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Biomedical subjects

Ling Zhou

Publications and source records attributed to Ling Zhou.

At least 19 recordsLinked to original sources

A novel allele of Sh1 facilitates the development of waxy-sweet corn from waxy corn.

Waxy corn and sweet corn represent 2 major classes of fresh-eating corn, each with distinct sensory attributes and nutritional compositions. Developing a new variety that combines both waxy and sweet traits would address rising consumer demand and expand new market potential. From a fast neutron-mutagenized population of the waxy corn inbred line HB522, we isolated a novel mutant, designated as wx-sweet, whose kernels simultaneously exhibit waxy and sweet characteristics at the milk-filling stage. Through bulked segregant analysis combined with fine mapping, we mapped the causal locus to SHRUNKEN1 (Sh1) on chromosome 9, which was confirmed by an allelism test with a characterized Mu-insertion allele of Sh1. A 7,227-bp Copia-type long terminal repeat retrotransposon insertion was identified in exon 2 of Sh1 in the wx-sweet mutant by long-read sequencing. Consistently, the novel sh1 allele significantly reduced sucrose synthase activity. Genetic and physiological analyses demonstrate that sh1 and wx1 act synergistically to fine-tune carbohydrate metabolism in the endosperm. Integrated transcriptomic and metabolomic profiling uncover extensive transcriptional reprogramming and redirected metabolic flux, leading to substantial accumulation of sucrose and a range of oligosaccharides. These metabolic shifts underlie the unique simultaneous dual waxy-sweet texture in fresh-eating wx-sweet kernels. In summary, our work not only provides valuable genetic resources for breeding next-generation fresh-eating corn but also, for the first time, elucidates the molecular mechanism by which the sh1 and wx1 mutations cooperatively shape the waxy-sweet endosperm phenotype.

Zea mays↗

Structural and functional characterization of a conserved cryptic epitope on SARS-CoV-2 spike S2 subunit.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone extensive evolution since its emergence in 2019, underscoring the continuous need for vaccines and therapeutics effective against multiple variants of concern (VOCs). The S2 subunit of the viral spike (S) glycoprotein is highly conserved among sarbecoviruses, making it an attractive target for broadly protective countermeasures. To elucidate the S2 antigenic landscape, we employed yeast surface display to isolate S2-targeted antibodies from COVID-19 convalescent donors. Biophysical characterization revealed that these S2 apex-directed antibodies preferentially bind to open spike conformations and a stabilized S2 construct but not to the closed, trimeric prefusion spike. Cryo-electron microscopy structures defined a cryptic epitope encompassing the upper helix and fusion peptide proximal region on S2. This epitope is conserved among sarbecoviruses but remains largely occluded in the closed prefusion conformation of the spikes. As a result, the antibodies exhibited weak neutralization activity against SARS-CoV-2 pseudoviruses, failed to neutralize authentic viruses, and did not provide protection in a lethal mouse challenge model using a mouse-adapted SARS-CoV-2 strain. These findings highlight a non-neutralizing epitope on S2 capable of eliciting antibodies during SARS-CoV-2 infection in humans and provide valuable reagents for probing S2 conformational dynamics and optimizing S2-based vaccine antigens.

Spike Glycoprotein, Coronavirus↗

Prospective clinical validation of targeted long-read sequencing for preimplantation genetic testing of α-thalassaemia.

