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Biomedical subjects

Jie Hu

Publications and source records attributed to Jie Hu.

At least 19 recordsLinked to original sources

Understanding psychosocial adjustment in military-to-civilian transition: A latent profile analysis of ex-serving Australian Defence Force members.

Military-to-civilian transition is a critical life stage that can expose veterans to elevated risks of psychological distress, social difficulties, and reduced wellbeing. Although psychosocial factors are central to successful reintegration, little is known about distinct patterns of needs among ex-serving Australian Defence Force (ADF) members. This study used latent profile analysis (LPA) to identify psychosocial needs profiles across five domains of the Military-Civilian Adjustment and Reintegration Measure (M-CARM) in a sample of 725 ex-serving ADF members. The optimal three-class solution identified: a Low Adjustment Need (LAN) group (20.7%) reporting minimal reintegration challenges; a Cultural Adjustment Need (CAN) group (42.9%) characterized by cultural adaptation difficulties, particularly beliefs about civilians and regimentation; and a Cultural and Psychological Need (CPN) group (36.4%) showing broader challenges across beliefs about civilians, purpose and connection, regimentation, and resentment and regret. The CAN group was more likely to be male, have lower educational attainment, and have no combat deployment history. The CPN group was similarly male dominated with lower education, and was additionally characterized by Navy service, unemployment or not being in the labor force, and medical discharge. Compared with the LAN group, both CAN and CPN groups reported higher levels of depression, anxiety, posttraumatic stress, and nightmare distress, as well as poorer quality of life and greater functional impairment. These findings highlight persistent reintegration challenges among veterans and support the need for stratified support models, ranging from psychoeducation to intensive multidisciplinary care, to better address diverse psychosocial needs of ex-serving ADF members.

Australian defense force↗

Proteomic profiling of plasma extracellular vesicles reveals a therapeutically targetable liver-heart axis in cardiac transplantation.

Extracellular vesicle-mediated interorgan communication represents a promising frontier in transplant immunology; however, its role in cardiac allograft rejection remains poorly characterized. We performed proteomic profiling of plasma-derived extracellular vesicles in a rat heterotopic heart transplantation model and identified a distinct liver-predominant protein signature during acute rejection, with antithrombin III (ATIII) emerging as a top candidate. Functional validation revealed that pharmacological extracellular vesicle inhibition intensified systemic and intragraft inflammation, whereas adeno-associated virus-mediated silencing of hepatic ATIII directly accelerated allograft rejection. Conversely, adeno-associated virus-mediated hepatocyte-specific ATIII overexpression attenuated rejection pathology, reduced immune cell recruitment, and markedly prolonged median graft survival. This protective effect was achieved without evidence of coagulopathic complications, indicating an immunomodulatory mechanism beyond ATIII's canonical anticoagulant function. Mechanistically, ATIII overexpression was associated with upregulation of heme oxygenase-1 (HO-1) in the liver and suppression of proinflammatory cytokine expression in the graft. These findings highlight hepatocyte-derived extracellular vesicles as important mediators of a liver-heart signaling axis in transplant rejection and further implicate the protein ATIII as a contributor to this axis. Our study reveals a therapeutically targetable liver-heart signaling axis in transplant rejection, whereby enhancing liver-derived ATIII or its downstream pathways (such as HO-1) could attenuate acute cardiac allograft rejection.

Animals↗

Maternal and Fetal HLA Heterozygosity in Preeclampsia: Insights From a Large Multi-Ancestry Pregnancy Cohort.

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity, with immune dysregulation at the maternal-fetal interface central to its pathogenesis. The highly polymorphic HLA region mediates maternal immune tolerance of the semi-allogeneic fetus, yet the contribution of HLA diversity to PE risk remains poorly defined. Whether the HLA heterozygote advantage observed in other immune disorders is relevant to PE has not been systematically evaluated. Using data from the multi-ancestry TOPMed Boston-Colombia Collaborative for Adverse Pregnancy Outcomes (n = 12,790; 4770 PE, 8020 controls; 10,808 maternal, 1982 fetal, including 1848 pairs), we evaluated associations between heterozygosity across eight classical HLA loci and PE and four sub-phenotypes, adjusting for genetic ancestry. HLA heterozygosity was common across most loci (> 80%). No individual maternal HLA locus was associated with overall PE; however, heterozygosity across Class I loci showed a protective effect in preterm PE (OR = 0.81, 95% CI: 0.68-0.97), with a similar pattern for HLA-A heterozygosity (OR = 0.78, 95% CI: 0.64-0.97). In contrast, fetal heterozygosity at HLA-DQB1 was nominally associated with increased risk of PE (OR = 1.36, 95% CI: 1.03-1.80) and preterm PE (OR = 1.73, 95% CI: 1.13-2.74). No individual maternal or fetal HLA alleles were associated with PE. Maternal-fetal mismatch analysis demonstrated locus-specific associations with preterm PE, including increased risk with HLA-DQA1 mismatch and reduced risk with HLA-C mismatch. These findings highlight distinct maternal and fetal immunogenetic contributions to PE risk and underscore the importance of considering HLA diversity-rather than individual alleles alone-in studies of PE aetiology.

