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Vaccination against COVID-19 was integral to controlling the pandemic that persisted with the continuous emergence of SARS-CoV-2 variants. Using a mathematical model describing SARS-CoV-2 within-host infection dynamics, we estimate differences in virus and immunity due to factors of infecting variant, age, and vaccination history (vaccination brand, number of doses and time since vaccination). We fit our model in a Bayesian framework to upper respiratory tract viral load measurements obtained from cases of Delta and Omicron infections in Singapore, of whom the majority only had one nasopharyngeal swab measurement. With this dataset, we are able to recreate similar trends in URT virus dynamics observed in past within-host modelling studies fitted to longitudinal patient data. We found that Omicron had higher R 0,within values than Delta, indicating greater initial cell-to-cell spread of infection within the host. Moreover, heterogeneities in infection dynamics across patient subgroups could be recreated by fitting immunity-related parameters as vaccination history-specific, with or without age modification. Our model results are consistent with the notion of immunosenescence in SARS-CoV-2 infection in elderly individuals, and the issue of waning immunity with increased time since last vaccination. Lastly, vaccination was not found to subdue virus dynamics in Omicron infections as well as it had for Delta infections. This study provides insight into the influence of vaccine-elicited immunity on SARS-CoV-2 within-host dynamics, and the interplay between age and vaccination history. Furthermore, it demonstrates the need to disentangle host factors and changes in pathogen to discern factors influencing virus dynamics. Finally, this work demonstrates a way forward in the study of within-host virus dynamics, by use of viral load datasets including a large number of patients without repeated measurements.

Studies have reported increased risk of autoimmune sequelae after SARS-CoV-2 infection. However, risk may potentially be attenuated by milder Omicron (B.1.1.529) variant infection and availability of booster vaccination. To estimate the 300-day risk of new-incident autoimmune sequelae after SARS-CoV-2 Delta or Omicron BA.1 or BA.2 variant infection in adults who received COVID-19 vaccines and boosters, compared with a contemporary control group without infection. This cohort study in Singapore enrolled adults from September 1, 2021, to March 7, 2022, and followed up for 300 days. Participants were adults aged 18 years or older with SARS-CoV-2 infection during the predominance of the Delta and Omicron BA.1 or BA.2 variants and were still alive at 30 days after COVID-19 diagnosis. The national SARS-CoV-2 testing registry was used to construct cohorts of adults with SARS-CoV-2 Delta or Omicron BA.1 or BA.2 variant infection (hereafter, cases) and a contemporaneous group with negative polymerase chain reaction or rapid antigen test results (hereafter, controls). New-incident autoimmune diagnoses after SARS-CoV-2 infection. This information was recorded in the MediClaims national health care claims database and identified 31 to 300 days after index date of infection. Risks and excess burdens were estimated using Cox proportional hazards regression model with overlap weights applied. In total, 1 766 036 adults (915 096 females [51.9%]; mean [SD] age, 49 [18] years) were included in the study population, with 480 082 (27.2%) categorized as cases and 1 285 954 (72.8%) as controls. Of these adults, 73.1% had Chinese, 13.7% Malay, and 9.9% Indian ethnicity. There were 104 179 cases and 666 575 controls included during the Delta variant-predominance transmission, while 375 903 cases and 619 379 controls were included during the Omicron variant-predominance transmission. During the Delta variant period, 81.1% of cases had completed primary vaccination; during the Omicron variant period, 74.6% of cases received boosters. No significantly elevated risk of 12 prespecified autoimmune sequelae was recorded across the Omicron and Delta variant cohorts. Elevated risks of inflammatory bowel disease (adjusted hazard ratio [AHR], 2.23; 95% CI, 1.45-3.46; P < .001) and bullous skin disorders (AHR, 4.88; 95% CI, 2.47-9.66; P < .001) were observed only in the subset of COVID-19 cases requiring hospitalization during the predominance of the Omicron variant. While elevated risk of vasculitis (AHR, 5.74; 95% CI, 1.48-22.23; P = .01) was observed in vaccine-breakthrough Omicron variant infections, no increased risk of vasculitis was observed in the corresponding subgroup who received boosters. This cohort study observed no significantly elevated long-term risk of autoimmune sequelae after SARS-CoV-2 Delta and Omicron BA.1 or BA.2 variant infection, except for a modestly increased risk of inflammatory bowel disease and bullous skin disorders in the hospitalized subgroup during the predominance of the Omicron variant. Booster vaccination appeared to mitigate the risk of long-term autoimmune sequelae.

