Targeted therapy of kidney disease with nanoparticle drug delivery materials.

With the development of nanomedicine, nanomaterials have been widely used, offering specific drug delivery to target sites, minimal side effects, and significant therapeutic effects. The kidneys have filtration and reabsorption functions, with various potential target cell types and a complex structural environment, making the strategies for kidney function protection and recovery after injury complex. This also lays the foundation for the application of nanomedicine in kidney diseases. Currently, evidence in preclinical and clinical settings supports the feasibility of targeted therapy for kidney diseases using drug delivery based on nanomaterials. The prerequisite for nanomedicine in treating kidney diseases is the use of carriers with good biocompatibility, including nanoparticles, hydrogels, liposomes, micelles, dendrimer polymers, adenoviruses, lysozymes, and elastin-like polypeptides. These carriers have precise renal uptake, longer half-life, and targeted organ distribution, protecting and improving the efficacy of the drugs they carry. Additionally, attention should also be paid to the toxicity and solubility of the carriers. While the carriers mentioned above have been used in preclinical studies for targeted therapy of kidney diseases both in vivo and in vitro, extensive clinical trials are still needed to ensure the short-term and long-term effects of nano drugs in the human body. This review will discuss the advantages and limitations of nanoscale drug carrier materials in treating kidney diseases, provide a more comprehensive catalog of nanocarrier materials, and offer prospects for their drug-loading efficacy and clinical applications.

Establishment of a prognosis predictive model for liver cancer based on expression of genes involved in the ubiquitin-proteasome pathway.

BACKGROUND: The ubiquitin-proteasome pathway (UPP) has been proven to play important roles in cancer. AIM: To investigate the prognostic significance of genes involved in the UPP and develop a predictive model for liver cancer based on the expression of these genes. METHODS: In this study, UPP-related E1, E2, E3, deubiquitylating enzyme, and proteasome gene sets were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, aiming to screen the prognostic genes using univariate and multivariate regression analysis and develop a prognosis predictive model based on the Cancer Genome Atlas liver cancer cases. RESULTS: Five genes (including autophagy related 10, proteasome 20S subunit alpha 8, proteasome 20S subunit beta 2, ubiquitin specific peptidase 17 like family member 2, and ubiquitin specific peptidase 8) were proven significantly correlated with prognosis and used to develop a prognosis predictive model for liver cancer. Among training, validation, and Gene Expression Omnibus sets, the overall survival differed significantly between the high-risk and low-risk groups. The expression of the five genes was significantly associated with immunocyte infiltration, tumor stage, and postoperative recurrence. A total of 111 differentially expressed genes (DEGs) were identified between the high-risk and low-risk groups and they were enriched in 20 and 5 gene ontology and KEGG pathways. Cell division cycle 20, Kelch repeat and BTB domain containing 11, and DDB1 and CUL4 associated factor 4 like 2 were the DEGs in the E3 gene set that correlated with survival. CONCLUSION: We have constructed a prognosis predictive model in patients with liver cancer, which contains five genes that associate with immunocyte infiltration, tumor stage, and postoperative recurrence.

Barley yellow dwarf virus-GAV 17K protein disrupts thiamine biosynthesis to facilitate viral infection in plants.

Thiamine functions as a crucial activator modulating plant health and broad-spectrum stress tolerances. However, the role of thiamine in regulating plant virus infection is largely unknown. Here, we report that the multifunctional 17K protein encoded by barley yellow dwarf virus-GAV (BYDV-GAV) interacted with barley pyrimidine synthase (HvTHIC), a key enzyme in thiamine biosynthesis. HvTHIC was found to be localized in chloroplast via an N-terminal 74-amino acid domain. However, the 17K-HvTHIC interaction restricted HvTHIC targeting to chloroplasts and triggered autophagy-mediated HvTHIC degradation. Upon BYDV-GAV infection, the expression of the HvTHIC gene was significantly induced, and this was accompanied by accumulation of thiamine and salicylic acid. Silencing of HvTHIC expression promoted BYDV-GAV accumulation. Transcriptomic analysis of HvTHIC silenced and non-silenced barley plants showed that the differentially expressed genes were mainly involved in plant-pathogen interaction, plant hormone signal induction, phenylpropanoid biosynthesis, starch and sucrose metabolism, photosynthesis-antenna protein, and MAPK signaling pathway. Thiamine treatment enhanced barley resistance to BYDV-GAV. Taken together, our findings reveal a molecular mechanism underlying how BYDV impedes thiamine biosynthesis to uphold viral infection in plants.

