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Biomedical subjects

Jin Zhao

Publications and source records attributed to Jin Zhao.

At least 19 recordsLinked to original sources

Library strategies differentially shape microbial, functional, and host signals in clinical metagenomic sequencing.

Metagenomic next-generation sequencing (mNGS) is increasingly used in infectious disease diagnostics, yet how library preparation shapes the microbial, functional, and host signals recovered from clinical samples remains poorly defined. Here, we performed a within-sample parallel comparison of three mNGS library preparation strategies-DNA-based libraries (DNAlib), RNA-based libraries (RNAlib), and total nucleic acid-based libraries (TNAlib)-across a diverse range of clinical specimens spanning five sample types. Using a curated clinical infectome as a benchmark, we show that library strategies are not interchangeable but capture distinct biological dimensions of the same specimen. RNAlib provided the most comprehensive standalone recovery of the clinical infectome, with improved detection of RNA viruses and cellular pathogens, enhanced resolution of resistance and virulence signals, and preservation of infection-associated host immune signatures. DNAlib showed stronger baseline recovery of DNA viruses and broader host genome coverage, whereas the TNAlib workflow evaluated here largely behaved as an intermediate strategy rather than a consistent improvement over dedicated DNA- or RNA-based workflows. Together, these results establish that the library preparation protocol is a major determinant of how clinical mNGS data should be interpreted and provide a framework for selecting sequencing strategies according to specific diagnostic and biological questions.IMPORTANCEMetagenomic sequencing is increasingly used in infectious disease research and clinical diagnostics, but different library preparation strategies may recover fundamentally different biological signals from the same sample. These signals include not only pathogens but also background microbes, microbial functional activity, and host immune-response patterns. Here, we systematically compared DNA-, RNA-, and total nucleic acid-based metagenomic sequencing libraries using the same clinical samples processed in parallel. We found that the three strategies did not provide equivalent information. RNA-based sequencing generated the most informative single-library view of infection, particularly for RNA viruses, cellular pathogens, functional microbial signals, and host immune-response patterns. DNA-based sequencing was more effective for DNA virus and host genome recovery, whereas the total nucleic acid sequencing workflow evaluated here generally behaved as an intermediate strategy. These findings show that library preparation can substantially influence the interpretation of metagenomic data.

functional characterization↗

Automated Classification of Lymphoma Subtypes From Histopathological Images Using a U-Net Deep Learning Model: Comparative Evaluation Study.

BACKGROUND: Accurate classification and grading of lymphoma subtypes are essential for treatment planning. Traditional diagnostic methods face challenges of subjectivity and inefficiency, highlighting the need for automated solutions based on deep learning techniques. OBJECTIVE: This study aimed to investigate the application of deep learning technology, specifically the U-Net model, in classifying and grading lymphoma subtypes to enhance diagnostic precision and efficiency. METHODS: In this study, the U-Net model was used as the primary tool for image segmentation integrated with attention mechanisms and residual networks for feature extraction and classification. A total of 620 high-quality histopathological images representing 3 major lymphoma subtypes were collected from The Cancer Genome Atlas and the Cancer Imaging Archive. All images underwent standardized preprocessing, including Gaussian filtering for noise reduction, histogram equalization, and normalization. Data augmentation techniques such as rotation, flipping, and scaling were applied to improve the model's generalization capability. The dataset was divided into training (70%), validation (15%), and test (15%) subsets. Five-fold cross-validation was used to assess model robustness. Performance was benchmarked against mainstream convolutional neural network architectures, including fully convolutional network, SegNet, and DeepLabv3+. RESULTS: The U-Net model achieved high segmentation accuracy, effectively delineating lesion regions and improving the quality of input for classification and grading. The incorporation of attention mechanisms further improved the model's ability to extract key features, whereas the residual structure of the residual network enhanced classification accuracy for complex images. In the test set (N=1250), the proposed fusion model achieved an accuracy of 92% (1150/1250), a sensitivity of 91.04% (1138/1250), a specificity of 89.04% (1113/1250), and an F1-score of 90% (1125/1250) for the classification of the 3 lymphoma subtypes, with an area under the receiver operating characteristic curve of 0.95 (95% CI 0.93-0.97). The high sensitivity and specificity of the model indicate strong clinical applicability, particularly as an assistive diagnostic tool. CONCLUSIONS: Deep learning techniques based on the U-Net architecture offer considerable advantages in the automated classification and grading of lymphoma subtypes. The proposed model significantly improved diagnostic accuracy and accelerated pathological evaluation, providing efficient and precise support for clinical decision-making. Future work may focus on enhancing model robustness through integration with advanced algorithms and validating performance across multicenter clinical datasets. The model also holds promise for deployment in digital pathology platforms and artificial intelligence-assisted diagnostic workflows, improving screening efficiency and promoting consistency in pathological classification.

