Overexpression of LAG-3: a potential indicator of low immune function in tuberculosis.

Background: Tuberculosis (TB) persists as a global health challenge, with its treatment hampered by the side effects of long-term combination drug therapies and the growing issue of drug resistance. Therefore, the development of novel therapeutic strategies is critical. This study focuses on the role of immune checkpoint molecules (ICs) and functions of CD8+ T cells in the search for new potential targets against TB. Methods: We conducted differential expression genes analysis and CD8+ T cell functional gene analysis on 92 TB samples and 61 healthy individual (HI) samples from TB database GSE83456, which contains data on 34,603 genes. The GSE54992 dataset was used to validated the findings. Additionally, a cluster analysis on single-cell data from primates infected with mycobacterium tuberculosis and those vaccinated with BCG was performed. Results: The overexpression of LAG-3 gene was found as a potentially important characteristic of both pulmonary TB (PTB) and extrapulmonary TB (EPTB). Further correlation analysis showed that LAG-3 gene was correlated with GZMB, perforin, IL-2 and IL-12. A significant temporal and spatial variation in LAG-3 expression was observed in T cells and macrophages during TB infection and after BCG vaccination. Conclusion: LAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis.

ImTooth: Neural Implicit Tooth for Dental Augmented Reality.

The combination of augmented reality (AR) and medicine is an important trend in current research. The powerful display and interaction capabilities of the AR system can assist doctors to perform more complex operations. Since the tooth itself is an exposed rigid body structure, dental AR is a relatively hot research direction with application potential. However, none of the existing dental AR solutions are designed for wearable AR devices such as AR glasses. At the same time, these methods rely on high-precision scanning equipment or auxiliary positioning markers, which greatly increases the operational complexity and cost of clinical AR. In this work, we propose a simple and accurate neural-implicit model-driven dental AR system, named ImTooth, and adapted for AR glasses. Based on the modeling capabilities and differentiable optimization properties of state-of-the-art neural implicit representations, our system fuses reconstruction and registration in a single network, greatly simplifying the existing dental AR solutions and enabling reconstruction, registration, and interaction. Specifically, our method learns a scale-preserving voxel-based neural implicit model from multi-view images captured from a textureless plaster model of the tooth. Apart from color and surface, we also learn the consistent edge feature inside our representation. By leveraging the depth and edge information, our system can register the model to real images without additional training. In practice, our system uses a single Microsoft HoloLens 2 as the only sensor and display device. Experiments show that our method can reconstruct high-precision models and accomplish accurate registration. It is also robust to weak, repeating and inconsistent textures. We also show that our system can be easily integrated into dental diagnostic and therapeutic procedures, such as bracket placement guidance.

Induction of Ferroptosis in Glioblastoma and Ovarian Cancers by a New Pyrrole Tubulin Assembly Inhibitor.

We synthesized new aroyl diheterocyclic pyrrole (ARDHEP) 15 that exhibited the hallmarks of ferroptosis. Compound 15 strongly inhibited U-87 MG, OVCAR-3, and MCF-7 cancer cells, induced an increase of cleaved PARP, but was not toxic for normal human primary T lymphocytes at 0.1 µM. Analysis of the levels of lactoperoxidase, malondialdehyde, lactic acid, total glutathione, and ATP suggested that the in vivo inhibition of cancer cell proliferation by 15 went through stimulation of oxidative stress injury and Fe2+ accumulation. Quantitative polymerase chain reaction analysis of the mRNA expression in U-87 MG and SKOV-3 tumor tissues from 15-treated mice showed the presence of Ptgs2/Nfe2l2/Sat1/Akr1c1/Gpx4 genes correlated with ferroptosis in both groups. Immunofluorescence staining revealed significantly lower expressions of proteins Ki67, CD31, and ferroptosis negative regulation proteins glutathione peroxidase 4 (GPX4) and FTH1. Compound 15 was found to be metabolically stable when incubated with human liver microsomes.

Case report: Meningoencephalocele and recurrent bacterial meningitis in chronic idiopathic intracranial hypertension.