Diverse ALS mutations and cross-and multiple-resistance to ALS and EPSPS inhibitors in flucarbazone­sodium-resistant Bromus japonicus populations from Hebei province, China.

Japanese brome (Bromus japonicus) has become one of the main weeds in wheat fields in Hebei province of China and causes a large decrease of wheat production. A total of 44 putative resistant and 2 susceptible Japanese brome populations were collected in the 2021/2022 crop season from Hebei province of China to determine resistance levels to flucarbazone­sodium and to investigate the diversity of acetolactate synthase (ALS) mutations, as well as to confirm the cross-and multiple-resistance levels to ALS and EPSPS (5-enolpyruvate shikimate-3-phosphate synthetase) inhibitors. Whole plant bioassay results showed that 15 out of 44 populations tested or 34% were resistant to flucarbazone­sodium. The resistance indices of Japanese brome to flucarbazone­sodium ranged from 43 to 1977. The resistant populations were mainly distributed in Baoding and Shijiazhuang districts, and there was only one resistant population in Langfang district. Resistant Japanese brome had diverse ALS mutations, including Pro-197-Ser, -Thr, -Arg and Asp-376-Glu. The incidence of Pro-197-Ser mutation was the highest at 68%. Application of the CYP450 inhibitor malathion suggested that CYP450 was involved in metabolic resistance in a population without an ALS mutation. The population with Pro-197-Thr mutation evolved weak cross-resistance to mesosulfuron-methyl and pyroxsulam, and it is in the process of evolving multiple-resistance to glyphosate.

Near-Infrared Perylenecarboximide Fluorophores for Live-Cell Super-Resolution Imaging.

Organic near-infrared (NIR) photoblinking fluorophores are highly desirable for live-cell super-resolution imaging based on single-molecule localization microscopy (SMLM). Herein we introduce a novel small chromophore, PMIP, through the fusion of perylenecarboximide with 2,2-dimetheylpyrimidine. PMIP exhibits an emission maximum at 732 nm with a high fluorescence quantum yield of 60% in the wavelength range of 700-1000 nm and excellent photoblinking without any additives. With resorcinol-functionalized PMIP (PMIP-OH), NIR SMLM imaging of lysosomes is demonstrated for the first time in living mammalian cells under physiological conditions. Moreover, metabolically labeled nascent DNA is site-specifically detected using azido-functionalized PMIP (PMIP-N3) via click chemistry, thereby enabling the super-resolution imaging of nascent DNA in phosphate-buffered saline with a 9-fold improvement in spatial resolution. These results indicate the potential of PMIP-based NIR blinking fluorophores for biological applications of SMLM.

Ti2C3 MXene-based nanocomposite as an intelligent nanoplatform for efficient mild hyperthermia treatment.

Photothermal therapy (PTT) has attracted much attention due to its less invasive, controllable and highly effective nature. However, PTT also suffers from intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by a variety of proteins, among which heat shock protein (HSP) triggers thermotolerance and protects tumor cells from hyperthermia-induced apoptosis. Confronted by this challenge, we propose and validate here a novel MXene-based HSP-inhibited mild photothermal platform, which significantly enhances the sensitivity of tumor cells to heat-induced stress and thus improves the PPT efficacy. The Ti3C2@Qu nanocomposites are constructed by utilizing the high photothermal conversion ability of Ti3C2 nanosheets in combination with quercetin (Qu) as an inhibitor of HSP70. Qu molecules are loaded onto the nanoplatform in a pH-sensitive controlled release manner. The acidic environment of the tumor causes the burst-release of Qu molecules, which deplete the level of heat shock protein 70 (HSP70) in tumor cells and leave the tumor cells out from the protection of the heat-resistant survival pathway in advance, thus sensitizing the hyperthermia efficacy. The nanostructure, photothermal properties, pH-responsive controlled release, synergistic photothermal ablation of tumor cells in vitro and in vivo, and hyperthermia effect on subcellular structures of the Ti3C2@Qu nanocomposites were systematically investigated.

