Biomedical subjects

Fang Fang

Publications and source records attributed to Fang Fang.

At least 19 recordsLinked to original sources

PubMed2026

A chromosome-level genome assembly of Lycoris radiata reveals the evolutionary origin of Amaryllidaceae alkaloids and elucidates the complete galanthamine biosynthetic pathway.

Amaryllidaceae alkaloids (AmAs) comprise a structurally diverse group of specialized metabolites produced almost exclusively by species of the Amaryllidoideae subfamily and are of substantial pharmacological importance. However, the limited availability of high-quality genomes from Amaryllidoideae plants has constrained systematic investigations of the genes and evolutionary processes underlying AmA biosynthesis. Here, we present a chromosome-level genome assembly of Lycoris radiata, which enabled the discovery of key downstream enzymes in the galanthamine biosynthetic pathway and uncovered reversible reactions between two critical metabolite pairs. These findings provide new mechanistic insight into pathway architecture and enable reconstruction of the galanthamine biosynthetic pathway in Yarrowia lipolytica. Comparative genomic analyses indicate that several core genes for AmA biosynthesis originated in ancestral angiosperms, whereas the complete pathway was likely assembled in the Amaryllidoideae subfamily through gene duplication and neofunctionalization. Furthermore, integrated metabolomic and transcriptomic analyses suggest that roots contribute actively to AmA metabolism in Lycoris. Together, these findings provide a genomic and biochemical framework for understanding the evolution and engineering of AmA biosynthesis.

Lycoris↗

PubMed2026

Acute COVID-19 severity and impaired cognitive function up to 32 months after diagnosis: an observational study.

BACKGROUND: Cognitive dysfunction ("brain fog") is a commonly reported post-COVID-19 symptom. Leveraging data from five general population cohorts across four European countries (Estonia, Iceland, Norway, and Sweden), we assessed long-term prevalence of impaired subjective cognitive function among individuals diagnosed with COVID-19 by acute illness severity. METHODS: The included cohorts consisted of adult participants recruited from March 2020 and followed with self-report measures of cognitive function and past COVID-19 infection (except one cohort consisting of clinically confirmed COVID-19 cases) through February 2023. In a cross-sectional analysis we contrasted the prevalence of impaired cognitive function among individuals with and without a COVID-19 diagnosis, overall and by illness severity up to 32 months post-diagnosis. We adjusted for age, gender, education, relationship status, binge drinking, body mass index, previous psychiatric diagnosis, number of chronic medical conditions, and response period. In a longitudinal analysis, we assessed potential changes in cognitive function scores before and after COVID-19 diagnosis. RESULTS: The study population consisted of 153,841 participants (71% women), with 31,359 (20.4%) reporting a positive COVID-19 test. Overall, a COVID-19 diagnosis was not statistically significantly associated with increased prevalence ratio (PR) of impaired cognitive function (PR 1.30 [95% CI: 0.98-1.71]). Individuals bedridden due to COVID-19 for 1-6 days (PR 1.38 [95% CI 0.96-1.99]) or ≥ 7 days (2.59 [1.55-4.33]) had higher prevalence of impaired cognitive function compared to those never diagnosed, while individuals never bedridden had a lower prevalence to those never diagnosed with COVID-19 (0.89 [0.80-1.00]). These findings were corroborated in the longitudinal analysis where a pre- to post diagnosis decline in cognitive function was observed among individuals bedridden due to COVID-19 (p < 0.0001). CONCLUSIONS: The data indicates that a severe COVID-19 acute illness course is associated with impaired cognitive function up to 18-32 months after COVID-19 diagnosis.

Adult↗

PubMed2026

Protein Biomarkers in Risk and Prognosis of Amyotrophic Lateral Sclerosis.