BACKGROUND: Preimplantation genetic testing for monogenic disorders (PGT-M) can prevent transmission of severe α-thalassaemia, but conventional workflows remain limited by family-specific assay design for direct variant detection, dependence on additional family samples for haplotype construction, and labour-intensive multi-step procedures across several platforms. Targeted long-read sequencing-based PGT-M for α-thalassaemia (tlrPGT-α-thal) integrates direct variant detection and haplotype linkage analysis within a single assay, but prospective clinical validation is lacking. METHODS: This prospective clinical study enrolled 103 families at high risk of transmitting α-thalassaemia at a reproductive medicine centre between August 2024 and March 2025. All families underwent blinded parallel analysis using both conventional NGS-based PGT-M (comparator) and tlrPGT-α-thal. RESULTS: In the primary concordance analysis, tlrPGT-α-thal was fully concordant with conventional NGS-based PGT-M (507/507, 100.0%; exact 95% CI, 99.3-100.0). Direct variant detection was successful in 501/507 embryos (98.82%; 95% CI, 97.4-99.6), haplotype linkage was established in 505/507 embryos (99.61%; 95% CI, 98.6-100.0), and one meiotic recombination event was identified. Among 93 families proceeding to embryo transfer, 57 pregnancies underwent invasive prenatal diagnosis, and all were concordant with the corresponding tlrPGT-α-thal results. Of the 26 comparator-inconclusive embryos, tlrPGT-α-thal resolved 6 complex cases, including cases with incomplete pedigrees or insufficient informative SNPs. Among the remaining 20 embryos with HBA-region aneuploidies, genotype and parental origin could be determined in 12. CONCLUSIONS: The findings show that tlrPGT-α-thal enables direct detection of diverse α-thalassaemia-causing variants together with efficient haplotype linkage analysis within a single workflow, without requiring family-specific assay design or additional family samples. The method demonstrated high diagnostic accuracy while providing added value in complex scenarios. Taken together, tlrPGT-α-thal represents a simplified and broadly applicable strategy for α-thalassaemia PGT-M.

Humans↗

Genome-Wide In Vivo RNAi Screening Identifies HOXD4 as a Tumor Metastasis Suppressor in Colorectal Cancer.

Metastasis remains a major therapeutic challenge in colorectal cancer, highlighting an urgent need to elucidate its underlying molecular mechanisms. In this study, an in vivo screening system integrating genome-wide short hairpin RNA library and next-generation sequencing identifies six candidate metastasis suppressors, among which Homeobox D4 (HOXD4) shows the most pronounced effects. Clinicopathological analyses reveal significant HOXD4 downregulation in tumor tissues relative to adjacent normal tissues, with reduced expression strongly correlating with aggressive tumor features. Functional assays demonstrate that HOXD4 depletion enhances migration, invasion, and tumorsphere formation in HCT116 cells, while ectopic HOXD4 overexpression reverses these malignant phenotypes in SW620 cells. Mechanistically, HOXD4 suppresses epithelial-mesenchymal transition (EMT) by directly binding to the promoter of Forkhead box Q1 (FOXQ1), a key driver of EMT and stemness, and thereby transcriptionally repressing its expression. Immunohistochemistry confirms an inverse correlation between HOXD4 and FOXQ1 expression in clinical specimens. Rescue experiments substantiate that HOXD4 exerts its metastasis-suppressing functions via FOXQ1 regulation. Collectively, these findings not only establish an efficient platform for screening tumor metastasis suppressors, but also identify HOXD4 as a master transcriptional regulator of the FOXQ1-EMT axis, providing a promising target for metastasis interception.

Humans↗

Distribution of Cryptosporidium parvum subtypes in calves in eastern United States.

Cryptosporidium parvum DNA from 175 neonatal calves on 16 farms in eight eastern states in the United States was subtyped by sequence analysis of the 60-kDa glycoprotein gene to determinate the parasite genetic diversity. Six subtypes of the IIa subtype family were found. Subtype IIaA15G2R1, which is the predominant C. parvum subtype in calves in many parts of the world, was identified in 77% of the C. parvum DNA from calves. Several farms had more than one C. parvum subtype and a few calves had infections with mixed subtypes. Distribution of subtypes differed geographically. Diversity of C. parvum in calves in eastern United States was lower than that previously seen in Michigan and southern Ontario. The high prevalence of one subtype in calves worldwide and frequent detection of this subtype in humans suggests that parasite fitness probably plays an important role in transmission of cryptosporidiosis among cattle and in zoonotic infections.

