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Biomedical subjects

Yue Zhao

Publications and source records attributed to Yue Zhao.

At least 19 recordsLinked to original sources

Comparison of Keverprazan-based versus esomeprazole-based dual therapy for initial treatment of Helicobacter pylori infection: a prospective, multicenter, randomized controlled trial.

BACKGROUND: Keverprazan offers a new perspective for Helicobacter pylori eradication. This study compared 14-day keverprazan-amoxicillin therapy with esomeprazole-amoxicillin therapy to explore a superior treatment strategy. METHODS: This was a prospective, open-label, multicenter, randomized controlled trial in adult patients with treatment-naive H. pylori infection. Participants were randomly assigned to receive either 14-day of KA therapy (Keverprazan 20&#x2009;mg b.i.d plus amoxicillin 1&#x2009;g t.i.d) or 14-day of EA therapy (Esomeprazole 40&#x2009;mg b.i.d plus amoxicillin 1&#x2009;g t.i.d). The primary outcome was the H. pylori eradication rate. Secondary outcomes were the incidence of adverse events and patient adherence. RESULTS: A total of 264 patients were enrolled in the study. In the intention-to-treat (ITT) analysis, the eradication rates for the 14-day KA group and the 14-day EA group were 87.9% and 80.3%, respectively (p&#x2009;=&#x2009;0.092); in the modified intention-to-treat (mITT) analysis, the eradication rates were 92.1% and 86.2%, respectively (p&#x2009;=&#x2009;0.135); and in the per-protocol (PP) analysis, the eradication rates were 93.5% and 88.3%, respectively (p&#x2009;=&#x2009;0.155). Non-inferiority was confirmed between the two groups (all p&#x2009;<&#x2009;0.001). Adverse events and patient adherence were similar between the two groups. CONCLUSION: For treatment-naive H. pylori infection, the 14-day KA therapy is non-inferior to EA therapy. Given its good tolerability, pharmacogenomic independence, and potent acid suppression, KA is a rational first-line alternative to EA in the Chinese population.

Humans↗

ResSAT: enhancing spatial transcriptomics prediction from H&E-stained histology images with an interactive spot transformer.

Spatial transcriptomics has revolutionized RNA quantification with spatial resolution. Hematoxylin and eosin (H&E) images, the gold standard in medical diagnosis, offer insights into tissue structure, correlating with gene expression patterns. We introduce ResSAT (Residual networks with Spatial encoding-self-Attention Transformer), a framework for predicting spatially resolved transcriptomic profiles from H&E images by integrating image features, spatial locations, and self-attention transformer-based spot interactions. Benchmarking on 10&#x2009;&#xd7;&#x2009;Visium datasets, ResSAT outperforms existing methods and preserved biologically meaningful spatial patterns, promising reduced spatial transcriptomics profiling costs and rapid acquisition of numerous profiles.

Spatial Transcriptomics↗

To cleave or not to cleave: a systemic evaluation of DSS versus DSSO for cross-linking mass spectrometry analysis.

Cross-linking mass spectrometry is a powerful method for structural analysis, but&#xa0;choosing between&#xa0;cleavable and non-cleavable&#xa0;cross-linkers&#xa0;remains challenging. We rigorously compared non-cleavable DSS with cleavable DSSO and found that&#xa0;DSS consistently yields more cross-link identifications from isolated protein complexes to bacterial lysates. The advantage of DSS diminishes as sample complexity increases. At the highest complexity tested-human cell lysate-the trend reverses, with DSSO outperforming DSS.&#xa0;The superior performance of DSS in&#xa0;less complex samples&#xa0;is likely&#xa0;explained by its longer and more flexible spacer arm, which interrogates a spatial volume >40% larger than that of DSSO. For both&#xa0;cross-linkers, the number of&#xa0;identified cross-links decreases as the search space expands, but more steeply for DSS. This sharper decline arises from DSS cross-links&#xa0;producing slightly lower fragment ion coverage, not from&#xa0;the absence of signature ions that could reduce search space. Fragment ion coverage is key to interactome mapping: when coverage reaches 85% or above, identification sensitivity hardly decreases as the search space expands, regardless of the cross-linker used. In summary, we recommend DSS&#xa0;for samples no more complex than bacterial lysates. For interactome mapping of mammalian cells, although DSSO outperforms DSS, neither achieves deep interactome coverage.

Cross-Linking Reagents↗

Risk factors for lung metastasis in children and adolescent patients with papillary thyroid cancer: A retrospective cohort study.

