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Yi Hu

Publications and source records attributed to Yi Hu.

At least 19 recordsLinked to original sources

Advances in the Application of Adenine Base Editor (ABE) in Biology and Medicine: Prospects and Challenges.

Adenine base editors (ABEs), which achieve A·T to G·C conversions in the genome precisely, symbolize a groundbreaking development in genetic engineering across animal, plant, and microbial systems. This review systematically summed up the research progress and current challenges of ABE in medical and biological applications: it outlined the historical context and pivotal milestones of its technological development; it emphasized major therapeutic advances for genetic diseases including spinal muscular atrophy, mitochondrial genetic disorders, and hyperlipidemia; it provided a comprehensive overview of its prospective uses for enhancing genetic traits in agricultural crops, including grains and fruits; this review conducted a multidimensional assessment of ABE performance through systematic comparison with other base editing technologies, comprehensively evaluating both editing efficiency and inherent limitations. It specifically addresses biosecurity risks such as off-target effects and genomic instability. Finally, safety concerns were proposed as the central challenge hindering its clinical translation, although ABE holds immense promise for precision medicine and agricultural breeding. Unlike previous reviews that mainly summarized early ABE development and general applications, this review particularly emphasizes recently engineered ABE systems, translational bottlenecks, delivery strategies, comparative clinical feasibility, and unresolved biosafety challenges that currently limit broader therapeutic and agricultural applications.

Adenine base editors↗

Context-dependent abstraction of temporal relationships during naturalistic episodic memory.

How does the human brain represent how far apart in time two remembered moments occurred? Healthy adults played a first-person interactive video game and subsequently judged the temporal order of pairs of event moments during functional MRI. Using representational similarity analysis, we identified a distributed multivoxel activity pattern in the precuneus and surrounding posterior medial cortex whose representational geometry tracked retrieved temporal-distance magnitude across intervals ranging from less than 1 s to approximately 18 min. This representation could not be explained by perceptual similarity, situational change, or task difficulty, and was stronger for events sharing a common episodic context. Applying inhibitory brain stimulation to the precuneus before retrieval attenuated this representational pattern while leaving overall BOLD activity levels unchanged. These findings suggest that the precuneus contributes to organizing temporal relationships among remembered events, representing temporal distance within structured episodic contexts rather than as a simple metric of elapsed time.

autobiographical memory↗

Current Diagnostic Pathways for Rheumatoid Arthritis-Associated Interstitial Lung Disease Result in Substantial Underdiagnosis and Excess Mortality: A Multicenter Norwegian Quality Assurance Audit.

OBJECTIVE: Recent guidelines suggest risk-stratified screening for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the diagnostic gap between current routine care and this screening approach remains unquantified. We assessed currently detected RA-ILD in Norway, benchmarking findings against recent screening-based estimates of the true disease burden. METHODS: This 10-year quality assurance audit across six centers covered 43% of the Norwegian population. RA-ILD cases identified via ICD-10 codes were confirmed by manual chart review. Prevalence was calculated relative to a registry-derived total RA background population and benchmarked against a 10% expected target derived from recent prospective studies. Mortality was compared to a 3:1 frequency-matched RA control group using Cox proportional hazards regression. RESULTS: Among 17,305 RA patients, 188 (1.1%) had verified ILD; when benchmarked against an expected 10% prevalence, this indicates an 89% diagnostic gap in routine clinical care. Mean age at ILD detection was 67.5 years. Most cases (93.6%) possessed &#x2265;2 established risk factors for RA-ILD: 93.6% were seropositive, 76.1% had smoking histories, while RA onset age &#x2265;60 and persistently increased inflammatory laboratory markers were present in over half of patients. RA-ILD was associated with significantly increased mortality; 66 (4.1/100 person-years) deaths occurred in the RA-ILD group vs. 120 (2.3/100 person-years) among RA controls (HR 1.77; 95% CI: 1.31-2.39, p<0.001). CONCLUSION: When comparing to prevalence expectations, current routine care may leave a substantial proportion of cases undetected, primarily capturing a high-risk phenotype with excess mortality. Systematic, risk-stratified screening is needed to bridge this diagnostic gap, aiming to enable earlier intervention.

Interstitial lung disease↗

The Protective Role of DDIT4 in Helicobacter pylori-induced Gastric Metaplasia Through Metabolic Regulation of Ferroptosis.