Identification of prognostic biomarkers of smoking-related lung cancer.

Background: The early diagnosis and effective prognostic treatment measures for lung cancer are still limited, leading to a 5-year survival rate of less than 15% for these patients. Smoking is one of the causes of lung cancer, but it is not the initial carcinogenic factor. It is not clear what specific mechanism cigarette induces lung cancer, and there is a lack of research on the relationship between related genes and the prognosis of patients with smoking lung cancer. The objective of this study was to provide new theoretical evidence and potential therapeutic targets for the mechanisms of smoking-related lung cancer formation. Methods: The gene expression profile data from the GSE12428 dataset which includes 63 lung cancer and normal tissue pairs were downloaded from the Gene Expression Omnibus (GEO) database, and data from smokers with lung cancer [both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC)] from The Cancer Genome Atlas (TCGA) database were analyzed. The differential genes in smokers with lung cancer were screened using the linear model for microarray data via R software. The differential gene enrichment analysis was performed using the online analysis software Database for Annotation, Visualization and Integrated Discovery (DAVID). The expression levels of differential genes and their correlation with patient tumor clinical stage were analyzed using gene expression profiling interactive analysis (GEPIA). The overall survival rate was analyzed using Kaplan-Meier curves. Results: In the GSE12428 dataset, 225 upregulated genes and 565 downregulated genes were identified in cancer tissues; based on smoking status, 1 upregulated gene and 4 downregulated genes were identified. Among smokers who also had lung cancer, 4 genes were downregulated, namely CSH1, BPIFA1, SLPI, and SCGB3A1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these genes were mainly associated with biological functions such as antibacterial response, humoral immune response, and response to external stimuli. Among them, BPIFA1, SLPI, and SCGB3A1 expression was decreased in lung cancer tissues, with SCGB3A1 showing significant differences. Additionally, high expression of SCGB3A1 was associated with favorable prognosis in patients with lung cancer. Conclusions: Three genes BPIFA1, SLPI and SCGB3A1, were identified as being associated with smokers with lung cancer, with SCGB3A1 showing a close correlation with patient prognosis. These findings provide potential new targets for the treatment of lung cancer. Certainly, this study needs to more investigate the mechanism of these genes regulation.

Determinant of m6A regional preference by transcriptional dynamics.

N6-Methyladenosine (m6A) is the most abundant chemical modification occurring on eukaryotic mRNAs, and has been reported to be involved in almost all stages of mRNA metabolism. The distribution of m6A sites is notably asymmetric along mRNAs, with a strong preference toward the 3' terminus of the transcript. How m6A regional preference is shaped remains incompletely understood. In this study, by performing m6A-seq on chromatin-associated RNAs, we found that m6A regional preference arises during transcription. Nucleosome occupancy is remarkedly increased in the region downstream of m6A sites, suggesting an intricate interplay between m6A methylation and nucleosome-mediated transcriptional dynamics. Notably, we found a remarkable slowdown of Pol-II movement around m6A sites. In addition, inhibiting Pol-II movement increases nearby m6A methylation levels. By analyzing massively parallel assays for m6A, we found that RNA secondary structures inhibit m6A methylation. Remarkably, the m6A sites associated with Pol-II pausing tend to be embedded within RNA secondary structures. These results suggest that Pol-II pausing could affect the accessibility of m6A motifs to the methyltransferase complex and subsequent m6A methylation by mediating RNA secondary structure. Overall, our study reveals a crucial role of transcriptional dynamics in the formation of m6A regional preference.

The industrial robot reducer testing instrument dynamic torsional moment measurement error calibration, based on the Bisquare curve fitting-improved Bayes particle swarm optimization-nonlinear echo state network (BCF-IBPSO-NESN) method.

