Biomedical subjects

Yan Xu

Publications and source records attributed to Yan Xu.

At least 19 recordsLinked to original sources

PubMed2026

Circulating tumor cells identify a disseminated genomic high-risk phenotype within IMS-IMWG 2025 staging in newly diagnosed multiple myeloma.

The 2025 IMS-IMWG consensus genomic staging (CGS) system has improved genomic risk stratification in newly diagnosed multiple myeloma (NDMM), yet does not capture whether high-risk clones have acquired a disseminated phenotype. We investigated whether circulating tumor cells (CTC) refine CGS and enable longitudinal residual disease monitoring. We retrospectively analyzed 631 MM patients from the NICHE cohort (NCT04645199) who underwent CTC assessment across disease phases. Among 410 patients assessed at diagnosis, CTC were detectable in 63.9% and correlated with both bone marrow plasma cell infiltration and accumulation of high-risk cytogenetic abnormalities. In 359 NDMM patients with adequate follow-up, a cohort-derived CTC threshold of 0.38% independently predicted inferior progression-free survival (PFS) after multivariable adjustment. Importantly, CTC refined prognostic stratification specifically within the CGS high-risk subgroup. Patients with CGS high-risk/CTC-high disease had the shortest PFS, thereby defining a disseminated genomic high-risk phenotype comprising 12.4% (39/314) of evaluable NDMM patients. In follow-up cohorts, detectable CTC were associated with inferior outcomes in 127 patients assessed during non-progressive disease states, whereas combined CTC and bone marrow minimal residual disease assessment stratified outcomes in 120 patients with paired measurements. Overall, CTC-integrated CGS supports minimally invasive baseline risk stratification and longitudinal disease monitoring.

Journal Article↗

PubMed2026

Physiologic age modifies the association between visceral fat predominance and urinary calcium excretion in adults with nephrolithiasis.

Although adiposity is associated with kidney stone disease, the relationship between abdominal fat distribution and urinary calcium excretion remains unclear. We investigated whether the CT-derived visceral-to-subcutaneous fat ratio (VSR) was associated with 24-hour urinary calcium excretion and whether physiologic age modified this association. This retrospective cross-sectional study included 308 adults with nephrolithiasis who underwent preoperative CT, stone removal, and postoperative metabolic evaluation. Participants were stratified into prespecified younger (men aged < 50 years and premenopausal women) and older (men aged ≥ 50 years and postmenopausal women) physiologic-age groups. Multivariable linear regression assessed the association between VSR and urinary calcium excretion and its modification by physiologic age. Results showed that VSR was not associated with urinary calcium excretion in the overall cohort, but its association differed significantly by physiologic age (P for interaction < 0.001). Among younger participants, each 1-unit higher VSR was associated with 2.07 mmol/day greater urinary calcium excretion (95% CI, 1.23-2.90), whereas no significant association was observed in the older group. These findings suggest that the metabolic relevance of visceral fat predominance differs by physiologic age, with a significant association observed only in younger adults. Prospective studies are needed to confirm these findings and determine their clinical implications.

Humans↗

PubMed2026

Higher Rates of PASS and SCB After Arthroscopic Subspine Decompression Are Associated With a Positive Diagnostic AIIS Injection: A Propensity Score-Matched Cohort Study.