Animals↗

In vitro anti-tumor immune response induced by dendritic cells transfected with EBV-LMP2 recombinant adenovirus.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is a high-incidence tumor in southern China. Latent membrane proteins 2 (LMP2) is a subdominant antigen of EBV. The present study was to develop a dendritic cells (DCs)-based cancer vaccine (rAd-LMP2-DC) and to study its biological characteristics and its immune functions. Our results showed that LMP2 gene transfer did not alter the typical morphology of mature DC, and the representative phenotypes of mature DC (CD80, CD83, and CD86) were highly expressed in rAd-LMP2-DCs. The expression of LMP2 in rAd-LPM2-DCs was about 84.54%, which suggested efficient gene transfer. Transfected DCs markedly increased antigen-specific T-cell proliferation. The specific cytotoxicity against NPC cell was significantly higher than that in controls (p < 0.05), and enhanced with increased stimulations by transfected DCs. In addition, phenotypic analysis demonstrated that the LMP2-specific CTLs consisted of both CD4(+) and CD8(+) T cells. These results showed that development of DC-based vaccine by transfection with malignancy-associated virus antigens could elicit potent CTL response and provide a potential strategy of immunotherapy for EBV-associated NPC.

Adenoviridae↗

Endovascular stent-grafts treatment in acute aortic dissection (type B): clinical outcomes during early, late, or chronic phases.

OBJECTIVE: This is a prospective study to evaluate the clinical outcomes of endovascular repair in patients with different phases of type B aortic dissection. BACKGROUND: Endovascular repairing with stent-grafts is an innovative technique for type B acute aortic dissection. There is no previous study regarding outcomes in different time phases. METHODS: Sixty-two patients underwent endovascular stent-grafts. There were 23 in the early phase (<24 hr), 20 in the late phase (>or=24 hr to 2 weeks), and 19 in the chronic phase (>2 weeks). RESULTS: The early phase group had the lowest ratio of stent-grafts to patient and the shortest stent-graft length. The chronic phase group had the largest diameter of false lumen. The technical success rate was 100%; no patient died within hospital. Three patients died within 30 days, with the same death rate in every group. Compared with acute patients, the chronic group had a higher volume of contrast, a higher creatinine post-procedure, and a higher incidence of contrast-induced nephropathy. Multiple regression analysis demonstrated that creatinine and endoleak were independent factors in predicting late death (95% CI, 3.4-26%, P < 0.01). The overall cardiovascular event-free survival was 88.9% +/- 2.1% at 30 days, 87.2% +/- 4.1% at 1 year, and 81.4% +/- 6.3% at 2 years. CT angiography identified the complete or partial thrombosis of the false lumen to be 95.7%. CONCLUSIONS: Endovascular repairing with stent-graft is safe, feasible, and able to treat type B aortic dissection in all phases. However, chronic renal dysfunction was an independent factor which contributed to a lower survival rate of chronic phase patients.

Acute Disease↗

[Study on the characteristics of population distribution of TCM syndromes and its related factors in patients of depression].

OBJECTIVE: To study the rules of occurrence and development of TCM syndromes in patients of depression by analysing the population distribution and related factors of it. METHODS: A clinical epidemiologic survey was carried out with the materials collected by the four-diagnostic method from patients of depression to gain the syndrome types of 397 patients through dynamic cluster analysis, factor analysis and TCM syndrome differentiation. The constitution of syndrome types in different population and the relation between TCM syndrome types and the clinical types differentiated by Western medicine of depression was analyzed. RESULTS: Six syndrome types were found in 397 patients with depression. They were, ranging in occurrence order, the Gan-Qi stagnation with mental uneasiness type (108 cases, 27.2%); the Xin-Pi deficiency with dampness retention type (94 cases, 23.7%); the Xin-Gan Qi-stagnation with Phlegm retention type (76 cases, 19.1%); the Xin-Gan Qi stagnation with Jing-Luo disharmony type (57 cases, 14.3%); the Xin-Shen Qi stagnation with collateral obstruction type (34 cases, 8.6%); and the Xin-Gan Qi stagnation with Heat interfering mental type (28 cases, 7.1%). There were statistical significance (P < 0.01) in comparison of the syndrome types constitution among patients of different ages or different Western medicinal types (mild, with or without psychotic symptoms), but no significant difference was shown in that among patients of different sexes, with or without familial history of mental diseases, with monophasic or biphasic, initial or recurrent episode (P > 0.05). CONCLUSION: The result obtained in this study is basically in accord with the cognitive rule of TCM theory, it provides a reliable base of syndrome differentiation for treatment.

