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Biomedical subjects

Zhi Xu

Publications and source records attributed to Zhi Xu.

At least 19 recordsLinked to original sources

Polygenic risk scores in major depressive disorder: A systematic review across diagnostic, treatment, course/severity, and subtype domains.

BACKGROUND: Major depressive disorder (MDD) is heterogeneous across diagnostic, treatment-related, course/severity, and subtype domains. Polygenic risk score (PRS) studies have examined these domains, but differences in PRS sources, samples, methods, and endpoint definitions have fragmented the evidence. We synthesised findings and examined potential contributors to heterogeneity. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science were searched for studies published from January 2016 through 25 November 2025. Result records were synthesised using SWiM, and certainty was assessed with an adapted GRADE framework. RESULTS: Sixty studies contributed 493 retained records; 450 were descriptively classified as positive, null, or reverse, although records were not independent. Positive findings accounted for 44/56 diagnostic, 61/273 treatment-related, 64/100 course/severity, and 14/21 subtype records. For MDD/depression-derived PRSs and case-control MDD status, all 10 contributing studies showed higher liability in cases (exploratory exact sign test p = 0.002; FDR q = 0.004). The same PRS group showed positive findings for overall depressive symptom severity (14/18), although the study-level test was imprecise (5/5 studies; p = 0.063). Pharmacological response/remission findings for these PRSs were mostly null or directionally mixed (10 positive, 18 null, and 9 reverse). Treatment-resistant depression (TRD) findings differed by operational definition. Atypical and psychotic subtype signals arose mainly from single-study PRS and endpoint contrasts. CONCLUSIONS: PRS evidence was clearest for MDD diagnostic status and showed a tentative pattern for overall symptom burden. Treatment and subtype findings were less consistent or less replicated. Larger, ancestrally diverse studies with standardised endpoints and transparent PRS methods are needed.

Humans↗

Mechanism of cholesterol transfer from the Niemann-Pick type C2 protein to model membranes supports a role in lysosomal cholesterol transport.

Cells acquire cholesterol either by de novo synthesis in the endoplasmic reticulum or by internalization of cholesterol-containing lipoproteins, particularly low density lipoprotein (LDL), via receptor-mediated endocytosis. The inherited disorder Niemann-Pick type C (NPC), in which abnormal LDL-cholesterol trafficking from the endo/lysosomal compartment leads to substantial cholesterol and glycolipid accumulation in lysosomes, is caused by defects in either of two genes that encode for proteins designated as NPC1 and NPC2. NPC2 is a small intralysosomal protein that has been characterized biochemically as a cholesterol binding protein. We determined the rate and mechanism by which NPC2 delivers cholesterol to model phospholipid membranes. A fluorescence dequenching assay was used to monitor the kinetics of cholesterol transfer from the protein to membranes. The endogenous tryptophan fluorescence of the NPC2 was quenched upon binding of cholesterol, and the subsequent addition of acceptor vesicles resulted in dequenching of the tryptophan signal, enabling the monitoring of cholesterol transfer to membranes. The rates of cholesterol transfer were evaluated as a function of acceptor vesicle concentration, acceptor vesicle phospholipid headgroup composition, and aqueous phase properties. The results suggest that NPC2 rapidly transports cholesterol to phospholipid vesicles via a collisional mechanism which involves a direct interaction with the acceptor membrane. Transfer of cholesterol to membranes is faster in an acidic environment and is greatly enhanced by the presence of the unique lysosomal/late endosomal phospholipid lyso-bisphosphatidic acid (LBPA) (also known as bismonoacylglycerol phosphate). Finally, we found that the rate of transfer of cholesterol from vesicles to NPC2 was dramatically increased by the presence of lyso-bisphosphatidic acid in the donor vesicles. These results support a role for the NPC2 protein in the egress of LDL derived cholesterol out of the endosomal/lysosomal compartment.

Animals↗

Multiwall carbon nanotubes made of monochirality graphite shells.

A multiwall carbon nanotube (MWCNT) consists of several or many concentric carbon shells, each of which could be metallic or semiconducting. Both theoretical predictions and experimental results suggest that MWCNTs have exotic electronic structures and intriguing transport properties, which are highly dependent on chirality of each shell. However, the structural defects and the random distribution of chirality of each concentric graphitic shell make the MWCNTs difficult for basic research and technological applications. Thus far, it is still a challenge to get the high crystalline MWCNTs with limited atomic conformation. Here, we report the synthesis of high crystalline MWCNTs made of monochirality graphite shells by a low-temperature chemical vapor deposition (CVD) process in plasma environment. Structural analysis, carried out by transmission electron microscopy (TEM) image and electron diffraction methods, reveal that the MWCNTs are well-crystallized and that most of them have nearly identical chiralities.

