Search

Ochratoxin A (OTA) is a common fungal toxin frequently detected in food and human plasma samples. Currently, the physiologically based toxicokinetic (PBTK) model plays an active role in dose translation and can improve and enhance the risk assessment of toxins. In this study, the PBTK model of OTA in rats and humans was established based on knowledge of OTA-specific absorption, distribution, metabolism, and excretion (ADME) in order to better explain the disposition of OTA in humans and the discrepancies with other species. The models were calibrated and optimized using the available kinetic and toxicokinetic (TK) data, and independent test datasets were used for model evaluation. Subsequently, sensitivity analyses and population simulations were performed to characterize the extent to which variations in physiological and specific chemical parameters affected the model output. Finally, the constructed models were used for dose extrapolation of OTA, including the rat-to-human dose adjustment factor (DAF) and the human exposure conversion factor (ECF). The results showed that the unbound fraction (Fup) of OTA in plasma of rat and human was 0.02–0.04% and 0.13–4.21%, respectively. In vitro experiments, the maximum enzyme velocity (Vmax) and Michaelis–Menten constant (Km) of OTA in rat and human liver microsomes were 3.86 and 78.17 μg/g min−1, 0.46 and 4.108 μg/mL, respectively. The predicted results of the model were in good agreement with the observed data, and the models in rats and humans were verified. The PBTK model derived a DAF of 0.1081 between rats and humans, whereas the ECF was 2.03. The established PBTK model can be used to estimate short- or long-term OTA exposure levels in rats and humans, with the capacity for dose translation of OTA to provide the underlying data for risk assessment of OTA.

Abstract Background Vacuum sealing drainage (VSD) is widely applied in complex wound repair. We aimed to compare traditional debridement and drainage and VSD in treating Fournier’s gangrene (FG). Methods Data of patients surgically treated for FG were retrospectively analyzed. Results Of the 36 patients (men: 31, women: 5; mean age: 53.5 ± 11.3 [range: 28–74] years) included in the study, no patients died. Between-group differences regarding sex, age, BMI, time from first debridement to wound healing, number of debridements, FGSI, and shock were not statistically significant (P > 0.05). However, lesion diameter, colostomy, VAS score, dressing changes, analgesic use, length of hospital stay, and wound reconstruction method (χ2 = 5.43, P = 0.04) exhibited statistically significant differences. Tension-relieving sutures (6 vs. 21) and flap transfer (4 vs. 2) were applied in Groups I and II, respectively. Conclusion VSD can reduce postoperative dressing changes and analgesic use, and shrunk the wound area, thereby reducing flap transfer in wound reconstruction.

Introduction:Ginkgo biloba L. leaf extract (GBLE) has been reported to be effective for alleviating cognitive and memory impairment in Alzheimer’s disease (AD). Nevertheless, the potential mechanism remains unclear. Herein, this study aimed to explore the neuroprotective effects of GBLE on AD and elaborate the underlying therapeutic mechanism.Methods: Donepezil, the most widely prescribed drug for AD, was used as a positive control. An integrated metabolomics and lipidomics approach was adopted to characterize plasma metabolic phenotype of APP/PS1 double transgenic mice and describe the metabolomic and lipidomic fingerprint changes after GBLE intervention. The Morris water maze test and immunohistochemistry were applied to evaluate the efficacy of GBLE.Results: As a result, administration of GBLE significantly improved the cognitive function and alleviated amyloid beta (Aβ) deposition in APP/PS1 mice, showing similar effects to donepezil. Significant alterations were observed in metabolic signatures of APP/PS1 mice compared with wild type (WT) mice by metabolomic analysis. A total of 60 markedly altered differential metabolites were identified, including 28 lipid and lipid-like molecules, 13 organic acids and derivatives, 11 organic nitrogen compounds, and 8 other compounds, indicative of significant changes in lipid metabolism of AD. Further lipidomic profiling showed that the differential expressed lipid metabolites between APP/PS1 and WT mice mainly consisted of phosphatidylcholines, lysophosphatidylcholines, triglycerides, and ceramides. Taking together all the data, the plasma metabolic signature of APP/PS1 mice was primarily characterized by disrupted sphingolipid metabolism, glycerophospholipid metabolism, glycerolipid metabolism, and amino acid metabolism. Most of the disordered metabolites were ameliorated after GBLE treatment, 19 metabolites and 24 lipids of which were significantly reversely regulated (adjusted-p