Humans↗

MTO Schiff-base complexes: synthesis, structures and catalytic applications in olefin epoxidation.

Several Schiff-base ligands readily form complexes with methyltrioxorhenium(VII) (MTO) by undergoing a hydrogen transfer from a ligand-bound OH group to a ligand N atom. The resulting complexes are stable at room temperature and can be handled and stored in air without problems. Due to the steric demands of the ligands they display distorted trigonal-bipyramidal structures in the solid state, as shown by X-ray crystallography, with the O(-) moiety binding to the Lewis acidic Re atom and the Re-bound methyl group being located either in cis or trans position to the Schiff base. In solution, however, the steric differences seem not to be maintained, as can be deduced from (17)O NMR spectroscopy. Furthermore, the Schiff-base ligands exchange with donor ligands. Nevertheless, the catalytic behaviour is influenced significantly by the Schiff bases coordinated to the MTO moiety, which lead either to high selectivities and good activities or to catalyst decomposition. A large excess of ligand, in contrast to the observations with aromatic N-donor ligands, is detrimental to the catalytic performance as it leads to catalyst decomposition.

Journal Article↗

Potent and orally bioavailable 8-bicyclo[2.2.2]octylxanthines as adenosine A1 receptor antagonists.

In the search for a selective adenosine A1 receptor antagonist with greater aqueous solubility than the compounds currently in clinical trials as diuretics, a series of 1,4-substituted 8-cyclohexyl and 8-bicyclo[2.2.2]octylxanthines were investigated. The binding affinities of a variety of cyclohexyl and bicyclo[2.2.2]octylxanthines for the rat and human adenosine A1, A2A, A2B, and A3 receptors are presented. Bicyclo[2.2.2]octylxanthine 16 exhibited good pharmaceutical properties and in vivo activity in a rat diuresis model (ED50=0.3 mg/kg po). Optimization of the bridgehead substituent led to propionic acid 29 (BG9928), which retained high potency (hA1, Ki=7 nM) and selectivity for the adenosine A1 receptor (915-fold versus adenosine A2A receptor; 12-fold versus adenosine A2B receptor) with improved oral efficacy in the rat diuresis model (ED50=0.01 mg/kg) as well as high oral bioavailability in rat, dog, and cynomolgus monkey.

Adenosine A1 Receptor Antagonists↗

Ultrafast interfacial proton-coupled electron transfer.

The coupling of electron and nuclear motions in ultrafast charge transfer at molecule-semiconductor interfaces is central to many phenomena, including catalysis, photocatalysis, and molecular electronics. By using femtosecond laser excitation, we transferred electrons from a rutile titanium dioxide (110) surface into a CH3OH overlayer state that is 2.3 +/- 0.2 electron volts above the Fermi level. The redistributed charge was stabilized within 30 femtoseconds by the inertial motion of substrate ions (polaron formation) and, more slowly, by adsorbate molecules (solvation). According to a pronounced deuterium isotope effect (CH3OD), this motion of heavy atoms transforms the reverse charge transfer from a purely electronic process (nonadiabatic) to a correlated response of electrons and protons.

Deuterium↗

Structural and reactivity properties of finite length cap-ended single-wall carbon nanotubes.

The reaction of C2 with growing single-wall carbon nanotubes of different chiralities is investigated using density functional theory. It is found that the energy of the frontier orbitals for (5,5) and (6,6) armchair carbon nanotubes exhibits periodic behavior with an increasing number of carbon atoms in the nanotube. Such periodic behavior induces oscillations in the reaction energy released by adsorption of C2 to the nanotube open edge. In contrast, the energy of the frontier orbitals of the (6,5) chiral tube remains constant as the number of C atoms increases, and the same stability is observed in the adsorption energy. It is suggested that this may be one of the reasons for the low percent of armchair single-wall carbon nanotubes found in the experimental synthesis.

Journal Article↗

Single-electron tunneling spectroscopy of single C60 in double-barrier tunnel junction.

The single-electron tunneling (SET) spectroscopy of C(60) molecule in a double-barrier tunnel junction is investigated by combining the scanning tunneling spectroscopy experiment and the theoretical simulation using the modified orthodox theory. The interplay between the SET effect and the discrete energy levels of C(60) molecule is studied. Three types of SET spectroscopies with different characters are obtained, corresponding to different tunneling processes and consistent with the previous theoretical prediction. Both the charging mode and resonance mode can arouse the current increase in the SET spectroscopy. The resonance mode is realized mainly by two mechanisms, including the resonance when the electron spans the second junction after already spanning the first junction. Some previous confused results have been clarified. Our results show that three types of SET spectroscopies can be together examined to quantitatively determine the frontier orbitals of the nanostructure by identifying the modes of various current increases.