BACKGROUND: Pediatric papillary thyroid cancer (pPTC) exhibits a higher incidence of lung metastasis (LM) compared to its adult counterpart. This study supplements the gap in pediatric management guidelines by exploring factors associated with LM in pPTC and characterizing relevant genetic alterations. METHODS: We retrospectively analyzed pPTC patients under 20 years who underwent initial surgery at our center between December 2008 and December 2022. Clinicopathological features, treatment approaches, outcomes, and target-gene sequencing were reviewed to identify risk factors and genetic variations. RESULTS: Among 114 pPTC cases, 17 developed LM. Risk factors associated with LM included younger age, male gender, larger tumor size, multifocality, extrathyroidal extension, lymphatic invasion, and the number of metastatic lymph nodes (NMLNs), with NMLNs&#x2009;>&#x2009;14 identified as an independent predictor (OR&#x2009;=&#x2009;18.20, p&#x2009;=&#x2009;0.037). Treatment responses with radioiodine related to postoperative stimulated thyroglobulin (sTg) levels (p&#x2009;=&#x2009;0.003). Genomic analysis identified 1007 somatic mutations, including in the BRAF, APC, RET, and ATM genes, with RET-NCOA4 fusions observed in the LM subgroup. CONCLUSION: LM is common in pPTC, and NMLNs&#x2009;>&#x2009;14 is a critical risk indicator. The genetic profile, particularly RET mutations, highlights potential therapeutic targets. Further large-scale studies are needed to validate these findings.

Humans↗

Single-dose cathepsin L CRISPR nanotherapy mitigates PASC-like lung damage in hamsters.

Respiratory post-acute sequelae of COVID-19 (PASC) persists in many SARS-CoV-2 survivors, yet no therapies specifically address its long-term pulmonary damage. We demonstrate that a single-dose CRISPR-CasRx nanotherapy targeting the host enzyme cathepsin L (SCNC) effectively reduces acute SARS-CoV-2 infection in Syrian hamsters, with antiviral efficacy comparable to Paxlovid. Importantly, SCNC outperforms Paxlovid in alleviating alveolar epithelial hyperplasia and lung inflammation at 31 days post-infection, a recognized PASC time point. Single-cell RNA sequencing reveals that SCNC enhances alveolar repair by promoting the differentiation of alveolar type 2 cells into alveolar type 1 cells and by reducing inflammatory infiltration through multiple signaling pathways. Thus, SCNC exerts a dual mechanism: host-directed viral inhibition and promotion of epithelial repair with reduced inflammation. This distinguishes it from therapies focused solely on viral suppression or symptom relief. These findings support SCNC as a promising therapeutic candidate for acute infection and, particularly, for PASC-related lung injury, where options remain limited.

alveolar epithelial regeneration↗

The R203M and D377Y mutations of the nucleocapsid protein promote SARS-CoV-2 infectivity by impairing RIG-I-mediated antiviral signaling.

The viral protein mutations can modify virus-host interactions during virus evolution, and thus alter the extent of infection or pathogenicity. Studies indicate that nucleocapsid (N) protein of SARS-CoV-2 participates in viral genome assembly, intracellular signal regulation and immune interference. However, its biological function in viral evolution is not well understood. SARS-CoV-2&#x2009;N protein mutations were analyzed in Delta, Omicron, and original strains. Two mutations with a methionine (M) residue at site 203 and a tyrosine (Y) residue at site 377 of the N protein were found in Delta strain but not in Omicron and original strains, and promoted SARS-CoV-2 infection therein. Those mutations, R203M and D377Y, enhanced the inhibitory impact of N protein on the impairment of RIG-I-mediated antiviral signaling, such as IRF3 phosphorylation and IFN-&#x3b2; activation. The viral RNA-binding activity of N protein was promoted by these mutations, effectively attenuating the recognition and interaction of RIG-I with viral RNA compared to the original or other variants. The R203M/D377Y mutations thus enhanced the suppressive activity of the N protein on RIG-I-mediated interferon induction both in vitro and in vivo, which in turn promoted viral replication. This study helps to understand the variability of SARS-CoV-2 in regulating host immunity.

SARS-CoV-2↗

Bending and radial deformation of lipid tubules on self-assembled thiol monolayers.