We present a tunable spin Hall effect of light (SHEL) by introducing a monolayer of graphene on the hexagonal boron nitride (hBN). The interaction between the phonon polaritons in hBN and the plasmon polaritons in graphene can significantly enhance the SHEL around epsilon-near-zero (ENZ) near reststrahlen band-I (RB-I) in a very wide range of incident angles and compress it obviously in reststrahlen band-II (RB-II). The spin shifts can be obtained by adjusting the ratio of reflective coefficient and the phase difference for s- and p-waves which can be easily manipulated by the chemical potential. The effect of the tilted angle, thickness of hBN and incident angle on the SHEL is also discussed. These findings may lead to the potential applications for the nano-optical device based on the spin optics and the control of photons.

miRNA-15a(miR-15a)is a non-coding small molecule RNA located on 13q14 gene. It affects the growth, development, differentiation and apoptosis of all organs and cells of the whole body. As the study progressively deepened, it was found that the role of miR-15a in different tissues and cells was not entirely consistent. Sometimes it plays a role in suppressing cancer, and sometimes it promotes cancer. The signal pathways it affects are complex and diverse. With the deepening of biological research into cell signaling pathways, miRNA-15a has become a miRNA more extensively studied. But in the ophthalmology, the corresponding research is not much. In this article, we mainly focus on the mechanism of miR-15a and its current research situation in ophthalmic diseases, so as to provide a reference for further study and their treatment.

As an emerging sequencing technology, single-cell RNA sequencing (scRNA-Seq) has become a powerful tool for describing cell subpopulation classification and cell heterogeneity by achieving high-throughput and multidimensional analysis of individual cells and circumventing the shortcomings of traditional sequencing for detecting the average transcript level of cell populations. It has been applied to life science and medicine research fields such as tracking dynamic cell differentiation, revealing sensitive effector cells, and key molecular events of diseases. This review focuses on the recent technological innovations in scRNA-Seq, highlighting the latest research results with scRNA-Seq as the core technology in frontier research areas such as embryology, histology, oncology, and immunology. In addition, this review outlines the prospects for its innovative application in traditional Chinese medicine (TCM) research and discusses the key issues currently being addressed by scRNA-Seq and its great potential for exploring disease diagnostic targets and uncovering drug therapeutic targets in combination with multiomics technologies.

Bile acids has gradually become a new focus in various diseases, and ASBT as a transporter responsible for the reabsorption of ileal bile acids, is a key hinge associated to the bile acids-cholesterol balance and bile acids of enterohepatic circulation. The cumulative studies have also shown that ASBT is a promising target for treatment of liver, gallbladder, intestinal and metabolic diseases. This article briefly reviewed the process of bile acids enterohepatic circulation, as well as the regulations of ASBT expression, covering transcription factors, nuclear receptors and gut microbiota. In addition, the relationship between ASBT and various diseases were discussed in this paper. According to the structural classification of ASBT inhibitors, the research status of ASBT inhibitors and potential ASBT inhibitors of traditional Chinese medicine (such resveratrol, jatrorrhizine in Coptis chinensis) were summarized. This review provides a basis for the development of ASBT inhibitors and the treatment strategy of related diseases.

The construction of zero correlation zone (ZCZ) Gaussian integer sequence set was researched.Based on binary orthogonal matrices,ZCZ ternary sequence sets were constructed by adding zeros at first.Then the ternary ZCZ squences were transformed into Gaussian integer sequences by using a perfect Gaussian integer sequence without changing the ideal autocorrelation functions and crosscorrelation functions in the zero correlation zone.The proposed ZCZ Gaussian integer sequence sets are optimal or almost optimal with respect to the Tang-Fan-Matsufuji bound.

Based on orthogonal matrices,a construction of zero-correlation zone (ZCZ) periodic complementary sequence sets are proposed.The resultant ZCZ periodic complementary sets have flexible number of subsequences.Moreover,the ZCZ periodic complementary sequence sets are optimal.ZCZ periodic complementary sequence sets with flexible subsequences are more useful in communication systems.

Objective To investigate the predictive effect of initial cranial CT on early hematoma enlargement in spontaneous intracerebral hemorrhage. Methods Three hundred patients with spontaneous intracerebral hemorrhage within 6 hours after onset were studied. Chi⁃square test and logistic regression analysis were used to detect the related factors which may indicate hematoma enlargement. Results Sixty⁃ one (20.33% ) patients presented hematoma enlargement on cranial CT. Single factor and multivariate regression analysis showed that the following factors were associated with early hematoma enlargement: early onset, uneven density hematoma, moderate and severe brain atrophy and hematoma located at the basal ganglia. Conclusion Early onset uneven density hematoma, moderate and severe brain atrophy, and hematoma at basal ganglia are the factors which may indicate early hematoma enlargement in patiens with spontaneous intracerebral hemorrhage. DOI：10.3969/j.issn.1672⁃6731.2012.03.022

