjected to 44°C and 37°C water bath for 30 min using antibody affinity enrichment together with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were validated by western blot (WB), immunoprecipitation (IP), and co-immunoprecipitation (Co-IP). Then, bioinformatic analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, motif characterization, secondary structure, and protein–protein interaction (PPI) was performed. Results: A total of 119 proteins with 197 succinylated sites were upregulated in 44°C-treated HaCaT cells. GO annotation demonstrated that differential proteins were involved in the immune system process and viral transcription. Succinylation was significantly upregulated in annexin A2. We found that hyperthermia upregulated the succinylated level of global proteins in HaCaT cells by downregulating the desuccinylase sirtuin7 (SIRT7), which can interact with annexin A2. Conclusions: Taken together, these data indicated that succinylation of annexin A2 may serve as a new drug target, which could be intervened in combination with local hyperthermia for better treatment of cutaneous warts

Three Capsular Polysaccharide Synthesis-Related Glucosyltransferases, GT-1, GT-2 and WcaJ, Are Associated With Virulence and Phage Sensitivity of Klebsiella pneumoniae

Klebsiella pneumoniae (K. pneumoniae) spp. are important nosocomial and community-acquired opportunistic pathogens, which cause various infections. We observed that K. pneumoniae strain K7 abruptly mutates to rough-type phage-resistant phenotype upon treatment with phage GH-K3. In the present study, the rough-type phage-resistant mutant named K7RR showed much lower virulence than K7. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis indicated that WcaJ and two undefined glycosyltransferases (GTs)- named GT-1, GT-2- were found to be down-regulated drastically in K7RR as compared to K7 strain. GT-1, GT-2, and wcaJ are all located in the gene cluster of capsular polysaccharide (CPS). Upon deletion, even of single component, of GT-1, GT-2, and wcaJ resulted clearly in significant decline of CPS synthesis with concomitant development of GH-K3 resistance and decline of virulence of K. pneumoniae, indicating that all these three GTs are more likely involved in maintenance of phage sensitivity and bacterial virulence. Additionally, K7RR and GT-deficient strains were found sensitive to endocytosis of macrophages. Mitogen-activated protein kinase (MAPK) signaling pathway of macrophages was significantly activated by K7RR and GT-deficient strains comparing with that of K7. Interestingly, in the presence of macromolecular CPS residues (>250 KD), K7(ΔGT-1) and K7(ΔwcaJ) could still be bounded by GH-K3, though with a modest adsorption efficiency, and showed minor virulence, suggesting that the CPS residues accumulated upon deletion of GT-1 or wcaJ did retain phage binding sites as well maintain mild virulence. In brief, our study defines, for the first time, the potential roles of GT-1, GT-2, and WcaJ in K. pneumoniae in bacterial virulence and generation of rough-type mutation under the pressure of bacteriophage

T cell repertoire profiling in allografts and native tissues in recipients with COVID–19 after solid organ transplantation: Insight into T cell–mediated allograft protection from viral infection

IntroductionThe effects of the SARS-CoV-2 virus on the body, and why the effects are more severe in certain patients, remain incompletely understood. One population of special interest is transplant recipients because of their immunosuppressed state. Understanding the pathophysiology of graft dysfunction in transplant patients with the COVID-19 viral syndrome is important for prognosticating the risk to the graft as well as understanding how best to prevent and, if necessary, treat graft injury in these patients.MethodsWe analyzed multiple types of solid organ transplant recipients (liver, kidney, heart or lung) at our institution who died from SARS-CoV-2 and underwent autopsy (n = 6) or whose grafts were biopsied during active SARS-CoV-2 infection (n = 8). Their serum inflammatory markers were examined together with the histological appearance, viral load, and TCR repertoire of their graft tissue and, for autopsy patients, several native tissues.ResultsHistology and clinical lab results revealed a systemic inflammatory pattern that included elevated inflammatory markers and diffuse tissue damage regardless of graft rejection. Virus was detected throughout all tissues, although most abundant in lungs. The TCR repertoire was broadly similar throughout the tissues of each individual, with greater sharing of dominant clones associated with more rapid disease course. There was no difference in viral load or clonal distribution of overall, COVID-associated, or putative SARS-CoV-2-specific TCRs between allograft and native tissue. We further demonstrated that SARSCoV-2-specific TCR sequences in transplant patients lack a donor HLArestricted pattern, regardless of distribution in allograft or native tissues,suggesting that recognition of viral antigens on infiltrating recipient cells can effectively trigger host T cell anti-viral responses in both the host and graft.DiscussionOur findings suggest a systemic immune response to the SARS-CoV-2 virus in solid organ transplant patients that is not associated with rejection and consistent with a largely destructive effect of recipient HLA-restricted T cell clones that affects donor and native organs similarly

A Method for Generation Phage Cocktail with Great Therapeutic Potential

Background: Bacteriophage could be an alternative to conventional antibiotic therapy against multidrug-resistant bacteria. However, the emergence of resistant variants after phage treatment limited its therapeutic application. Methodology/Principal Findings: In this study, an approach, named ‘‘Step-by-Step’ ’ (SBS), has been established. This method takes advantage of the occurrence of phage-resistant bacteria variants and ensures that phages lytic for wild-type strain and its phage-resistant variants are selected. A phage cocktail lytic for Klebsiella pneumoniae was established by the SBS method. This phage cocktail consisted of three phages (GH-K1, GH-K2 and GH-K3) which have different but overlapping host strains. Several phage-resistant variants of Klebsiella pneumoniae were isolated after different phages treatments. The virulence of these variants was much weaker [minimal lethal doses (MLD).1.3610 9 cfu/mouse] than that of wild-type K7 countpart (MLD = 2.5610 3 cfu/mouse). Compared with any single phage, the phage cocktail significantly reduced the mutation frequency of Klebsiella pneumoniae and effectively rescued Klebsiella pneumoniae bacteremia in a murine K7 strain challenge model. The minimal protective dose (MPD) of the phage cocktail which was sufficient to protect bacteremic mice from lethal K7 infection was only 3.0610 4 pfu, significantly smaller (p,0.01) than that of single monophage. Moreover, a delayed administration of this phage cocktail was still effective in protection against K7 challenge. Conclusions/Significance: Our data showed that the phage cocktail was more effective in reducing bacterial mutatio

Towards efficient photoinduced charge separation in carbon nanodots and TiO 2

In this work, photoinduced charge separation behaviors in non-long-chain-molecule-functionalized carbon nanodots (CDs) with visible intrinsic absorption (CDs-V) and TiO2 composites were investigated. Efficient photoinduced electron injection from CDs-V to TiO2 with a rate of 8.8 × 108 s−1 and efficiency of 91% was achieved in the CDs-V/TiO2 composites. The CDs-V/TiO2 composites exhibited excellent photocatalytic activity under visible light irradiation, superior to pure TiO2 and the CDs with the main absorption band in the ultraviolet region and TiO2 composites, which indicated that visible photoinduced electrons and holes in such CDs-V/TiO2 composites could be effectively separated. The incident photon-to-current conversion efficiency (IPCE) results for the CD-sensitized TiO2 solar cells also agreed with efficient photoinduced charge separation between CDs-V and the TiO2 electrode in the visible range. These results demonstrate that non-long-chain-molecule-functionlized CDs with a visible intrinsic absorption band could be appropriate candidates for photosensitizers and offer a new possibility for the development of a well performing CD-based photovoltaic system