Journal Article↗

Clinical application of plasma shock wave lithotripsy in treating impacted stones in the bile duct system.

AIM: To verify the safety and efficacy of plasma shock wave lithotripsy (PSWL) in fragmenting impacted stones in the bile duct system. METHODS: From September 1988 to April 2005, 67 patients (26 men and 41 women) with impacted stones underwent various biliary operations with tube (or T-tube) drainage. Remnant and impacted stones in the bile duct system found by cholangiography after the operation were fragmented by PSWL and choledochofiberscopy. A total of 201 impacted stones were fragmented by PSWL setting the voltage at 2.5-3.5 kV, and the energy output at 2-3 J for each pulse of PSWL. Then the fragmented stones were extracted by choledochofiberscopy. The safety and efficacy of PSWL were observed during and after the procedure. RESULTS: One hundred and ninety-nine of 201 impacted stones (99.0%) in the bile duct system were successfully fragmented using PSWL and extracted by choledochofiberscopy. The stone clearance rate for patients was 97% (65/67). Ten patients felt mild pain in the right upper quadrant of the abdomen, and could tolerate it well. Eleven patients had a small amount of bleeding from the mucosa of the bile duct. The bleeding was transient and stopped spontaneously within 2 min of normal saline irrigation. There were no significant complications during and after the procedure. CONCLUSION: PSWL is a safe and effective method for fragmenting impacted stones in the bile duct system.

Adult↗

Plasminogen activator inhibitor-1 potentiates LPS-induced neutrophil activation through a JNK-mediated pathway.

Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor superfamily, modulates fibrinolysis by interacting with proteolytic mediators, including urokinase plasminogen activator (uPA). Although the roles of uPA and PAI-1 in plasmin generation and the degradation of fibrin are well known, recent evidence also suggests that they can participate in acute inflammatory conditions that involve neutrophil activation. In the present experiments, we found that the addition of PAI-1 to LPS- stimulated neutrophils resulted in enhanced nuclear translocation of NF-kappaB and increased production of the proinflammatory cytokines IL-1beta, Tnf-alpha, and Mip-2. uPA and the kringle domain (KD) of uPA potentiated cytokine expression and NF-kappaB activation by neutrophils cultured with LPS, and had additive effects when combined with PAI-1. The c-Jun N-terminal kinase (JNK) was activated after exposure of resting neutrophils to PAI-1 or the uPA KD. Enhanced JNK activation, but not that of other kinases induced by LPS, was present in neutrophils cocultured with PAI-1 or uPA KD. Inhibition of JNK activation prevented the potentiation of expression of proinflammatory cytokines induced by PAI-1 or uPA KD in LPS stimulated neutrophils. These results demonstrate that PAI-1 and uPA KD enhance LPS-induced neutrophil responses through their effects on JNK mediated pathways.

Active Transport, Cell Nucleus↗

[FTIR spectroscopic characterization of freshly removed breast cancer tissues].

OBJECTIVE: To identify the FTIR spectroscopic characterization of breast cancer and explore the possibility of application of FTIR in differentiation of malignant and benign breast lesions. METHODS: FTIR spectra of surgically removed fresh breast tissues were measured by spectrometer equipped with mid-infrared fiber optics and an ATR probe. Peaks in the spectra were measured and relative intensity ratios were calculated and analyzed if there are significant differences between the spectra of malignant and benign breast lesions. RESULTS: There were significant differences (P < 0.05) between the spectra of malignant breast cancers and benign breast tissues in the relative intensity ratios of different peaks (I1640/ I1550 and I1160/I1120 for protein structures; I1640/I1460 and I1550/I1460 for relative content of protein and lipid; I1460/I1400 for lipid structures; I1310/I1240 for nucleic acid). CONCLUSION: FTIR spectroscopy could be a useful tool in clinical diagnosis of breast cancer.

Adolescent↗

Development of ultra-low-noise spectrophotometry for analytical applications.