BACKGROUND: Meningoencephalocele is a rare malformation caused by congenital and acquired lesions. The association between recurrent bacterial meningitis and meningoencephaloceles with cerebrospinal fluid (CSF) leak is reported in the literature. We report a rare case of meningoencephalocele secondary to chronic idiopathic intracranial hypertension as a result of hospitalization repeatedly for meningitis due to the lack of CSF leak. CASE PRESENTATION: This study presents a case of a patient with a decade of recurrent meningitis. With clinical symptoms and imaging examination with chronic idiopathic intracranial hypertension, this patient was diagnosed with meningoencephalocele. With the treatment of acetazolamide to decrease CSF product, the patient had no recurrence of meningitis over the 6-months follow-up period. CONCLUSION: In patients with recurrent intracranial infections but no history of immunodeficiency, cranial trauma, or neurosurgery, the possibility of meningitis should be considered appropriately, even in the absence of CSF otorrhea or rhinorrhea.

Preparation and application of chikungunya pseudovirus containing double reporter genes.

Chikungunya virus (CHIKV), a highly infectious and rapidly spread viral pathogen, is classified as a pathogenic agent at the biosafety level 3. Operation of live authentic CHIKV needs a specific laboratory with the P3 or above containment, which greatly confines the CHIKV-associated studies. To establish an evaluation system of CHIKV that can be utilized in a BSL2 laboratory, we constructed a pseudovirus (PsV) system of CHIKV containing double reporter genes (ZsGreen1 and luciferase). The fluorescent ZsGreen1 is a convenient and cheap reporter for monitoring the efficiency of transfection and titration of PsV. The enzyme luciferase is a sensitive reporter for the application of PsV to neutralization assay or drug screening. The CHIKV PsV produced in this study, with a titer of up to 3.16 × 106 TU/ml, was confirmed by Western blotting and transmission electronic microscopy (TEM). Finally, we developed a microneutralization assay with the CHIKV PsV produced in this study, which was successfully applied to evaluate neutralizing activities of convalescent sera from CHIKV-infected patients. In summary, we have established a convenient and sensitive double-reporter CHIKV pseudovirus system, which provides a safe and effective platform for screening anti-CHIKV drugs and evaluating vaccines against CHIKV.

RS-5645 attenuates inflammatory cytokine storm induced by SARS-CoV-2 spike protein and LPS by modulating pulmonary microbiota.

An inflammatory cytokine storm is considered an important cause of death in severely and critically ill COVID-19 patients, however, the relationship between the SARS-CoV-2 spike (S) protein and the host's inflammatory cytokine storm is not clear. Here, the qPCR results indicated that S protein induced a significantly elevated expression of multiple inflammatory factor mRNAs in peripheral blood mononuclear cells (PBMCs), whereas RS-5645 ((4-(thiophen-3-yl)-1-(p-tolyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone) attenuated the expression of the most inflammatory factor mRNAs. RS-5645 also significantly reduced the cellular ratios of CD45+/IFNγ+, CD3+/IFNγ+, CD11b+/IFNγ+, and CD56+/IFNγ+ in human PBMCs. In addition, RS-5645 effectively inhibited the activation of inflammatory cells and reduced inflammatory damage to lung tissue in mice. Sequencing results of 16S rRNA v3+v4 in mouse alveolar lavage fluid showed that there were 494 OTUs overlapping between the alveolar lavage fluid of mice that underwent S protein+ LPS-combined intervention (M) and RS-5645-treated mice (R), while R manifested 64 unique OTUs and M exhibited 610 unique OTUs. In the alveoli of group R mice, the relative abundances of microorganisms belonging to Porphyromonas, Rothia, Streptococcus, and Neisseria increased significantly, while the relative abundances of microorganisms belonging to Psychrobacter, Shimia, and Sporosarcina were significantly diminished. The results of KEGG analysis indicated that the alveolar microbiota of mice in the R group can increase translation and reduce the activity of amino acid metabolism pathways. COG analysis results indicated that the abundance of proteins involved in ribosomal structure and biogenesis related to metabolism was augmented in the alveolar microbiota of the mice in the R group, while the abundance of proteins involved in secondary metabolite biosynthesis was significantly reduced. Therefore, our research results showed that RS-5645 attenuated pulmonary inflammatory cell infiltration and the inflammatory storm induced by the S protein and LPS by modulating the pulmonary microbiota.

