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Jian Shen

Publications and source records attributed to Jian Shen.

At least 19 recordsLinked to original sources
PubMed2026

Microglial PICALM: A novel genetic driver and therapeutic target in vascular dementia.

BACKGROUND: Vascular dementia (VaD) lacks well-defined genetic mechanisms. Cell-type-specific effects of GWAS loci remain unexplored. METHODS: We integrated single&#x2011;cell eQTL data (183 donors, eight cell types) with VaD GWAS (3624 cases, 475,484 controls) using Mendelian randomization and Bayesian colocalization, replicated in an independent cohort (2074 cases, 456,366 controls). Subtype, snRNA&#x2011;seq, cell&#x2011;cell communication, PheWAS, expression profiling, and drug prediction with BBB permeability assessment were performed. RESULTS: Microglial PICALM was the only robustly replicated signal (OR = 0.8334, p = 5.3 &#xd7; 10&#x207b;&#x2074;; colocalization PP.H4 > 0.75). The effect was strongest in multiple infarctions dementia (OR = 0.7746). Exploratory snRNA-seq analysis (4 VaD vs. 4 controls; GSE282111) provided supporting evidence for microglial PICALM enrichment and downregulation (p < 0.001). PICALM&#x2011;high microglia showed enhanced neurovascular&#x2011; and phagocytosis&#x2011;related communication (e.g., SPP1, GAS6, GRN). PheWAS revealed no pleiotropy. In silico drug repurposing prioritised three FDA-approved BBB-penetrant compounds (disopyramide, benzocaine, amantadine) as candidates warranting further mechanistic validation. CONCLUSIONS: Microglial PICALM is identified as a likely genetic determinant of VaD, especially in the multiple infarctions subtype. Upregulating PICALM may be associated with a neuroprotective microglial phenotype, highlighting PICALM as a candidate therapeutic target warranting further experimental validation.

Humans↗
PubMed2006

Formation of FePt nanoparticles having high coercivity.

Ultrasonication of toluene solutions of the heteropolynuclear cluster complex, Pt3Fe3(CO)15, in the presence of oleic acid and oleylamine affords surface-capped fcc FePt nanoparticles having an average diameter of ca. 2 nm. Self-assembled arrays of these nanoparticles on oxidized Si wafers undergo a fcc-to-fct phase transition at 775 degrees C to form ferromagnetic FePt nanocrystals ca. 5.8 nm in diameter well dispersed on the Si wafer surface. Room-temperature coercivity measurements of these annealed FePt nanoparticles confirm a high coercivity of ca. 22.3 kOe. Such high coercivity for fct FePt nanoparticles might result from use of a heterpolynuclear complex as a single-source precursor of Fe and Pt neutral atoms or from use of ultrasonication to form fcc FePt nanoparticles under conditions of exceptionally rapid heating. Experiments to determine the critical experimental conditions required to achieve such high room-temperature coercivities in ferromagnetic nanoparticles are underway.

Journal Article↗
PubMed2006

Inverse estimation of nonpoint sources of fecal coliform for establishing allowable load for Wye River, Maryland.

An estimation of the nonpoint sources of fecal coliform (FC) has been formulated as an inverse parameter estimation problem, using FC observation data from the receiving waters. An inverse algorithm was integrated into the three-dimensional transport model, HEM-3D. The modified Gauss-Newton method was used for the optimal estimation of the loads. The approach is straightforward and requires less effort in modification of the existing hydrodynamic model. Model experiments were conducted to investigate the feasibility of load estimation in a tidal river. The parameter uncertainty and accuracy associated with load estimation are discussed using data sets with different sampling sizes. The inverse model was applied to the tidal Wye River, Maryland, USA, to estimate FC nonpoint sources and to develop an allowable load for the river to attain water quality standards. The model results suggest that the inverse modeling approach is suitable for estimating FC nonpoint sources. The inverse method not only provides an efficient approach to assess the contribution of nonpoint sources, but has the additional advantage of addressing the problems of the uncertainty and error associated with FC simulation in the estuary using hydrodynamic models.

Feces↗
PubMed2006

The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant.