BACKGROUND: Plasma and cerebrospinal fluid (CSF) protein biomarkers in amyotrophic lateral sclerosis (ALS) may provide insight into disease mechanisms and yield clinically useful biomarkers. METHODS: Overall, 363 proteins in plasma and CSF from 198 patients with ALS and 125 matched controls were profiled using Olink assays. Associations with disease status, survival, and functional decline, as well as longitudinal biomarker stability across the disease course were assessed, together with network and enrichment analyses. ALS risk-associated biomarkers were externally validated in the UK Biobank (UKB). RESULTS: Overall, 125 proteins were significantly associated with at least one outcome (i.e., case status, risk, survival, or functional decline), and 21 were associated with three or more outcomes. NEFL was the most robust biomarker in plasma and CSF, alongside TNFRSF12A in plasma and CSF, EDA2R in plasma, and FABP4 in plasma and CSF. Most biomarkers remained stable longitudinally across the disease course. ALS risk-associated biomarkers were replicated in UKB, in which > 3000 plasma proteins were measured in 52,990 participants, including 298 with ALS. Network and enrichment analyses highlighted their roles in immune response and extracellular-matrix remodeling, and their enrichments in the brain and T-cell subsets. Construction of an ALS risk-prediction model achieved an ROC-AUC of 0.72 in the UKB validation cohort. CONCLUSIONS: These findings suggest candidate protein biomarkers for ALS risk stratification, early detection, and clinical therapeutic monitoring.

Humans↗

PubMed2025

Associations of Genetic Liability to Six Psychiatric Disorders With Cardiometabolic Diseases.

IMPORTANCE: Individuals with psychiatric disorders have increased risk of cardiometabolic diseases (CMDs). Evaluating how psychiatric genetic liability relates to CMD may clarify mechanisms. OBJECTIVE: Identify genetic overlap between psychiatric disorders and CMDs independent of cross-disorder pleiotropy, BMI, and smoking. DESIGN SETTING AND PARTICIPANTS: Three Northern European cohorts (the Swedish Twin Registry, the Estonian Biobank, and the Norwegian Mother, Father and Child Cohort Study [MoBa]) totaling 355,159 individuals. Associations with CMDs were estimated as adjusted odds ratios (AORs) from logistic models mutually adjusted for all psychiatric PRSs and in models additionally adjusting for body mass index (BMI) and smoking. Cohort-specific AORs were pooled by inverse-variance weighting. MAIN OUTCOMES AND MEASURES: Exposures were PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), anxiety disorder, posttraumatic stress disorder (PTSD), bipolar disorder, and schizophrenia. Outcomes were diagnoses of CMDs (hyperlipidemia, obesity, type 2 diabetes, hypertensive diseases, arteriosclerosis, ischemic heart disease, heart failure, thromboembolic disease, cerebrovascular disease, and arrhythmias), ascertained from electronic health records. RESULTS: The MDD PRS was associated with increased risk of all CMDs across analyses (AORs ranged from 1.13 [95% CI, 1.10-1.15] for heart failure to 1.02 [95% CI, 1.00-1.05] for arrhythmias). The ADHD PRS was associated with increased risk of all CMDs (AOR ranged from 1.11 [95% CI, 1.09-1.12] for obesity to 1.02 [95% CI, 1.01-1.03] for hyperlipidemia), however associations where attenuated when adjusting for BMI and smoking (lifestyle adjusted AOR for obesity: 1.03 [95% CI, 1.02-1.05]). When not mutually adjusting for all psychiatric PRSs, anxiety disorder and PTSD PRSs were associated with all CMDs; these associations diminished after adjustment. The bipolar and schizophrenia PRSs were inversely associated with most CMDs (AOR for schizophrenia PRS and obesity, 0.93 [95% CI, 0.92-0.94]). CONCLUSIONS AND RELEVANCE: Associations between psychiatric PRSs and CMDs diverged: ADHD, MDD, anxiety disorder, and PTSD PRSs were positively associated with CMDs, whereas bipolar and schizophrenia PRSs were inversely associated. Genetic liability to MDD showed robust associations with CMDs independent of cross-disorder pleiotropy, BMI, and smoking status, whereas associations between the ADHD PRS and CMDs were largely attenuated after adjustment for BMI and smoking.