Lipid tubules represent a hollow, cylindrical supramolecular structure formed by rolled-up lipid bilayers. We find that the lipid tubules of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine can be bent into a loopike shape by the shrinking contact line of droplets on self-assembled monolayers (SAMs) of 1-dodecanethiol. The persistence length of individual lipid tubules is estimated to be approximately 41 microm. The radial deformation of the lipid tubules on SAMs is studied under applied load using atomic force microscope. The stiffness of the tubules in the radial direction is found to increase when the number of the lipid bilayers in the tubule wall increases.

Biomechanical Phenomena↗

Photochemical phase transition versus photochemical phase separation.

When a nematic liquid crystal is doped with a large amount of a liquid crystalline azobenzene compound (15 wt %), the photoisomerization of azobenzene under UV and visible light irradiation can give rise to reversible and interconvertible photochemical phase transition and photochemical phase separation. Both normal and reverse modes of photocontrolled switching of transmittance through crossed polarizers can be realized with the same mixture of liquid crystal/azobenzene dopant.

Journal Article↗

Nanoscale ripples in self-assembled lipid tubules.

Self-assembled cylindrical tubules of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC(8,9)PC) have been studied by atomic force microscopy in both the height and amplitude modes. Nanoscale ripple structures in the cylindrical lipid tubules are clearly resolved in amplitude mode images. The periodicity of the ripples is found to be 200 +/- 30 nm for tubules with diameters in the range from 200 to 650 nm. The angle of the ripples with respect to the equator of the tubules shows a bimodal distribution with centers at approximately 28 degrees and approximately 5 degrees.

Journal Article↗

Zeolite nanoparticle modified microchip reactor for efficient protein digestion.

An enzymatic microreactor has been fabricated based on the poly(methyl methacrylate) (PMMA) microchchip surface-modified with zeolite nanoparticles. By introducing the silanol functional groups, the surface of PMMA microchannel has been successfully modified with silicalite-1 nanoparticle for the first time due to its large external surface area and high dispersibility in solutions. Trypsin can be stably immobilized in the microchannel to form a bioreactor using silica sol-gel matrix. The immobilization of enzyme can be realized with a stable gel network through a silicon-oxygen-silicon bridge via tethering to those silanol groups, which has been investigated by scanning electron microscopy and microchip capillary electrophoresis with laser-induced fluorescence detection. The maximum proteolytic rate constant of the immobilized trypsin is measured to be about 6.6 mM s(-1). Using matrix assisted laser desorption and ionization time-of-flight mass spectrometry, the proposed microreactor provides an efficient digestion of cytochrome c and bovine serum albumin at a fast flow rate of 4.0 microL min(-1), which affords a very short reaction time of less than 5 s.

Amino Acid Sequence↗

Positioning and alignment of lipid tubules on patterned Au substrates.

This paper presents a method for positioning and aligning self-assembled tubules of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphochloline (DC(8,9)PC) by withdrawing a patterned Au substrate from tubule solution. The patterned Au substrates with alternating bare Au stripes and thiol monolayer stripes are formed by microcontact printing. We find that the lipid tubules selectively adsorb on the bare Au stripes but show no orientation order. By withdrawing the patterned Au substrates at the direction along the stripes from tubule solution, the lipid tubules are found to be aligned along the direction of the Au stripes. The angular distribution and the density of the aligned lipid tubules depend on the withdrawal rates and the adsorption time, respectively. We conclude that forces causing tubule alignment that originate in the surface tension associated with the moving meniscus dominate alignment forces exerted by the patterned Au substrates.

Journal Article↗

Increased heat shock protein 70 expression in the pancreas of rats with endotoxic shock.

AIM: To investigate the ultra-structural changes and heat shock protein 70 (HSP70) expression in the pancreas of rats with endotoxic shock and to detect their possible relationship. METHODS: A total of 33 Wistar rats were randomly divided into three groups: control group (given normal saline), small dose lipopolysaccharide (LPS) group (given LPS 5 mg/kg) and large dose LPS group (given LPS 10 mg/kg). Pancreas was explanted to detect the ultra-structural changes by TEM and the HSP70 expression by immunohistochemistry and Western blot. RESULTS: Rats given small doses of LPS showed swelling and loss of mitochondrial cristae of acinar cells and increased number of autophagic vacuoles in the cytoplasm of acinar cells. Rats given large doses of LPS showed swelling, vacuolization, and obvious myeloid changes of mitochondrial cristae of acinar cells, increased number of autophagic vacuoles in the cytoplasm of acinar cells. HSP70 expression was increased compared to the control group (P<0.05). CONCLUSION: Small doses of LPS may induce stronger expression of HSP70, promote autophagocytosis and ameliorate ultra-structural injuries.

