Time-dependent risk of atopic dermatitis following nontyphoidal Salmonella infection.

BACKGROUND: The pathogenesis of atopic dermatitis (AD) remains unclear. Nontyphoidal Salmonella (NTS) infection might trigger immune-mediated reactions. We aimed to examine NTS and the risk of subsequent AD. METHODS: From 2002 to 2015, eligible patients (aged 0-100 years) with NTS were identified. NTS and non-NTS groups were matched at a 1:10 ratio on age and sex. We utilized conditional multivariable Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for AD development. Subgroup analyses were conducted based on age, sex, and severity of NTS infection. We utilized landmark analysis to explore the time-dependent hazard of AD following NTS. RESULTS: In the NTS group (N = 6624), 403 developed AD. After full adjustment of demographics and comorbidities, the NTS group had a higher risk of AD than the reference group (aHR = 1.217, 95% CI = 1.096-1.352). Age-stratified analysis revealed that NTS group exhibited an elevated risk compared to the reference group, particularly among those aged 13-30 years (aHR = 1.25, 95% CI = 1.017-1.559), individuals aged 31-50 years (aHR = 1.388, 95% CI = 1.112-1.733), those aged 51-70 years (aHR = 1.301, 95% CI = 1.008-1.679), and individuals aged 71 years and over (aHR = 1.791, 95% CI = 1.260-2.545). Severe NTS was associated with a higher risk of AD than the reference group (aHR = 2.411, 95% CI = 1.577-3.685). Landmark analysis showed generally consistent findings. CONCLUSIONS: Minimizing exposure to NTS infection may represent a prospective strategy for averting the onset and progression of atopic dermatitis.

The plant pathogen enzyme AldC is a long-chain aliphatic aldehyde dehydrogenase.

Aldehyde dehydrogenases are versatile enzymes that serve a range of biochemical functions. Although traditionally considered metabolic housekeeping enzymes because of their ability to detoxify reactive aldehydes, like those generated from lipid peroxidation damage, the contributions of these enzymes to other biological processes are widespread. For example, the plant pathogen Pseudomonas syringae strain PtoDC3000 uses an indole-3-acetaldehyde dehydrogenase to synthesize the phytohormone indole-3-acetic acid to elude host responses. Here we investigate the biochemical function of AldC from PtoDC3000. Analysis of the substrate profile of AldC suggests that this enzyme functions as a long-chain aliphatic aldehyde dehydrogenase. The 2.5 Å resolution X-ray crystal of the AldC C291A mutant in a dead-end complex with octanal and NAD+ reveals an apolar binding site primed for aliphatic aldehyde substrate recognition. Functional characterization of site-directed mutants targeting the substrate- and NAD(H)-binding sites identifies key residues in the active site for ligand interactions, including those in the "aromatic box" that define the aldehyde-binding site. Overall, this study provides molecular insight for understanding the evolution of the prokaryotic aldehyde dehydrogenase superfamily and their diversity of function.

Reevaluating the mechanism of excitation energy regulation in iron-starved cyanobacteria.

This paper presents spectroscopic investigations of IsiA, a chlorophyll a-binding membrane protein produced by cyanobacteria grown in iron-deficient environments. IsiA, if associated with photosystem I, supports photosystem I in light harvesting by efficiently transferring excitation energy. However, if separated from photosystem I, IsiA exhibits considerable excitation quenching observed as a substantial reduction of protein-bound chlorophyll a fluorescence lifetime. Previous spectroscopic studies suggested that carotenoids are involved in excitation energy dissipation and in addition play a second role in this antenna complex by supporting chlorophyll a in light harvesting by absorbing in the spectral range inaccessible for chlorophyll a and transferring excitation to chlorophylls. However, this investigation does not support these proposed roles of carotenoids in this light harvesting protein. This study shows that carotenoids do not transfer excitation energy to chlorophyll a. In addition, our investigations do not support the hypothesis that carotenoids are quenchers of the excited state of chlorophyll a in this protein complex. We propose that quenching of chlorophyll a fluorescence in IsiA is maintained by pigment-protein interaction via electron transfer from an excited chlorophyll a to a cysteine residue, an excitation quenching mechanism that was recently proposed to regulate the light harvesting capabilities of the bacteriochlorophyll a-containing Fenna-Mathews-Olson protein from green sulfur bacteria.