PurposeTo explore whether tumor-associated lymphatic vessel density (LVD) could be a biomarker for the prognosis of patients with esophageal cancer after radical resection.MethodsA systematic literature search was performed through PubMed, EMBASE, Wanfang Data, and Cochrane Library from the inception of databases until March 19, 2024. The selected studies investigated overall survival (OS) and/or recurrence-free survival (RFS) of patients with esophageal cancer with different levels of LVD after radical resection. The OS and RFS data were pooled as hazard ratios (HR) and 95% confidential interval (CI). Furthermore, the standardized mean differences (SMDs) and 95% CI were aggregated to evaluate the correlation between LVD and clinicopathological features.ResultsA total of 10 retrospective studies of 1,201 patients were finally included for the meta-analysis. Patients with esophageal cancer with a high level of LVD exhibited worse OS (HR 1.65, 95% CI 1.18 to 2.31) and RFS (HR 1.57, 95% CI 1.09 to 2.26) than those with a low level of LVD. Subgroup analysis of different pathological subtypes revealed that patients with esophageal adenocarcinoma with a high level of LVD had significantly worse RFS (HR 2.84, 95% CI 1.61 to 5.02) than those with a low level of LVD; while patients with esophageal squamous cell carcinoma with a high level of LVD had similar OS (HR 1.52, 95% CI 0.93 to 2.47) and RFS (HR 1.03, 95% CI 0.72 to 1.48) to those with a low level of LVD. Furthermore, tumors with lymph node metastasis had significantly higher levels of LVD than those without lymph node metastasis (SMD = 1.11, 95% CI 0.54 to 1.67). Tumors at the stages III-IV had significantly higher levels of LVD than those at the stages I-II (SMD = 1.62, 95% CI 0.90 to 2.34).ConclusionA high level of LVD in tumor was associated with worse survival of patients with esophageal cancer after radical resection, especially in patients with esophageal adenocarcinoma. Tumor-associated LVD is a new parameter that should be measured in postoperative pathology for predicting the prognosis of patients with esophageal cancer.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42024553766.

Abstract Background A novel approach known as intraosseous regional administration (IORA) has emerged as a technique for delivering prophylactic antibiotics, and it results in higher tissue concentrations around the knee. It is hypothesized that IORA of cefazolin for antibiotic prophylaxis during total knee arthroplasty will result in sustained effective levels for a longer duration. The aim of the current study was to investigate temporal changes in peri-knee cefazolin blood concentrations after IORA of cefazolin. Methods Twelve rabbits were randomly divided into two groups, with six rabbits in each group. In control group a single intravenous bolus injection of cefazolin (10 mL, 100 mg) was administered into the marginal ear vein. In experimental groupexperimental group the same dose of cefazolin was injected into the left tibial marrow cavity after tourniquet inflation at the base of the left thigh. Blood samples were collected periodically at different timepoints, and cefazolin concentrations were determined. Results The intraosseous treatment resulted in significant differences in plasma cefazolin concentrations at all timepoints. Experimental group exhibited higher plasma cefazolin concentrations than control group. Conclusions Cefazolin in intraosseous regional prophylaxis exhibits effectiveness in intraoperative antibiotic prophylaxis by maintaining concentrations above the minimum inhibitory concentration for extended durations, rather than relying solely on high concentrations.

Abstract The material realization of charge-4e/6e superconductivity (SC) is a big challenge. Here, we propose to realize charge-4e SC in maximally-twisted homobilayers, such as 45∘-twisted bilayer cuprates and 30∘-twisted bilayer graphene, referred to as twist-bilayer quasicrystals (TB-QC). When each monolayer hosts a pairing state with the largest pairing angular momentum, previous studies have found that the second-order interlayer Josephson coupling would drive chiral topological SC (TSC) in the TB-QC. Here we propose that, above the T c of the chiral TSC, either charge-4e SC or chiral metal can arise as vestigial phases, depending on the ordering of the total- and relative-pairing-phase fields of the two layers. Based on a thorough symmetry analysis to get the low-energy effective Hamiltonian, we conduct a combined renormalization-group and Monte-Carlo study and obtain the phase diagram, which includes the charge-4e SC and chiral metal phases.

Background Robotic‐assisted technology may be useful in hip revision cases with acetabular defects. However, data on the use of robotic‐assisted technology for such complex diseases is lacking. Case Presentation This case study described the adoption of MAKO robotic‐assisted treatment of revision total hip arthroplasty (THA) combined with severe acetabular defect (Paprosky type IIIB). Robotic‐assisted technology accurately achieved preoperative planning; the acetabular component and augment were placed in the original position and angle as planned. Robotic‐assisted acetabular reaming was successful in a single pass, preserving the remaining acetabular bone mass very well with no procedure‐related complications. The Harris Hip Score (HHS) at 6 months postoperatively was 84 and the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index was 24. Conclusion Robotic‐assisted technology can help in the accurate reconstruction of acetabular defect in complex hip revision surgery.

