[Mechanism of liver injury induced by alcohol extract of salt-processed Psoraleae Fructus based on chemical modification of protein].

Salt-processed Psoraleae Fructus is a commonly used tonic in clinical practice. However, its usage is restricted due to the inherent toxicity. The covalent modification of proteins by reactive metabolites(RMs) plays a role in the hepatotoxicity of salt-processed Psoraleae Fructus. This study delves into the protein covalent modification by RMs generated from psoralen/isopsoralen, the primary toxic components of salt-processed Psoraleae Fructus, by liquid chromatography-mass spectrometry(LC-MS), aiming to elucidate the mechanism underlying the hepatic injury induced by salt-processed Psoraleae Fructus. Biochemical methods were utilized to measure the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), catalase(CAT), malondialdehyde(MDA), superoxide dismutase(SOD), reduced glutathione(GSH), and glutathione S-transferase(GST) in mice. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining. Subsequently, ultra performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS) was employed to identify the primary toxic components of psoralen/isopsoralen and the RMs in salt-processed Psoraleae Fructus. Covalent bonding adducts of the toxic components/RMs with GSH and free amino acids were identified to investigate the effects of the toxic components on modification sites and patterns of amino acids. The modifications of RMs were incorporated into the variable modifications of Proteome Discoverer, and the target proteins of psoralen/isopsoralen were detected by liquid chromatography-quadrupole exactive-mass spectrometry. Lastly, Label-free quantitative proteomics was adopted to screen differential proteins, which were further subjected to KEGG and GO enrichment analyses and confirmed by qPCR. The results indicated that compared with the control group, salt-processed Psoraleae Fructus significantly elevated the ALT, AST, and MDA levels and lowered the SOD, CAT, GSH, and GST levels in a dose-dependent manner, while causing obvious vacuolization and inflammatory cell infiltration in mouse hepatocytes. Furthermore, the livers of mice in the salt-processed Psoraleae Fructus group showed the presence of five RMs of psoralen/isopsoralen, two adducts with GSH, and one adduct with cysteine. In addition, 10 proteins modified by the RMs of psoralen/isopsoralen were identified. A total of 133 differential proteins were detected in the livers of mice in the salt-processed Psoraleae Fructus group, including 92 with up-regulated expression and 41 with down-regulated expression. These differential proteins mainly involved ribosomes, rRNAs, and glutathione, affecting the proteasome pathway. The qPCR results were consistent with the differential proteins. These findings suggest that the RMs of psoralen/isopsoralen can covalently bind to GSH and modify cysteine and lysine residues of liver proteins. This covalent modification of proteins by harmful substances can potentially result in liver damage. Therefore, it can be inferred that the oxidative stress damage induced by salt-processed Psoraleae Fructus may be associated with the abnormality of proteasome and its complex, biosynthesis of ribosomes and their nucleoprotein complex, rRNA binding, and glutathione binding.

[Clinical characteristics of Ureaplasma urealyticum infection and colonization in extremely preterm infants]. / è¶ æ—©äº§å„¿è§£è„²è„²åŽŸä½“æ„ŸæŸ“åŠå®šæ¤çŠ¶æ€çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the clinical characteristics of Ureaplasma urealyticum (UU) infection and colonization in extremely preterm infants and its impact on the incidence of bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was conducted on 258 extremely preterm infants who were admitted to the Department of Neonatology, Shenzhen Maternity and Child Healthcare Hospital, from September 2018 to September 2022. According to the results of UU nucleic acid testing and the evaluation criteria for UU infection and colonization, the subjects were divided into three groups: UU-negative group (155 infants), UU infection group (70 infants), and UU colonization group (33 infants). The three groups were compared in terms of general information and primary and secondary clinical outcomes. RESULTS: Compared with the UU-negative group, the UU infection group had significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay (P<0.05), while there were no significant differences in the incidence rates of BPD and moderate/severe BPD between the UU colonization group and the UU-negative group (P>0.05). CONCLUSIONS: The impact of UU on the incidence of BPD in extremely preterm infants is associated with the pathogenic state of UU (i.e., infection or colonization), and there are significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay in extremely preterm infants with UU infection. UU colonization is not associated with the incidence of BPD and moderate/severe BPD in extremely preterm infants.

Active smectics on a sphere.

