Explore the vast range of titles available.

Diabetic nephropathy is the leading cause of chronic kidney disease (CKD) in western countries. Notably, it has a rapidly rising prevalence in China. The patients, commonly complicated with cardiovascular diseases and neurologic disorders, are at high risk to progress into end-stage renal disease (ESRD) and death. However, the pathogenic mechanisms of diabetic nephropathy have not been determined. Cellular senescence, which recently has gained broad attention, is thought to be an important player in the onset and development of diabetic nephropathy. In this issue, we generally review the mechanisms of cellular senescence in diabetic nephropathy, which involve telomere attrition, DNA damage, epigenetic alterations, mitochondrial dysfunction, loss of Klotho, Wnt/β-catenin signaling activation, persistent inflammation, and accumulation of uremic toxins. Moreover, we highlight the potential therapeutic targets of cellular senescence in diabetic nephropathy and provide important clues for clinical strategies.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women at reproductive age. However, the underlying pathogenic mechanisms have not been completely understood. Hyperandrogenism is an important clinic feature in patients with PCOS, suggesting its pathologic role in the development and progression of PCOS. However, the actual role of androgen and the related signals in PCOS and PCOS‐related complications have not yet been clarified. In this review, we surveyed the origin and effects of androgen on PCOS and the related complications, highlighted the cellular signals affecting androgen synthesis and summarized the pathological processes caused by hyperandrogenism. Our review well reveals the important mechanisms referring the pathogenesis of PCOS and provides important clues to the clinic strategies in patients with PCOS.

In this paper, we mainly propose a chaotic secure communication scheme which is based on the synchronization of double-layered and multiple complex dynamical networks. Compared with the previous chaotic secure communication schemes, in which only two chaotic systems or just a single-layer network composed of multiple chaotic systems is used, the introduction of a double-layered and multiple complex networks model composed of many encryption/encryption units can not only reflect the complex characteristics of different nodes, but also can improve the complexity and security of information encryption. By using a clustering method, nodes with the same characteristics belong to the same subnet, while the nodes with different characteristics belong to different ones. The subnets in the transmitter and receiver are one-to-one correspondence and form a pair of matching subnets, but the node size of each subnet can be inconsistent. Each subnet is only responsible for encrypting a certain part of information, and thus, the synchronization between each pair of matching subnets plays a crucial role on the correct recovery of information. Multiple encryption/decryption units operating in parallel way can speed up the encryption of information, and the key space can grow with the number of nodes in the transmitter. The proposed scheme utilizes the chaotic signals generated by many chaotic systems as the key sequences and adopts the one-time-one-cipher encryption method. Moreover, this scheme is not subject to the constraint that the amplitude of the encrypted signal should be much smaller than that of the chaotic signal, and it is particularly suitable for the big data encryption. Both theoretical analysis and numerical simulation demonstrate the feasibility and effectiveness of the proposed scheme.

l -lactate modifies proteins through lactylation 1 , but how this process occurs is unclear. Here we identify the alanyl-tRNA synthetases AARS1 and AARS2 (AARS1/2) as intracellular l -lactate sensors required for l -lactate to stimulate the lysine lactylome in cells. AARS1/2 and the evolutionarily conserved Escherichia coli orthologue AlaRS bind to l -lactate with micromolar affinity and they directly catalyse l -lactate for ATP-dependent lactylation on the lysine acceptor end. In response to l -lactate, AARS2 associates with cyclic GMP–AMP synthase (cGAS) and mediates its lactylation and inactivation in cells and in mice. By establishing a genetic code expansion orthogonal system for lactyl-lysine incorporation, we demonstrate that the presence of a lactyl moiety at a specific cGAS amino-terminal site abolishes cGAS liquid-like phase separation and DNA sensing in vitro and in vivo. A lactyl mimetic knock-in inhibits cGAS, whereas a lactyl-resistant knock-in protects mice against innate immune evasion induced through high levels of l -lactate. MCT1 blockade inhibits cGAS lactylation in stressed mice and restores innate immune surveillance, which in turn antagonizes viral replication. Thus, AARS1/2 are conserved intracellular l -lactate sensors and have an essential role as lactyltransferases. Moreover, a chemical reaction process of lactylation targets and inactivates cGAS. The tRNA synthases AARS1 and AARS2 are identified as evolutionarily conserved sensors of intracellular l -lactate to mediate the global lysine lactylome.

Age-related disorders such as chronic kidney disease (CKD) are increasingly prevalent globally and pose unprecedented challenges. In many aspects, CKD can be viewed as a state of accelerated and premature aging. Aging kidney and CKD share many common characteristic features with increased cellular senescence, a conserved program characterized by an irreversible cell cycle arrest with altered transcriptome and secretome. While developmental senescence and acute senescence may positively contribute to the fine-tuning of embryogenesis and injury repair, chronic senescence, when unresolved promptly, plays a crucial role in kidney fibrogenesis and CKD progression. Senescent cells elicit their fibrogenic actions primarily by secreting an assortment of inflammatory and profibrotic factors known as the senescence-associated secretory phenotype (SASP). Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. In this review, we discuss current understanding of the role and mechanism of cellular senescence in kidney fibrosis. We also highlight potential options of targeting senescent cells for the treatment of CKD.