Adolescent↗

[Abnormal expression of cCD79a/cCD22 in acute myeloid leukemia with t (8;21)].

OBJECTIVE: To report abnormal expression of cCD79a/cCD22 in four cases of acute myeloid leukemia (AML) with t (8;21). METHODS: The characteristics of morphology, immunophenotype, chromosome karyotype (MIC) and clinical manifestations of 4 AML patients with t (8;21) expressing cCD79a/cCD22 were analyzed. RESULTS: The features of the 4 patients were: (1) no difference in gender; (2) young age; (3) exmedullary infiltration may be present; (4) normal number of white blood cells in peripheral blood; (5) morphology showed acute myeloid leukemia with high percentage of blast cells; (6) B-lymphoid and myeloid immunophenotype, and high expression of CD34; (7) frequent depletion of Y chromosome and complex changes of chromosomes; (8) positive for AML1/ETO fusion gene; (9) response well to chemotherapy regimen which simultaneously treated myeloid and lymphocytic leukemia. CONCLUSION: Abnormal expression of cCD79a/cCD22 in AML with t (8;21) (q22;q22) suggested that this kind of leukemia might be related with abnormal expression gene of B cell.

Adolescent↗

[Immune responses in rhesus induced by recombinant adenovirus Ad-LMP2].

BACKGROUND: To observe the LMP2 specific cellular and humoral immune responses after immunization with recombinant adenovirus Ad-LMP2 in rhesus. METHODS: The rhesuses were immunized with Ad-LMP2 through intra muscular injection in three groups, high dosage (4.5 x 10(11) VP/kg), medium dosage (1.5 x 10(11) VP/kg) and low dosage (0.5 x 10(11) VP/kg) groups. They were totally immunized six times at intervals of 5 days. The specific cellular immune responses were tested during the 7th week by ELISPOT after immunization. And the titers of anti-LMP2 antibody were tested by EIA throughout the period of immunization. RESULTS: LMP2 induced specific cellular and humoral immune responses in all three dosage group. The potency of immune responses was related with the dosage of immunization. Higher dosage elicited more potent immune response. Both the neutralizing antibody to adenovirus and anti-LMP2 antibody could be detected from 2 weeks after immunization. They would reach the peak during 3-4 weeks after immunization, then declined during the 7th week after immunization. CONCLUSION: The recombinant adenovirus LMP2 could induce specific cellular and humoral responses in rhesus after immunization.

Adenoviridae↗

Curcumin inhibits telomerase activity in human cancer cell lines.

Curcumin, one of the major components of tumeric, the dried rhizome of Curcuma longa L, has been shown to have anti-proliferating and anti-carcinogenic properties. In this study, we examined the effects of curcumin on cell growth and telomerase activity in human cancer cell lines Bel7402, HL60 and SGC7901. Curcumin (1-32 microM) showed anti-proliferating effects on these cell lines in a dose-dependent manner in vitro, and anti-tumor effects when curcumin (50-200 mg/kg) was orally administered to nude mice transplanted with the cancer cells. When the cells were treated with 1 microM of curcumin for 120 h, apoptotic cells were observed by means of the adridine orange/ethidium bromide staining method, single cell microgel electrophoresis and flow cytometric analysis. On the other hand, suppression of telomerase activity in extracts of the cells treated with 1 microM of curcumin was observed by means of a telomeric repeat amplification protocol - silver staining assay. These results suggest that curcumin could suppress telomerase activity in the cancer cell lines and that the decrease of telomerase expression followed by induction of apoptosis might be involved in the anti-proliferating effect of curcumin.

Animals↗

[Epidemiologic study on hearing impairment and ear diseases in old people].