Journal Article↗

PubMed2007

Prevalence of knee symptoms and radiographic and symptomatic knee osteoarthritis in African Americans and Caucasians: the Johnston County Osteoarthritis Project.

OBJECTIVE: To report contemporary estimates of the prevalence of knee-related osteoarthritis (OA) outcomes in African Americans and Caucasians aged > or = 45 years. METHODS: Weighted prevalence estimates for knee symptoms, radiographic knee OA, symptomatic knee OA, and severe radiographic knee OA were calculated for age, ethnic, and sex subgroups, in 3018 participants (33% African Americans, 38% men) in the baseline examination (1991-97) of The Johnston County Osteoarthritis Project, a population-based study of OA in North Carolina. Radiographic knee OA was defined as Kellgren-Lawrence radiographic grade > or = 2, severe radiographic knee OA as grades 3 and 4, and symptomatic knee OA as knee symptoms in a knee with radiographic OA. RESULTS: Knee symptoms were present in 43%, 28% had radiographic knee OA, 16% had symptomatic knee OA, and 8% had severe radiographic knee OA. Prevalence was higher in older individuals and women. African Americans had slightly higher prevalence of knee symptoms, radiographic knee OA, and symptomatic knee OA, but significantly higher prevalence of severe radiographic knee OA compared to Caucasians. CONCLUSION: Policy should be directed to increasing education of the public and the medical community about the high prevalence of these conditions, especially in these subgroups, to decrease their impact and ultimately prevent them.

Black or African American↗

PubMed2006

Phylogenetic mapping of recombination hotspots in human immunodeficiency virus via spatially smoothed change-point processes.

We present a Bayesian framework for inferring spatial preferences of recombination from multiple putative recombinant nucleotide sequences. Phylogenetic recombination detection has been an active area of research for the last 15 years. However, only recently attempts to summarize information from several instances of recombination have been made. We propose a hierarchical model that allows for simultaneous inference of recombination breakpoint locations and spatial variation in recombination frequency. The dual multiple change-point model for phylogenetic recombination detection resides at the lowest level of our hierarchy under the umbrella of a common prior on breakpoint locations. The hierarchical prior allows for information about spatial preferences of recombination to be shared among individual data sets. To overcome the sparseness of breakpoint data, dictated by the modest number of available recombinant sequences, we a priori impose a biologically relevant correlation structure on recombination location log odds via a Gaussian Markov random field hyperprior. To examine the capabilities of our model to recover spatial variation in recombination frequency, we simulate recombination from a predefined distribution of breakpoint locations. We then proceed with the analysis of 42 human immunodeficiency virus (HIV) intersubtype gag recombinants and identify a putative recombination hotspot.

Animals↗

PubMed2006

cBrother: relaxing parental tree assumptions for Bayesian recombination detection.

UNLABELLED: Bayesian multiple change-point models accurately detect recombination in molecular sequence data. Previous Java-based implementations assume a fixed topology for the representative parental data. cBrother is a novel C language implementation that capitalizes on reduced computational time to relax the fixed tree assumption. We show that cBrother is 19 times faster than its predecessor and the fixed tree assumption can influence estimates of recombination in a medically-relevant dataset. AVAILABILITY: cBrother can be freely downloaded from http://www.biomath.org/dormanks/ and can be compiled on Linux, Macintosh and Windows operating systems. Online documentation and a tutorial are also available at the site.

Algorithms↗

PubMed2006

Smoking, snuff dipping and the risk of amyotrophic lateral sclerosis--a prospective cohort study.