BACKGROUND: Hip arthroscopy effectively treats femoroacetabular impingement syndrome (FAIS), but persistent pain may be related to concomitant extra-articular pathology such as subspine impingement syndrome (SSI). Standard diagnosis of SSI often relies on 3-dimensional computed tomography (3D-CT) morphology (Hetsroni type II/III), although this morphology is common in individuals who are asymptomatic and correlates poorly with symptoms. PURPOSE: To compare minimum 2-year clinical outcomes after arthroscopic subspine decompression in patients with concurrent FAIS and type II/III anterior inferior iliac spine (AIIS) morphology, stratified by diagnostic method: 3D-CT morphology alone versus 3D-CT morphology plus a positive ultrasound-guided diagnostic injection. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study included patients aged 18 to 55 years with type II/III AIIS morphology who underwent primary hip arthroscopy for FAIS and SSI between January 2021 and November 2023 and had minimum 2-year follow-up. Patients diagnosed by CT morphology alone (CT classification group) were propensity score matched 1:1 to patients with a positive ultrasound-guided AIIS injection (injection group), with 57 patients per group. Matching variables were age, sex, body mass index, lateral center-edge angle, alpha angle, Tönnis grade, and Beighton score. All patients underwent arthroscopic subspine decompression. Patient-reported outcomes and rates of achieving the minimal clinically important difference, Patient Acceptable Symptom State (PASS), and substantial clinical benefit (SCB) were compared. RESULTS: Preoperative patient-reported outcome scores were similar between groups (all P > .05). At minimum 2-year follow-up, the injection group had significantly better scores on the modified Harris Hip Score (90.8 vs 84.2), Hip Outcome Score-Activities of Daily Living (88.4 vs 82.4), Hip Outcome Score-Sports Subscale (71.9 vs 64.1), 12-item International Hip Outcome Tool (83.9 vs 76.1), and visual analog scale for pain (1.2 vs 2.0) (all P < .001). Minimal clinically important difference rates were high in both groups, with higher rates in the injection group for modified Harris Hip Score (93% vs 77%; P = .033) and Hip Outcome Score-Activities of Daily Living (91% vs 75%; P = .042). PASS and SCB rates were significantly higher in the injection group across all patient-reported outcome measures (all P < .05). Revision and complication rates were low and did not differ significantly between groups. CONCLUSION: Both groups improved significantly after arthroscopic subspine decompression. However, patients with a positive ultrasound-guided diagnostic AIIS injection achieved higher PASS and SCB rates than those selected by CT morphology alone, suggesting that injection-confirmed SSI may improve patient selection for subspine decompression.

Humans↗

PubMed2025

Uncovering encrypted antimicrobial peptides in health-associated Lactobacillaceae by large-scale genomics and machine learning.

BACKGROUND: Antimicrobial peptides (AMPs) are well known for their broad-spectrum activity and have shown great promise in addressing the antibiotic-resistant crisis. The Lactobacillaceae family, recognized for its health-promoting effects in humans, represents a valuable source of novel AMPs. However, the global prevalence and distribution of AMPs within Lactobacillaceae remains largely unknown, which limits the efficient discovery and development of novel AMPs. RESULTS: We analyzed all available genomes (10,327 genomes), encompassing 38 genera and 515 species, to investigate the biosynthetic potential (indicated by the number of AMP sequences in the genome) of AMP in the Lactobacillaceae family. We demonstrated Lactobacillaceae species had ubiquitous (69.90%) biosynthetic potential of AMPs. Overall, 9601 AMPs were identified, clustering into 2092 gene cluster families (GCFs), which showed strong interspecies specificity (95.27%), intraspecies heterogeneity (93.31%), and habitat uniqueness (95.83%), that greatly expanded on the AMP sequence landscape. Novelty assessment indicated that 1516 GCFs (72.47%) had no similarity to any known AMPs in existing databases. Machine learning predictions suggested that novel AMPs from Lactobacillaceae possessed strong antimicrobial potential, with 664 GCFs having an additive minimum inhibitory concentration (MIC) below 100 μM. We randomly synthesized 16 AMPs (with predicted MIC < 100 μM) and identified 10 AMPs exhibiting varied-spectrum activity against 11 common pathogens. Finally, we identified one Lactobacillus delbrueckii-originated AMP (delbruin_1) having broad-spectrum (all 11 pathogens) and high antimicrobial activity (average MIC = 38.56 µM), which proved its potential as a clinically viable antimicrobial agent. CONCLUSIONS: We uncovered the global prevalence of AMPs in Lactobacillaceae and proved that Lactobacillaceae is an untapped and invaluable source of novel AMPs to combat the antibiotic-resistance crisis. Meanwhile, we provided a machine learning-guided framework for AMP discovery, offering a scalable roadmap for identifying novel AMPs not only in Lactobacillaceae but also in other organisms. Video Abstract.

Machine Learning↗

PubMed2025

A SlEIN2-centered epigenetic network equilibrates fruit ripening and innate immunity in tomato.