Monolayer transition metal dichalcogenides, such as MoS 2 and WSe 2 , have been known as direct gap semiconductors and emerged as new optically active materials for novel device applications. Here we reexamine their direct gap properties by investigating the strain effects on the photoluminescence of monolayer MoS 2 and WSe 2 . Instead of applying stress, we investigate the strain effects by imaging the direct exciton populations in monolayer WSe 2 –MoS 2 and MoSe 2 –WSe 2 lateral heterojunctions with inherent strain inhomogeneity. We find that unstrained monolayer WSe 2 is actually an indirect gap material, as manifested in the observed photoluminescence intensity–energy correlation, from which the difference between the direct and indirect optical gaps can be extracted by analyzing the exciton thermal populations. Our findings combined with the estimated exciton binding energy further indicate that monolayer WSe 2 exhibits an indirect quasiparticle gap, which has to be reconsidered in further studies for its fundamental properties and device applications. Monolayer transition metal dichalcogenides have so far been thought to be direct bandgap semiconductors. Here, the authors revisit this assumption and find that unstrained monolayer WSe 2 is an indirect-gap material, as evidenced by the observed photoluminescence intensity-energy correlation.

To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry-based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection.

Nutritional deprivation triggers a switch from a saprotrophic to predatory lifestyle in soil-dwelling nematode-trapping fungi (NTF). In particular, the NTF Arthrobotrys oligospora secretes food and sex cues to lure nematodes to its mycelium and is triggered to develop specialized trapping devices. Captured nematodes are then invaded and digested by the fungus, thus serving as a food source. In this study, we examined the transcriptomic response of A . oligospora across the stages of sensing, trap development, and digestion upon exposure to the model nematode Caenorhabditis elegans . A . oligospora enacts a dynamic transcriptomic response, especially of protein secretion–related genes, in the presence of prey. Two-thirds of the predicted secretome of A . oligospora was up-regulated in the presence of C . elegans at all time points examined, and among these secreted proteins, 38.5% are predicted to be effector proteins. Furthermore, functional studies disrupting the t-SNARE protein Sso2 resulted in impaired ability to capture nematodes. Additionally, genes of the DUF3129 family, which are expanded in the genomes of several NTF, were highly up-regulated upon nematode exposure. We observed the accumulation of highly expressed DUF3129 proteins in trap cells, leading us to name members of this gene family as T rap E nriched P roteins (TEPs). Gene deletion of the most highly expressed TEP gene, TEP1 , impairs the function of traps and prevents the fungus from capturing prey efficiently. In late stages of predation, we observed up-regulation of a variety of proteases, including metalloproteases. Following penetration of nematodes, these metalloproteases facilitate hyphal growth required for colonization of prey. These findings provide insights into the biology of the predatory lifestyle switch in a carnivorous fungus and provide frameworks for other fungal–nematode predator–prey systems.

Non-symmorphic crystals are generating great interest as they are commonly found in quantum materials, like iron-based superconductors, heavy-fermion compounds, and topological semimetals. A new type of surface state, a floating band, was recently discovered in the nodal-line semimetal ZrSiSe, but also exists in many non-symmorphic crystals. Little is known about its physical properties. Here, we employ scanning tunneling microscopy to measure the quasiparticle interference of the floating band state on ZrSiSe (001) surface and discover rotational symmetry breaking interference, healing effect and half-missing-type anomalous Umklapp scattering. Using simulation and theoretical analysis we establish that the phenomena are characteristic properties of a floating band surface state. Moreover, we uncover that the half-missing Umklapp process is derived from the glide mirror symmetry, thus identify a non-symmorphic effect on quasiparticle interferences. Our results may pave a way towards potential new applications of nanoelectronics. A new type of surface state has recently been reported in ZrSiSe but its physical properties remain unclear. Here, Zhu, Chang, Huang, et al. report rotational symmetry breaking, healing effect and anomalous Umklapp scattering arising from the nonsymmorphic effect of the floating band state on ZrSiSe (001) surface.

Aims Pulmonary artery pulsatility index (PAPi), defined as [(pulmonary artery systolic pressure − diastolic pulmonary artery pressure)/mean right atrial pressure], is a novel haemodynamic index that predicts right ventricular failure after myocardial infarction and left ventricular assist device implantation. We analysed if a low PAPi is associated with death in our 14 ‐ ​year pulmonary arterial hypertension (PAH) registry. Methods Consecutive patients with newly diagnosed PAH and complete haemodynamic data were prospectively enrolled into our standing registry between January 2003 and December 2016. PAPi was calculated from baseline invasive right heart catheterization data. A prognostic cut‐off value was determined with a decision tree. Baseline characteristics of ‘high’ and ‘low’ PAPi groups based on this cut‐off were compared, as well as odds of death and time‐to‐death. Results One hundred and two patients were included. Mean age was 53 years, and 77% were women. Our multi‐ethnic cohort was 64% Chinese, 23% Malay, and 10% Indian. The aetiologies were idiopathic (33%), connective tissue disease (31%), congenital heart disease (24%), and others (12%). The low PAPi group (<5.3) had a greater age (56 years vs. 49 years), lower pulmonary artery systolic pressure (71 mmHg vs. 85 mmHg), and higher mean right atrial pressure (14 mmHg vs. 6 mmHg). Mortality risk was higher in the low PAPi group (adjusted odds ratio: 2.98 and adjusted hazard ratio: 2.23). Mean right atrial pressure was the strongest predictor (hazard ratio 1.114, P = 0.009) when components of PAPi were analysed. Conclusions Pulmonary artery pulsatility index was found to be predictive of mortality in PAH and may be a valuable marker for risk stratification. Its prognostic strength may be driven by mean right atrial pressure.