Graphene-to-substrate energy transfer through out-of-plane longitudinal acoustic phonons.

Practically, graphene is often deposited on substrates. Given the major substrate-induced modification of properties and considerable energy transfer at the interface, the graphene-substrate interaction has been widely discussed. However, the proposed mechanisms were restricted to the two-dimensional (2D) plane and interface, while the energy conduction in the third dimension is hardly considered. Herein, we disclose the transfer of energy perpendicular to the interface of the combined system of the 2D graphene and the 3D base. More precisely, our observation of the energy dissipation of optically excited graphene via emitting out-of-plane longitudinal acoustic phonon into the substrate is presented. By applying nanoultrasonic spectroscopy with a piezoelectric nanolayer embedded in the substrate, we found that under photoexcitation by a femtosecond laser pulse graphene can emit longitudinal coherent acoustic phonons (CAPs) with frequencies over 1 THz into the substrate. In addition, the waveform of the CAP pulse infers that the photocarriers and sudden lattice heating in graphene caused modification of graphene-substrate bond and consequently generated longitudinal acoustic phonons in the substrate. The direct observation of this unexplored graphene-to-substrate vertical energy transfer channel can bring new insights into the understanding of the energy dissipation and limited transport properties of supported graphene.

A setup for hard x-ray time-resolved resonant inelastic x-ray scattering at SwissFEL.

We present a new setup for resonant inelastic hard x-ray scattering at the Bernina beamline of SwissFEL with energy, momentum, and temporal resolution. The compact R = 0.5 m Johann-type spectrometer can be equipped with up to three crystal analyzers and allows efficient collection of RIXS spectra. Optical pumping for time-resolved studies can be realized with a broad span of optical wavelengths. We demonstrate the performance of the setup at an overall ∼180 meV resolution in a study of ground-state and photoexcited (at 400 nm) honeycomb 5d iridate α-Li2IrO3. Steady-state RIXS spectra at the iridium L3-edge (11.214 keV) have been collected and are in very good agreement with data collected at synchrotrons. The time-resolved RIXS transients exhibit changes in the energy loss region <2 eV, whose features mostly result from the hopping nature of 5d electrons in the honeycomb lattice. These changes are ascribed to modulations of the Ir-to-Ir inter-site transition scattering efficiency, which we associate to a transient screening of the on-site Coulomb interaction.

Risk of autoimmune diseases in patients with COVID-19: A retrospective cohort study.