Abstract Background The black soldier fly (Hermetia illucens) has significant economic potential. The larvae can be used in financially viable waste management systems, as they are voracious feeders able to efficiently convert low-quality waste into valuable biomass. However, most studies on H. illucens in recent decades have focused on optimizing their breeding and bioconversion conditions, while information on their biology is limited. Methods About 200 fifth instar well-fed larvae were sacrificed in this work. The liquid chromatography-tandem mass spectrometry and scanning electron microscopy were employed in this study to perform a proteomic and ultrastructural analysis of the peritrophic matrix (PM) of H. illucens larvae. Results A total of 565 proteins were identified in the PM samples of H. illucen, of which 177 proteins were predicted to contain signal peptides, bioinformatics analysis and manual curation determined 88 proteins may be associated with the PM, with functions in digestion, immunity, PM modulation, and others. The ultrastructure of the H. illucens larval PM observed by scanning electron microscopy shows a unique diamond-shaped chitin grid texture. Conclusions It is the first and most comprehensive proteomics research about the PM of H. illucens larvae to date. All the proteins identified in this work has been discussed in details, except several unnamed or uncharacterized proteins, which should not be ignored and need further study. A comparison of the ultrastructure between H. illucens larval PM and those of other insects as observed by SEM indicates that the PM displays diverse textures on an ultra-micro scale and we suscept a unique diamond-shaped chitin grid texture may help H. illucens larval to hold more food. This work deepens our understanding of the molecular architecture and ultrastructure of the H. illucens larval PM.

Primary dysmenorrhea is a common gynecological disease garnering increasing attention and research. To investigate the clinical therapeutic effects of Jingqian Zhitong Fang (JQF) and the differences in serumsex hormone levels during the treatment of primary dysmenorrhea, we selected 30 healthy volunteers and 60 individuals with primary dysmenorrhea.On the third day of themenstrual cycle, we used ELISA to determine the levels of serum prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TEST), progesterone (PROG), and estradiol (E2) compared with normal levels and levels in the JQF group, the Western medicine group receiving continuous treatment during the first and third menstrual cycles, and the group followed up after the drug was stopped. We observed that after JQF treatment, the levels of the following hormones changed significantly: PRL, LH, TEST, and E2 levels decreased significantly and the PROG level increased significantly after treatment. After treatment with Western medicine, the serum levels of FSH, LH, PROG, and E2 showed no significant change. We conclude that the long-term effect of JQF treatment was better than that of Western medicine. JQF treatment of primary dysmenorrhea is related to adjustment of PRL, LH, TEST, and E2 hormone levels in the human body. [ABSTRACT FROM AUTHOR]

Abstract Background This prospective study is to evaluate the potential value of sonographic measurements in the flaccid penis for the screening of arteriogenic impotence. Methods A consecutive series of 260 Chinese males consulting for sexual dysfunction and 54 controls underwent sonographic examination. The sonographic parameters were correlated with the clinical gold standards, including the international index of erectile function (IIEF) and penile erectile hardness grading scale (EHGS). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUROC) of flaccid peak systolic velocity (PSV) in predicting patients with normal function were analyzed. Results The mean cavernous PSV of both sides in the patients with sexual dysfunction ranged from 7.76 to 11.12 cm/sec with a stepwise increase in IIEF and EHGS grading scale (P

In insects, trehalose accumulation is associated with the insulin/insulin-like growth factor signalling (IIS) pathway. However, whether insulin-like peptide is involved in the regulation of the trehalose metabolism during diapause termination remains largely unknown. This study assessed whether insulin-like peptide (ApILP) enhances the trehalose catabolism in the pupae of Antheraeapernyi during their diapause termination process. Injection of 10 μg of bovine insulin triggered diapause termination and synchronous adult eclosion in diapausing pupae. Moreover, treatment with bovine insulin increased the expression of trehalase 1A (ApTre-1A) and trehalase 2 (ApTre-2), as well as the activity of soluble and membrane-bound trehalase, resulting in a decline in trehalose levels in the haemolymph. Silencing ApILP via RNA interference significantly suppressed the expression of ApTre-1A and ApTre-2, thus leading to an increase in the trehalose concentration during diapause termination. However, neither injection with bovine insulin nor ApILP knockdown directly affected trehalase 1B (ApTre-1B) expression. Moreover, overexpression of the transcription factor forkhead box O (ApFoxO) induced an increase in trehalose levels during diapause termination; however, depletion of ApFoxO accelerated the breakdown of trehalose in diapausing pupae by increasing the expression of ApTre-1A and ApTre-2. The results of this study help to understand the contributions of ApILP and ApFoxO to the trehalose metabolism during diapause termination.