The dynamics of active smectic liquid crystals confined on a spherical surface is explored through an active phase field crystal model. Starting from an initially randomly perturbed isotropic phase, several types of topological defects are spontaneously formed, and then annihilate during a coarsening process until a steady state is achieved. The coarsening process is highly complex involving several scaling laws of defect densities as a function of time where different dynamical exponents can be identified. In general the exponent for the final stage towards the steady state is significantly larger than that in the passive and in the planar case, i.e. the coarsening is getting accelerated both by activity and by the topological and geometrical properties of the sphere. A defect type characteristic for this active system is a rotating spiral of evolving smectic layering lines. On a sphere this defect type also determines the steady state. Our results can in principle be confirmed by dense systems of synthetic or biological active particles.

The working experience of medical staff in the hospital-wide bed-sharing mode: A qualitative study.

AIM: The purpose of this study was to provide a comprehensive understanding of the attitudes and experiences of the medical staff regarding the hospital bed-sharing model. DESIGN: The present research was a qualitative study. METHODS: This qualitative study used in-depth individual interviews with 7 doctors, 10 clinical nurses and 3 head nurses, which were then transcribed and analysed thematically. RESULTS: The study identified six overall themes. Issues were raised about the efficient utilization of hospital bed resources, greater challenges for nursing work, adjustment of doctors' work modes, barriers to communication between doctors, nurses, and patients, potential medical risks, and differentiation of patients' medical experience. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital administrators and nurse managers should work together to solve the challenges that medical staff face, including strengthening nursing training, improving medical-nursing collaboration models, standardizing and effective communication strategies, and improving patient experiences.

Control of phase ordering and elastic properties in phase field crystals through three-point direct correlation.

Effects of three-point direct correlation on properties of the phase field crystal (PFC) modeling are examined for the control of various ordered and disordered phases and their coexistence in both three-dimensional and two-dimensional systems. Such effects are manifested via the corresponding gradient nonlinearity in the PFC free-energy functional that is derived from classical density functional theory. Their significant impacts on the stability regimes of ordered phases, phase diagrams, and elastic properties of the system, as compared to those of the original PFC model, are revealed through systematic analyses and simulations. The nontrivial contribution from three-point direct correlation leads to the variation of the critical point of order-disorder transition to which all the phase boundaries in the temperature-density phase diagram converge. It also enables the variation and control of system elastic constants over a substantial range as needed in modeling different types of materials with the same crystalline structure but different elastic properties. The capability of this PFC approach in modeling both solid and soft matter systems is further demonstrated through the effect of three-point correlation on controlling the vapor-liquid-solid coexistence and transitions for body-centered cubic phase and on achieving the liquid-stripe or liquid-lamellar phase coexistence. All these provide a valuable and efficient method for the study of structural ordering and evolution in various types of material systems.

Chiral derivatives of covalent organic framework TpBD (NH2 )2 used as stationary phases in gas chromatography.

Chiral covalent organic framework materials have many excellent properties, which have received much attention in the field of separation. Synthesized the covalent organic framework COF-TpBD (NH2 )2 modified, respectively, by L-valine trifluoroacetyl derivative, L-hydroxyproline, and (1S)-(+)-10-camphorsulfonyl chloride, three capillary columns of chiral covalent organic framework materials were obtained for gas chromatography. Those columns are able to separate some chiral compounds, positional isomers, n-alkanes, n-alcohols, aromatic hydrocarbon mixture, and Grob's reagents. They are complementary to other chiral capillary columns and are possible for potential applications.

[Distribution Characteristics and Risk Assessment of 209 Polychlorinated Biphenyls in Dongting Lake and the Inflow Rivers].

In order to fully understand the pollution of polychlorinated biphenyls (PCBs) in Dongting Lake, 209 PCB congeners were quantitatively detected and analyzed by isotope-dilution high-resolution mass spectrometry in 21 surface water sampling sites of Dongting Lake and the inflow rivers of the lake. The results showed that a total of 50 PCB congeners were detected in the study area. The ρ(ΣPCBs) ranged from 0.077 to 10 ng·L-1, with an average concentration of 2.7 ng·L-1 and a median concentration of 1.9 ng·L-1. The order of contamination concentrations were as follows:the inflow rivers of the lake > lake region > outlet. Compared with the reports of domestic and foreign studies, PCB pollution in Dongting Lake is at a low level. The main pollutants in the surface water were dichlorobiphenyls and tri- and tetrachlorobiphenyls, with relative abundances of 67%, 14%, and 16%, respectively. PCB11, PCB17, PCB18, PCB20+33, PCB28, PCB47+75, PCB52, and PCB68 were the most widely distributed and detected in more than 80% of samples. Among them, ρ(PCB11) was the highest, with an average concentration of 1.6 ng·L-1, accounting for 59% of ρ(ΣPCBs), from the domestic organic pigment production process of unintentional emissions. Atmospheric transport deposition and historical residue were the main sources of PCBs in water. According to the toxicity equivalent factor method, the ecological toxicity risk of the study area was evaluated, and the results showed that the TEQ in the water was far lower than the relevant standard limit, indicating that the pollution of PCBs in the surface water of Dongting Lake and the inflow rivers would not cause harm to exposed organisms.

