Hyperglycemia-triggered lipid peroxidation destabilizes STAT4 and impairs anti-viral Th1 responses in type 2 diabetes.

Patients with type 2 diabetes (T2D) are more susceptible to severe respiratory viral infections, but the underlying mechanisms remain elusive. Here, we show that patients with T2D and coronavirus disease 2019 (COVID-19) infections, and influenza-infected T2D mice, exhibit defective T helper 1 (Th1) responses, which are an essential component of anti-viral immunity. This defect stems from intrinsic metabolic perturbations in CD4 T cells driven by hyperglycemia.

Neutrophil plasticity in liver diseases.

The liver has critical digestive, metabolic, and immunosurveillance roles, which get disrupted during liver diseases such as viral hepatitis, fatty liver disease, and hepatocellular carcinoma. While previous research on the pathological development of these diseases has focused on liver-resident immune populations, such as Kupffer cells, infiltrating immune cells responding to pathogens and disease also play crucial roles. Neutrophils are one such key population contributing to hepatic inflammation and disease progression.

Secure impulsive tracking of multi-agent systems with directed hypergraph topologies against hybrid deception attacks.

This research delves into the challenges of achieving secure consensus tracking within multi-agent systems characterized by directed hypergraph topologies, in the face of hybrid deception attacks. The hybrid discrete and continuous deception attacks are targeted at the controller communication channels and the hyperedges, respectively. To overcome these threats, an impulsive control mechanism based on hypergraph theory are introduced, and sufficient conditions are established, under which consensus can be maintained in a mean-square bounded sense, supported by rigorous mathematical proofs.

The histone demethylase JMJD1C regulates CPS1 expression and promotes the proliferation of paroxysmal nocturnal haemoglobinuria clones through cell metabolic reprogramming.

Paroxysmal nocturnal haemoglobinuria (PNH) is a disorder resulting from erythrocyte membrane deficiencies caused by PIG-A gene mutations. While current treatments alleviate symptoms, they fail to address the underlying cause of the disease-the pathogenic PNH clones. In this study, we found that the expression of carbamoyl phosphate synthetase 1 (CPS1) was downregulated in PNH clones, and the level of CPS1 was negatively correlated with the proportion of PNH clones.

An engineered Sox17 induces somatic to neural stem cell fate transitions independently from pluripotency reprogramming.

Advanced strategies to interconvert cell types provide promising avenues to model cellular pathologies and to develop therapies for neurological disorders. Yet, methods to directly transdifferentiate somatic cells into multipotent induced neural stem cells (iNSCs) are slow and inefficient, and it is unclear whether cells pass through a pluripotent state with full epigenetic reset. We report iNSC reprogramming from embryonic and aged mouse fibroblasts as well as from human blood using an engineered Sox17 (eSox17).

GCSTI: A Single-Cell Pseudotemporal Trajectory Inference Method Based on Graph Compression.

The single-cell pseudotemporal trajectory inference is an important way to explore the process of developmental changes within a cell. Due to the uneven rate of cell growth, changes in gene expression depend less on the time of data collection and more on a cell's "internal clock". To overcome the challenges of gene analysis, and replicate biological developmental processes, several strategies have been put forth.

Chronic type I interferon signaling promotes lipid-peroxidation-driven terminal CD8 T cell exhaustion and curtails anti-PD-1 efficacy.

Identifying signals that govern the differentiation of tumor-infiltrating CD8 T cells (CD8 TILs) toward exhaustion can improve current therapeutic approaches for cancer. Here, we show that type I interferons (IFN-Is) act as environmental cues, enhancing terminal CD8 T cell exhaustion in tumors. We find enrichment of IFN-I-stimulated genes (ISGs) within exhausted CD8 T cells (Tex cells) in patients across various cancer types, with heightened ISG levels correlating with poor response to immune checkpoint blockade (ICB) therapy.

Comparing the B and T cell-mediated immune responses in patients with type 2 diabetes receiving mRNA or inactivated COVID-19 vaccines.

Acquiring protective immunity through vaccination is essential, especially for patients with type 2 diabetes who are vulnerable for adverse clinical outcomes during coronavirus disease 2019 (COVID-19) infection. Type 2 diabetes (T2D) is associated with immune dysfunction. Here, we evaluated the impact of T2D on the immunological responses induced by mRNA (BNT162b2) and inactivated (CoronaVac) vaccines, the two most commonly used COVID-19 vaccines.

Autoantibodies in systemic lupus erythematosus: From immunopathology to therapeutic target.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ inflammatory damage and wide spectrum of autoantibodies. The autoantibodies, especially anti-dsDNA and anti-Sm autoantibodies are highly specific to SLE, and participate in the immune complex formation and inflammatory damage on multiple end-organs such as kidney, skin, and central nervous system (CNS). However, the underlying mechanisms of autoantibody-induced tissue damage and systemic inflammation are still not fully understood.

FSG-based divinable time-varying formation tracking of multiple Lagrangian agents with unknown disturbances and directed graphs.