OBJECTIVE: To investigate the prevalence of hearing impairment and ear diseases in old people and provide scientific data for drawing up the prevention and treatment strategies. METHODS: Using the probability proportion to size (PPS) method, 1261 people over 60 years were investigated in 40 clusters in Jiangsu Province with the WHO protocol. RESULTS: The prevalence of hearing impairment was 58.1% (the standardized rate: 59.5% in the whole country, 60.9% in Jiangsu province). Degrees of hearing impairment were mild (33.1%), moderate (17.8%), severe (5.9%) and profound (1.3%). The prevalence of hearing disability was 25.0% (the standardized rate: 26.6% in the whole country, 28.1% in Jiangsu province). There were significant difference of the prevalence between male and female, as well as urban and rural, and different ages. The prevalence of the ear diseases was auricle malformation (0.2%), wax (1.7%), otitis externa (0.1%), fungi (0.5%), serous otitis media (1.2%), chronic suppurative otitis media (1.6%), dry perforation of tympanic membrance (2.3%). The causes of hearing impairment were ear diseases (2.9%), non-infectious condition (92.6%), genetic condition (0.3%) and undetermined causes (4.2%). Of which, 31.1% of persons needed hearing aids while 2.3% of persons needed medicine treatment, but 0.9% of persons needed non-urgent surgery and 1.0% of persons needed other treatment. CONCLUSIONS: The prevalence of hearing impairment and disability in the old rised obviously than the last investigation in 1987. It was a heavy burden for social development in China. The government and the whole society should take more concern about the problem. The scientific strategies of prevention and treatment were urgently needed and implemented.

Aged↗

[Expression of topoisomerase III alpha in epithelial ovarian tumors of different types and relation between the expression of topoisomerase III alpha and the clinical pathology of tumor].

OBJECTIVE: To investigate the expression status of topoisomerase IIIa in epithelial ovarian tumor and the relationship between the expression status of topoisomerase IIIa and pathological type and clinical stage of epithelial ovarian carcinoma. METHODS: Immunohistochemistry was carried out in the samples of ovarian tumor obtained during operation from 169 patients, aged 28 approximately 59, 18 cases with serous cystadenoma, 30 cases with serous borderline cystadenoma, 37 serous cystadenocarcinoma, 10 cases with mucous cystadenoma, 20 mucous borderline cystadenoma, 26 mucous cystadenocarcinoma, 19 cases with endometrial carcinoma of ovary, and 9 cases with clear cell carcinoma. RESULTS: The expression rate of topoisomerase IIIa was 17.9% in the benign ovarian tumors, 74.0% in the borderline cystadenoma, and 42.7% in the malignant tumors with statistical significance among them (chi(2) = 24.657, P < 0.001). There was no correlation between the expression of topoisomerase IIIa and the clinical stage or pathological grade of the tumors (P = 0.903 and P = 0.844). CONCLUSION: Topoisomerase IIIa is highly expressed in epithelial ovarian carcinoma, and its expression level is correlated with the character and type of tumor tissues.

Adult↗

A rapid test to monitor alloreactive responses in whole blood using real-time polymerase chain reaction.

Rapid, simple, and reliable assays to monitor allogeneic responses are essential for the safe development of novel protocols of tailored immunosuppression. Herein, we describe a real-time polymerase chain reaction method based on interleukin-2 and interferon-gamma mRNA quantification upon stimulation of whole blood with allogeneic T cell-depleted peripheral blood mononuclear cells. The technique requires only small blood volumes and results can be obtained within 48 hours. Data obtained in a liver transplant patient receiving a tolerance induction protocol based on the infusion of donor-type hematopoietic stem cells suggest that this rapid whole blood mixed lymphocyte reaction assay could be valuable for the monitoring of patients undergoing solid organ or hematopoietic stem cell transplantation.

Antibody Formation↗

Electron localization determines defect formation on ceria substrates.