Methodology and instrumentation that dramatically increase the signal-to-noise ratio of scanning spectrophotometers over present commercial instruments is presented. The increase was accomplished by greatly reducing all important noise components. The random noise from an incoherent light source, which is the dominant noise source for most commercial spectrophotometers, was effectively removed by use of unique noise cancellation circuitry implemented with a dual-beam spectrophotometer configuration. Several other noise sources were also minimized by appropriate instrumental design, so that the observed noise level was attributable to the shot noise of the detectors. Single-wavelength measurements taken with a home-built prototype instrument have achieved a signal-to-noise ratio increase near 100-fold over commercial instruments. A spectrum taken in the visible region with a home-built retrofit detector installed in a commercial instrument showed a 10-fold signal-to-noise ratio increase over the standard commercial instrument. Widespread implementation of the methodology should enable many new types of research activities.

Journal Article↗

Synthesis of triphenylamine-cored dendritic two-photon absorbing chromophores.

[structure: see text]. A new series of dendritic two-photon absorbing chromophores containing triphenylamine moiety as a core or branching points have been synthesized through a convergent synthetic strategy. One-photon and two-photon optical properties of these molecules were characterized. In the nanosecond time domain, these molecules exhibited large two-photon absorption (TPA) cross sections up to 7.56-12.2 x 10(-44) s cm(4) at 800 nm, indicating that these molecular structures were viable candidates for various two-photon related applications.

Journal Article↗

In vivo and in situ detection of colorectal cancer using Fourier transform infrared spectroscopy.

AIM: Real-time and rapid identification of the malignant tissue can be performed during or before surgical operation. Here we aimed to detect in vivo and in situ colorectal cancer by using Fourier transform infrared (FTIR) spectroscopy and fiber-optic technology. METHODS: A total of five patients with large intestine cancer were detected in vivo and in situ. Of them, three cases of colon cancer and one case of cecum cancer were detected intraoperatively and in vivo by using a FTIR spectrometer during surgical operation, and one case of rectum cancer was explored non-invasively and in vivo before the surgical operation. Normal and malignant colorectal tissues were detected in vivo and in situ using FTIR spectroscopy on the basis of fundamental studies. RESULTS: There were significant differences between FTIR spectra of normal and malignant colorectal tissues detected in vivo and in situ. Experimental results revealed that the spectral characteristics of normal and malignant tissues found in vivo and in situ were similar to those obtained from in vitro measurement in our previous fundamental research. CONCLUSION: FTIR fiber-optic attenuated total reflectance (ATR) spectroscopy can identify in situ and in vivo colorectal cancer. FTIR spectroscopic method with fiber optics is a non-invasive, rapid, accurate and in vivo cancer detection technique in clinical diagnosis.

Aged↗

[FTIR spectroscopic explorations of clinical practice of breast cancer].

The authors detected ten normal breast tissue samples and eight breast cancer samples by FTIR spectroscopy with an ATR probe. Nineteen variables of thirteen bands in the spectra were compared using standard statistic methods. The results demonstrated that bands of protein, lipid, carbohydrate, and nucleic acid from cancerous samples were significantly different from those from normal ones: (1) The relative intensity of N-H band increased and amide I band shifted to lower wave number significantly; (2) Symmetric and antisymmetric vibrations of -CH2 group, C=O vibration, and relative intensity of (-CH2)n decreased; (3) The intensity of 1160 cm(-1) band was much weaker than that of 1120 cm(-1); (4) The band of P=O or P-O-C shifted toward lower wave number. The authors believe that FTIR spectroscopy has a promising future in breast cancer diagnosis.

Breast↗

[Coronary artery motion estimation using X-ray cineangiogram].

This paper presents an approach for estimating the non-rigid motion of coronary arteries using digital angiographic images. Displacement vectors of vessel points are obtained by finding points correspondences in two successive frames. Smoothness of motion field and vessel deformation measurement are considered in matching, and unmatched regions are also dealt with in the fact that the vessel after deformation may have different size with its original station. The search strategy for optimal matching is carried out using dynamic programming (DP) so that computing cost is reduced. Results of this motion estimation method applied to synthetic and clinical images have shown that the method is accurate, with a root mean square error about one pixel for simulated data. For the case of actual X-ray coronary angiographic images, visual inspection of the detected pairs of points shows that the results are very encouraging.

Angiography, Digital Subtraction↗

Morphological study on the megakaryocytes with nuclear extrusion and nucleocytoplasmic separation in four cases.