Background: There are a growing number of case reports of various autoimmune diseases occurring after COVID-19, yet there is no large-scale population-based evidence to support this potential association. This study provides a closer insight into the association between COVID-19 and autoimmune diseases and reveals discrepancies across sex, age, and race of participants. Methods: This is a retrospective cohort study based on the TriNetX U.S. Collaborative Network. In the test-negative design, cases were participants with positive polymerase chain reaction (PCR) test results for SARS-CoV-2, while controls were participants who tested negative and were not diagnosed with COVID-19 throughout the follow-up period. Patients with COVID-19 and controls were propensity score-matched (1: 1) for age, sex, race, adverse socioeconomic status, lifestyle-related variables, and comorbidities. The primary endpoint is the incidence of newly recorded autoimmune diseases. Adjusted hazard ratios (aHRs) and 95% confident intervals (CIs) of autoimmune diseases were calculated between propensity score-matched groups with the use of Cox proportional-hazards regression models. Findings: Between January 1st, 2020 and December 31st, 2021, 3,814,479 participants were included in the study (888,463 cases and 2,926,016 controls). After matching, the COVID-19 cohort exhibited significantly higher risks of rheumatoid arthritis (aHR:2.98, 95% CI:2.78-3.20), ankylosing spondylitis (aHR:3.21, 95% CI:2.50-4.13), systemic lupus erythematosus (aHR:2.99, 95% CI:2.68-3.34), dermatopolymyositis (aHR:1.96, 95% CI:1.47-2.61), systemic sclerosis (aHR:2.58, 95% CI:2.02-3.28), Sjögren's syndrome (aHR:2.62, 95% CI:2.29-3.00), mixed connective tissue disease (aHR:3.14, 95% CI:2.26-4.36), Behçet's disease (aHR:2.32, 95% CI:1.38-3.89), polymyalgia rheumatica (aHR:2.90, 95% CI:2.36-3.57), vasculitis (aHR:1.96, 95% CI:1.74-2.20), psoriasis (aHR:2.91, 95% CI:2.67-3.17), inflammatory bowel disease (aHR:1.78, 95%CI:1.72-1.84), celiac disease (aHR:2.68, 95% CI:2.51-2.85), type 1 diabetes mellitus (aHR:2.68, 95%CI:2.51-2.85) and mortality (aHR:1.20, 95% CI:1.16-1.24). Interpretation: COVID-19 is associated with a different degree of risk for various autoimmune diseases. Given the large sample size and relatively modest effects these findings should be replicated in an independent dataset. Further research is needed to better understand the underlying mechanisms. Funding: Kaohsiung Veterans General Hospital (KSVGH111-113).

Genomic profiling and prognostic factors of H3 K27M-mutant spinal cord diffuse glioma.

H3 K27-altered diffuse midline glioma is a highly lethal pediatric-type tumor without efficacious treatments. Recent findings have highlighted the heterogeneity among diffuse midline gliomas with different locations and ages. Compared to tumors located in the brain stem and thalamus, the molecular and clinicopathological features of H3 K27-altered spinal cord glioma are still largely elusive, thus hindering the accurate management of patients. Here we aimed to characterize the clinicopathological and molecular features of H3 K27M-mutant spinal cord glioma in 77 consecutive cases. We found that the H3 K27M-mutant spinal cord glioma, with a median age of 35 years old, had a significantly better prognosis than H3 K27M-mutant brain tumors. We noticed a molecular heterogeneity of H3 K27M-mutant spinal cord astrocytoma via targeted sequencing with 34 cases. TP53 mutation which occurred in 58.8% of cases is mutually exclusive with PPM1D (26%) and NF1 (44%) mutations. The TP53-mutant cases had a significantly higher number of copy number variants (CNV) and a marginally higher proportion of pediatric patients (age at diagnosis <18 years old, p = 0.056). Cox regression and Kaplan-Meier curve analysis showed that the higher number of CNV events (≥3), chromosome (Chr) 9p deletion, Chr 10p deletion, ATRX mutation, CDK6 amplification, and retinoblastoma protein (RB) pathway alteration are associated with worse survival. Cox regression analysis with clinicopathological features showed that glioblastoma histological type and a high Ki-67 index (>10%) are associated with a worse prognosis. Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can also stratify molecular features of H3 K27M-mutant spinal cord glioma, including the RB pathway, KRAS/PI3K pathway, and chromosome arms CNV. In conclusion, although all H3 K27M-mutant spinal cord diffuse glioma were diagnosed as WHO Grade 4, the histological type, molecular features representing chromatin instability, and molecular alterations associated with accelerated cell proliferative activity should not be ignored in clinical management.

Disentangling the evolution of electrons and holes in photoexcited ZnO nanoparticles.