Humans↗

Cross-omics risk scores of inflammation markers are associated with all-cause mortality: The Canadian Longitudinal Study on Aging.

Inflammation is a critical component of chronic diseases, aging progression, and lifespan. Omics signatures may characterize inflammation status beyond blood biomarkers. We leveraged genetics (polygenic risk score [PRS]), metabolomics (metabolomic risk score [MRS]), and epigenetics (epigenetic risk score [ERS]) to build multi-omics-multi-marker risk scores for inflammation status represented by the level of circulating C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α). We found that multi-omics risk scores generally outperformed single-omics risk scores in predicting all-cause mortality in the Canadian Longitudinal Study on Aging. Compared with circulating inflammation biomarkers, some multi-omics risk scores had a higher hazard ratio (HR) for all-cause mortality when including both score and circulating IL-6 in the same model (1-SD IL-6 MRS-ERS: HR = 2.20 [1.55-3.13] vs. 1-SD circulating IL-6 HR = 0.94 [0.67,1.32]. 1-SD IL-6 PRS-MRS: HR = 1.47 [1.35,1.59] vs. 1-SD circulating IL-6 HR = 1.33 [1.18, 1.51]. 1-SD PRS-MRS-ERS: HR = 1.95 [1.40, 2.70] vs. 1-SD circulating IL-6: HR = 0.99 [0.71, 1.39]). In the Nurses' Health Study (NHS), NHS II, and Health Professional Follow-up Study with available omics, 1 SD of IL-6 PRS and 1-SD IL-6 PRS-MRS had HR = 1.12 [1.00,1.26] and HR = 1.13 [1.01,1.26] among individuals >65 years old without mutual adjustment of the score and circulating IL-6. Our study demonstrates that some multi-omics scores for inflammation markers may characterize important inflammation burden for an individual beyond those represented by blood biomarkers and improve our prediction capability for the aging process and lifespan.

Humans↗

Avian Migration-Mediated Transmission and Recombination Driving the Diversity of Gammacoronaviruses and Deltacoronaviruses.

In the wake of pandemics like COVID-19, which have zoonotic origins, the role of wildlife as reservoirs for emerging infectious diseases has garnered heightened attention. Migratory birds, traversing continents, represent a potent but under-researched vector for the spread of infectious diseases, including novel coronaviruses. This study delves into the genetic diversity and transmission dynamics of coronaviruses in migratory birds, presenting pivotal findings. From April 2019 to April 2023, we screened 5,263 migratory bird samples collected from Shanghai, China, identifying 372 coronavirus-positive samples belonging to five avian-related coronavirus subgenera and subsequently obtaining 120 complete genome sequences. To facilitate further research with a global perspective, the study curated all available 19,000 avian-associated coronaviruses and expanded the original 12 species to 16, including three novel coronavirus species identified in our study and one re-classified species from the public domain. The study illuminates the intricate genetic evolution and transmission dynamics of birds-related coronaviruses on a global scale. A notable aspect of our research is the identification of complex recombination patterns within the spike protein across different virus species and subgenera, highlighting migratory birds as a reservoir of coronavirus. Notably, the coronaviruses found in migratory birds, predominantly from the orders Anseriformes, Charadriiformes, and Pelecaniformes, with domestic ducks from Anseriformes playing a key role in bridging the transmission of coronaviruses between migratory and non-migratory birds. These findings reveal the genetic and recombination characteristics of coronaviruses in migratory birds, emphasizing the critical role of ecologically pivotal bird species in coronavirus transmission and genetic diversity shaping.

Animals↗

Implications of alternative substrate binding modes for catalysis by uracil-DNA glycosylase: an apparent discrepancy resolved.