Cytochrome P450 2A13 (CYP2A13), an enzyme predominantly expressed in human respiratory tissues, is highly efficient for the metabolic activation of two suspected human lung carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and aflatoxin B1 (AFB1). Functional genetic polymorphisms of CYP2A13 may therefore be an important factor in human susceptibility to related lung cancers. Among the reported CYP2A13 polymorphisms with missense variations, only CYP2A13*2 variant (containing either a single or double variation of R25Q and R257C) was studied for its NNK-metabolizing activity. The present study demonstrated that there was no remarkable difference in AFB1- and NNK-induced toxicity between the Flp-In Chinese Hamster Ovary (CHO) cells stably expressing wild-type CYP2A13 and the cells expressing the individual polymorphic variants R25Q, D158E, R257C, R25Q/R257C, V323L, F453Y, and R494C. In contrast, cells transfected with R101Q variant complementary DNA (cDNA), same as the vector control cells, showed no significant death even at highest concentrations of AFB1 (10microM) and NNK (200microM). This result correlated with the lack of CYP2A13 protein in the R101Q-CHO cells, although the genomic integration of transfected R101Q cDNA and the expression of R101Q messenger RNA were clearly demonstrated in these stable transfectants. Consistent with the possibility that the variation might reduce the protein stability, R101Q variant protein expressed in insect cells showed a loss of P450 peak and coumarin 7-hydroxylase activity as well as an increased susceptibility to limited protein digestion. Thus, the R101Q polymorphic change results in a null allelic variant of CYP2A13. Our results should be useful in designing and interpreting molecular epidemiological studies related to CYP2A13 genetic polymorphisms.

Aflatoxin B1↗
PubMed2006

Electric field enhancement in guided-mode resonance filters.

Electric fields inside guided-mode resonance filters (GMRFs) may be intensified by resonance effects. The electric field enhancement is investigated in two GMRFs: one is resonant at normal incidence, the other at oblique incidence. It is shown that the two GMRFs exhibit different behaviors in their electric enhancement. Differences between the electric field distributions of the two GMRFs arise because coupling between counterpropagating modes occurs in the first case. It is also shown that the order of the electric field of maximum amplitude can be controlled by modulation of the dielectric constant of the grating.

Journal Article↗
PubMed2006

Protection of Procambarus clarkii against white spot syndrome virus using recombinant oral vaccine expressed in Pichia pastoris.

The potential for oral vaccination of crayfish against white spot syndrome virus was investigated. The envelope proteins VP19 and VP28 were expressed in yeast (Pichia pastoris). The expressed proteins were used as oral vaccines in different forms viz., in whole culture form, whole culture sonicated form, whole culture centrifuged supernatant form, and cell residue form. The recombinant proteins were mixed with food pellets and fed to crayfish for 25 days. The vaccinated groups were divided into two even groups and challenged on the 3rd and 21st day of post vaccination. Among different vaccine groups the relative percent survival (RPS) values of sonicated form and supernatant form vaccines were found the best and met the criterion (>RPS 60%) of effective vaccine even after 21st day of post vaccination. Development of vaccine by using recombinant proteins VP19 and VP28 in yeast as expression vector was feasible with significant effects.

Administration, Oral↗
PubMed2006

Epitaxial stabilization of ferromagnetism in the nanophase of FeGe.

Epitaxial nanocrystals of FeGe have been stabilized on Ge(111). The nanocrystals assume a quasi-one-dimensional shape as they grow exclusively along the <110> direction of the Ge(111) substrate, culminating in a compressed monoclinic modification of FeGe. Whereas monoclinic FeGe is antiferromagnetic in the bulk, the nanowires are surprisingly strong ferromagnets below approximately 200 K with an average magnetic moment of 0.8 microB per Fe atom. Density functional calculations indicate an unusual stabilization mechanism for the observed ferromagnetism: lattice compression destabilizes the antiferromagnetic Peierls-like ground state observed in the bulk while increased p-d hybridization suppresses the magnetic moments and stabilizes ferromagnetism.

Journal Article↗
PubMed2006

The efficacy of recombinant vaccines against white spot syndrome virus in Procambarus clarkii.