Industrial robots are important components in the production and manufacturing industry. As a core component of the industrial robot, the industrial robot reducer plays a crucial role in the performance of the entire industrial robot. The error analysis and accuracy traceability of the industrial robot reducer testing instrument are of great significance in improving the quality of the precision reducer. Therefore, it is essential to calibrate the dynamic torsional moment measurement error of the instrument. The features of the dynamic torsional moment measurement error are analyzed in this paper. Based on these features, a new dynamic torsional moment measurement error calibration method is proposed based on the Bisquare curve fitting-improved Bayes particle swarm optimization-nonlinear echo state network (BCF-IBPSO-NESN) algorithm. The proposed method focuses on calibrating the dynamic torsional moment measurement error of the industrial robot reducers in real time. The experimental results show that the dynamic torsional moment measurement error of the input side torsional moment measurement module and the output side torsional moment measurement module can be reduced to ±0.05 Nm and ±1 Nm, respectively. The contribution of this paper is that the method calibrates the dynamic torsional moment measurement error. It supplies a guideline for calibrating the dynamic torsional moment measurement error of the instrument under any load.

Numerical Simulations of Combined Dielectrophoresis and Alternating Current Electrothermal Flow for High-Efficient Separation of (Bio)Microparticles.

High-efficient separation of (bio)microparticles has important applications in chemical analysis, environmental monitoring, drug screening, and disease diagnosis and treatment. As a label-free and high-precision separation scheme, dielectrophoresis (DEP) has become a research hotspot in microparticle separation, especially for biological cells. When processing cells with DEP, relatively high electric conductivities of suspending media are sometimes required to maintain the biological activities of the biosample, which results in high temperature rises within the system caused by Joule heating. The induced temperature gradient generates a localized alternating current electrothermal (ACET) flow disturbance, which seriously impacts the DEP manipulation of cells. Based on this, we propose a novel design of the (bio)microparticle separator by combining DEP with ACET flow to intensify the separation process. A coupling model that incorporates electric, fluid flow, and temperature fields as well as particle tracking is established to predict (bio)microparticle trajectories within the separator. Numerical simulations reveal that both ACET flow and DEP motion act in the same plane but in different directions to achieve high-precision separation between particles. This work provides new design ideas for solving the very tricky Joule heating interference in the DEP separation process, which paves the way for further improving the throughput of the DEP-based (bio)microparticle separation system.

EPIC-0628 abrogates HOTAIR/EZH2 interaction and enhances the temozolomide efficacy via promoting ATF3 expression and inhibiting DNA damage repair in glioblastoma.

The efficacy of temozolomide (TMZ) treatment in glioblastoma (GBM) is influenced by various mechanisms, mainly including the level of O6-methylguanine-DNA methyltransferase (MGMT) and the activity of DNA damage repair (DDR) pathways. In our previous study, we had proved that long non-coding RNA HOTAIR regulated the GBM progression and mediated DDR by interacting with EZH2, the catalytic subunit of PRC2. In this study, we developed a small-molecule inhibitor called EPIC-0628 that selectively disrupted the HOTAIR-EZH2 interaction and promoted ATF3 expression. The upregulation of ATF3 inhibited the recruitment of p300, p-p65, p-Stat3 and SP1 to the MGMT promoter. Hence, EPIC-0628 silenced MGMT expression. Besides, EPIC-0628 induced cell cycle arrest by increasing the expression of CDKN1A and impaired DNA double-strand break repair via suppressing the ATF3-p38-E2F1 pathway. Lastly, EPIC-0628 enhanced TMZ efficacy in GBM in vitro and vivo. Hence, this study provided evidence for the combination of epigenetic drugs EPIC-0628 with TMZ for GBM treatment through the above mechanisms.

1,3-Disubstituted-1,2,4-triazin-6-ones with potent activity against androgen receptor-dependent prostate cancer cells.