Van der Waals heterobilayers of transition metal dichalcogenides with spin–valley coupling of carriers in different layers have emerged as a new platform for exploring spin/valleytronic applications. The interlayer coupling was predicted to exhibit subtle changes with the interlayer atomic registry. Manually stacked heterobilayers, however, are incommensurate with the inevitable interlayer twist and/or lattice mismatch, where the properties associated with atomic registry are difficult to access by optical means. Here, we unveil the distinct polarization properties of valley-specific interlayer excitons using epitaxially grown, commensurate WSe 2 /MoSe 2 heterobilayers with well-defined (AA and AB) atomic registry. We observe circularly polarized photoluminescence from interlayer excitons, but with a helicity opposite to the optical excitation. The negative circular polarization arises from the quantum interference imposed by interlayer atomic registry, giving rise to distinct polarization selection rules for interlayer excitons. Using selective excitation schemes, we demonstrate the optical addressability for interlayer excitons with different valley configurations and polarization helicities. The interlayer coupling in van der Waals heterostructures is sensitive to the interlayer atomic registry. Here, the authors investigate the polarisation properties of epitaxially grown, commensurate WSe 2 /MoSe 2 heterobilayers with well-defined atomic registry, and observe negative, circularly polarized photoluminescence from interlayer excitons.

Antigen-specific regulatory T cells (Tregs) suppress pathogenic autoreactivity and are potential therapeutic candidates for autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis is associated with autoreactivity to the Smith (Sm) autoantigen and the human leucocyte antigen (HLA)-DR15 haplotype; hence, we investigated the potential of Sm-specific Tregs (Sm-Tregs) to suppress disease. Here we identify a HLA-DR15 restricted immunodominant Sm T cell epitope using biophysical affinity binding assays, then identify high-affinity Sm-specific T cell receptors (TCRs) using high-throughput single-cell sequencing. Using lentiviral vectors, we transduce our lead Sm-specific TCR into Tregs derived from patients with SLE who are anti-Sm and HLA-DR15 positive. Compared with polyclonal mock-transduced Tregs, Sm-Tregs potently suppress Sm-specific pro-inflammatory responses in vitro and suppress disease progression in a humanized mouse model of lupus nephritis. These results show that Sm-Tregs are a promising therapy for SLE. Antigen specific regulatory T cells (Treg) play key roles in the peripheral tolerance to suppress autoreactive immune cells and represent potential avenue for therapeutic intervention. Here the authors identify Smith specific Treg and engineer Treg based cell therapy showing suppression of inflammation in a murine model of lupus nephritis.

Background Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is a rare inherited mitochondrial disease mainly caused by the m.8344A > G mutation in mitochondrial tRNA Lys gene, and usually manifested as complex neurological disorders and muscle weakness. Currently, the pathogenic mechanism of this disease has not yet been resolved, and there is no effective therapy for MERRF syndrome. In this study, MERRF patients-derived iPSCs were used to model patient-specific neurons for investigation of the pathogenic mechanism of neurological disorders in mitochondrial disease. Methods MERRF patient-derived iPSCs were differentiated into excitatory glutamatergic neurons to unravel the effects of the m.8344A > G mutation on mitochondrial bioenergetic function, neural-lineage differentiation and neuronal function. By the well-established differentiation protocol and electrophysiological activity assay platform, we examined the pathophysiological behaviors in cortical neurons of MERRF patients. Results We have successfully established the iPSCs-derived neural progenitor cells and cortical-like neurons of patients with MERRF syndrome that retained the heteroplasmy of the m.8344A > G mutation from the patients’ skin fibroblasts and exhibited the phenotype of the mitochondrial disease. MERRF neural cells harboring the m.8344A > G mutation exhibited impaired mitochondrial bioenergetic function, elevated ROS levels and imbalanced expression of antioxidant enzymes. Our findings indicate that neural immaturity and synaptic protein loss led to the impairment of neuronal activity and plasticity in MERRF neurons harboring the m.8344A > G mutation. By electrophysiological recordings, we monitored the in vivo neuronal behaviors of MERRF neurons and found that neurons harboring a high level of the m.8344A > G mutation exhibited impairment of the spontaneous and evoked potential-stimulated neuronal activities. Conclusions We demonstrated for the first time the link of mitochondrial impairment and synaptic dysfunction to neurological defects through impeding synaptic plasticity in excitatory neurons derived from iPSCs of MERRF patients harboring the m.8344A > G mutation. This study has provided new insight into the pathogenic mechanism of the tRNA Lys gene mutation of mtDNA, which is useful for the development of a patient-specific iPSCs platform for disease modeling and screening of new drugs to treat patients with MERRF syndrome.