The effectiveness of oral, mock-, and immersion vaccination was investigated against white spot syndrome virus (WSSV) in crayfish. The most exposed WSSV envelope proteins VP19 and VP28 were used in different compositions and with different modes of applications. In experiment 1 crayfish were fed recombinant protein coated food pellets for 25 days, in experiment 2 the purified proteins were directly injected to them followed by one booster dose on 5th day and in experiment 3 the crayfish were left immersed in vaccines for 7 h. Experimental crayfish were challenged on 3rd and 21st days after last vaccination. The overall result showed that VP28 group has lowest cumulative mortality percentage accounting 39.6% at 3rd day and 39.83% at 21st day when injected and it was 43.2% and 49% when fed orally and 46.3% and 46.5% when immersed at 3rd and 21st days, respectively (p<0.05). In VP19 and VP28 (50:50) mixture, mock vaccination showed better performance (36.5%) over immersion (53%) and oral vaccination (53.2%) when challenged on 3rd day and mock vaccination (36.50%) followed by oral (51%) and immersion vaccination (56.5%) on 21st day as well. The VP19 recombinant mock vaccination group performed better (52.91% of 3rd day and 56.46% of 21st day) than oral (76% of 3rd day and 82% of 21st day) and immersion (83% of 3rd day and 86.3% of 21st day) vaccine groups. All the experimental groups except VP19 were significantly different (p<0.05) from the control groups. A positive cumulative effect was observed when VP28 was mixed with VP19 in equal proportion in all the experimental trials, which shows the effectiveness of VP19 as a vaccine component too. In the present trial on the basis of cumulative mortality percentage it is found that mock-vaccination group is more effective than the oral vaccination and immersion vaccination. It also suggests that specific memory exists in crayfish and the effects of VP28 are significant. The effect of VP19 along with VP28 has also shown significant effect against WSSV.

Animals↗
PubMed2006

How muscles recover from paresis and atrophy after intramuscular injection of botulinum toxin A: Study in juvenile rats.

Botulinum toxin A (BoNT-A) is a potent biological toxin widely used for the management of skeletal muscle spasticity or dynamic joint contracture. Intramuscular injection of BoNT-A causes muscle denervation, paresis, and atrophy. This clinical effect of botulinum toxin A lasts 3 to 6 months, and injected muscle eventually regains muscle mass and recovers muscle function. The goal of the present study was to characterize the molecular and cellular mechanisms leading to neuromuscular junction (NMJ) regeneration and skeletal muscle functional recovery after BoNT-A injection. Fifty-six 1-month-old Sprague-Dawley rats were used. Botulinum toxin A was injected into the left gastrocnemius muscle at a dosage of 6 units/kg body weight. An equivalent volume of saline was injected into the right gastrocnemius muscle to serve as control. The gastrocnemius muscle samples were harvested from both hind limbs at 3 days, 7 days, 15 days, 30 days, 60 days, 90 days, 180 days, and 360 days after administration of toxin. In addition, the gastrocnemius muscles from 1-month-old rats with no injections were harvested to serve as uninjected control group. Muscle samples were processed and mRNA was extracted. Real-time polymerase chain reaction (PCR) and gene microarray technology were used to identify key molecules involved in NMJ stabilization and muscle functional recovery. More than 28,000 rat genes were analyzed and approximately 9000 genes are expressed in the rat gastrocnemius muscle. Seven days following BoNT-A injection, 105 genes were upregulated and 59 genes were downregulated. Key molecules involved in neuromuscular junction (NMJ) stabilization and muscle functional recovery were identified and their time course of gene expression following BoNT-A injection were characterized. This animal study demonstrates that following intramuscular injection of BoNT-A, there is a sequence of cellular events that eventually leads to NMJ stabilization, remodeling, and myogenesis and muscle functional recovery. This recovery process is divided into two stages (aneural and neural) and that the IGF-1 signaling pathway play a central role in the process.

Animals↗
PubMed2006

Molecular profiling of the Clostridium leptum subgroup in human fecal microflora by PCR-denaturing gradient gel electrophoresis and clone library analysis.