A theoretical study showed that the base excision repair enzyme uracil-DNA glycosylase (UDG) exploits electrostatic interactions with backbone phosphate groups in the substrate for catalysis. Although experiments performed to test the calculated results confirmed the predicted importance of the -2, -1, and +1 phosphate groups, there was an apparent disagreement with regard to the +2 phosphate group. The calculations indicated that it made an important contribution, while experimentally, the effect of its deletion or neutralization was small. The +2 phosphate group interacts directly with an active site histidine (H148 in humans) in the crystal structure of UDG in complex with double-stranded (ds) DNA. We previously calculated that H148 has a strong anticatalytic effect due to its protonation, and here we use alchemical free energy simulations to estimate its site-specific pKa. We find that it is positively charged over the entire experimental pH range (4-10), so its deprotonation cannot compensate for deletion or neutralization of the +2 phosphate group. The free energy simulations are facilitated by an efficient charge-scaling procedure that allows quantitative correction for the implicit treatment of solvent far from the active site; improvements are made to that method to account carefully for differences in the truncation of electrostatic interactions in the contributing molecular-mechanical and continuum-electrostatic approaches. Additional simulations are used to demonstrate that the +2 phosphate group is fully solvent exposed in complexes with single-stranded DNA substrates like those used in the experiments. In contrast, it is well-structured and buried in the dsDNA complex used in the original simulations. Differences in solvent shielding thus account for the apparent lack of an effect observed experimentally upon neutralization or deletion of this group.

Catalysis↗

Protective effects of transcription factor HESR1 on retinal vasculature.

HESR1 is a basic helix-loop-helix transcription factors regulated by the Notch signaling pathway in vertebrate and Drosophila embryos, and is related to the HES/Hairy/E (sp1) family. HESR1 is a downstream target of Notch in endothelial cells and could be an effector of Notch signaling in these cells. HESR1 is necessary for the induction of a tubular network and for continued maintenance of mature and quiescent blood vessels. To examine the role of HESR1 in retinal neovascularization, we transfected retinal vascular endothelial cells (HRCECs) with the HESR1 gene and studied its effects on the expression of angiogenic factors, on the proliferation and migration of endothelial cells, and on the formation of tube-like structures (TLSs). Overexpression of HESR1 downregulated VEGFR-2 expression, upregulated occludin expression, inhibited the migration and proliferation of HRCECs, and inhibited the formation of TLSs. Thus, HESR1 plays a key role in the finely tuned network of molecules involved in the regulation of retinal vascular homeostasis. HESR1 seems to inhibit the vessel-promoting effects of VEGF, shift endothelial cells from a proliferative state to a quiescent state, and restore normal vessel structures. Expression of the HESR1 gene in retinal vascular endothelial cells may protect retinal blood vessels and may be useful in the treatment of diseases involving damage to the retinal vasculature, including diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion.

Adult↗

Bias annealing: a method for obtaining transition paths de novo.

Computational studies of dynamics in complex systems require means for generating reactive trajectories with minimum knowledge about the processes of interest. Here, we introduce a method for generating transition paths when an existing one is not already available. Starting from biased paths obtained from steered molecular dynamics, we use a Monte Carlo procedure in the space of whole trajectories to shift gradually to sampling an ensemble of unbiased paths. Application to basin-to-basin hopping in a two-dimensional model system and nucleotide-flipping by a DNA repair protein demonstrates that the method can efficiently yield unbiased reactive trajectories even when the initial steered dynamics differ significantly. The relation of the method to others and the physical basis for its success are discussed.

Journal Article↗

Increased migration and metastatic potential of tumor cells expressing aquaporin water channels.

Aquaporin (AQP) water channels are expressed in high-grade tumor cells of different tissue origins. Based on the involvement of AQPs in angiogenesis and cell migration, we tested whether AQP expression in tumor cells might enhance their migration and metastatic potential. Transfection of B16F10 and 4T1 tumor cells with AQP1 did not affect their appearance, size, growth, or substrate adherence but increased their plasma membrane osmotic water permeability by 5- to 10-fold. In vitro analysis of cell migration by transwell assay, wound healing and video microscopy showed a 2- to 3-fold accelerated migration of the AQP1-expressing tumor cells compared to control cells. In mice, AQP1 expression increased tumor cell extravasation by >1.5-fold as quantified by counting tumor cells in lung at 6 h after tail vein injection of a mixture of fluorescently tagged AQP1-expressing and control tumor cells. AQP1 expression also increased by 3-fold the number of lung metastases 14 days after tail vein injection of tumor cells, with alveolar wall infiltration seen with AQP1-expressing tumor cells. Our results provide evidence for AQP-facilitated tumor cell migration and spread, suggesting a novel function for AQP expression in high-grade tumors. AQP inhibition may thus reduce the metastatic potential of some tumors.

