The inactivated whole-virion vaccine, CoronaVac, is one of the most widely used coronavirus disease 2019 (COVID-19) vaccines worldwide. There is a paucity of data indicating the durability of the ...immune response and the impact of immune imprinting induced by CoronaVac upon Omicron infection. In this prospective cohort study, 41 recipients of triple-dose CoronaVac and 14 unvaccinated individuals were recruited. We comprehensively profiled adaptive immune parameters in both groups, including spike-specific immunoglobulin (Ig) G and IgA titers, neutralizing activity, B cells, circulating follicular helper T (cTfh) cells, CD4
and CD8
T cells, and their memory subpopulations at 12 months after the third booster dose and at 4 and 20 weeks after Omicron BA.5 infection. Twelve months after the third CoronaVac vaccination, spike-specific antibodies and cellular responses were detectable in most vaccinated individuals. BA.5 infection significantly augmented the magnitude, cross-reactivity, and durability of serum neutralization activities, Fc-mediated phagocytosis, nasal spike-specific IgA responses, memory B cells, activated cTfh cells, memory CD4
T cells, and memory CD8
T cells for both the ancestral strain and Omicron subvariants, compared to unvaccinated individuals. Notably, the increase in BA.5-specific immunity after breakthrough infection was consistently comparable to or higher than that of the ancestral strain, suggesting no evidence of immune imprinting. Immune landscape analyses showed that vaccinated individuals have better synchronization of multiple immune components than unvaccinated individuals upon heterologous infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immunity to Omicron infection.
There is a paucity of data indicating the durability of the immune response and the impact of immune imprinting induced by CoronaVac upon Omicron breakthrough infection. In this prospective cohort study, the anti-severe acute respiratory syndrome coronavirus 2 adaptive responses were analyzed before and after the Omicron BA.5 infection. Our data provide detailed insight into the protective role of the inactivated COVID-19 vaccine in shaping humoral and cellular immune responses to heterologous Omicron infection.
This study is registered with ClinicalTrials.gov as NCT05680896.
Abstract
Observational studies suggest certain sleep traits are associated with telomere length, but the causal nature of these associations is unclear. The study aimed to determine the causal ...associations between 11 sleep-related traits and leukocyte telomere length (LTL) through two-sample Mendelian randomization and colocalization analyses using the summary statistics from large-scale genome-wide association studies. Univariable Mendelian randomization indicates that genetically determined short sleep is associated with decreased LTL, while morning chronotype is associated with increased LTL. Multivariable Mendelian randomization further supports the findings and colocalization analysis identifies shared common genetic variants for these two associations. No genetic evidence is observed for associations between other sleep-related traits and LTL. Sensitivity MR methods, reverse MR and re-running MR after removing potential pleiotropic genetic variants enhance the robustness of the results. These findings indicate that prioritizing morning chronotype and avoiding short sleep is beneficial for attenuating telomere attrition. Consequently, addressing sleep duration and chronotype could serve as practical intervention strategies.
It is challenging to trace the complicated individual-based variations of HIV-specific immunocompetence shift during the successful antiretroviral therapy (ART) era. Using eight rhesus monkeys ...simulating a longitudinal stage-dependent cohort (baseline-SIV acute infection-SIV suppression by ART-ART withdrawal), baseline immunocompetence monitoring for 28 days (SIV-negative stage, SN) was compared with host immunocompetence undergoing 90-day ART treatment (SIV-suppressed stage, SS) to reveal the SIV-specific immunity shift aroused by undetectable individual viral replication. During acute SIV infection for 98 days (SIV-emerged stage, SE), immune activation was compared with re-immune activation post ART for 49-day follow-up (SIV-rebounded stage, SR) to reveal the SIV-specific immune activation variation aroused by detectable individual viral replication. Individual immunocompetence was measured by co-expression of CD4, CD8, CD38, HLA-DR, CCR7, CD45RA, and PD-1 on T cells and a cytokine panel. Compared with SN, mild immune activation/exhaustion was characterized by increased CD38
+
HLA-DR
–
CD4
+
/CD8
+
T-cell subsets and PD-1
+
memory CD4
+
/CD8
+
T-cell subsets with three elevated cytokines (MIP-1β, IL-8, and IL-10) significantly emerged in SS. Compared with SE, SR produced more exhaustion characterized by increased PD-1
+
CD4
+
T
CM
cells and decreased PD-1
+
CD4
+
T
EM
cells with four elevated pro-inflammatory cytokines (IFN-γ, IL-1β, IL-6, and TNF-α). By such individualized stage-dependent comparison, the sustainable immune activation was found from activation/exhaustion shifted into exhaustion during the longitudinal viral persistence. Further, validated SIV accelerates host immunosenescence continuously independent of viral replication.
Background
Tislelizumab combined with radiotherapy as a salvage treatment for patients with end-stage metastatic castration-resistant prostate cancer (mCRPC) is not reported. This study aimed to ...describe a protocol to evaluate the safety and efficacy of multisite radiotherapy combined with tislelizumab as a salvage therapy for mCRPC in patients who had at least one second-line treatment failure.