Journal Article↗

Norbornyllactone-substituted xanthines as adenosine A(1) receptor antagonists.

During the search for second-generation adenosine A(1) receptor antagonist alternatives to the clinical candidate 8-(3-oxa-tricyclo[3.2.1.0(2,4)]oct-6-yl)-1,3-dipropyl-3,7-dihydro-purine-2,6-dione (BG9719), we developed a series of novel xanthines substituted with norbornyl-lactones that possessed high binding affinities for adenosine A(1) receptors and in vivo activity.

Adenosine A1 Receptor Antagonists↗

Intraprostatic spermatozoa: zonal distribution and association with atrophy.

Intraprostatic spermatozoa (IS) have been demonstrated in only 2 articles in the literature reporting on postmortem prostates. Intraprostatic spermatozoa have not been previously described in radical prostatectomies. This is the first study that describes the presence of IS in radical prostatectomies with prostatic carcinoma (PC) and its association with atrophy. We examined whole mount sagittal sections from 69 consecutive radical prostatectomy cases for PC. A central section including the seminal vesicle ejaculatory duct urethra complex (SVEDU) from each case was stained with Berg's stain to identify spermatozoa and their location. The extent and the type of atrophy were assessed on the entire prostate by using a grid method. Eighteen cases (26.1%) revealed spermatozoa both in the SVEDU and in the prostate (IS) (group 1). Twenty-two cases (31.9%) showed spermatozoa exclusively in the SVEDU but not in the prostate (group 2). The remaining 29 cases (42.0%) had no spermatozoa in either site. Location of IS was 72.2% peripheral zone, 22.2% central zone, and 5.6% transitional zone. Intraprostatic spermatozoa were frequently seen accompanied by inflammatory infiltrate in the periglandular stroma. The extent of atrophy was greater in group 1 than in group 2 (25.7% versus 15.3%; P = .006). Postatrophic hyperplasia was seen more frequently in group 1 than in group 2 (72.2% versus 40.9%; P = .025). In conclusion, the frequency of IS is 26.1% when including all prostates and 45.0% when including prostates with evidence of residual ejaculate (spermatozoa in the SVEDU), more than previously reported. Intraprostatic spermatozoa are predominantly located in the peripheral zone similar to atrophy and PC. Prostates with IS have larger atrophic areas and increased frequency of postatrophic hyperplasia. The role of IS in the pathogenesis of prostate inflammation and atrophy should be investigated.

Adenocarcinoma↗

Role of the catalyst in the growth of single-wall carbon nanotubes.

Classical molecular dynamics simulations are carried out to analyze the physical state of the catalyst, and the growth of single-wall carbon nanotubes under typical temperature and pressure conditions of their experimental synthesis, emphasizing the role of the catalyst/substrate interactions. It is found that a strong cluster/substrate interaction increases the cluster melting point, modifying the initial stages of carbon dissolution and precipitation on the cluster surface. Experiments performed on model Co-Mo catalysts clearly illustrate the existence of an initial period where the catalyst is formed and no nanotube growth is observed. To quantify the nature of the Co-Mo2C interaction, quantum density functional theory is applied to characterize structural and energetic features of small Co clusters deposited on a (001) Mo2C surface, revealing a strong attachment of Co-clusters to the Mo2C surface, which may increase the melting point of the cluster and prevent cluster sintering.

Catalysis↗

[The expression of pseudogene HMGA1L2 in thyroid lesions].

Pseudogene HMGA1L2 mRNA level was detected using RT-PCR in 50 cases of thyroid lesions. The results show that HMGA1L2 mRNA was found in all 12 cases of nodular goiter, all 9 cases of thyroid adenoma and all 15 cases of papillary carcinoma. In 14 cases of thyroid follicular carcinoma, However, the frequency of HMGA1L2 mRNA expression was 35.7%, which was significantly different from that in other types of thyroid lesions (P < 0.05). This is the first report of mRNA expression of pseudogene HMGA1L2 in nodular goiter and thyroid tumors. It indicate that pseudogene HMGA1L2 expression analysis could be helpful in differentiation between follicular carcinoma and adenoma.

Base Sequence↗

Transsphenoidal microsurgery: past, present and future.

In this report, we first describe the history of transsphenoidal surgery. We further elaborate on three fundamental surgical anatomy principles of transsphenoidal surgery for pituitary adenomas. First, the pituitary gland and, therefore, pituitary adenomas are extra-arachnoid structures, therefore the operation should be executed without penetration into the subarachnoid space. Second, the pituitary gland and, therefore, pituitary adenomas are midline structures, thus, veering off midline can result in potentially serious complications. Third, pituitary adenomas commence inside the pituitary gland, which distends around them as they grow. Thus, pituitary macroadenomas are surrounded on their surface by a layer of attenuated residual normal anterior pituitary. The operative technique for pituitary micro- and macroadenomas is described in detail. Finally, we discuss the likely future treatment methods for pituitary adenomas.