Mesoscale Defect Motion in Binary Systems: Effects of Compositional Strain and Cottrell Atmospheres.

The velocity of dislocations is derived analytically to incorporate and predict the intriguing effects induced by the preferential solute segregation and Cottrell atmospheres in both two-dimensional and three-dimensional binary systems of various crystalline symmetries. The corresponding mesoscopic description of defect dynamics is constructed through the amplitude formulation of the phase-field crystal model, which has been shown to accurately capture elasticity and plasticity in a wide variety of systems. Modifications of the Peach-Koehler force as a result of solute concentration variations and compositional stresses are presented, leading to interesting new predictions of defect motion due to effects of Cottrell atmospheres. These include the deflection of dislocation glide paths, the variation of climb speed and direction, and the change or prevention of defect annihilation, all of which play an important role in determining the fundamental behaviors of complex defect network and dynamics. The analytic results are verified by numerical simulations.

[Therapeutic effect of acupuncture combined with medication on chronic prostatitis of damp and heat stasis].

OBJECTIVE: To observe the clinical therapeutic effect of electroacupuncture (EA) combined with tamsulosin hydrochloride sustained release capsule on chronic prostatitis (CP) of damp and heat stasis. METHODS: A total of 70 patients with CP of damp and heat stasis were randomized into an acupuncture plus medication group (35 cases, 4 cases dropped off) and a medication group (35 cases, 5 cases dropped off). In the medication group, tamsulosin hydrochloride sustained release capsule was given orally, 0.2 mg a time, once each night. On the basis of treatment in the medication group, EA was applied at Guanyuan (CV 4), Sanyinjiao (SP 6) and Yinglingquan (SP 9), with disperse-dense wave, 5 mA in intensity for 30 min. Treatment for 30 days was as one course, and totally 3 courses were required in both groups. Before treatment, 1, 2, 3 months into treatment and at the follow-up of 2 months after treatment, the TCM syndrome score and National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score were observed, and the clinical efficacy was evaluated in both groups. RESULTS: Compared before treatment, the TCM syndrome scores of 3 months into treatment and follow-up were decreased in the acupuncture plus medication group (P<0.01), and were lower than those in the medication group (P<0.05). Compared before treatment, the NIH-CPSI scores of 3 months into treatment and follow-up were decreased in both groups (P<0.01), and those in the acupuncture plus medication group were lower than the medication group (P<0.05). The total effective rate was 90.3% (28/31) in the acupuncture plus medication group, which was superior to 80.0% (24/30) in the medication group (P<0.05). CONCLUSION: Acupuncture combined with medication can improve the clinical symptoms in patients with CP of damp and heat stasis, and its therapeutic effect is superior to simple western medication.

Dynamical Crystallites of Active Chiral Particles.

One of the intrinsic characteristics of far-from-equilibrium systems is the nonrelaxational nature of the system dynamics, which leads to novel properties that cannot be understood and described by conventional pathways based on thermodynamic potentials. Of particular interest are the formation and evolution of ordered patterns composed of active particles that exhibit collective behavior. Here we examine such a type of nonpotential active system, focusing on effects of coupling and competition between chiral particle self-propulsion and self-spinning. It leads to the transition between three bulk dynamical regimes dominated by collective translative motion, spinning-induced structural arrest, and dynamical frustration. In addition, a persistently dynamical state of self-rotating crystallites is identified as a result of a localized-delocalized transition induced by the crystal-melt interface. The mechanism for the breaking of localized bulk states can also be utilized to achieve self-shearing or self-flow of active crystalline layers.

Nonautonomous dynamics of acute cell injury.

Medical conditions due to acute cell injury, such as stroke and heart attack, are of tremendous impact and have attracted huge amounts of research effort. The biomedical research that seeks cures for these conditions has been dominated by a qualitative, inductive mind-set. Although the inductive approach has not been effective in developing medical treatments, it has amassed enough information to allow construction of quantitative, deductive models of acute cell injury. In this work we develop a modeling approach by extending an autonomous nonlinear dynamic theory of acute cell injury that offered new ways to conceptualize cell injury but possessed limitations that decrease its effectiveness. Here we study the global dynamics of the cell injury theory using a nonautonomous formulation. Different from the standard scenario in nonlinear dynamics that is determined by the steady state and fixed points of the model equations, in this nonautonomous model with a trivial fixed point, the system property is dominated by the transient states and the corresponding dynamic processes. The model gives rise to four qualitative types of dynamical patterns that can be mapped to the behavior of cells after clinical acute injuries. The nonautonomous theory predicts the existence of a latent stress response capacity (LSRC) possessed by injured cells. The LSRC provides a theoretical explanation of how therapies, such as hypothermia, can prevent cell death after lethal injuries. The nonautonomous theory of acute cell injury provides an improved quantitative framework for understanding cell death and recovery and lays a foundation for developing effective therapeutics for acute injury.