Ethylene and DNA/RNA methylation serve as essential factors in controlling fruit ripening. In tomato, the mRNA N6-methyladenosine (m6A) demethylase SlALKBH2 regulates mRNA stability of the DNA 5-methylcytosine demethylase gene SlDML2 via modulating m6A modifications. However, the interplay between ethylene and these epigenetic marks remains unclear. Here, we show that SlDML2 expression is significantly inhibited in slein2 fruits, but remains unchanged in the high-order sleil mutant (sleil1 sleil2 sleil3/SlEIL3 sleil4 and sleil1 sleil2/SlEIL2 sleil3 sleil4) fruits, indicative of post-transcriptional regulation of SlDML2 expression by SlEIN2, a core ethylene signaling component acting upstream of the master transcription factors SlEILs. Interestingly, SlEIN2 preferentially regulates the asymmetric CHH methylation in promoters of several key ripening regulator genes. Mechanistically, SlEIN2 physically interacts with SlALKBH2, which promotes SlDML2 expression in a SlEIN2-dependent manner. Furthermore, SlAGO4A and SlAGO4B, components of the RNA-directed DNA methylation pathway, were upregulated in slein2 fruits. Silencing SlAGO4A/B in wild-type fruit caused precocious ripening with necrosis, indicative of hyperimmunity. Conversely, SlAGO4A/B silencing in slein2 markedly delayed this hyperimmunity. Taken together, our study reveals that ethylene, beyond transcriptional regulation, employs an elaborate epigenetic machinery mediated by the SlAGO4A/B-SlEIN2-SlALKBH2 module to balance fruit ripening and innate immunity.

Solanum lycopersicum↗

PubMed2024

Decoding the trajectory of antibiotic resistance genes in saline and alkaline soils: Insights from different fertilization regimes.

The soil salinity and alkalinity play an important role in the occurrence and proliferation of antibiotic resistance genes (ARGs). Yet, little is known the underlying mechanism by which soil salinity and alkalinity affect antibiotic resistance evolution. Here we investigated the ARGs variation in soil salinity and alkalinity environments created by different fertilization, and explored the biological mechanisms that salinity and alkalinity alter the evolutionary paradigm of antibiotic resistance. The results showed the soil treated by organic fertilizer exhibited a low salinity, neutral level (TSD 239.20 μS/cm, pH 7.17). The ARG abundance in the OF treatment was the highest, keeping an average of 67.83 TPM. Beside the effect of direct input of organic fertilizer at the beginning, it was important to note that, ARGs abundance during planting showed significant correlations with pH and electric conductivity. We observed that changes in microbial survival strategies under different salinity and alkalinity conditions further affected ARG hosts abundance. Indoor experiments demonstrated that there was a survival trade-off between the growth of resistant bacteria and the evolution of antibiotic resistance in salinity and alkalinity environments. Meta-genomic and Meta-transcriptomic analysis consistently demonstrated bacterial antibiotic resistance was primarily associated with pyruvate, energy and lipid metabolic pathways. The functional gene related to salinity and alkalinity, like cysH, cysK, plsB and plsC showed negative correlations with MDR. Prokaryotic transcription assays validated these relations. This study well explains the prevalence of soil ARGs after different fertilization regimes and will give a deeper understanding for the effect of soil salinity and alkalinity on antibiotic resistance evolution.

Soil↗

PubMed2007

Microbial synthesis of ethyl (R)-4,4,4-trifluoro-3-hydroxybutanoate by asymmetric reduction of ethyl 4,4,4-trifluoroacetoacetate in an aqueous-organic solvent biphasic system.

In this study, whole cells of Saccharomyces uvarum SW-58 were applied in an aqueous-organic solvent biphasic system for the asymmetric reduction of ethyl 4,4,4-trifluoroacetoacetate to ethyl (R)-4,4,4-trifluoro-3-hydroxybutanoate [(R)-2]. The results of reduction in different aqueous-organic solvent biphasic systems showed that dibutylphthalate provided the best compromise between the biocompatibility and the partition of substrate and product among the solvents tested. To optimize the reaction, several factors such as reaction pH, temperature, shaking speed, volume ratio of the aqueous phase to the organic phase and ratio of biomass/substrate were investigated. It was found that the change of these factors obviously influenced the conversion and initial reaction rate, and had a minor effect on the enatiomeric excess of the product. Under the optimal conditions, 85.0% of conversion and 85.2% of enatiomeric excess were achieved. The bioconversion in the biphasic system was more efficient compared with that in the monophasic aqueous system, and product concentration as high as 54.6 g/L was reached in the organic phase without addition of co-enzyme.