Animals↗

[Extracellular matrix of xenogenic femoral fascia for the repair of renal trauma].

OBJECTIVE: To study the effect of extracellular matrix of xenogenic femoral fascia in repair of renal trauma. METHODS: Twelve adult dogs were used and randomly assigned to 6 groups, and the animals were sacrificed separately in 1 and 2 weeks 1,2,4 and 8 months after renal repair operations. The examinations of blood and urine routine, blood urea nitrogen and creatinine, electrolyte and serum renin were performed before and after operations at various times. The creatinine clearances of affected and contralateral normal kidneys were evaluated before death and the local areas of renal repair were studied by light and electron microscopy. RESULTS: Bleeding was stopped completely after the entire patch was sutured, and only mild adhesions to around tissues were found in various times after operations. As time passed, the repair patch was replaced by smooth neocapsule like normal renal capsule. CONCLUSION: Extracellular matrix of xenogenic femoral fascia might be an ideal tissue engineering material for renal repair.

Animals↗

Genetic diversity of Chinese water deer (Hydropotes inermis inermis): implications for conservation.

The Chinese water deer (Hydropotes inermis inermis) is endemic to China. Historically, the species was widely distributed, but now, habitat loss and poaching have reduced its range and number drastically. In order to provide useful information for its conservation, we have investigated the genetic diversity and population structure of the Chinese water deer by analyzing the 403 bp fragment of the mitochondrial DNA (mtDNA) control region (D-loop). Eighteen different haplotypes were detected in 40 samples. Overall, Chinese water deer have a relatively high-genetic diversity compared to other rare cervid species, with a haplotype diversity of 0.923+/-0.025 and nucleotide diversity of 1.318 +/- 0.146%. No obvious phylogenetic structure among haplotypes was found for samples of different origin. An analysis of molecular variance (AMOVA) showed significant differentiation between the Zhoushan and the mainland population (F(ST)= 0.088, P < 0.001; Phi( ST ) = 0.075, P = 0.043), which suggests that exchanges of individuals between Zhoushan and the mainland should be avoided. We also recommend that a breeding center be set up for the mainland population.

Animals↗

Solubility of silybin in aqueous poly(ethylene glycol) solution.

Silybin is a main component in silymarin, which is an antihepatotoxic polyphenolic substance isolated from the milk thistle plant, Silybum marianum. A major problem in the development of an oral solid dosage form of this drug is the extremely poor aqueous solubility. In present work, the solubility of silybin in aqueous poly(ethylene glycol) 6,000 (PEG 6,000) solution at the temperature range from 293.15 to 313.15K was measured by a solid liquid equilibrium method. The aim of this study is to investigate the possible effect of poly(ethylene glycol) concentration and temperature on the solubility of the drug, and to reveal the solubilization capacity of the polymer for the drug. Experimental results reveal that the solubility of silybin increases with the increase both in PEG's concentration and temperature. With the increase in PEG's concentration, the transfer enthalpy and entropy for silybin from water to aqueous PEG solution increases first in a positive region, and then decreases to a negative region. The transfer enthalpy is lower than the entropy term. A modified Universal Quasi Chemical (UNIQUAC) model was used to correlate solubility data.

Silybum marianum↗

Monte Carlo simulations of biomolecules: The MC module in CHARMM.

We describe the implementation of a general and flexible Monte Carlo (MC) module for the program CHARMM, which is used widely for modeling biomolecular systems with empirical energy functions. Construction and use of an almost arbitrary move set with only a few commands is made possible by providing several predefined types of moves that can be combined. Sampling can be enhanced by noncanonical acceptance criteria, automatic optimization of step sizes, and energy minimization. A systematic procedure for improving MC move sets is introduced and applied to simulations of two peptides. The resulting move sets allow MC to sample the configuration spaces of these systems much more rapidly than Langevin dynamics. The rate of convergence of the difference in free energy between ethane and methanol in explicit solvent is also examined, and comparable performances are observed for MC and the Nosé-Hoover algorithm. Its ease of use combined with its sampling efficiency make the MC module in CHARMM an attractive alternative for exploring the behavior of biomolecular systems.

Alanine↗

[Choice of the surgical approach to petroclival tumor].