Synthesis and biological evaluation of a small, focused library of 1,3-disubstituted-1,2,4-triazin-6-ones for in vitro inhibitory activity against androgen-receptor-dependent (22Rv1) and androgen-receptor independent (PC3) castration-resistant prostate cancer (CRPC) cells led to highly active compounds with in vitro IC50 values against 22Rv1 cells of <200 nM, and with apparent selectivity for this cell type over PC3 cells. From metabolic/PK evaluations of these compounds, a 3-benzyl-1-(2,4-dichlorobenzyl) derivative had superior properties and showed considerably stronger activity, by nearly an order of magnitude, against AR-dependent LNCaP and C4-2B cells compared to AR-independent DU145 cells. This lead compound decreased AR expression in a dose and time dependent manner and displayed promising therapeutic effects in a 22Rv1 CRPC xenograft mouse model. Computational target prediction and subsequent docking studies suggested three potential known prostate cancer targets: p38a MAPK, TGF-ß1, and HGFR/c-Met, with the latter case of c-Met appearing stronger, owing to close structural similarity of the lead compound to known pyridazin-3-one derivatives with potent c-Met inhibitory activity. RNA-seq analysis showed dramatic reduction of AR signalling pathway and/or target genes by the lead compound, subsequently confirmed by quantitative PCR analysis. The lead compound was highly inhibitory against HGF, the c-Met ligand, which fitted well with the computational target prediction and docking studies. These results suggest that this compound could be a promising starting point for the development of an effective therapy for the treatment of CRPC.

Effects of abiotic stress on chlorophyll metabolism.

Chlorophyll, an essential pigment in the photosynthetic machinery of plants, plays a pivotal role in the absorption of light energy and its subsequent transfer to reaction centers. Given that the global production of chlorophyll reaches billions of tons annually, a comprehensive understanding of its biosynthetic pathways and regulatory mechanisms is important. The metabolic pathways governing chlorophyll biosynthesis and catabolism are complex, encompassing a series of interconnected reactions mediated by a spectrum of enzymes. Environmental fluctuations, particularly abiotic stressors such as drought, extreme temperature variations, and excessive light exposure, can significantly perturb these processes. Such disruptions in chlorophyll metabolism have profound implications for plant growth and development. This review delves into the core aspects of chlorophyll metabolism, encompassing both biosynthetic and degradative pathways. It elucidates key genes and enzymes instrumental in these processes and underscores the impact of abiotic stress on chlorophyll metabolism. Furthermore, the review aims to deepen the understanding of the interplay between chlorophyll metabolic dynamics and stress responses, thereby shedding light on potential regulatory mechanisms.

The relationship between diabetic retinopathy and diabetic nephropathy in type 2 diabetes.

Context: Diabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship between the severity of DR and the pathological severity of diabetic glomerulopathy remains unclear. Objective: To investigate the relationship between severity of diabetic retinopathy (DR) and histological changes and clinical indicators of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM (n=272) who underwent a renal biopsy were eligible. Severity of DR was classified as non-diabetic retinopathy, non-proliferative retinopathy, and proliferative retinopathy (PDR). Relationship between DN and DR and the diagnostic efficacy of DR for DN were explored. Results: DN had a higher prevalence of DR (86.4%) and DR was more severe. The sensitivity and specificity of DR in DN were 86.4% and 78.8%, while PDR was 26.4% and 98.5%, respectively. In DN patients, the severity of glomerular lesions (p=0.001) and prevalence of KW nodules (p<0.001) significantly increased with increasing severity of DR. The presence of KW nodules, lower hemoglobin levels, and younger age were independent risk factors associated with more severe DR in patients with DN. Conclusion: DR was a good predictor of DN. In DN patients, the severity of DR was associated with glomerular injury, and presence of KW nodules, lower hemoglobin levels and younger age were independent risk factors associated with more severe DR. Trial registration: ClinicalTrails.gov, NCT03865914.

Interior and Exterior Surface Modification of Zr-Based Metal-Organic Frameworks for Trace Benzene Removal.