The high performance of ceria (CeO2) as an oxygen buffer and active support for noble metals in catalysis relies on an efficient supply of lattice oxygen at reaction sites governed by oxygen vacancy formation. We used high-resolution scanning tunneling microscopy and density functional calculations to unravel the local structure of surface and subsurface oxygen vacancies on the (111) surface. Electrons left behind by released oxygen localize on cerium ions. Clusters of more than two vacancies exclusively expose these reduced cerium ions, primarily by including subsurface vacancies, which therefore play a crucial role in the process of vacancy cluster formation. These results have implications for our understanding of oxidation processes on reducible rare-earth oxides.

Journal Article↗

Occurrence and molecular characterization of Cryptosporidium spp. in mammals and reptiles at the Lisbon Zoo.

The presence of Cryptosporidium parasites in mammals and reptiles kept at the Lisbon Zoo was investigated. A total of 274 stool samples were collected from 100 mammals and 29 reptiles. The species and genotype of the isolates identified by light microscopy were determined by nested PCR and sequence analysis of a fragment of the small subunit rRNA gene. Cryptosporidium oocysts were found in one black wildebeest (Connochaetes gnou), one Prairie bison (Bison bison bison) and in one Indian star tortoise (Geochelone elegans). The PCR and sequence analysis of these three isolates showed that those excreted by the Prairie bison were Cryptosporidium mouse genotype, those from the black wildebeest were from a new Cryptosporidium genotype and those infecting the Indian star tortoise were Cryptosporidium tortoise genotype. The present work reports a new Cryptosporidium genotype in a black wildebeest and the first finding of the Cryptosporidium mouse genotype in a ruminant.

Animals↗

Ultrasound enhances gene delivery of human factor IX plasmid.

Delivery of plasmid DNA can be enhanced by treatment with ultrasound (US); acoustic cavitation appears to play an important role in the process. Ultrasound contrast agents (UCAs; stabilized microbubbles) nucleate acoustic cavitation, and lower the acoustic pressure threshold for inertial cavitation occurrence. Fifty micrograms of a liver-specific, high-expressing human factor IX plasmid, pBS-HCRHP-FIXIA, mixed with UCA or phosphate-buffered saline was delivered to mouse livers by intrahepatic injection, with simultaneous exposure to 1 MHz-pulsed US using various acoustic protocols. Variable pulse duration (PD) at constant treatment time, pulse repetition frequency, and an acoustic peak negative pressure amplitude of 1.8 MPa produced 2- to 13-fold enhancements in hFIX gene expression, but PD was not a strong determinant. In contrast, a dose-response relationship was demonstrated for the peak negative pressure (P-), with significant enhancement of gene transduction at P- >/= 2 MPa. Up to 63 ng/ml (approaching the therapeutic range for treating hemophilia patients) could be achieved by transducing one liver lobe at 4-MPa P-, corresponding to a 66- fold increment relative to treatment with naked DNA alone. Under the same conditions, mouse livers could also be transduced with a GFP plasmid. Histology showed transient liver damage caused by intrahepatic injection and US exposure at 4-MPa P-; however, the damage was repaired in a few days. We conclude that therapeutic US in combination with UCA has the potential to promote safe and efficient nonviral gene transfer of hFIX for the treatment of hemophilia.

Alanine Transaminase↗

Unique endemicity of cryptosporidiosis in children in Kuwait.

To understand the transmission of Cryptosporidium infection in children, fecal specimens from 62 Kuwaiti children with gastrointestinal symptoms found to be positive by microscopy were genotyped and subtyped with a small subunit rRNA-based PCR-restriction fragment length polymorphism analysis and a 60-kDa glycoprotein-based DNA sequencing tool. The median age of infected children was 4.5 years, and 77% of infections occurred during the cool season of November to April. Fifty-eight of the children (94%) had Cryptosporidium parvum, three (5%) had Cryptosporidium hominis, and one (1%) had both C. parvum and C. hominis. Altogether, 13 subtypes of C. parvum (belonging to four subtype allele families) and C. hominis (belonging to three subtype allele families) were observed, with 92% of specimens belonging to the common allele family IIa and the unusual allele family IId. Thus, the transmission of cryptosporidiosis in Kuwaiti children differed significantly from other tropical countries.

Adolescent↗