BACKGROUND & AIMS: Helicobacter pylori (H&#xa0;pylori) infection is a significant factor leading to gastric atrophy, metaplasia and cancer development. Here, we investigated the role of the stress response gene DDIT4 in the pathogenesis of H&#xa0;pylori infection. METHODS: Cell lines, transgenic mice, and human tissue samples were implemented. Proteomics were performed on Ddit4+/+ and Ddit4-/- mice infected with H&#xa0;pylori strain PMSS1. C57BL/6 mice were administered with tamoxifen to induce gastric metaplasia. Stomach tissues were analyzed for histopathologic features, reactive oxygen species, Fe2+, lipid peroxidation, expression of DDIT4, and ferroptosis-related proteins. RESULTS: DDIT4 expression was upregulated at 6 hours but significantly decreased at 24 hours in response to H&#xa0;pylori infection in gastric epithelial cells. Gastric DDIT4 were downregulated in INS-GAS mice at 4 months post H&#xa0;pylori infection. Notably, H&#xa0;pylori infection led to more severe gastric metaplasia lesion in Ddit4-knockout mice. The proteomic profiling revealed an increase in ferroptosis in the gastric tissues of infected Ddit4-deficient mice, compared with infected wild-type mice. Mechanistically, knockout of DDIT4 promoted H&#xa0;pylori-induced ferroptosis through the accumulation of lipid peroxides and ROS levels, and alterations in proteins such as GPX4, ALOX15, and HMOX1. Overexpression of DDIT4 counteracted H&#xa0;pylori-induced stem cell marker CD44V9 through modulation of ferroptosis. Similarly, in another mouse model of gastric metaplasia treated with tamoxifen, as well as in human GIM tissues, we observed the loss of DDIT4 and induction of ferroptosis. CONCLUSIONS: Our results indicate that DDIT4 serves as a protective factor against H&#xa0;pylori-induced gastric metaplasia by metabolic resistance to ferroptosis.

Ferroptosis↗

EST database for early flower development in California poppy (Eschscholzia californica Cham., Papaveraceae) tags over 6,000 genes from a basal eudicot.

The Floral Genome Project (FGP) selected California poppy (Eschscholzia californica Cham. ssp. Californica) to help identify new florally-expressed genes related to floral diversity in basal eudicots. A large, non-normalized cDNA library was constructed from premeiotic and meiotic floral buds and sequenced to generate a database of 9,079 high quality Expressed Sequence Tags (ESTs). These sequences clustered into 5,713 unigenes, including 1,414 contigs and 4,299 singletons. Homologs of genes regulating many aspects of flower development were identified, including those for organ identity and development, cell and tissue differentiation, cell cycle control, and secondary metabolism. Over 5% of the transcriptome consisted of homologs to known floral gene families. Most are the first representatives of their respective gene families in basal eudicots and their conservation suggests they are important for floral development and/or function. App. 10% of the transcripts encoded transcription factors and other regulatory genes, including nine genes from the seven major lineages of the important MADS-box family of developmental regulators. Homologs of alkaloid pathway genes were also recovered, providing opportunities to explore adaptive evolution in secondary products. Furthermore, comparison of the poppy ESTs with the Arabidopsis genome provided support for putative Arabidopsis genes that previously lacked annotation. Finally, over 1,800 unique sequences had no observable homology in the public databases. The California poppy EST database and library will help bridge our understanding of flower initiation and development among higher eudicot and monocot model plants and provide new opportunities for comparative analysis of gene families across angiosperm species.

DNA, Complementary↗

Neutron and electron diffraction studies of La(Zn1/2Ti1/2)O3 perovskite.

The crystallography and microwave dielectric properties of La(Zn(1/2)Ti(1/2))O(3) (LZT) ceramics prepared via the mixed-oxide route were investigated in this study. While samples were largely single phase, small amounts of ZnO impurity were detected in sintered pellets. Observed reflections in electron and neutron diffraction patterns indicate that the symmetry of LZT is P2(1)/n. The B site is ordered on {110} or pseudocubic {111}, but the presence of the pseudocubic 1/2(111) reflection is in itself insufficient to indicate the existence of such order. Rietveld refinements of the neutron diffraction data yield an excellent fit for such a model. The structure is highly twinned, with variants related through common {211} composition planes and 90 degrees rotations about <011>. The microwave dielectric properties measured were epsilon(r) = 34, Qf = 36,090 and tau(f) = -70 MK(-1).