Methods
The study included patients with mCRPC who had at least one lesion suitable for radiotherapy and failed androgen deprivation therapy (ADT), followed by at least one novel second-line endocrine therapy. All patients received tislelizumab monotherapy induction therapy for two cycles, then combined with multisite radiotherapy for one cycle, followed by tislelizumab maintenance therapy, until either disease progressed or the patient developed unacceptable toxicity. Radiation methods and lesions were individually selected according to the specified protocol. Primary endpoints included safety and objective response rate. Secondary endpoints included prostate-specific antigen (PSA) response rate, disease control rate, overall survival, radiographic progression-free survival (rPFS), and biochemical progression-free survival (bPFS). Furthermore, the exploratory endpoints included the identification of the predictive biomarkers and exploration of the correlation between biomarkers and the tumor response to the combined regimen.
Discussion
This study included three treatment stages to evaluate the efficacy of immunotherapy and the combination of immunotherapy and radiotherapy for patients with mCRPC who have had at least second-line treatment failure. Additionally, radiation-related and immune-related early and late toxicities were determined, respectively. Furthermore, the study also aimed to identify the predictive biomarkers associated with immunotherapy for treating mCRPC.
Trial Registration
https://www.chictr.org.cn/showproj.aspx?proj=126359
, identifier ChiCTR2100046212.
Evidence from longitudinal studies is crucial to enhance our understanding of the role of metabolites in the progression of gestational diabetes mellitus (GDM). Herein, a longitudinal untargeted ...metabolomic study was conducted to reveal the metabolomic profiles and biomarkers associated with the progression of GDM, and characterize the changing patterns of metabolites.
We collected serum samples at three trimesters from 30 patients with GDM and 30 healthy Chinese pregnant women with pre-pregnancy BMI, age, and parity matched, and untargeted metabolomic analysis was performed, followed by machine learning approaches that integrated bootstrap and LASSO. Cluster analysis was conducted to elucidate the patterns of metabolite changes. Pathway analyses were conducted to gain insights into the underlying pathways involved.
A total of 32 metabolites, mainly belonging to amino acid and its derivatives, were significantly associated with GDM across three trimesters, and were clustered into three distinct patterns. Metabolites belonging to phosphatidylcholines, lysophosphatidylcholines, lysophosphatidic acids, and lysophosphatidylethanolamines were consistently upregulated, and 2,3-Dihydroxypropyl dihydrogen phosphate was downregulated in GDM group. Amino acid-related, glycerophospholipid, and vitamin B6 metabolism were enriched in multiple trimesters. The levels of allantoic acid, which was positively correlated with blood glucose, was consistently higher in GDM patients and exhibited good discriminatory ability for GDM in the early and mid-pregnancy.
We identified and characterized distinct patterns of metabolites associated with GDM throughout pregnancy, and found that allantoic acid was a potential biomarker for early diagnosis of GDM.
Display omitted
•Traditional statistical and machine learning methods were applied to uncover the metabolomic profiles of GDM progression.•Thirty-two metabolites, which were clustered into three distinct patterns, were associated with GDM throughout pregnancy.•Allantoic acid, an oxidative byproduct of uric acid, was identified as a potential biomarker for early diagnosis of GDM.
Metal–organic frameworks (MOFs) have received increasing attention as promising electrode materials in supercapacitors (SCs). Yet poor conductivity in most MOFs largely thwarts their capacitance ...and/or rate performance. In this work, an effective strategy was developed to reduce the bulk electric resistance of MOFs by interweaving MOF crystals with polyaniline (PANI) chains that are electrochemically deposited on MOFs. Specifically we synthesized cobalt-based MOF crystals (ZIF-67) onto carbon cloth (CC) and further electrically deposited PANI to give a flexible conductive porous electrode (noted as PANI-ZIF-67-CC) without altering the underlying structure of the MOF. Electrochemical studies showed that the PANI-ZIF-67-CC exhibits an extraordinary areal capacitance of 2146 mF cm–2 at 10 mV s–1. A symmetric flexible solid-state supercapacitor was also assembled and tested. This strategy may shed light on designing new MOF-based supercapacitors and other electrochemical devices.
The pentazolate anion, or cyclo-N5-, which is a five-membered ring composed solely of nitrogen atoms, has a unique structure among polynitrogen compounds. Cyclo-N5- is receiving ever-increasing ...levels of attention because of its potential ability to store large amounts of energy compared to the azide ion, its environmentally friendly decomposition products, and its carbon- and hydrogen-free composition, which are promising characteristics for advancing the field of high-energy-density materials (HEDMs), that include explosives, oxidisers, and propellants in closed environments. In this review, we provide a detailed introduction to cyclo-N5- and cover the following topics: (1) substituted pentazoles as precursors of cyclo-N5-, with a focus on the syntheses and stabilities of substituted pentazole derivatives; (2) routes to cyclo-N5- through cleavage of C-N bonds in substituted pentazoles, during which competitive reactions between pentazole decomposition and C-N bond cleavage need to be considered to ensure a successful outcome; (3) complexes of cyclo-N5-, summarising recent progress toward producing cyclo-N5--based complexes through the assembly of isolated cyclo-N5- with both metallic and nonmetallic components; and (4) interactions between cyclo-N5- and metal cations and non-metal species, as well as factors that influence the stability of these complexes; in particular, the thermal stabilities of prepared cyclo-N5- salts are discussed. This review summarises recent studies and is intended to improve the understanding of polynitrogen chemistry while supporting further research into its potential application as an efficient, safe, and environmentally friendly HEDM.