Animals↗

Estimation of cellobiohydrolase I activity by numerical differentiation of dynamic ultraviolet spectroscopy.

1,4-beta-D-glucan cellobiohydrolase I (CBH I), p-nitrophenyl beta-D-cellobioside, p-nitrophenol and cellobiose show distinct ultraviolet spectra, allowing the design of an assay to track the dynamic process of p-nitrophenyl beta-D-cellobioside hydrolysis by CBH I. Based on the linear relationship between p-nitrophenol formation in the hydrolysate and its first derivative absorption curve of AUC340-400 nm (area under the curve), a new sensitive assay for the determination of CBH I activity was developed. The dynamic parameters of catalysis reaction, such as Vm and kcat, can all be derived from this result. The influence of beta-glucosidase and endoglucanase in crude enzyme sample on the assay was discussed in detail. This approach is useful for accurate determination of the activity of CBHs.

Algorithms↗

[Inoculating microbes on municipal solid wastes composting affects organic acids and maturity].

Inoculating microbes (Meishang compound microbes, MS; Zhongjia fermentation microbes, ZJ) on municipal solid wastes composting which adopted industrialized technology was studied. The dynamic changes of low molecule weight organic acid and high molecule weight humic substance were discussed. The results show that inoculating microbes on municipal solid wastes composting could increase the content of organic acid at initial stage of composting, and decrease that at final stage. But humic substance and humic acid decline at the initial stage, then increase at the final stage of composting. The dynamic changes of organic acid and humification index indicate that inoculating microbes on municipal solid wastes can obviously increase the maturity of composting, and order as follow: MS+ ZJ>ZJ > MS>CK.

Acids↗

How can azobenzene block copolymer vesicles be dissociated and reformed by light?

The underlying mechanism of UV light-induced dissociation and visible light-induced reformation of vesicles formed by an azobenzene diblock copolymer was investigated. These processes were studied in situ by monitoring changes in optical transmittance of the vesicular solution while being exposed to UV or visible light irradiation. The results indicate that the UV-induced dissociation of the vesicles results from their thermodynamic instability due to a shift of the hydrophilic/hydrophobic balance arising from the trans-cis isomerization, while their reaggregation takes place upon visible light irradiation that shifts the hydrophilic/hydrophobic balance in the opposite direction after the reverse cis-trans isomerization. The study suggests a specific design principle for obtaining UV light-dissociable and visible light-recoverable vesicles based on azobenzene block copolymers. On one hand, the structure of azobenzene moiety used in the hydrophobic block should have a small (near zero) dipole moment in the trans form and a significantly higher dipole moment in the cis form, which ensures a significant increase in polarity of the hydrophobic block under UV light irradiation. On the other hand, the hydrophilic block should be weakly hydrophilic. The conjunction of the two conditions can make the light-induced shift of the hydrophilic/hydrophobic balance important enough to lead to the reversible change in vesicular aggregation.

Journal Article↗

A new design for light-breakable polymer micelles.

A new and general design strategy is presented for amphiphilic block copolymers whose micellar aggregates can be dissociated by light. A diblock copolymer composed of hydrophilic poly(ethylene oxide) (PEO) and a hydrophobic polymethacrylate bearing pyrene pendant groups (PPy) was synthesized using ATRP. Upon UV light irradiation of polymer micellar solutions, the photosolvolysis of pyrene moieties results in their detachment from the polymer and converts the hydrophobic PPy block into hydrophilic poly(methacrylic acid). This effect leads to complete dissociation of polymer micelles.

Drug Carriers↗

Liquid-crystal imaging of molecular-tilt ordering in self-assembled lipid tubules.

Self-assembled cylindrical tubules of chiral phospholipids are interesting supramolecular structures. Understanding the molecular-tilt order is a key step in controlling the size and shape of the tubules and designing new functional materials. The current theories based on the chiral interactions, coupled with molecular tilt, have predicted that the tubules could have both uniform and modulated tilt states. Here, we image the molecular-tilt order in the self-assembled tubules of a chiral phospholipid by using liquid crystals as an optical amplification probe. We demonstrate that the organization of the molecular-tilt azimuth in the lipid tubules can induce an azimuthal orientation in the liquid crystals. Both uniform and modulated tilt states of the lipid tubules are observed after liquid-crystal optical amplification.

Diagnostic Imaging↗