In this paper, a flexible shape generator (FSG) is designed to achieve the divinable transformation process of the time-varying formation, and consider the FSG-based time-varying formation tracking (TVFT) problem of multiple Lagrangian agents with unknown disturbances and directed graphs. A hierarchical control algorithm is newly designed to achieve the control goal without using the prior information of the system model and bounded disturbances, and the specific implementation of the proposed hierarchical algorithms is also provided. By using the Hurwitz criterion and adaptive system theory, the sufficient conditions are derived and the stability analysis show that the formation tracking errors of the considered system are uniform ultimate bounded.

Intranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 strain confers sterilizing immunity in animals.

Live attenuated vaccines might elicit mucosal and sterilizing immunity against SARS-CoV-2 that the existing mRNA, adenoviral vector and inactivated vaccines fail to induce. Here, we describe a candidate live attenuated vaccine strain of SARS-CoV-2 in which the NSP16 gene, which encodes 2'-O-methyltransferase, is catalytically disrupted by a point mutation. This virus, designated d16, was severely attenuated in hamsters and transgenic mice, causing only asymptomatic and nonpathogenic infection.

Stochastic quasi-synchronization of heterogeneous delayed impulsive dynamical networks via single impulsive control.

This paper investigates the quasi-synchronization problem of the stochastic heterogeneous complex dynamical networks with impulsive couplings and multiple time-varying delays. It is shown that this kind of dynamical networks can achieve exponential quasi-synchronization by exerting impulsive control added on only one chosen pinning node. By employing the Lyapunov stability theory, some sufficient criteria on quasi-synchronization for this dynamical network are established, revealing the relationship between the quasi-synchronization performance and the stochastic perturbations as well as the frequency and strength of impulsive coupling.

Type I interferons affect the metabolic fitness of CD8 T cells from patients with systemic lupus erythematosus.

The majority of patients with systemic lupus erythematosus (SLE) have high expression of type I IFN-stimulated genes. Mitochondrial abnormalities have also been reported, but the contribution of type I IFN exposure to these changes is unknown. Here, we show downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4 and CD8 T cells.

Identification of Diagnostic Biomarkers and Subtypes of Liver Hepatocellular Carcinoma by Multi-Omics Data Analysis.

As liver hepatocellular carcinoma (LIHC) has high morbidity and mortality rates, improving the clinical diagnosis and treatment of LIHC is an important issue. The advent of the era of precision medicine provides us with new opportunities to cure cancers, including the accumulation of multi-omics data of cancers. Here, we proposed an integration method that involved the Fisher ratio, Spearman correlation coefficient, classified information index, and an ensemble of decision trees (DTs) for biomarker identification based on an unbalanced dataset of LIHC.

[Effect and cost-effectiveness of three commonly used molluscicides in largescale field application].

Objective: To evaluate the effect and cost-effectiveness of three commonly used molluscicides, 4% "Luo-wei" (tea-seed distilled saponins, TDS), 50% niclosamide ethanolamine salt wettable powder (NESWP), and 26% metaldehyde and niclosamide suspension concentrate (MNSC) in large-scale field application, so as to provide the references for formulating the strategy of snail control.

Methods: The field test and parallel comparison were implemented. A marshland with snails of the Yangtze River was divided into 4 parts (10 hm) for the research, and three of them were experimental areas while the last one was a blank control area.

C1q restrains autoimmunity and viral infection by regulating CD8 T cell metabolism.

Deficiency of C1q, the initiator of the complement classical pathway, is associated with the development of systemic lupus erythematosus (SLE). Explaining this association in terms of abnormalities in the classical pathway alone remains problematic because C3 deficiency does not predispose to SLE. Here, using a mouse model of SLE, we demonstrate that C1q, but not C3, restrains the response to self-antigens by modulating the mitochondrial metabolism of CD8 T cells, which can themselves propagate autoimmunity.

Multistability and Bifurcation Analysis of Inhibitory Coupled Cyclic Genetic Regulatory Networks With Delays.

Many biological systems have the conspicuous property to present more than one stable state and diverse rhythmic behaviors. A closed relationship between these complex dynamic behaviors and cyclic genetic structures has been witnessed by pioneering works. In this paper, a typical structure of inhibitory coupled cyclic genetic networks is introduced to further enlighten this mechanism of stability and biological rhythms of living cells.

Multisynchronization of Coupled Heterogeneous Genetic Oscillator Networks via Partial Impulsive Control.

This paper focuses on the collective dynamics of multisynchronization among heterogeneous genetic oscillators under a partial impulsive control strategy. The coupled nonidentical genetic oscillators are modeled by differential equations with uncertainties. The definition of multisynchronization is proposed to describe some more general synchronization behaviors in the real.

Complement receptor 3 mediates renal protection in experimental C3 glomerulopathy.

C3 glomerulopathy is a complement-mediated renal disease that is frequently associated with abnormalities in regulation of the complement alternative pathway. Mice with deficiency of factor H (Cfh(-/-)), a negative alternative pathway regulator, are an established experimental model of C3 glomerulopathy in which complement C3 fragments including iC3b accumulate along the glomerular basement membrane. Here we show that deficiency of complement receptor 3 (CR3), the main receptor for iC3b, enhances the severity of spontaneous renal disease in Cfh(-/-) mice.