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Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease (CKD) on a global scale, with its incidence witnessing a consistent annual rise, thereby imposing a substantial burden on public health. The pathogenesis of DKD is primarily rooted in metabolic disorders and inflammation. Recent years have seen a surge in studies highlighting the regulatory impact of energy metabolism on innate immunity, forging a significant area of research interest. Within this context, fibroblast growth factor 21 (FGF21), recognized as an energy metabolism regulator, assumes a pivotal role. Beyond its role in maintaining glucose and lipid metabolism homeostasis, FGF21 exerts regulatory influence on innate immunity, concurrently inhibiting inflammation and fibrosis. Serving as a nexus between energy metabolism and innate immunity, FGF21 has evolved into a therapeutic target for diabetes, nonalcoholic steatohepatitis, and cardiovascular diseases. While the relationship between FGF21 and DKD has garnered increased attention in recent studies, a comprehensive exploration of this association has yet to be systematically addressed. This paper seeks to fill this gap by summarizing the mechanisms through which FGF21 operates in DKD, encompassing facets of energy metabolism and innate immunity. Additionally, we aim to assess the diagnostic and prognostic value of FGF21 in DKD and explore its potential role as a treatment modality for the condition.

Respiratory disease, such as lung cancer, is a major risk factor that seriously endangers human health. In the development of new drugs, conventional preclinical and clinical testing stages rely on cell culture and animal experiment. However, the two methods may fall short of fully representing human biology, thereby presenting an opportunity to advance technological innovation. In this review, we focus on the structure and the composition of supporting cells of organ-on-a-chip (OOAC), whose most notable feature is its biomimetic representation of the human body. Its core advantage lies in its biomimetic human structure, which enables broad application scenarios in the field of pulmonary diseases including lung cancer, pneumonia, pulmonary edema, and pulmonary embolism. Finally, this review summarizes the current challenges and prospects of OOAC, highlighting its vast potential for advancement.

Background Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer with high morbidity and mortality rates. Due to the heterogeneity of LUAD, its characteristics remain poorly understood. Exploring the clinical and molecular characteristics of LUAD is challenging but vital for early diagnosis. Methods This observational and validation study enrolled 80 patients and 13 healthy controls. Nuclear and mtDNA-captured sequencings were performed. Results This study identified a spectrum of nuclear and mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with diagnosis. The correlation coefficient for somatic mutations in cfDNA and patient-matched tumor tissues was high in nuclear and mitochondrial genomes. The mutation number of highly mutated genes was evaluated, and the Least Absolute Shrinkage and Selection Operator (LASSO) established a diagnostic model. Receiver operating characteristic (ROC) curve analysis explored the diagnostic ability of the two panels. All models were verified in the testing cohort, and the mtDNA panel demonstrated excellent performance. This study identified somatic mutations in the nuclear and mitochondrial genomes, and detecting mutations in cfDNA displayed good diagnostic performance for early-stage LUAD. Moreover, detecting somatic mutations in the mitochondria may be a better tool for diagnosing early-stage LUAD. Conclusions This study identified specific and sensitive diagnostic biomarkers for early-stage LUAD by focusing on nuclear and mitochondrial genome mutations. This also further developed an early-stage LUAD-specific mutation gene panel for clinical utility. This study established a foundation for further investigation of LUAD molecular pathogenesis.

Cholangiopathies lack effective medicines and can progress into end-stage liver diseases. Mining natural product transcriptome databases for bioactive ingredients, which can reverse disease-associated transcriptomic phenotypes, holds promise as an effective approach for drug discovery. To identify disease-associated transcriptomic changes, we performed RNA-sequencing on bile duct ligation (BDL)-induced cholestatic liver fibrosis mice, as well as PBC and PSC patients, and found that PANoptosis and activation of type-I interferon (IFN) signaling were observed in BDL mice and patients with PBC and PSC. We then established a transcriptotype-driven screening system based on HERB and ITCM databases. Among 283 natural ingredients screened, apigenin (Api), which is widely distributed in varieties of food and medicinal plants, was screened out by our screen system since it reversed the expression pattern of key genes associated with PANoptosis and type-I IFN responses. In BDL, Abcb4−/−, and DDC-fed mice, Api effectively ameliorated liver injuries, inflammation, and fibrosis. It also protected cholangiocytes from bile acid-stimulated PANoptosis, thus alleviating damage-associated molecular pattern-mediated activation of TBK1-NF-κB in macrophages. Additionally, Api directly inhibited type-I IFN-induced downstream inflammatory responses. Our study demonstrated the pathogenic roles of PANoptosis and type-I IFN signaling in cholestatic liver fibrosis and verified the feasibility of transcriptotype-based drug screening. Furthermore, this study revealed a novel anti-inflammatory mechanism of Api and identified it as a promising candidate for the treatment of cholestatic liver fibrosis.