353 hospitalized children diagnosed with  Mycoplasma pneumoniae  (MP) pneumonia were included in the study. They were divided into MP co-infection group and MP single infection group. 143 (40.5%) of the enrolled children had MP co-infections. The most common co-infecting pathogen was Rhinovirus (30.8%). Among the MP co-infections, 82 cases (57.3%) involved one pathogen, 44 cases (30.7%) involved two pathogens, 12 cases (8.4%) involved three pathogens, 4 cases (2.8%) involved four pathogens, and 1 case (0.7%) involved five pathogens. Significant differences were observed between the two groups in terms of severe MP pneumonia, macrolide resistance, bronchial mucus plug, and hormone use, with  P -values of 0.039, 0.000, 0.000, and 0.035. The MP mixed virus or bacteria infection group was more likely to develop drug resistance compared to the mixed virus and bacteria group ( P  = 0.007 and  P  = 0.046). The MP mixed virus and bacteria group was more likely to develop severe pneumonia compared to the mixed virus or bacteria infection group ( P  = 0.032 and  P  = 0.017). In conclusion, MP was most commonly co-infected with Rhinovirus. Children with MP co-infections tend to exhibit higher rates of macrolide resistance, require more frequent use of hormones, and are more likely to develop severe pneumonia and bronchial mucus plug.

Adult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during spinal cord repair. Neurogenesis of glutamatergic and GABAergic neurons restores the excitatory/inhibitory balance after injury. In addition, a transient population of injury-responsive neurons (iNeurons) show elevated plasticity 1 week post-injury. We found iNeurons are injury-surviving neurons that acquire a neuroblast-like gene expression signature after injury. CRISPR/Cas9 mutagenesis showed iNeurons are required for functional recovery and employ vesicular trafficking as an essential mechanism that underlies neuronal plasticity. This study provides a comprehensive resource of the cells and mechanisms that direct spinal cord regeneration and establishes zebrafish as a model of plasticity-driven neural repair. The roadmap to promote neural repair after spinal cord injury remains elusive. Here, longitudinal single-cell sequencing in adult zebrafish identifies intersecting modes of neuronal plasticity and neurogenesis during innate neural repair.

Loss of Klotho, an anti-aging protein, plays a critical role in the pathogenesis of chronic kidney diseases. As Klotho is a large transmembrane protein, it is challenging to harness it as a therapeutic remedy. Here we report the discovery of a Klotho-derived peptide 1 (KP1) protecting kidneys by targeting TGF-β signaling. By screening a series of peptides derived from human Klotho protein, we identified KP1 that repressed fibroblast activation by binding to TGF-β receptor 2 (TβR2) and disrupting the TGF-β/TβR2 engagement. As such, KP1 blocked TGF-β-induced activation of Smad2/3 and mitogen-activated protein kinases. In mouse models of renal fibrosis, intravenous injection of KP1 resulted in its preferential accumulation in injured kidneys. KP1 preserved kidney function, repressed TGF-β signaling, ameliorated renal fibrosis and restored endogenous Klotho expression. Together, our findings suggest that KP1 recapitulates the anti-fibrotic action of Klotho and offers a potential remedy in the fight against fibrotic kidney diseases. Klotho is an anti-ageing protein whose expression is downregulated in chronic kidney disease, but the large size of the protein makes it challenging to deliver therapeutically. Here, the authors develop a Klotho-derived peptide, and show that it recapitulates the anti-fibrotic action of Klotho and prevents kidney fibrosis in mice by targeting TGF-β signalling.

Recognition of pathogen-associated molecular patterns (PAMPs) triggers expression of antiviral interferons and proinflammatory cytokines, which functions as the frontier of host defense against microbial pathogen invasion. Hippo-YAP pathway regulates cell proliferation, survival, differentiation and is involved in diverse life processes, including tissue homeostasis and tumor suppression. Emerging discoveries elucidated that the components of Hippo-YAP pathway, such as MST1/2, NDR1/2, and YAP/TAZ played crucial regulatory roles in innate immunity. Meanwhile the innate immune signaling also exhibited regulatory effect on Hippo-YAP pathway. As for the importance of these two pathways, it would be interesting to figure out the deeper biological implications of their interplays. This review focuses on the regulation between Hippo-YAP pathway and innate immune signaling. We also propose the possible contribution of these interplays to tumor development.

Ferroptosis represents a form of programmed cell death that is propelled by iron-dependent lipid peroxidation, thereby being distinguished by the prominent features of iron accumulation and lipid peroxidation. Ferroptosis has been implicated in numerous physiological and pathological phenomena, with mounting indications that it holds significant implications for cancer and other medical conditions. On one side, it demonstrates anti-cancer properties by triggering ferroptosis within malignant cells, and on the other hand, it damages normal cells causing other diseases. Therefore, in this paper, we propose to review the paradoxical regulation of ferroptosis in tumors and other diseases. First, we introduce the development history, concept and mechanism of ferroptosis. The second part focuses on the methods of inducing ferroptosis in tumors. The third section emphasizes the utilization of ferroptosis in different medical conditions and strategies to inhibit ferroptosis. The fourth part elucidates the key contradictions in the control of ferroptosis. Finally, potential research avenues in associated domains are suggested.