[Finite element analysis of the effect of plate placement angle on cervical spine stability in anterior cervical fusion surgery].

OBJECTIVE: Using the method of finite element analysis, to compare the biomechanical properties between the plate deviating from the long axis of the cervical spine and the standard placement of the plate in the anterior cervical fusion surgery. METHODS: A healthy female volunteer was selected and CT scan (C1-T1) was performed. Using Mimics 19.0, Geomagic Studio 2015, Solidworks 2018, Ansys Workbench 17.2 to establish a lower cervical spine (C3-C7) model and to verify the reliability of the model. Subsequently, anterior cervical plates of different angles and lengths were placed to establish an anterior cervical discectomy fusion (ACDF) model. Applying 73.6 N axial pressure and 1 NM pure moment on C3 to make the model produce flexion, extension, lateral bending and rotation activities, observed the model stress cloud diagram and recorded the maximum stress value of the instrument and the intervertebral mobility. RESULTS: The lower cervical spine (C3-C7) finite element model was established and verified against the published literature on the range of motion (ROM) of cervical spine. Effect of steel plate offset axis on stress distribution, maximum stress value and intervertebral ROM of internal fixation apparatus was minimal, and the mechanical effect of steel plate offset was less in double section steel plate than in single section steel plate. CONCLUSION: Little effect on the mechanical stability of the cervical spine was anticipated when the anterior cervical plate was not perfectly aligned with the long axis of the cervical spine. If the tilt of the plate in clinical surgery is less than 20°, there is no need to readjust the position of the plate.

Durable clinical benefit from pyrotinib combined with carboplatin in HER2-positive relapsed breast cancer previously treated with taxanes, anthracyclines, and trastuzumab.

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer inevitably progressed after a short response to initial trastuzumab treatment, suggesting a possibility of acquired-resistance to trastuzumab. Pyrotinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor (TKI), has been reported as an effective and safe drug for the treatment of HER2-positive relapsed or metastatic breast cancer. Pyrotinib combined with capecitabine is widely used to treat HER2-positive metastatic breast cancer in patients who have been previously treated with anthracyclines, taxanes, and trastuzumab. However, the efficacy of pyrotinib combined with other chemotherapy drugs is still unclear. Here we report pyrotinib combined with carboplatin in treating a patient with HER2-positive relapsed breast cancer who had acquired resistance to trastuzumab. The patient received three cycles of treatments of pyrotinib (400 mg, orally once per day, days 1-21) combined with carboplatin (600 mg, iv drip, day 1, cycled every 21 days). The patient showed an excellent response to the therapy, including faded rashes on the skin of her breast, no obvious signs of recurrence from the breast magnetic resonance imaging (MRI), decreased skin thickness and cord shadow of the right breast, unchanged degree of right pleural effusion, and no enlarged LN. The patient had a stable disease time of more than four months. Our case provides evidence for the feasibility and efficacy of pyrotinib with carboplatin in treating patients with HER2-positive relapsed or metastatic breast cancer who may develop resistance to trastuzumab.

[Research progress on minimally invasive treatment of anterior pelvic ring fracture].

OBJECTIVE: To summarize the related research results of minimally invasive treatment of anterior pelvic ring fracture, and to improve the understanding of minimally invasive treatment of anterior pelvic ring fracture. METHODS: The literature of minimally invasive treatment of anterior pelvic ring fracture at domestic and overseas in recent years was reviewed, and the reduction and fixation methods of minimally invasive treatment were summarized and analyzed. RESULTS: The pelvic reduction frame may be an effective auxiliary method for minimally invasive reduction of pelvis. The fixation methods of anterior pelvic ring include percutaneous screw fixation, stent fixation, and percutaneous plate fixation. CONCLUSION: One kind of fixation is not applicable to all types of anterior pelvic ring fracture, and the fixation method should be selected according to the type of fracture and the patient's condition to minimize the complications.