To investigate the morphological changes of megakaryocytes with nuclear extrusion and nucleocytoplasmic separation, the morphological characteristics of megakaryocytes in peripheral blood films, bone marrow smears, and bone marrow biopsies from 4 newly diagnosed patients with primary myelofibrosis (PMF), myelodysplastic syndrome (MDS), myeloblastic leukemia with maturation (M(2)) and erythroleukemia (M(6)) were studied by using light microscope. The results showed that many kinds of dysmegakaryocytes were observed in bone marrow smears of 4 cases, while in case A (PMF) and case D (M(6)) micromegakaryocytes were ripped apart; in case B (MDS) and case C (M(2)) megakaryocytes were accompanied by nuclear extrusion or nucleocytoplasmic separation, and their bodies were large or giant, the part of nucleus separated from their body and little cytoplasm remained as micromegakaryocytes. The nucleocytoplasmic separation could be displayed by immunocytochemistry stain. It is concluded that the phenomenon of nuclear extrusion and nucleocytoplasmic separation in megakaryocytes suggested the process that dispersed multinuclear releasing towards surround or even totally left the cell body during the megakaryocyte maturation. It also showed that the micromegakaryocytes may be the result of nucleocytoplasmic separation or splittings from multi-separated nucleus.

Aged↗

[Novel infrared spectroscopy methods for clinical diagnosis of tumor].

In this paper, the authors have reviewed their investigation on the clinical detection of tumor tissues by infrared spectroscopy in recent ten years. Based on the comparison of different IR spectroscopic methods such as IR transmission spectroscopy, micro-IR spectroscopy etc, the authors found the good consistency of the results of ATR (attenuated total reglection) IR spectroscopic method with those of pathological biopsy. The authors have directly measured the IR spectra of frozen tissues stored in liquid nitrogen and freshly resected tissues, and have realized the measurement of tumor tissues in vito during the operation process using a specially designed IR spectrometer connected with a mid-IR fiberoptic with an ATR probe. The authors have investigated the malignant and normal tissues including parotid, esophagus, stomach, colon, liver, gallbladder, breast, thyroid etc. and compared with the pathological results. The accuracy of this novel IR detection method is more than 90%.

Humans↗

[Nodular goiter surface detection by FTIR spectroscopy].

A novel non-invasive diagnosis method of nodular goiter is proposed in the present study by recording FTIR spectra on the skin overlying thyroids using fiber optical technique and attenuated total reflection probe. FTIR spectra from 20 nodular goiters and 34 normal controls were collected. Twenty seven spectral variables of 13 bands including peak position and relative intensities were extracted from the FTIR spectra so that statistic work could be conducted using SPSS. The results demonstrate that peak positions of 2 925 and 1 250 cm(-1) both shifted toward lower wave number (P < 0.05) in the FTIR spectra of nodular goiter. The relative intensity ratios of H1 740/H1 460, H1 160/H1 460, and H1 160/H1 120 decreased significantly in FTIR spectra of nodular goiter (P < 0.05). Inversely, H1 080/H1 460 increased significantly (P < 0.05) in nodular goiter. The above statistic differences suggest that nodular goiter may produce some characteristic chemical substance which can diffuse onto the surface of skin and therefore be detectable using FTIR spectroscopy with fiber optic techniques. These differences are the basis of diagnosing nodular goiter by FTIR surface detection.

Goiter, Nodular↗

Redox regulation of Ito remodeling in diabetic rat heart.

Oxidative stress and the resulting change in cell redox state are proposed to contribute to pathogenic alterations in ion channels that underlie electrical remodeling of the diseased heart. The present study examined whether K(+) channel remodeling is controlled by endogenous oxidoreductase systems that regulate redox-sensitive cell functions. Diabetes was induced in rats by streptozotocin, and experiments were conducted after 3-5 wk of hyperglycemia. Spectrophotometric assays of ventricular tissue extracts from diabetic rat hearts revealed divergent changes in two major oxidoreductase systems. The thioredoxin (TRX) system in diabetic rat heart was characterized by a 52% decrease in TRX reductase (TRXR) activity from control heart (P < 0.05), whereas TRX activity was 1.7-fold greater than control heart (P < 0.05). Diabetes elicited similar changes in the glutaredoxin (GRX) system: glutathione reductase was decreased 35% from control level (P < 0.05), and GRX activity was 2.5-fold greater than in control heart (P < 0.05). The basal activity of glucose-6-phosphate dehydrogenase, which generates NADPH required by the TRX and GRX systems, was not altered by diabetes. Voltage-clamp studies showed that the characteristically decreased density of the transient outward K(+) current (I(to)) in isolated diabetic rat myocytes was normalized by in vitro treatment with insulin (0.1 microM) or the metabolic activator dichloroacetate (1.5 mM). The effect of these agonists on I(to) was blocked by inhibitors of glucose-6-phosphate dehydrogenase. Moreover, inhibitors of TRXR, which controls the reducing activity of TRX, also blocked upregulation of I(to) by insulin and dichloroacetate. These data suggest that K(+) channels underlying I(to) are regulated in a redox-sensitive manner by the TRX system and the remodeling of I(to) that occurs in diabetes may be due to decreased TRXR activity. We propose that oxidoreductase systems are an important repair mechanism that protects ion channels and associated regulatory proteins from irreversible oxidative damage.