Singly or doubly bonded polynitrogen compounds can decompose to dinitrogen (N
) with an extremely large energy release. This makes them attractive as potential explosives or propellants, but also ...challenging to produce in a stable form. Polynitrogen materials containing nitrogen as the only element exist in the form of high-pressure polymeric phases, but under ambient conditions even metastability is realized only in the presence of other elements that provide stabilization. An early example is the molecule phenylpentazole, with a five-membered all-nitrogen ring, which was first reported in the 1900s and characterized in the 1950s. Salts containing the azide anion (N
) or pentazenium cation (N
) are also known, with compounds containing the pentazole anion, cyclo-N
, a more recent addition. Very recently, a bulk material containing this species was reported and then used to prepare the first example of a solid-state metal-N
complex. Here we report the synthesis and characterization of five metal pentazolate hydrate complexes Na(H
O)(N
)·2H
O, M(H
O)
(N
)
·4H
O (M = Mn, Fe and Co) and Mg(H
O)
(N
)
·4H
O that, with the exception of the Co complex, exhibit good thermal stability with onset decomposition temperatures greater than 100 °C. For this series we find that the N
ion can coordinate to the metal cation through either ionic or covalent interactions, and is stabilized through hydrogen-bonding interactions with water. Given their energetic properties and stability, pentazole-metal complexes might potentially serve as a new class of high-energy density materials or enable the development of such materials containing only nitrogen. We also anticipate that the adaptability of the N
ion in terms of its bonding interactions will enable the exploration of inorganic nitrogen analogues of metallocenes and other unusual polynitrogen complexes.
Display omitted
•Two series of fused triazoles featuring the N4 linkage are presented.•All these compounds show low mechanical and good structural stability.•The potential structure-property ...relationships of these compounds were studied.
It is the main task and challenge to reach a fine balance between high energy density and good molecular stability in energetic material research. In this study, two series of energetic compounds, 3-amino-7,7′-azo-1,2,4 triazolo4,3–b1,2,4triazole and 3,6-diamino-7,7′-azo-1,2,4triazolo4,3–b1,2,4 triazole featuring the N4 N-N=N-N linkage and fused triazoles, are presented. Their structures were determined by single crystal X-ray diffraction, elemental analysis, NMR, and IR spectroscopy. Their properties were studied in terms of density, thermal stability, detonation performance, and mechanical sensitivity. The N4 N-N=N-N linkages accord these compounds with high heat of formation, thus increasing the detonation performance. All fused triazoles exhibit planar structures, which result in low mechanical sensitivity. Through careful investigation of crystal data, strong π-π stacking and extensive hydrogen-bonding interactions were observed between molecules, which gives positive impact on mechanical sensitivity and thermal stability. The properties between different cations (or ions) were carefully studied. Quantum chemistry calculations were performed to investigate the potential relationship between structures and properties. Among them, compound 5 possesses high thermal stability (Td: 275 °C), good detonation performance (D: 8677 m s−1; P: 36.1 GPa), and excellent insensitivity (IS: 40 J; FS: 360 N), which makes it a balanced and promising energetic material.
Energetic metal-organic frameworks (EMOFs) with a high oxygen content are currently a hot spot in the field of energetic materials research. In this article, two series of EMOFs with different ...ligands were obtained by reacting 1-(trinitromethyl)-1H-1,2,4-triazole-3-carboxylic acid (tntrza) with metal iodide and metal nitrate, respectively. Furthermore, their structure, thermal stability, thermal decomposition kinetics, and energy performance are fully characterized. The research results revealed that the synthesized EMOFs possess a wide range of density (ρ = 1.88∼2.595 g cm
), oxygen balance (OB(CO
) = -21.1∼ -4.3%), and acceptable energy performance (
= 7.73∼8.74 km s
and
= 28.1∼41.1 GPa). The difference in OB(CO
) caused by the ligand structure and metal properties has a great impact on the distribution of gas-phase products after the decomposition of these EMOFs. Noteworthy, Ag(tntrza)
is particularly prominent among these EMOFs, not only because of its excellent detonation performance (
= 8.74 km s
and
= 41.1 GPa) endowed by its extremely high density (ρ = 2.595 g cm
) and oxygen balance (OB(CO
) = -4.3%) but also because of its effective catalytic effect on the decomposition of ammonium perchlorate (AP). This article broadens the horizon for the study of oxygen-enriched EMOFs with catalytic effects and helps understand the mechanism of thermal decomposition of EMOFs with nitroform and dinitro groups.
PDF
![[N-N=N-N]-linked fused tria...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1385-8947/small "[N-N=N-N]-linked fused triazoles with π-π stacking and hydrogen bonds: Towards thermally stable, Insensitive, and highly energetic materials")