Erratum: Exploring spiral defect chaos in generalized Swift-Hohenberg models with mean flow [Phys. Rev. E 84, 046215 (2011)].

This corrects the article DOI: 10.1103/PhysRevE.84.046215.

Mechanical relaxation and fracture of phase field crystals.

A computational method is developed for the study of mechanical response and fracture behavior of phase field crystals (PFC), to overcome a limitation of the PFC dynamics which lacks an effective mechanism for describing fast mechanical relaxation of the material system. The method is based on a simple interpolation scheme for PFC (IPFC) making use of a condition of the displacement field to satisfy local elastic equilibration, while preserving key characteristics of the original PFC model. We conduct a systematic study on the mechanical properties of a sample nanoribbon system with honeycomb lattice symmetry subjected to uniaxial tension, for numerical validation of the IPFC scheme and the comparison with the original PFC and modified PFC methods. Results of mechanical response, in both elasticity and fracture regimes, show the advantage and efficiency of the IPFC method across different system sizes and applied strain rates, due to its effective process of mechanical equilibration. A brittle fracture behavior is obtained in IPFC calculations, where effects of system temperature and chirality on the fracture strength and Young's modulus are also identified, with results agreeing with those found in previous atomistic simulations of graphene. The IPFC scheme developed here is generic and applicable to the mechanical studies using different types of PFC free-energy functionals designed for various material systems.

[Clinical value of droplet digital PCR in rapid diagnosis of invasive fungal infection in neonates].

OBJECTIVE: To evaluate the clinical value of droplet digital PCR (ddPCR) in rapid and accurate diagnosis of invasive fungal infection (IFI) in neonates. METHODS: The highly conserved sequence of fungi 18S RNA was selected as the target sequence, and primers were designed to establish a ddPCR fungal detection system. Blood samples were collected from 83 neonates with high-risk factors for IFI and/or related clinical symptoms in the neonatal intensive care unit (NICU) of a hospital in Shenzhen, China. Blood culture and ddPCR were used for fungal detection. RESULTS: The ddPCR fungal detection system had a specificity of 100% and a sensitivity of 3.2 copies/µL, and had a good reproducibility. Among the 22 blood samples from neonates with a confirmed or clinical diagnosis of IFI, 19 were detected positive by ddPCR. Among the 61 blood samples from neonates who were suspected of IFI or had no IFI, 2 were detected positive by ddPCR. CONCLUSIONS: The ddPCR technique can be used for the detection of neonatal IFI and is a promising tool for the screening and even diagnosis of neonatal IFI.

An exploration of nucleic acid liquid biopsy using a glucose meter.

The development of non-invasive techniques for the diagnosis of cancer, characterization of mutation and monitoring treatment response could greatly reduce the morbidity and mortality caused by cancer. Nevertheless, the extremely low amount of cell free nucleic acids makes liquid biopsy a very challenging task. Herein, taking advantage of the pocket size, reliable quantitative results and simple operation of the pocket-sized personal glucose meter (PGM), we report an approach of circulating microRNA-21 (miR-21) detection with high precision and low cost. Via target-induced release of invertase from the DNA-invertase conjugate, which could convert sucrose into glucose, the detection of miR-21 in serum was linked to PGM readings. Combining the DNAzyme feedback amplification (DFA) program and highly efficient enzymatic turnover, an ultralow detection limit of 7 × 10-16 M for miR-21 was achieved using a PGM as the reporter. The high sensitivity and selectivity of the proposed method meets the requirement of quantifying cell free nucleic acids in serum. In addition, this approach fills the shortage of quantitative RT-PCR and next-generation sequencing in quantifying miRNAs with a short length and greatly reduces the cost of detection. We believe that widely used personal diagnosis devices could hold an important place in the booming area of liquid biopsy.

Abstraction and Idealization in Biomedicine: The Nonautonomous Theory of Acute Cell Injury.