The emission of volatile organic compounds (VOCs) significantly contributes to air pollution and poses a serious threat to human health. Benzene, one of the most toxic VOCs, is difficult for the human body to metabolize and is classified as a Group 1 carcinogen. The development of efficient adsorbents for removing trace amounts of benzene from ambient air is thus of great importance. In this work, we studied the benzene adsorption properties of four Zr-based metal-organic frameworks (Zr-MOFs) through static volumetric and dynamic breakthrough experiments. Two previously reported Zr-MOFs, BUT-12 and STA-26, were prepared with a tritopic carboxylic acid ligand (H3L1) functionalized with three methyl groups, and STA-26 is a 2-fold interpenetrated network of BUT-12. Two new isoreticular Zr-MOFs, BUT-12-Et and STA-26-Et, were synthesized using a similar ligand, H3L2, where the methyl groups are replaced with ethyl groups. There are mesopores in BUT-12 and BUT-12-Et and micropores in STA-26 and STA-26-Et. The four Zr-MOFs all showed high stability in liquid water and acidic aqueous solutions. The microporous STA-26 and STA-26-Et showed much higher benzene uptakes than mesoporous BUT-12 and BUT-12-Et at room temperature under low pressures. Particularly, the benzene adsorption capacity of STA-26-Et was high up to 2.21 mmol/g at P/P0 = 0.001 (P0 = 12.78 kPa), higher than those of the other three Zr-MOFs and most reported solid adsorbents. Breakthrough experiments confirmed that STA-26-Et could effectively capture trace benzene (10 ppm) from dry air; however, its benzene capture capacity was reduced by 90% under humid conditions (RH = 50%). Coating of the crystals of STA-26-Et with polydimethylsiloxane (PDMS) increased the hydrophobicity of the exterior MOF surfaces, leading to a more than 2-fold improvement in its benzene capture capacity in the breakthrough experiment under humid condition. PDMS coating of STA-26-Et likely slowed down the water adsorption process, and thus, the adsorbent afforded more efficient capture of benzene. This work demonstrates that modifying both the interior and exterior surfaces of MOFs can effectively enhance their performance in capturing trace benzene from ambient air, even under humid conditions. This finding is meaningful for the development of new adsorbents for effective air purification applications.

Two-level coding for efficient digital radio-over-fiber transmission with unequal bit protection.

The digital radio-over-fiber (D-RoF) transmission with two-level coding (TLC) is proposed and demonstrated in this Letter. A joint design considering the importance of quantization bits, the protection ability of forward error correction (FEC), and the bit error ratio of quadrature amplitude modulation (QAM) symbols is realized. In TLC-based D-RoF systems, the more significant bits among quantization bits are protected by a FEC and are assigned to the least reliable bits of modulated QAM symbols. Conversely, the less significant bits, without FEC protection, are allocated to the more reliable bits of QAM symbols. Experiments on an 11-km standard single-mode fiber transmission are conducted to evaluate the performance. The results indicate that, with a maximum iteration number of 2, compared to the conventional bit-interleaved coded modulation (BICM) with all bits encoded, the D-RoF based on TLC attains nearly identical performance under the 0.34% error vector magnitude threshold of 65536QAM wireless signals, specifically achieving complexity reductions of 54.55% and 67.66% for 16QAM and 64QAM optical transmissions, respectively.

Transcriptome analysis of salivary glands of rabies-virus-infected mice.

Rabies is a fatal zoonotic disease that poses a threat to public health. Rabies virus (RABV) is excreted in the saliva of infected animals, and is primarily transmitted by bite. The role of the salivary glands in virus propagation is significant, but has been less studied in the pathogenic mechanisms of RABV. To identify functionally important genes in the salivary glands, we used RNA sequencing (RNA-seq) to establish and analyze mRNA expression profiles in parotid tissue infected with two RABV strains, CVS-11 and PB4. The biological functions of differentially expressed genes (DEGs) were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which revealed 3,764 DEGs (678 up-regulated and 3,086 down-regulated) in the CVS-11 infected group and 4,557 DEGs (874 up-regulated and 3,683 down-regulated) in the PB4 infected group. Various biological processes are involved, including the salivary secretion pathway and the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. This study provides the first mapping of the transcriptome changes in response to RABV infection in parotid tissue, offering new insights into the study of RABV-affected salivary gland function and RABV pathogenic mechanisms in parotid tissue. The salivary gland-enriched transcripts may be potential targets of interest for rabies disease control.

Progress in the study of aging marker criteria in human populations.