Acetoacetates↗

PubMed2007

A2 pulley incision or one slip of the superficialis improves flexor tendon repairs.

Outcomes of flexor tendon repairs in the area covered by major pulleys are often unpredictable. We performed an in vivo study to investigate biomechanical effects of pulley incision, Kapandji pulley plasty, excision of one slip of the flexor digitorum superficialis, or closure of the incised pulley on function of the profundus tendons. Both long toes (104 total) of 52 leghorn chickens were divided into four experimental groups and one control group. The pulley and flexor digitorum superficialis tendon were subjected to the above-mentioned treatments in four groups, with 22 toes per group, after tendon transection in the A2 pulley area. Eight weeks after surgery, incision of the pulley improved excursion of the flexor digitorum profundus tendon and decreased the work of digital flexion over pulley closure. Resection of the one slip of the flexor digitorum superficialis tendon had results similar to pulley incision. Kapandji pulley plasty did not increase tendon excursion and decrease the work compared with a simpler pulley incision. Adhesions were more severe with pulley plasty or closure than with pulley incision. In this avian model, incision of the pulley or partial flexor digitorum superficialis resection improved outcomes of tendon repairs compared with pulley closure. Kapandji pulley plasty did not improve the outcomes over a simple pulley incision.

Animals↗

PubMed2006

Structure of the first transmembrane domain of the neuronal acetylcholine receptor beta2 subunit.

The recent cryoelectron microscopy structure of the Torpedo nicotinic acetylcholine receptor (nAChR) at 4-A resolution shows long helices for all transmembrane (TM) domains. This is in disagreement with several previous reports that the first TM domain of nAChR and other Cys-loop receptors are not entirely helical. In this study, we determined the structure and backbone dynamics of an extended segment encompassing the first TM domain (TM1e) of nAChR beta(2) subunit in dodecylphosphocholine micelles, using solution-state NMR and circular dichroism (CD) spectroscopy. Both CD and NMR results show less helicity in TM1e than in Torpedo nAChR structure (Protein Data Bank: 2BG9). The helical ending residues at the C-terminus are the same in the TM1e NMR structure and the Torpedo nAChR structure, but the helical starting residue (I-217) in TM1e is seven residues closer to the C-terminus. Interestingly, the helical starting residue is two residues before the highly conserved P-219, in accordance with the hypothesis that proline causes helical distortions at three residues preceding it. The NMR relaxation measurements show a dynamics pattern consistent with TM1e structure. The substantial nonhelical content adds greater flexibilities to TM1e, thereby implicating a different molecular basis for nAChR function compared to a longer and more rigid helical TM1.

Amino Acid Sequence↗

PubMed2006

Sweeping from the superfluid to the Mott phase in the Bose-Hubbard model.

We study the sweep through the quantum phase transition from the superfluid to the Mott state for the Bose-Hubbard model with a time-dependent tunneling rate J(t). In the experimentally relevant case of exponential decay J(t) proportional variant e -gamma t, an adapted mean-field expansion for large fillings n yields a scaling solution for the fluctuations. This enables us to analytically calculate the evolution of the number and phase variations (on-site) and correlations (off-site) for slow (gamma< >mu) sweeps, where mu is the chemical potential. Finally, we derive the dynamical decay of the off-diagonal long-range order as well as the temporal shrinkage of the superfluid fraction in a persistent ring-current setup.

Journal Article↗

PubMed2006

I-motif and quadruplex-based device that can control a protein release or bind and release small molecule to influence biological processes.

To expand the function of DNA machines, we constructed a non-DNA-fuel machine based on the G-quadruplex and i-motif structures within the telomere DNA sequence. Depending on the binding or non-binding of the specified form, the DNA machine is able to bind or release the telomere-binding protein TRF 1, and to release small quadruplex-binding molecules to impede progress of the polymerase. This DNA machine, driven by pH change, does not accumulate duplex DNA waste products to poison the system. These new functions undertaken by structured nucleic acids open many opportunities to create and expand the further functions and use of DNA and RNA.

Circular Dichroism↗

PubMed2006

The cumate gene-switch: a system for regulated expression in mammalian cells.