Journal Article↗

Microarray: a versatile platform for high-throughput functional proteomics.

The advent of microarray technologies has dramatically accelerated the functional study of proteins, including enzymes (catalomics) in a proteome. Herein, we review recent advances and exciting new developments of microarrays in high-throughput functional proteomics.

Oligonucleotide Array Sequence Analysis↗

[Benign gastric strictures after transthoracic esophagectomy and esophagogastrostomy: an analysis of 9 cases].

OBJECTIVE: To investigate the manifestations,etiology,diagnosis and treatment of benign gastric strictures after transthoracic esophagectomy and esophagogastrostomy. METHODS: From January 1998 to December 2004, 9 cases with benign gastric strictures following esophagectomy were enrolled in the study. The manifestations,radiographic and endoscopic findings, treatment were analyzed retrospectively. RESULTS: The patients included 8 males and 1 female. Benign gastric stricture is characterized by mucosa absence and proliferation of fibrous tissue in the stomach below the stoma. The age ranged from 49 to 71 years old (median age 62). The common symptom was postoperative dysphagia. The length of stricture ranged from 1.5 to 5.0 cm, and the width from 0.1 to 0.5 cm. Seven cases were treated ineffectively with simple dilation,while esophageal stent placement was performed in 8 cases successfully. After follow- up from 5 to 60 months, restenosis occurred for 11 times including stent fall-off for 6 times,stent migration for 1 times, overgrowth of granular tissues for 4 times. Other complications included cervical incision infection and massive hemorrhage in one case respectively. Restenoses were all solved with stent replacement. CONCLUSIONS: Benign gastric stricture should be diagnosed through dysphagia, barium meal and endoscopy. Placement of non-self-expandable stent or whole covered self-expandable metallic stent is the primary treatment.

Aged↗

[Evaluating prophylactic ligation of thoracic duct during radical resection of esophageal carcinoma].

BACKGROUND & OBJECTIVE: Prophylactic ligation of thoracic duct during the radical resection of esophageal carcinoma is usually used to prevent and treat chylothorax, but there is dispute about the effect. Its correlation to other complications and prognosis of esophageal carcinoma patients after operation has seldom been reported. The study was to evaluate its preventive effect on chylothorax and its influences on other complications and prognosis of esophageal carcinoma patients. METHODS: Clinical data from 389 patients who underwent radical transthoracic esophagectomy from Jun. 1991 to Jun. 1996 in Cancer Center of Sun Yat-sen University were retrospectively analyzed. Of the 389 patients, 171 received thoracic duct ligation (ligation group), and 218 had thoracic duct preserved (preservation group). The occurrence rates of chylothorax and other complications, and the survival rates were compared between the 2 groups. RESULTS: The occurrence rates of chylothorax were 1.17% in ligation group and 0.46% in preservation group (P<0.001). The occurrence rates of complication were 18.2% in ligation group and 11.5% in preservation group (P=0.063). Perioperative mortalities were 1.75% in ligation group and 0.92% in preservation group (P=0.658). The 1-, 2-, 3-, and 5-year survival rates were 74.3%, 52.1%, 42.1%, and 29.2% in ligation group, and 74.3%, 53.2%, 43.1%, and 29.8% in preservation group (P=0.992, 0.819, 0.841, 0.902). CONCLUSION: Prophylactic ligation of thoracic duct during esophagectomy for patients with esophageal carcinoma could not prevent chylothorax effectively, and has no obvious influence on the occurrence of other complications and survival of the patients after operation.

Chylothorax↗

[Differential diagnosis and treatment of esophageal stromal tumors and smooth muscle tumors].