A group-specific PCR-based denaturing gradient gel electrophoresis (DGGE) method was developed and combined with group-specific clone library analysis to investigate the diversity of the Clostridium leptum subgroup in human feces. PCR products (length, 239 bp) were amplified using C. leptum cluster-specific primers and were well separated by DGGE. The DGGE patterns of fecal amplicons from 11 human individuals revealed host-specific profiles; the patterns for fecal samples collected from a child for 3 years demonstrated the structural succession of the population in the first 2 years and its stability in the third year. A clone library was constructed with 100 clones consisting of 1,143-bp inserts of 16S rRNA gene fragments that were amplified from one adult fecal DNA with one forward universal bacterial primer and one reverse group-specific primer. Eighty-six of the clones produced the 239-bp C. leptum cluster-specific amplicons, and the remaining 14 clones did not produce these amplicons but still phylogenetically belong to the subgroup. Sixty-four percent of the clones were related to Faecalibacterium prausnitzii (similarity, 97 to 99%), 6% were related to Subdoligranulum variabile (similarity, approximately 99%), 2% were related to butyrate-producing bacterium A2-207 (similarity, 99%), and 28% were not identified at the species level. The identities of most bands in the DGGE profiles for the same adult were determined by comigration analysis with the 86 clones that harbored the 239-bp group-specific fragments. Our results suggest that DGGE combined with clone library analysis is an effective technique for monitoring and analyzing the composition of this important population in the human gut flora.

Adult↗
PubMed2006

Extended bidirectional reflectance distribution function for polarized light scattering from subsurface defects under a smooth surface.

By introducing the scattering probability of a subsurface defect (SSD) and statistical distribution functions of SSD radius, refractive index, and position, we derive an extended bidirectional reflectance distribution function (BRDF) from the Jones scattering matrix. This function is applicable to the calculation for comparison with measurement of polarized light-scattering resulting from a SSD. A numerical calculation of the extended BRDF for the case of p-polarized incident light was performed by means of the Monte Carlo method. Our numerical results indicate that the extended BRDF strongly depends on the light incidence angle, the light scattering angle, and the out-of-plane azimuth angle. We observe a 180 degrees symmetry with respect to the azimuth angle. We further investigate the influence of the SSD density, the substrate refractive index, and the statistical distributions of the SSD radius and refractive index on the extended BRDF. For transparent substrates, we also find the dependence of the extended BRDF on the SSD positions.

Journal Article↗
PubMed2006

[The promotive effects of N-nitrosopiperidine on the malignant transformation of the immortalized esophageal epithelium induced by human papillomavirus].

BACKGROUND: Study on the promotive effects of N-nitrosopiperidine on carcinogenesis process was performed, based on the immortalization of human fetal esophageal epithelium induced by human papillomavirus (HPV) 18E6E7 genes. METHODS: The immortalized esophageal epithelium SHEE was induced by HPV18E6E7. The cells at 17th passages were cultured in 50 ml flasks. The N-nitrosopiperidine (NPIP) 0, 2, 4, 8 mmol/L added to the cultured medium of SHEE cells for 3 weeks. The morphology, proliferation and apoptosis of the cells were studied by phase contrast microscopy and flow cytometry. Modal number of chromosomes was analyzed by standard method. Tumorigenicity of the cells was assessed by soft agar colony formation and by transplantation of cells into nude mice. Expression of HPV was detected by Western blot. RESULTS: When cells were exposed to high concentration (8 mmol/L) of NPIP, cell death was increased, leaving a few live cells. In normal cultural medium instead of NPIP proliferative status of the cells restored after 4 weeks and the cells progressed to the proliferation stage with continuous replication and atypical hyperplasia. At the end of the 8th week, the cells appeared with large colonies in soft-agar and tumor formation in transplanted nude mice. When the cells were cultured in 2, 4 mmol/L NPIP the doubling passage was delayed and without tumor formation in transplanted nude mice. Modal number of chromosomes was 61-65, in 8 mmol/L NPIP group and control group, 56-61. Expression of HPV18 appeared in experimental and control groups. CONCLUSION: NPIP promotes malignant change of the immortalized esophageal epithelial cells induced by HPV18E6E7. HPV18E6E7 synergy with NPIP will accelerate malignant transformation in esophageal epithelium.

Animals↗
PubMed2005

Platelet adhesion and protein adsorption on silicone rubber surface by ozone-induced grafted polymerization with carboxybetaine monomer.