The evolution of charge carriers in photoexcited room temperature ZnO nanoparticles in solution is investigated using ultrafast ultraviolet photoluminescence spectroscopy, ultrafast Zn K-edge absorption spectroscopy, and ab initio molecular dynamics (MD) simulations. The photoluminescence is excited at 4.66 eV, well above the band edge, and shows that electron cooling in the conduction band and exciton formation occur in <500 fs, in excellent agreement with theoretical predictions. The x-ray absorption measurements, obtained upon excitation close to the band edge at 3.49 eV, are sensitive to the migration and trapping of holes. They reveal that the 2 ps transient largely reproduces the previously reported transient obtained at 100 ps time delay in synchrotron studies. In addition, the x-ray absorption signal is found to rise in ∼1.4 ps, which we attribute to the diffusion of holes through the lattice prior to their trapping at singly charged oxygen vacancies. Indeed, the MD simulations show that impulsive trapping of holes induces an ultrafast expansion of the cage of Zn atoms in <200 fs, followed by an oscillatory response at a frequency of ∼100 cm-1, which corresponds to a phonon mode of the system involving the Zn sub-lattice.

Metabolomic Mechanisms of Radix Fici Hirtae against Carbon Tetrachloride-Induced Acute Liver Damage in Mice.

Background: Radix Fici Hirtae (RFH), known as Cantonese ginseng, is an alternative folk medicine that is widely used to treat various diseases in southern China. The aim of this study was to investigate the effect and metabolic mechanisms of pretreatment with RFH on the serum metabolic profiles of carbon tetrachloride (CCl4) induced acute liver injury in mice. Methods: Mice fed with the water extract of RFH at a dose of 1.5 g/kg and 0.75 g/kg for consecutive 7 days, and then serum samples were taken for the metabolomic analysis. Furthermore, the bioinformatics and pathways analysis were measured. Results: The UHPLC-Orbitrap/MS based-metabolomic analysis identified 20 differential metabolic markers in serum of CCl4-induced liver injury mice compared to that of the normal controls, which were mainly related to the metabolism of amino acids and fatty acids. Furthermore, most of these biomarkers contributing to CCl4 induction were ameliorated by RFH, and the bioinformatics and pathways analysis revealed that therapeutic actions of RFH were mainly involved in the regulation of the oxidative stress responses and energy homeostasis. Conclusion: These findings provide potential metabolic mechanism for future study and allow for hypothesis generation about the hepatoprotective effects of Radix Fici Hirtae.

Female Human Papillomavirus Infection Associated with Increased Risk of Ectopic Pregnancy: Early Evidence from Taiwan Population-Based Cohort Study.

BACKGROUND: This is an investigation of the human papillomavirus (HPV) infection and its correlation with the risk of ectopic pregnancy (EP). METHODS: The cohort study includes 11,239 patients with newly diagnosed HPV infections between 2000 and 2012, and by using computer-generated random numbers, patients who do not have HPV infections are selected randomly as the comparison cohort. The HPV infection cohort is matched to comparison individuals at a 1:10 ratio by age and index year. All individuals included in the study were followed up to the point they developed EP, pulled-out from the insurance program, lost to follow-up, or until the end of 2013. A Cox proportional-hazards regression analysis was used to analyze the risk of EP with the hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. RESULTS: The adjusted hazard ratio (aHR) of EP for HPV patients relative to controls is 1.70 (95% CI = 1.04, 2.78), indicating a positive correlation between EP and HPV in the 13-year follow-up period, after adjusting for age and relevant comorbidities. The sensitivity analyses yield similar results. CONCLUSIONS: A history of HPV infection is a potential risk factor associated with the development of subsequent EP in Taiwanese individuals, especially those diagnosed with an HPV infection within 3 years.

A Novel Mode of Photoprotection Mediated by a Cysteine Residue in the Chlorophyll Protein IsiA.