BACKGROUND & OBJECTIVE: Esophageal stromal tumors and smooth muscle tumors are not easy to be distinguished in clinic though they have different pathologic features. This study was to compare the clinicopathologic features of esophageal stromal tumors and smooth muscle tumors, and discuss their treatments. METHODS: The expression of CD117 and CD34 in 16 specimens of primarily diagnosed esophageal leiomyoma, 4 specimens of esophageal leiomyosarcoma, and 1 specimen of stromal tumor was detected by immunohistochemistry. The clinicopathologic features of the patients were analyzed, and the treatment principles and curative efficacies were summarized. RESULTS: Of the 16 cases of primarily diagnosed esophageal leiomyoma, 5 were CD117(+) and finally diagnosed as non-high aggressive fatal stromal tumor according to the assessment criteria of stromal tumors; 11 were CD117(-). The stromal tumor was CD117(+) and CD34(+), and diagnosed as high aggressive fatal stromal tumor. The 4 cases of primarily diagnosed esophageal leiomyosarcoma were CD117(-) and CD34(-). There was no obvious difference in clinicopathologic manifestations, treatment and prognosis between esophageal non-high aggressive fatal stromal tumor and leiomyoma, and between esophageal high aggressive fatal stromal tumor and leiomyosarcoma. CONCLUSIONS: Esophageal stromal tumors and smooth muscle tumors can not be distinguished with clinicopathologic exhibitions. The immunohistochemical examination of antibody CD117 is necessary for identifying them. Lumpectomy or esophageal partial resection is enough for esophageal non-high aggressive fatal stromal tumor and leiomyoma. Esophageal partial resection is necessary for esophageal high aggressive fatal stromal tumor and leiomyosarcoma.

Actins↗

[Phase II multicenter clinical trial of nedaplatin in the treatment of malignant tumors].

OBJECTIVE: To evaluate and compare the efficacy and safety of Nedaplatin (NDP)-based regimen and cisplatin (DDP)-based regimen for head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), esophageal cancer and ovary epithelial cell carcinoma. METHODS: Single agent group: NDP was administered at a dose of 100 mg/m(2) on D1, every 3 weeks for at least 2 cycles. Combination chemotherapy group: combined with 5-Fu, NVB, VDS + 5-Fu, PTX or CTX respectively, NDP 80 mg/m(2) on D1 or DDP 30 mg/m(2) on D1-3, every 3 weeks for at least 2 cycles was given. RESULTS: Of 237 patients in this trial, 37 were treated by single Nedaplatin, 139 by NDP-based regimen, 61 by DDP-based regimen in the control group. The response rate of single Nedaplatin chemotherapy for advanced NSCLC was 10.5% (2/19), for ovary carcinoma (1/3) and HNSCC (1/1). For NSCLC and ovary carcinoma patients who had failed in the previous DDP-based chemotherapy, the response rates by single NDP chemotherapy were still 9.1% and 33.3%. The response rate of NDP-based combination regimen for NSCLC, ovary carcinoma, HNSCC and esophageal cancer was 33.9% (21/62), 44.8% (13/29), 20.0% (3/15) and 18.2% (4/22), respectively, which was not statistically different from the rate of controlled group treated by DDP-based regimen. For chemonaive NSCLC, the effect of NDP-based combination regimen (35.7%) was significantly superior to the effect of DDP-based regimen (17.1%) (P = 0.045). The most common adverse events of nedaplatin were myelosuppression (leukopenia, thrombocytopenia, anemia), nausea and vomiting. The myelosuppression and renal toxicity of NDP-based regimen were similar to that of DDP-based regimen, but vomiting was milder than that of DDP-based regimen (54% vs. 75.4%), and grade I/II liver toxicity was more common in the NDP-based regimen than in DDP-based regimen (10.8% vs. 0). CONCLUSION: Nedaplatin is effective in the treatment for HNSCC, NSCLC and ovary carcinoma. Compared with the control group treated by DDP-based regimen, nedaplatin-based combination chemotherapy has similar effect on HNSCC, NSCLC, ovary carcinoma and esophageal cancer. Gastrointestinal reaction of nedaplatin is milder than that of cisplatin but the liver function during chemotherapy must be monitored closely.

Adolescent↗

Glucose biosensor based on Au nanoparticles-conductive polyaniline nanocomposite.

In this paper, we report a novel glucose biosensor based on composite of Au nanoparticles (NPs)-conductive polyaniline (PANI) nanofibers. Immobilized with glucose oxidase (GOx) and Nafion on the surface of nanocomposite, a sensitive and selective biosensor for glucose was successfully developed by electrochemical oxidation of H2O2. The glucose biosensor shows a linear calibration curve over the range from 1.0x10(-6) to 8.0x10(-4) mol/L, with a slope and detection limit (S/N=3) of 2.3 mA/M and 5.0x10(-7) M, respectively. In addition, the glucose biosensor system indicates excellent reproducibility (less than 5% R.S.D.) and good operational stability (over 2 weeks).