BACKGROUND: Little is known about the etiology of amyotrophic lateral sclerosis (ALS). The association between cigarette smoking, but not other types of smoking and snuff dipping, and the risk of ALS has been evaluated in several epidemiologic studies. The findings were inconclusive. METHODS: We studied the association of smoking and snuff dipping with the risk of ALS in the Swedish Construction Workers Cohort, which includes 280,558 male construction workers enrolled between 1978 and 1993 with detailed information on tobacco use. Incident cases of ALS were identified through cross-linkage to the Swedish Inpatient Register. Relative risks and their corresponding 95% confidence intervals (CIs) were estimated using the Cox proportional hazards regression model. RESULTS: After a mean follow-up duration of 19.6 years, we identified 160 incident cases of ALS through 2004. Compared with non-tobacco use, the relative risk of ALS was 0.8 (95% CI 0.6-1.1) for tobacco smoking and 0.6 (95% CI 0.3-1.5) for snuff dipping, respectively. For tobacco smoking, further stratified analyses of smoking status or types of tobacco smoking did not reveal any excess risks in any strata. CONCLUSIONS: Our study provides no evidence that smoking or snuff dipping is associated with an increased ALS risk among men.

Adult↗

PubMed2006

A gender- and sexual orientation-dependent spatial attentional effect of invisible images.

Human observers are constantly bombarded with a vast amount of information. Selective attention helps us to quickly process what is important while ignoring the irrelevant. In this study, we demonstrate that information that has not entered observers' consciousness, such as interocularly suppressed (invisible) erotic pictures, can direct the distribution of spatial attention. Furthermore, invisible erotic information can either attract or repel observers' spatial attention depending on their gender and sexual orientation. While unaware of the suppressed pictures, heterosexual males' attention was attracted to invisible female nudes, heterosexual females' attention was attracted to invisible male nudes, gay males behaved similarly to heterosexual females, and gay/bisexual females performed in-between heterosexual males and females.

Adult↗

PubMed2006

Substrate consumption and biomass growth of Ralstonia eutropha at various S0/X0 levels in batch cultures.

The biomass growth, substrate consumption and polyhydrobutyrate (PHB) production of Ralstonia eutropha with butyric acid and fructose as the carbon and energy sources at various ratios of initial substrate concentration (S0) to initial biomass concentration (X0) were investigated in this study. Results indicated that the PHB content increased with the increasing S0/X0 ratio. Different substrates exhibited a similar trend for cell growth and substrates consumption with the changing S0/X0 ratio. The specific consumption rates of both butyric acid and fructose increased with the increasing S0/X0 ratio. An S0/X0-dependent kinetic model was modified to describe the kinetics of biomass growth and substrate consumption for R. eutropha. This model was verified with the experimental results from this work and in literature.

Biomass↗

PubMed2006

Intravenous repeated-dose toxicity study of ZnPcS2P2-based-photodynamic therapy in Wistar rats.

The purpose of the current study was to investigate the potential repeated-dose toxicity of ZnPcP2S2-based photodynamic therapy (ZnPc-PDT) in Wistar rats. The animals were administered ZnPcS2P2 intravenously ten times successively every 4 d and irradiated with a 670 nm laser light for 6 min at subsequent 48 h and 72 h. At the end of the treatment period, 10 rats/sex/group were sacrificed, while 5 rats/sex/group were sacrificed after a two-week recovery period. During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, hematology, serum biochemistry, urinalysis, organ weights, gross findings and histopathology were examined. The association between the increased liver weight and hepatic spotty and lytic necrosis seen in high dose females corroborates the conclusion that high dose ZnPc-PDT could induce hepatic injury in Wistar rats and they are probably related to the abnormality of certain biochemical parameters of females in the high dose group. Furthermore, microscopic examination for the ZnPc-PDT groups shows the presence of some Kelly and khaki granules in Kupffer cells and endothelia of the livers, epithelia of the renal tubules, marginal sinus and medulla of the spleens, alveolar walls of the lungs, reticular cells and macrophages of the mesenteric lymph nodes, testicular Leydig cells, epididymal epithelial cells, endometrial stromal cells, and interstitial cells and corpora lutea of the ovaries from all or most of the animals. There were no adverse effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, uranalysis, hematology, serum biochemistry, body weights and necropsy findings in control, low and mid dose groups. Based on these results, it was concluded that the intravenous repeated-dose of ZnPcP2S2-PDT induced the abnormalities of liver weights, hepatic biochemistry and histopathology, and pigmentation in the several important organs in Wistar rats at 4 mg kg(-1) d(-1). The target organ was determined to be liver (and spleen perhaps), but this was not so obvious in males. The no-observed-adverse-effect level (NOAEL) was considered to be 1.0 mg kg(-1) for both sexes.