Animals↗

Study of the interaction of carbamazepine with bovine serum albumin by fluorescence quenching method.

The interaction between carbamazepine (CBZ) and bovine serum albumin (BSA) was studied using fluorescence spectroscopy (FS) and ultraviolet spectroscopy (UV). The experimental results showed that the CBZ could insert into the BSA and quench the inner fluorescence of BSA by forming the CBZ-BSA complex. It was found that both static quenching and non-radiation energy transfer were the main reasons leading to the fluorescence quenching. The apparent binding constants (K) between CBZ and BSA were found to be 1.8 x 10(4) (27 degrees C) and 2.8 x 10(4) (37 degrees C) and the binding site values (n) were 0.97 (27 degrees C) and 1.01 (37 degrees C), respectively. According to the Forster theory of non-radiation energy transfer, the binding distances (r) between CBZ and BSA were 3.6 nm and 3.4 nm at 27 degrees C and 37 degrees C, respectively. The process of the binding was a spontaneous molecular interaction in which entropy increased and Gibbs free energy decreased, indicating that the interaction between CBZ and BSA was mainly driven by the hydrophobic force.

Animals↗

[Effect of growth inhibition of the secretory protein SPLUNC1 on Pseudomonas aeruginosa].

OBJECTIVE: To express the recombinant SPLUNC1 protein in HNE1 cells and to study its function of bactericidal and binding to lipopolysaccharide (LPS). METHODS: Full length of SPLUNC1 gene was cloned into pCMV-tag4A vector and stably transfected into HNE1 cell lines, the supernatant of cell cultures was collected. After being treated with the supernatant, the Pseudomonas aeruginosa was seeded to LB soft agar plate, and the bacteria clones were counted and analyzed. For in vitro LPS binding assay, LPS was coated to 96-well plates. We incubated in the plate with SPLUNC1 protein, and detected the binded SPLUNC1 protein by ELISA. Incubating the FITC-LPS with the SPLUNC1 stably transfected or control cells, the intracellular intensity of fluorescence was observed under the fluorescence microscope. RESULTS: SPLUNC1 inhibited the bacteria clone formation obviously. Although the binding efficiency of LPS and SPLUNC1 in vitro was very low, more FITC-LPS entered into the SPLUNC1 stably transfected cells. CONCLUSION: SPLUNC1 can inhibit the growth of Pseudomonas aeruginosa and bind LPS, and play an important defensive role in innate immunity of the upper airway.

Cell Line, Tumor↗

[Interaction between strychnine and bovine serum albumin].

AIM: To study the interaction between strychnine and bovine serum albumin. METHODS: Fluorescence spectroscopy and ultraviolet spectroscopy were used. RESULTS: The static quenching and the non-radiation energy transfer are the two main reasons to leading the fluorescence quenching of BSA. The apparent combining constants (K(A)) between strychnine and BSA are 3.72 x 10(3) at 27 degrees C, 4.27 x 10(3) at 37 degrees C, 4.47 x 10(3) at 47 degrees C and the combining sites are 1.01 +/- 0.03. The combining distance (r = 3.795 nm) and energy transfer efficiency (E = 0.0338) are obtained by Förster's non-radiation energy transfer mechanism. CONCLUSION: The interaction between strychnine and BSA was driven mainly by hydrophobic force.

Animals↗

[Simultaneous determination of levodopa and methyldopa in human serum by capillary electrophoresis].

A simple capillary electrophoresis method was developed for the determination of levodopa and methyldopa in human serum. The effects of pH and concentration of buffer, voltage and injection time on separation were investigated. As a result, an optimized separation was obtained with a fused-silica capillary of 60.2 cm (50 cm effective length) x 75 microm i. d. in a running buffer of 40 mmol/L sodium tetraborate (pH 9.5) with an applied voltage of 22 kV at 25 degrees C. Sample introduction was performed at 3.45 kPa (0.5 psi) for 7 s and on-column detection was made with a diode array detector at 200 nm. The linear responses covered the ranges from 1.0 to 64.0 mg/L (r = 0.999 8) for methyldopa and from 1.0 to 71.0 mg/L (r = 0.999 4) for levodopa. The detection limits (S/N = 3) of methyldopa and levodopa were shown to be 0.6 mg/L and 0.8 mg/L, respectively. The recoveries for levodopa and methyldopa in human serum were between 82.8% and 88.8% with relative standard deviations between 2.10% and 2.63%.

English Abstract↗