The use of human aging markers, which are physiological, biochemical and molecular indicators of structural or functional degeneration associated with aging, is the fundamental basis of individualized aging assessments. Identifying methods for selecting markers has become a primary and vital aspect of aging research. However, there is no clear consensus or uniform principle on the criteria for screening aging markers. Therefore, we combine previous research from our center and summarize the criteria for screening aging markers in previous population studies, which are discussed in three aspects: functional perspective, operational implementation perspective and methodological perspective. Finally, an evaluation framework has been established, and the criteria are categorized into three levels based on their importance, which can help assess the extent to which a candidate biomarker may be feasible, valid, and useful for a specific use context.

Internal Carotid Artery Dissecting Aneurysm Associated with Persistent Trigeminal Artery: A Case Report.

BACKGROUND: Persistent trigeminal artery (PTA) is the most common vascular anastomosis between the carotid artery and vertebrobasilar systems. We report a very rare case of dissecting aneurysm in the right internal carotid artery (ICA) with ipsilateral PTA and discuss its clinical importance. CASE REPORT: A 38-year-old male presented to the emergency department with paroxysmal dysphasia for 6h. Brain magnetic resonance (MR) imaging showed acute cerebral infarction of the right corona radiata and right parietal lobe. Three-dimensional time-of-flight MR angiography (3D TOF MRA) revealed severe stenosis of the petrous segment (C1 portion) of the right internal carotid artery and a PTA originating from the right ICA cavernous segment (C4 portion), with a length of approximately 1.8cm and a diameter of approximately 0.2cm. The ICA segments are all named according to the Bouthilier classification. The basilar artery (BA) under union was well developed. The bilateral posterior communicating arteries were also present. One day later, the high-resolution vessel-wall MR demonstrated a dissecting aneurysm in the C1 portion of the right ICA. The length of the dissecting aneurysm is approximately 4.4cm, the diameter of the true lumen at the most severe stenosis is approximately 0.2cm, and the diameter of the false lumen is approximately 0.8cm. Subsequent digital subtraction angiography (DSA) confirmed a dissecting aneurysm in the C1 portion of the right ICA. The patient was treated conservatively and did not undergo interventional surgery. Four months later, head and neck MRA showed that the right ICA blood flow was smooth and that the dissecting aneurysm had disappeared. The Ethics Committee of Liaocheng People's Hospital approved the research protocol in compliance with the Helsinki Declaration. Written informed consent was obtained from the individual for the publication of any potentially identifiable images or data included in this article. CONCLUSION: Flow alteration with PTA may have influenced the formation of ICA dissection in this patient. Awareness of this is crucial in clinical practice because it can influence treatment options and intervention procedures.

A Dual-domain Engineered Antibody for Efficient HBV Suppression and Immune Responses Restoration.

Chronic hepatitis B (CHB) remains a major public health concern because of the inefficiency of currently approved therapies in clearing the hepatitis B surface antigen (HBsAg). Antibody-based regimens have demonstrated potency regarding virus neutralization and HBsAg clearance. However, high dosages or frequent dosing are required for virologic control. In this study, a dual-domain-engineered anti-hepatitis B virus (HBV) therapeutic antibody 73-DY is developed that exhibits significantly improved efficacy regarding both serum and intrahepatic viral clearance. In HBV-tolerant mice, administration of a single dose of 73-DY at 2 mg kg-1 is sufficient to reduce serum HBsAg by over 3 log10 IU mL-1 and suppress HBsAg to < 100 IU mL-1 for two weeks, demonstrating a dose-lowering advantage of at least tenfold. Furthermore, 10 mg kg-1 of 73-DY sustainably suppressed serum viral levels to undetectable levels for ≈ 2 weeks. Molecular analyses indicate that the improved efficacy exhibited by 73-DY is attributable to the synergy between fragment antigen binding (Fab) and fragment crystallizable (Fc) engineering, which conferred sustained viral suppression and robust viral eradication, respectively. Long-term immunotherapy with reverse chimeric 73-DY facilitated the restoration of anti-HBV immune responses. This study provides a foundation for the development of next-generation antibody-based CHB therapies.