Animals↗

PubMed2006

Duration-dependent FMRI adaptation and distributed viewer-centered face representation in human visual cortex.

Two functional magnetic resonance imaging (fMRI) face viewpoint adaptation experiments were conducted to investigate whether fMRI adaptation in high-level visual cortex depends on the duration of adaptation and how different views of a face are represented in the human visual system. We found adaptation effects in multiple face-selective areas, which suggest a distributed, viewer-centered representation of faces in the human visual system. However, the nature of the adaptation effects was dependent on the length of adaptation. With long adaptation durations, face-selective areas along the hierarchy of the visual system gradually exhibited viewpoint-tuned adaptation. As the angular difference between the adapter and test stimulus increased, the blood oxygen level-dependent (BOLD) signal evoked by the test stimulus gradually increased as a function of the amount of 3-dimensional (3D) rotation. With short adaptation durations, however, face-selective areas in the ventral pathway, including the lateral occipital cortex and right fusiform area, exhibited viewpoint-sensitive adaptation. These areas showed an increase in the BOLD signal with a 3D rotation, but this signal increase was independent of the amount of rotation. Further, the right superior temporal sulcus showed little or very weak viewpoint adaptation with short adaptation durations. Our findings suggest that long- and short-term fMRI adaptations may reflect selective properties of different neuronal mechanisms.

Adaptation, Physiological↗

PubMed2006

Predicting methylation status of CpG islands in the human brain.

MOTIVATION: Over 50% of human genes contain CpG islands in their 5'-regions. Methylation patterns of CpG islands are involved in tissue-specific gene expression and regulation. Mis-epigenetic silencing associated with aberrant CpG island methylation is one mechanism leading to the loss of tumor suppressor functions in cancer cells. Large-scale experimental detection of DNA methylation is still both labor-intensive and time-consuming. Therefore, it is necessary to develop in silico approaches for predicting methylation status of CpG islands. RESULTS: Based on a recent genome-scale dataset of DNA methylation in human brain tissues, we developed a classifier called MethCGI for predicting methylation status of CpG islands using a support vector machine (SVM). Nucleotide sequence contents as well as transcription factor binding sites (TFBSs) are used as features for the classification. The method achieves specificity of 84.65% and sensitivity of 84.32% on the brain data, and can also correctly predict about two-third of the data from other tissues reported in the MethDB database. AVAILABILITY: An online predictor based on MethCGI is available at http://166.111.201.7/MethCGI.html CONTACT: mzhang@cshl.edu SUPPLEMENTARY INFORMATION: Supplementary data available at Bioinformatics online and http://166.111.201.7/help.html.

Algorithms↗

PubMed2006

Inhibition of CD147 expression reduces tumor cell invasion in human prostate cancer cell line via RNA interference.

CD147, also named extracelluar matrix metalloproteinase inducer (EMMPRIN), has been proved to be involved in the invasion and metastasis processes of tumor cells in many types of cancers. To determine the role of CD147 in the invasiveness properties of prostate cancer, we successfully downregulated CD147 by RNA interference (RNAi) technology, in PC-3 cell line at high level of CD147 expression. PC-3 cells were transfected with a pSilencer 4.1-CMV neo Vector coding for an RNA composed of two identical 19-nucleotide sequence motifs in an inverted orientation, separated by a 9-bp spacer to form a hairpin dsRNA capable of mediating target CD147 inhibition. Gelatin zymography was employed to determine the effect on reducing secretions of MMP-2 and MMP-9 of the transfected cells. Matrigel invasion assay was performed to evaluate the invasion ability of PC-3 cells in vitro. Our results showed that CD147 expression was significantly inhibited by small interfering RNAs (siRNA) transfectants in PC-3 cells at mRNA and protein levels, which resulted in dramatic reduction of invasion ability in tumor cells. Moreover, downregulation of CD147 resulted in reducing secretions of MMP-2, MMP-9. Taken together, CD147 downregulation by RNAi technology decreases the invasive capability of prostate cancer cells, demonstrating that stable expression of siRNA CD147 could potentially be an experimental approach for prostate cancer gene therapy.