OBJECTIVE: To discuss the reasonable choice of the surgical approach to petroclvial tumors. METHODS: The clinical data of consecutive 53 patients with the petroclival tumors, treated from June 2002 to June 2004, were reviewed to compare the different surgical approaches to pertroclival region. RESULT: Subtemporal transtentorial approach were used in 11 patients, suboccipital retrosigmoid approach in 12 patients, (transzygomatic or orbitozygomatic) frontotemporal (pterional) approach in 12 patients, presigmoid sinus approach in 2 patients, subtemporal and retrosigmoid sinus combined approach in 7 patients, subtemporal anterior petrosal extradural approach in 7 patients and extended transfrontal base extradural approach in 2 patients. Of all patients in this group, total tumor removal was achieved in 32 patients, subtotal in 9, largely partial in 12. The new cranial nerve deficit took place in 16 patients postoperatively, two patients died from coma and serious pneumonia. CONCLUSIONS: Using perfect microsurgical technique, conventional surgical approaches on petroclival region such as suboccipital retrosigmoid approach, subtemporal transtentorial approach can be suitable for most petroclival tumor with the help of neuro-navigation and neuro-endoscopy. To the epidural tumor on petroclival region, the epidural approach should be used with less invasion to the brain tissue. And to the giant petroclival tumor, the combined-tentorial approach can provide an excellent access and exposure to the tumor.

Adolescent↗

Properties of immobilized pepsin on Modified PMMA microspheres.

In this work we use micro-size poly(methyl methacrylate)/acrylaldehyde microspheres as a support for pepsin immobilization. The aldehyde groups on the microspheres offer a very simple, mild and firm combination for enzyme immobilization. The amount of enzyme we can bind to this support reaches 82 mg/g, which is much higher than for other supports (mostly less than 10 mg/g). Compared to free enzyme, the Km of immobilized enzyme is increased, whereas the Vmax is decreased. Further, the Vmax/Km value for immobilized pepsin is about 50% of the value for free enzyme. This is better than values reported previously, generally lower than 35%. The optimum temperature shifts from 43 degrees C for free pepsin to 47 degrees C. However, the optimum pH does not change between free and immobilized enzyme. This improved resistance of the immobilized enzyme towards changes in temperature and pH also shows that the aldehyde modified poly(methyl methacrylate)/acrylaldehyde microspheres can be a valuable support for pepsin immobilization.

Coated Materials, Biocompatible↗

Factors associated with future offending: comparing youth in grandparent-headed homes with those in parent-headed homes.

This study examined risk factors for reoffending by youth in grandparent-headed homes and those in parent-headed homes. Using data abstracted from the juvenile justice records of youth in a variety of living arrangements, we compared the records of 29 youth living in grandparent-headed homes with those of 37 youth living in parent-headed homes. Youth in grandparent-headed homes were significantly more likely to have risk factors and needs associated with reoffending. The findings suggest that youth in grandparent-headed homes are at greater risk for reoffending and that factors predisposing youth in grandparent-headed homes to reoffend may differ from those that predispose youth in non-grandparent-headed homes.

Adolescent↗

Chronic effects of maternal smoking on pulse waves in the fetal aorta.

OBJECTIVE: In order to evaluate the impact of maternal smoking on arterial stiffness in utero, pulse wave characteristics in the fetal aorta were investigated. A prospective clinical study was made of 34 smoking and 34 non-smoking healthy volunteers with uncomplicated pregnancies at 31-40 weeks of gestation. METHODS: The mechanical properties of the fetal thoracic aorta were assessed by an ultrasonic phase-locking echo-tracking system. For each fetus with a smoking mother, a non-smoking control matched for gestational and maternal age was monitored. Women with later appearing pregnancy complications were excluded. Pulse wave velocity (PWV), maximum diameter in systole (Ds), end-diastolic diameter (Dd), pulse amplitude (DeltaD), and maximum incremental velocity (MIV) in the fetal aorta were measured and analyzed in relation to maternal smoking and gestational age. RESULTS: Results were computed on fetuses of 32 smokers and 30 non-smokers. PWV increased with gestational age in smokers (corr. coeff. 0.49, p < 0.006) but not in non-smokers (corr. coeff. -0.12). MIV did not change in smokers (corr. coeff. -0.15) but increased in non-smokers (corr. coeff. 0.40, p < 0.03). Differences in regression lines between the groups regarding PWV and MIV were significant (p < 0.02 for both). CONCLUSIONS: Maternal smoking seems to promote the stiffening of the fetal aorta during gestation.

Adult↗