This paper proposes DNA-PKC, an asymmetric encryption and signature cryptosystem by combining the technologies of genetic engineering and cryptology. It is an exploratory research of biological cryptology. Similar to conventional public-key cryptology, DNA-PKC uses two pairs of keys for encryption and signature, respectively. Using the public encryption key, everyone can send encrypted message to a specified user, only the owner of the private decryption key can decrypt the ciphertext and recover the message; in the signature scheme, the owner of the private signing key can generate a signature that can be verified by other users with the public verification key, but no else can forge the signature. DNA-PKC differs from the conventional cryptology in that the keys and the ciphertexts are all biological molecules. The security of DNA-PKC relies on diffcult biological problems instead of computational problems; thus DNA-PKC is immune from known attacks, especially the quantum computing based attacks.

Inducing the senescence of activated hepatic stellate cells (HSCs) has emerged as a promising therapeutic strategy for liver fibrosis, with potential connections to the Yes-associated protein (YAP)-controlled cGAS-STING pathway. However, the regulatory role of cytoskeletal dynamics on HSC senescence and its potential as a target for natural products have remained poorly understood. We employed preclinical and transcriptome analyses, experimental systems, Tmem173 mice and liver-specific STING knockdown mice to demonstrate the anti-fibrotic effects and mechanism of ligustilide (LIG). LIG selectively bound to monomeric globular actin (G-actin), thereby preventing its polymerization into polymeric filamentous actin (F-actin), which disturbed its interaction with intermediate filament component lamin A/C and initially destroyed the nuclear membrane. Moreover, the disruption of nuclear membrane caused YAP leakage from nuclear, which in turn suppressed lamin A/C and created a deleterious feedback loop that exacerbated nuclear membrane destabilization. Consequently, nuclear double stranded DNA (dsDNA) leakage caused by the above damage cascade ultimately triggered the activation of the cGAS-STING signaling pathway, promoting senescence-associated secretory phenotypes (SASPs) release and inducing HSC senescence. Moreover, the induction of HSC senescence and anti-fibrotic effects of LIG were completely abrogated in both whole-body STING knockout and liver-specific STING knockdown mice. By interacting with G-actin, LIG disrupted the cytoskeleton to compromise nuclear integrity with the involvement of YAP and further stimulated the cGAS-STING pathway, leading to the release of SASPs and HSC senescence, which ultimately mitigated liver fibrosis.

Asia harbors substantial cultural and linguistic diversity, but the geographic structure of genetic variation across the continent remains enigmatic. Here we report a large-scale survey of autosomal variation from a broad geographic sample of Asian human populations. Our results show that genetic ancestry is strongly correlated with linguistic affiliations as well as geography. Most populations show relatedness within ethnic/linguistic groups, despite prevalent gene flow among populations. More than 90% of East Asian (EA) haplotypes could be found in either Southeast Asian (SEA) or Central-South Asian (CSA) populations and show clinal structure with haplotype diversity decreasing from south to north. Furthermore, 50% of EA haplotypes were found in SEA only and 5% were found in CSA only, indicating that SEA was a major geographic source of EA populations.

Personalized therapy is “the right drug for the right patient at the right time”. Here we reported a case of personalized therapy using gene expression signature (GES) related drug discovery to treat a patient with drug-resistant metastases from breast-tumor. Methods :After mRNA obtained from metastatic liver tissue was performed by microarray, GES of genomic profiles were uncovered by bioinformatics tool and targeting drugs related with GES were mined by drug-bank. Several targeting-drugs approved by FDA were selected to treat the patient. Results :1198 genes were uncovered for the higher expression by two-fold to compare normal liver specimens in which 10 of mined genes were identified as set-1 GES for metastasis and 16 of genes were uncovered as set-2 directly for primary breast tumor. Drug-bank platform were used to discover drugs for target set-1/2 genes. Eventually, medropxyoprogesterone (MPA) targeting set-I gene and doxorubicin targeting set-2 gene were selected for the patient because the two drugs have already been approved by FDA. After doxorubicin and MPA were administered, patient's metastatic-tumor showed complete response. Conclusions :We not only analyze genomic expression profiles but also discover sensitive compounds for drug-resistant tumor. We successfully select drugs approved by FDA to treat the patient.

Human peripheral blood is a useful material for biomedical research, since it can be used to investigate responses to treatment and predict diseases. However, various biological and technological factors produce a large degree of variation in blood of gene expression profiles. This study was based on gene expression profiling analysis on peripheral blood of 45 healthy volunteers, 21 females and 24 men. The blood cells were concentrated, and the total RNA was isolated for the analysis of gene expression using the Affymetrix Gene Chip technology. The results were obtained by a fluorescent scanner, and the numerical data was analyzed using Bioconductor. Samples were clearly divided by gender through the unsupervised clustering analysis. 40 identified genes, differentiating samples by gender were analyzed, according to their biological function and chromosomal location. Most of them are located on the X and Y chromosomes. These results provide new insights into the genetic makeup which distinguishes both sexes probably associated with diseases and sex determination.