Antigens, CD↗

PubMed2006

Determination of nucleic acids with a near infrared cyanine dye using resonance light scattering technique.

A new method for the determination of nucleic acids has been developed based on the enhancement effect of resonance light scattering (RLS) with a cationic near infrared (NIR) cyanine dye. Under the optimal conditions, the enhanced RLS intensity at 823 nm is proportional to the concentration of nucleic acids in the range of 0-400 ng mL-1 for both calf thymus DNA (CT DNA) and fish sperm DNA (FS DNA), 0-600 ng mL-1 for snake ovum RNA (SO RNA). The detection limits are 3.5 ng mL-1, 3.4 ng mL-1 and 2.9 ng mL-1 for CT DNA, FS DNA and SO RNA, respectively. Owing to performing in near infrared region, this method not only has high sensitivity endowed by RLS technique but also avoids possible spectral interference from background. It has been applied to the determination of nucleic acids in synthetic and real samples and satisfactory results were obtained.

Carbocyanines↗

PubMed2006

Controlled release of proteins from polymer-modified surfaces.

The ability to control the rate of adsorption and desorption of proteins from surfaces is studied by using a molecular theory. We show how changing the chemical structure and charge of short linear and branched grafted polymers to an electrode surface can be used to promote fast adsorption of charged proteins on a time scale of seconds and control the desorption in a time scale ranging from milliseconds to hours. The optimal controlled release is found from the interplay of electrostatic attractions at short distances from the surface and the proper electrostatic and steric repulsive barrier at distances from the surfaces larger than the proteins' size. The implications of our results to the design of controlled-release devices is discussed.

Adsorption↗

PubMed2006

Protection against avian influenza H9N2 virus challenge by immunization with hemagglutinin- or neuraminidase-expressing DNA in BALB/c mice.

Avian influenza viruses of H9N2 subtype are widely spread in avian species. The viruses have recently been transmitted to mammalian species, including humans, accelerating the efforts to devise protective strategies against them. In this study, an avian influenza H9N2 virus strain (A/Chicken/Jiangsu/7/2002), isolated in Jiangsu Province, China, was used to infect BALB/c mice for adaptation. After five lung-to-lung passages, the virus was stably proliferated in a large quantity in the murine lung and caused the deaths of mice. In addition, we explored the protection induced by H9N2 virus hemagglutinin (HA)- and neuraminidase (NA)-expressing DNAs in BALB/c mice. Female BALB/c mice aged 6-8 weeks were immunized once or twice at a 3-week interval with HA-DNA and NA-DNA by electroporation, respectively, each at a dose of 3, 10 or 30microg. The mice were challenged with a lethal dose (40x LD(50)) of influenza H9N2 virus four weeks after immunization once or one week after immunization twice. The protections of DNA vaccines were evaluated by the serum antibody titers, residual lung virus titers, and survival rates of the mice. The result showed that immunization once with not less than 10microg or twice with 3microg HA-DNA or NA-DNA provided effective protection against homologous avian influenza H9N2 virus.

Animals↗

PubMed2006

Facile construction of the pentacyclic framework of subincanadine B. Synthesis of 20-deethylenylated subincanadine B and 19,20-dihydrosubincanadine B.

[reaction: see text] We describe a facile approach for effectively constructing the pentacyclic framework of subincanadine B. The seven-step assembly of tetracyclic ketone 14 featured Michael addition, Pictet-Spengler cyclization, and Dieckmann condensation. From this key ketone intermediate, two analogues of subincanadine B, i.e., 20-deethylenylated subincanadine B (27) and 19,20-dihydrosubincanadine B (31), were synthesized in four steps, respectively.

Ethylenes↗