Platelet adhesion and protein adsorption on the silicone rubber film grafted with N,N'-dimethyl-N-methacryloyloxyethyl-N-(2-carboxyethyl) ammonium (DMMCA) was studied. The grafting was carried out by means of ozone-induced method and was confirmed by ATR-FTIR and XPS investigations. The grafted films possessed relatively hydrophilic surface revealed by contact angle measurement. The blood compatibility of the grafted film was evaluated in vitro by platelet adhesion in platelet-rich plasma (PRP) and protein absorption in bovine fibrinogen (BFG) using silicone film as the reference. No substantial platelet adhesion was observed for the grafted films incubated in PRP for 60 and 180 min. The protein absorption was also significantly reduced after incubated in bovine fibrinogen for 60 min. Both the results indicated that the blood compatibility of silicone rubber was greatly improved by ozone-induced grafting of carboxybetaine zwitterionic polymer onto its surface.

Animals↗
PubMed2005

The effect of increasing distraction on digital motion after external fixation of the wrist.

PURPOSE: Although several factors have been related to the development of digital stiffness after external fixation of distal radius fractures, distraction can be considered one of the most important. This study determined a threshold for distraction during external fixation of distal radius fractures and documented the effect of distraction of the wrist on metacarpophalangeal (MCP) joint motion. METHODS: Eight fresh-frozen cadaveric forearms were mounted on a testing frame and the flexor digitorum superficialis (FDS) tendon of each finger was pulled individually until a 90 degrees flexion at the MCP joint was generated. A load cell was used to record the force applied on the tendons. Tendon displacement was calculated by using a linear potentiometer. Sequential distraction across the wrist was applied through a distraction outrigger on the external fixator and was measured both on the external fixator in millimeters and on fluoroscopic images. Finger motion was captured by using a 2-dimensional motion tracking system. The experiment was repeated at different levels of wrist distraction (increments of 2 mm to a maximum of 14 mm). RESULTS: There was a significant difference in the effect of distraction on the individual fingers. For the index finger the load required for the FDS to produce a 90 degrees flexion at the MCP joint was increased linearly between 0 and 8 mm of wrist distraction. For the other fingers a threshold of distraction was found. A significant increase in the load was noticed after 5 mm of wrist distraction. CONCLUSIONS: More than 5 mm of wrist distraction increases the load required for the FDS to generate MCP joint flexion for the middle, ring, and small fingers. For the index finger, however, as much as 2 mm of wrist distraction significantly increases the load required for flexion at the MCP joint.

Cadaver↗
PubMed2005

Ulnar-positive variance as a predictor of distal radioulnar joint ligament disruption.

PURPOSE: Previous cadaveric data show that disruption of the triangular fibrocartilage complex (TFCC) at the wrist allows 0.5 to 3.0 mm of proximal radius migration. Anatomic studies have documented the presence of superficial and deep fibers of both the palmar and the dorsal distal radioulnar joint (DRUJ) ligaments. The aim of this study was to determine the contribution of the superficial and deep fibers of the DRUJ ligaments to longitudinal forearm stability as measured by ulnar-positive variance. METHODS: Eight fresh-frozen cadaver specimens were included in this study. Each specimen was secured with external fixation clamps to a sequential loading frame with the elbow in 90 degrees of flexion and the forearm and wrist in neutral pronation supination, neutral ulnar-radial deviation, and neutral volar-dorsal angulation. The radial head was resected and a force gauge was applied to the proximal radius. The peripheral TFCC was identified through an incision between the fifth and sixth extensor compartments and the dorsal capsulotomy of the DRUJ capsule. After baseline measurement sequential transection of the superficial and deep fibers of the TFCC was performed. Before and after each step load application and removal were performed by attaching an 88.90-N weight to the end of a force gauge and via longitudinal traction on the proximal part of the radius, and ulnar variance was measured with wrist fluoroscopy. RESULTS: Transection of the superficial TFCC fibers resulted in radius migration of 0.70 mm. This migration, however, was not significantly different from that observed at baseline. After both the superficial and deep TFCC fibers were transected the radius migrated proximately with load. This change of ulnar variance was significantly greater than that observed at baseline or after transection of only the superficial TFCC fibers. CONCLUSIONS: Traumatic injury to the TFCC with radiographic evidence of ulnar-positive variance may be an indication of disruption of the deep TFCC fibers.

Aged↗