Aniline Compounds↗

Synthesis and structure-activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7.

The structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPPs) was studied. In a series of N-cycloalkyl analogs, DPP4 and fibroblast activation protein-alpha (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs.

Adenosine Deaminase Inhibitors↗

Boro-norleucine as a P1 residue for the design of selective and potent DPP7 inhibitors.

Dipeptide-based inhibitors with C-substituted (alkyl or aminoalkyl) alpha-amino acids in the P2 position and boro-norleucine (boro-Nle) in the P1 position were synthesized. Relative to boro-proline, boro-Nle as a P1 residue was shown able to significantly dial out DPP4, FAP, DPP8, and DPP9 activity. Dab-boro-Nle (4g) proved to be the most selective and potent DPP7 inhibitor with a DPP7 IC50 value of 480 pM.

Boronic Acids↗

Floral gene resources from basal angiosperms for comparative genomics research.

BACKGROUND: The Floral Genome Project was initiated to bridge the genomic gap between the most broadly studied plant model systems. Arabidopsis and rice, although now completely sequenced and under intensive comparative genomic investigation, are separated by at least 125 million years of evolutionary time, and cannot in isolation provide a comprehensive perspective on structural and functional aspects of flowering plant genome dynamics. Here we discuss new genomic resources available to the scientific community, comprising cDNA libraries and Expressed Sequence Tag (EST) sequences for a suite of phylogenetically basal angiosperms specifically selected to bridge the evolutionary gaps between model plants and provide insights into gene content and genome structure in the earliest flowering plants. RESULTS: Random sequencing of cDNAs from representatives of phylogenetically important eudicot, non-grass monocot, and gymnosperm lineages has so far (as of 12/1/04) generated 70,514 ESTs and 48,170 assembled unigenes. Efficient sorting of EST sequences into putative gene families based on whole Arabidopsis/rice proteome comparison has permitted ready identification of cDNA clones for finished sequencing. Preliminarily, (i) proportions of functional categories among sequenced floral genes seem representative of the entire Arabidopsis transcriptome, (ii) many known floral gene homologues have been captured, and (iii) phylogenetic analyses of ESTs are providing new insights into the process of gene family evolution in relation to the origin and diversification of the angiosperms. CONCLUSION: Initial comparisons illustrate the utility of the EST data sets toward discovery of the basic floral transcriptome. These first findings also afford the opportunity to address a number of conspicuous evolutionary genomic questions, including reproductive organ transcriptome overlap between angiosperms and gymnosperms, genome-wide duplication history, lineage-specific gene duplication and functional divergence, and analyses of adaptive molecular evolution. Since not all genes in the floral transcriptome will be associated with flowering, these EST resources will also be of interest to plant scientists working on other functions, such as photosynthesis, signal transduction, and metabolic pathways.

Biodiversity↗

Gene discovery in Plasmodium vivax through sequencing of ESTs from mixed blood stages.

Despite the significance of Plasmodium vivax as the most widespread human malaria parasite and a major public health problem, gene expression in this parasite is poorly understood. To accelerate gene discovery and facilitate the annotation phase of the P. vivax genome project, we have undertaken a transcriptome approach to study gene expression in the mixed blood stages of a P. vivax field isolate. Using a cDNA library constructed from purified blood stages, we have obtained single-pass sequences for approximately 21,500 expressed sequence tags (ESTs), the largest number of transcript tags obtained so far for this species. Cluster analysis revealed that the library is highly redundant, resulting in 5407 clusters. Clustered ESTs were searched against public protein databases for functional annotation, and more than one-third showed a significant match, the majority of these to Plasmodium falciparum proteins. The most abundant clusters were to genes encoding ribosomal proteins and proteins involved in metabolism, consistent with the predominance of trophozoites in the field isolate sample. In spite of the scarcity of other parasite stages in the field isolate, we could identify genes that are expressed in rings, schizonts and gametocytes. This study should facilitate our understanding of the gene expression in P. vivax asexual stages and provide valuable data for gene prediction and annotation of the P. vivax genome sequence.

Animals↗