BACKGROUND: A number of expression systems have been developed where transgene expression can be regulated. They all have specific characteristics making them more suitable for certain applications than for others. Since some applications require the regulation of several genes, there is a need for a variety of independent yet compatible systems. RESULTS: We have used the regulatory mechanisms of bacterial operons (cmt and cym) to regulate gene expression in mammalian cells using three different strategies. In the repressor configuration, regulation is mediated by the binding of the repressor (CymR) to the operator site (CuO), placed downstream of a strong constitutive promoter. Addition of cumate, a small molecule, relieves the repression. In the transactivator configuration, a chimaeric transactivator (cTA) protein, formed by the fusion of CymR with the activation domain of VP16, is able to activate transcription when bound to multiple copies of CuO, placed upstream of the CMV minimal promoter. Cumate addition abrogates DNA binding and therefore transactivation by cTA. Finally, an adenoviral library of cTA mutants was screened to identify a reverse cumate activator (rcTA), which activates transcription in the presence rather than the absence of cumate. CONCLUSION: We report the generation of a new versatile inducible expression system.

Adenoviridae↗

PubMed2006

[Biomechanical study of four-bundle semitendinosus tendon autograft used for anterior cruciate ligament reconstruction in rabbits model].

OBJECTIVE: To observe the biomechanical change of the remodeling process of a four bundles model using semitendinosus tendon for the reconstruction of anterior cruciate ligament (ACL) in rabbits, and to explore the possibility of using braiding technique for improving the outcome for reconstruction of ACL. METHODS: Two techniques were employed for the ACL reconstruction, one group with the implant of parallel bundles and the other with the braided bundles. Specimen were collected at 26 and 52 weeks after surgery respectively for biomechanical test. Gross morphology was also observed. RESULTS: The group with the implant of the braided bundles showed a more fused rate. The biomechanical test showed that the strength of the reconstructed ACL with the unbraided bundles was 35.87% of the controlled normal ACL, while the braided bundles reached 67.20%. The strength of the graft of the 26 and 52 weeks with the braided bundles were significantly higher than that of the unbraided group, while the stiffness of the 52 weeks graft of the braided group was significantly higher than that of the unbraided group also. CONCLUSIONS: Braiding each bundle to become a single implant for reconstruction of ACL might have better outcome since it will decrease the movement between each bundles and improve the biomechanical properties.

Animals↗

PubMed2006

Quality of life in women with stress urinary incontinence.

The objective of this study was to identify clinical and demographic factors associated with incontinence-related quality of life (QoL) in 655 women with stress urinary incontinence who elected surgical treatment. The following factors were examined for their association with QoL as measured with the Incontinence Impact Questionnaire (IIQ): number of incontinence (UI) episodes/day; self-reported type of UI symptoms (stress and urge); sexual function as measured by the Prolapse/Urinary Incontinence Sexual Questionnaire; symptom bother as measured by the Urogenital Distress Inventory; as well as other clinical and sociodemographic factors. A stepwise least-squares regression analysis was used to identify factors significantly associated with QoL. Lower QoL was related to the greater frequency of stress UI symptoms, increasing severity, greater symptom bother, prior UI surgery or treatment, and sexual dysfunction (if sexually active). Health and sociodemographic factors associated with lower incontinence-related QoL included current tobacco use, younger age, lower socioeconomic status, and Hispanic ethnicity.

Adult↗

PubMed2006

Calcineurin/Nfat signaling is required for perinatal lung maturation and function.

Pulmonary surfactant proteins and lipids are required for lung function after birth. Lung immaturity and resultant surfactant deficiency cause respiratory distress syndrome, a common disorder contributing to morbidity and mortality in preterm infants. Surfactant synthesis increases prior to birth in association with formation of the alveoli that mediate efficient gas exchange. To identify mechanisms controlling perinatal lung maturation, the Calcineurin b1 (Cnb1) gene was deleted in the respiratory epithelium of the fetal mouse. Deletion of Cnb1 caused respiratory failure after birth and inhibited the structural maturation of the peripheral lung. Synthesis of surfactant and a lamellar body-associated protein, ABC transporter A3 (ABCA3), was decreased prior to birth. Nuclear factor of activated T cells (Nfat) calcineurin-dependent 3 (Nfatc3), a transcription factor modulated by calcineurin, was identified as a direct activator of Sftpa, Sftpb, Sftpc, Abca3, Foxa1, and Foxa2 genes. The calcineurin/Nfat pathway controls the morphologic maturation of lungs prior to birth and regulates expression of genes involved in surfactant homeostasis that are critical for adaptation to air breathing.