Animals↗

Orientation of peptides in aqueous monolayer films. Infrared reflection-absorption spectroscopy studies of a synthetic amphipathic beta-sheet.

Infrared reflection-absorption spectroscopy (IRRAS) intensities of the Amide I vibration are used to develop a quantitative approach for determining the Euler angles that describe the orientation of protein beta-sheets in aqueous monolayer films. A synthetic amphipathic peptide, Val-Glu-Val-Orn-Val-Glu-Val-Orn-Val-Glu-Val-Orn-Val-OH is used as a test case. The pattern of Amide I frequencies suggests that the molecule is organized as an antiparallel beta-sheet at the air/water interface. The model used to simulate the Amide I intensities reveals that the beta-sheet has a slight preferential alignment parallel to the direction of compression; i.e., deviation from uniaxial symmetry is observed. In addition, the sheet is found to lie flat on the aqueous surface, with (presumably) the polar side chains interacting with the aqueous subphase. Limitations and advantages of the theoretical approach are discussed.

Peptides↗

Conservation of critical functional domains in murine plasminogen activator inhibitor-1.

Plasminogen activator inhibitor-1 is the main physiological regulator of tissue-type plasminogen activator in normal plasma. In addition to its critical function in fibrinolysis, plasminogen activator inhibitor-1 has been implicated in roles in other physiological and pathophysiological processes. To investigate structure-function aspects of mouse plasminogen activator inhibitor-1, the recombinant protein was expressed in Escherichia coli and purified. Five variant recombinant murine proteins (R76E, Q123K, R346A, R101A, and Q123K/R101A) were also generated using site-directed mutagenesis. The variant (R346A) was found to be defective in its inhibitory activity against tissue plasminogen activator relative to its wild-type counterpart. Enzyme-linked immunosorbent assay and surface plasmon resonance experiments demonstrated reduced vitronectin-binding affinity of the (Q123K) variant (K(D) = 1800 nm) relative to the wild-type protein (K(D) = 5.4 nm). Kinetic analyses indicated that the (Q123K) variant had a slower association (k(on) = 2.92 x 10(4) m(-1) s(-1)) to, and a faster dissociation from, vitronectin (k(off) = 5.3 x 10(-2) s(-1)), (wild-type k(on) = 1.03 x 10(6) m(-1) s(-1) and k(off) = 5.27 x 10(-3) s(-1)). The Q123K/R101A variant demonstrated an even lower vitronectin-binding ability. Low density lipoprotein receptor-related protein binding was decreased for the (R76E) variant. It was also demonstrated that the plasminogen activator inhibitor-1/vitronectin complex decreased the interaction of plasminogen activator inhibitor-1 with low density lipoprotein receptor-related protein. These results indicate that the complex interactions traditionally associated with different plasminogen activator inhibitor-1 functions apply to the murine system, thus showing a commonality of subtle functions among different species and evolutionary conservation of this protein. Further, this study provides additional evidence that the human hemostasis system can be studied effectively in the mouse, which is a great asset for investigations with gene-altered mice.

Animals↗

[FTIR spectroscopic study of normal and malignant tissues of rectum].

Fourier transform infrared (FTIR) spectroscopy was used to study the normal and malignant tissues of rectum. The FTIR spectra of tissues were measured by Nicolet Magna IR-750 spectrometer equipped with mid-infrared fiber optics. The results show that the intensity ratios of five pairs of bands can be used to distinguish the normal and malignant tissues. In the spectra of malignant tissues the relative intensities ratios of I2,873/I2,852 and I1,312/I1,245 were higher than those of normal ones; however, the ratios of I1,745/I1,643, I1,458/I1,400 and I1,162/I1,082 were lower. These results, proved by data-analysis of spectra from 21 patients, were generally shown in the spectra of rectum tissues. The study of near-malignant tissues (one centimeter beside the malignant point) of rectum by FTIR shows that these ratios of bands were in a transient state between normal and malignant rectum tissues.

Humans↗