Oxygenic photosynthetic organisms have evolved a multitude of mechanisms for protection against high-light stress. IsiA, a chlorophyll a-binding cyanobacterial protein, serves as an accessory antenna complex for photosystem I. Intriguingly, IsiA can also function as an independent pigment protein complex in the thylakoid membrane and facilitate the dissipation of excess energy, providing photoprotection. The molecular basis of the IsiA-mediated excitation quenching mechanism remains poorly understood. In this study, we demonstrate that IsiA uses a novel cysteine-mediated process to quench excitation energy. The single cysteine in IsiA in the cyanobacterium Synechocystis sp. strain PCC 6803 was converted to a valine. Ultrafast fluorescence spectroscopic analysis showed that this single change abolishes the excitation energy quenching ability of IsiA, thus providing direct evidence of the crucial role of this cysteine residue in energy dissipation from excited chlorophylls. Under stress conditions, the mutant cells exhibited enhanced light sensitivity, indicating that the cysteine-mediated quenching process is critically important for photoprotection.IMPORTANCE Cyanobacteria, oxygenic photosynthetic microbes, constantly experience varying light regimes. Light intensities higher than those that saturate the photosynthetic capacity of the organism often lead to redox damage to the photosynthetic apparatus and often cell death. To meet this challenge, cyanobacteria have developed a number of strategies to modulate light absorption and dissipation to ensure maximal photosynthetic productivity and minimal photodamage to cells under extreme light conditions. In this communication, we have determined the critical role of a novel cysteine-mediated mechanism for light energy dissipation in the chlorophyll protein IsiA.

Adjustments to Photosystem Stoichiometry and Electron Transfer Proteins Are Key to the Remarkably Fast Growth of the Cyanobacterium Synechococcus elongatus UTEX 2973.

At the genome level, Synechococcus elongatus UTEX 2973 (Synechococcus 2973) is nearly identical to the model cyanobacterium Synechococcus elongatus PCC 7942 (Synechococcus 7942) with only 55 single nucleotide differences separating the two strains. Despite the high similarity between the two strains, Synechococcus 2973 grows three times faster, accumulates significantly more glycogen, is tolerant to extremely high light intensities, and displays higher photosynthetic rates. The high homology between the two strains provides a unique opportunity to examine the factors that lead to increased photosynthetic rates. We compared the photophysiology of the two strains and determined the differences in Synechococcus 2973 that lead to increased photosynthetic rates and the concomitant increase in biomass production. In this study, we identified inefficiencies in the electron transport chain of Synechococcus 7942 that have been alleviated in Synechococcus 2973. Photosystem II (PSII) capacity is the same in both strains. However, Synechococcus 2973 exhibits a 1.6-fold increase in PSI content, a 1.5-fold increase in cytochrome b6f content, and a 2.4-fold increase in plastocyanin content on a per cell basis. The increased content of electron carriers allows a higher flux of electrons through the photosynthetic electron transport chain, while the increased PSI content provides more oxidizing power to maintain upstream carriers ready to accept electrons. These changes serve to increase the photosynthetic efficiency of Synechococcus 2973, the fastest growing cyanobacterium known.IMPORTANCE As the global population increases, the amount of arable land continues to decrease. To prevent a looming food crisis, crop productivity per acre must increase. A promising target for improving crop productivity is increasing the photosynthetic rates in crop plants. Cyanobacteria serve as models for higher plant photosynthetic systems and are an important test bed for improvements in photosynthetic productivity. In this study, we identified key factors that lead to improved photosynthetic efficiency and increased production of biomass of a cyanobacterium. We suggest that the findings presented herein will give direction to improvements that may be made in other photosynthetic organisms to improve photosynthetic efficiency.

High Sensitivity of T-Ray for Thrombus Sensing.

Atherosclerotic plaque rupture or erosion and subsequent development of platelet-containing thrombus formation is the fundamental cause of cardiovascular disease, which is the most common cause of death and disability worldwide. Here we show the high sensitivity of 200-270 GHz T-ray to distinguish thrombus formation at its early stage from uncoagulated blood. A clinical observational study was conducted to longitudinally monitor the T-ray absorption constant of ex-vivo human blood during the thrombus formation from 29 subjects. Compared with the control group (28 subjects) with uncoagulated blood samples, our analysis indicates the high sensitivity of 200-270 GHz T-Ray to detect thrombus with a low p-value < 10-5. Further analysis supports the significant role of platelet-activated thrombotic cascade, which modified the solvation dynamics of blood and occurred during the early coagulation stage, on the measured T-Ray absorption change. The ability to sense the thrombus formation at its early stage would hold promise for timely identification of patients at risk of various atherothrombotic disorders and save billions of lives.