ATP-Binding Cassette Transporters↗

PubMed2006

Hydrothermal synthesis and structural characterizations of two new germanates with a novel topological framework and unusual Ge4(OH)4 cubane.

Two new germanates, Ge7O12(OH)4 (C4N3H13)(0.5)(H2O)5 (1) and Ge7O12(OH)4(H2O)6 (2) have been synthesized under hydrothermal conditions and characterized by IR spectroscopy, powder XRD, TG, and single-crystal X-ray diffraction. Compound 1 crystallizes in cubic space group P3m (No. 215) with a = b = c = 7.7119(5) A, v = 458.65(5) A(3), z = 1. Compound 2: cubic, P3m, a = b = c = 7.7653(17) A, v = 457.48(17) A(3), z = 1. Both germanates keep the same topological novel inorganic framework, which is assembled from Ge4(OH)4 cubane and chiral intertwined Ge-O double helices.

Bridged-Ring Compounds↗

PubMed2006

Expression of ABCA3 in developing lung and other tissues.

ABCA3 is a member of the ATP-binding cassette (ABC) family of transport proteins and is required for perinatal respiratory adaptation. Monoclonal and polyclonal antibodies were generated against a recombinant human ABCA3 peptide and used to assess its expression in the developing lung and adult tissues. Immunostaining for ABCA3 was detected at highest levels in type II epithelial cells of the lung but was also noted in other organs including liver, stomach, kidney, adrenal, pancreas, trachea, and brain. In the fetal lung, ABCA3 staining and mRNA increased prior to birth. Like other surfactant protein genes, ABCA3 expression was induced by thyroid transcription factor-1 in vitro. ABCA3 was coexpressed with SP-B and proSP-C in type II epithelial cells. ABCA3 staining was detected surrounding large, intracellular organelles consistent with its association with lamellar bodies. In the human fetal lung, ABCA3 staining was not detected prior to 22-23 weeks of gestation, except in the presence of pulmonary inflammation. ABCA3 was detected in type II epithelial cells of the human lung from 28 weeks of gestation and thereafter. Postnatally, intense ABCA3 staining was observed in hyperplastic epithelial cells relining injured airways in infants with chronic lung disease. Localization and regulation of ABCA3 in the respiratory epithelium is consistent with its proposed role in surfactant homeostasis. The role of ABCA3 in extrapulmonary tissues and organs remains to be elucidated. This manuscript contains online supplemental material at (www.jhc.org). Please visit this article online to view these materials.

ATP-Binding Cassette Transporters↗

PubMed2006

Potential treatment of cerebral global ischemia with Oct-4+ umbilical cord matrix cells.

Potential therapeutic effects of Oct-4-positive rat umbilical cord matrix (RUCM) cells in treating cerebral global ischemia were evaluated using a reproducible model of cardiac arrest (CA) and resuscitation in rats. Animals were randomly assigned to four groups: A, sham-operated; B, 8-minute CA without pretreatment; C, 8-minute CA pretreated with defined media; and D, 8-minute CA pretreated with Oct-4(+) RUCM cells. Pretreatment was done 3 days before CA by 2.5-microl microinjection of defined media or approximately 10(4) Oct-4(+) RUCM cells in left thalamic nucleus, hippocampus, corpus callosum, and cortex. Damage was assessed histologically 7 days after CA and was quantified by the percentage of injured neurons in hippocampal CA1 regions. Little damage (approximately 3%-4%) was found in the sham group, whereas 50%-68% CA1 pyramidal neurons were injured in groups B and C. Pretreatment with Oct-4(+) RUCM cells significantly (p < .001) reduced neuronal loss to 25%-32%. Although the transplanted cells were found to have survived in the brain with significant migration, few were found directly in CA1. Therefore, transdifferentiation and fusion with host cells cannot be the predominant mechanisms for the observed protection. The Oct-4(+) RUCM cells might repair nonfocal tissue damage by an extracellular signaling mechanism. Treating cerebral global ischemia with umbilical cord matrix cells seems promising and worthy of further investigation.

Animals↗