Neuroprotection seeks to halt cell death after brain ischemia and has been shown to be possible in laboratory studies. However, neuroprotection has not been successfully translated into clinical practice, despite voluminous research and controlled clinical trials. We suggested these failures may be due, at least in part, to the lack of a general theory of cell injury to guide research into specific injuries. The nonlinear dynamical theory of acute cell injury was introduced to ameliorate this situation. Here we present a revised nonautonomous nonlinear theory of acute cell injury and show how to interpret its solutions in terms of acute biomedical injuries. The theory solutions demonstrate the complexity of possible outcomes following an idealized acute injury and indicate that a "one size fits all" therapy is unlikely to be successful. This conclusion is offset by the fact that the theory can (1) determine if a cell has the possibility to survive given a specific acute injury, and (2) calculate the degree of therapy needed to cause survival. To appreciate these conclusions, it is necessary to idealize and abstract complex physical systems to identify the fundamental mechanism governing the injury dynamics. The path of abstraction and idealization in biomedical research opens the possibility for medical treatments that may achieve engineering levels of precision.

Effect of bone marrow mesenchymal stem cells on the polarization of macrophages.

Inflammation is a defensive response in the living tissue of the vascular system that acts against damage factors and involves various types of immune cells, including macrophages, neutrophils, endothelial cells and other associated immune molecules. If the release of inflammatory mediators is excessive, systemic inflammatory response syndrome may develop. Sepsis is the most common complication of severe burns and is a systemic inflammatory response syndrome that is caused by infectious factors and is capable of leading to multiple organ dysfunction and potentially death. Research concerning the mechanism and treatment of sepsis is crucial. Macrophages are an important type of immune cell that remove invasive pathogens and are involved in innate and adaptive immune responses. It has been previously reported that bone marrow mesenchymal stem cells (BMSCs) affect macrophages by regulating immunity. The present study aimed to investigate the effect of BMSCs on macrophage polarization in vivo and in vitro, in addition to the potential therapeutic effect of these cells on experimental sepsis. BMSCs and peritoneal macrophages were isolated from Sprague­Dawley rats and co­cultured overnight as a mixed culture or Transwell system, and subsequently stimulated with 100 ng/ml lipopolysaccharide (LPS). After 12 h, the medium was replaced with normal complete medium for various durations and supernatants were collected to extract proteins and cells for ELISA, western blot and flow cytometry analysis to investigate different aspects of macrophages. Sepsis was induced in Sprague­Dawley rats by injection of LPS (5 mg/kg), followed by tail vein injection of BMSCs or PBS 1 h later. After 6, 12, 24 and 48 h, lung tissues were harvested for pathological observation and peritoneal macrophages were collected for flow cytometry analysis to assess the expression of markers, including cluster of differentiation (CD)68 (used for gating), CD11c and CD206. The results demonstrated that, in the culture medium, LPS stimulation increased the expression of CD11c in macrophages, and the levels of tumor necrosis factor­α and inducible nitric oxide synthase were also increased. By contrast, in macrophages treated with BMSCs directly, the expression of CD11c was reduced compared with the LPS­stimulated macrophage alone group. However, the secretion of interleukin­10, transforming growth factor­ß and arginase­1 was increased in the direct co­culture group, compared with the LPS­stimulated macrophage alone group. BMSCs reduced the inflammation in lung tissues and inhibited macrophage expression of CD11c in the rat model of sepsis. The results of the present study demonstrated that BMSCs co­cultured with macrophages directly inhibited macrophage differentiation into the M1 phenotype and reduced inflammation in macrophages stimulated by LPS. In vivo, BMSCs decreased the expression of CD11c in peritoneal macrophages and reduced the pathological inflammatory response in the lungs. The findings of the present study demonstrated that BMSCs may reduce the extent of the systemic inflammatory response, which may contribute to the development for a novel type of treatment for sepsis in the future.

Grain Boundary Structures and Collective Dynamics of Inversion Domains in Binary Two-Dimensional Materials.

Understanding and controlling the properties and dynamics of topological defects is a lasting challenge in the study of two-dimensional materials, and is crucial to achieve high-quality films required for technological applications. Here grain boundary structures, energies, and dynamics of binary two-dimensional materials are investigated through the development of a phase field crystal model that is parametrized to match the ordering, symmetry, energy, and length scales of hexagonal boron nitride. Our studies reveal some new dislocation core structures for various symmetrically and asymmetrically tilted grain boundaries, in addition to those obtained in previous experiments and first-principles calculations. We also identify a defect-mediated growth dynamics for inversion domains governed by the collective atomic migration and defect core transformation at grain boundaries and junctions, a process that is related to inversion symmetry breaking in binary lattice.