Protraction of mandibular molars through a severely atrophic edentulous space in a case of juvenile periodontitis.

Moving the mandibular posterior teeth into a severely atrophic edentulous space is a challenge. A carefully designed force-and-moment system that results in bodily protraction of the posterior teeth with balanced bone resorption and apposition is needed in such cases. This report describes the treatment of a 19-year-old woman with missing mandibular first molars due to juvenile periodontitis. Miniscrews were used as absolute anchorage during protraction of the mandibular second and third molars. Bodily mesial movement of the mandibular second and third molars was achieved over a distance of 11 to 17 mm after 39 months of orthodontic treatment.

[Progress of research on the relationship between calcitonin gene-related peptide and RANK/RANKL/OPG system in the bone reconstruction].

OBJECTIVE: To summarize the research progress on the calcitonin gene-related peptide (CGRP) and receptor activator of nuclear factor κB (RANK)/receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) system during bone reconstruction to provide theoretical basis for further research on the prevention and treatment of bone-related diseases. METHODS: The relevant research results at home and abroad in recent years were analyzed and summarized. RESULTS: CGRP and RANK/RANKL/OPG system play important regulatory roles in the bone reconstruction. CONCLUSION: At present, the research on the mechanism of CGRP and RANK/RANKL/OPG system in bone reconstruction is insufficient. Therefore, it is necessary to study further on the process and interrelation of CGRP and RANK/RANKL/OPG system in bone reconstruction to confirm their mechanism, which will bring new ideas and methods for the treatment of bone related diseases in clinic.

The synthesized transporter K16APoE enabled the therapeutic HAYED peptide to cross the blood-brain barrier and remove excess iron and radicals in the brain, thus easing Alzheimer's disease.

Alzheimer's disease (AD) is currently incurable and places a large burden on the caregivers of AD patients. In the AD brain, iron is abundant, catalyzing free radicals and impairing neurons. The blood-brain barrier hampers antidementia drug delivery via circulation to the brain, which limits the therapeutic effects of drugs. Here, according to the method described by Gobinda, we synthesized a 16 lysine (K) residue-linked low-density lipoprotein receptor-related protein (LRP)-binding amino acid segment of apolipoprotein E (K16APoE). By mixing this protein with our designed therapeutic peptide HAYED, we successfully transported HAYED into an AD model mouse brain, and the peptide scavenged excess iron and radicals and decreased the necrosis of neurons, thus easing AD.

[Research progress of lateral wall injury of intertrochanteric fracture].

Objective: To summarize the general concept of lateral wall, the causes of lateral wall injury, and surgical strategies in order to improve the understanding of lateral wall and reduce the complications of operation. Methods: The related literature on lateral wall was extensively reviewed, summarized, and analyzed. Results: The superior extent of the lateral wall is vastus lateralis ridge and the inferior extent is the intersection between the lateral femoral cortex and a line drawn at a tangent to the inferior femoral neck. The integrity of the lateral wall is important to prevent the failure of fixation and reoperation of intertrochanteric fractures. The main causes of injury are that there is no suitable typing criteria as a guide, the fracture pattern shown by X-ray does not match with the actual situation of the fracture, the type of fracture is special, and the operation is improper. The main treatment is to reconstruct the lateral wall and choose different reconstruction methods according to different fracture patterns. Conclusion: The lateral wall is very important for the treatment of intertrochanteric fracture. Lateral wall fracture should be internal fixation in order to minimize the risk of reoperation.

Electro-Mechanical Impedance (EMI) Based Interlayer Slide Detection Using Piezoceramic Smart Aggregates-A Feasibility Study.

Interlayer slide damage is one of the main causes of landslide hazard, inflicting huge economic losses and casualties. It is urgent to accurately detect the initiation and development of the interlayer slide damage in real time. In this paper, a study on the feasibility of using the electro-mechanical impedance (EMI) technique to detect the interlayer slide damage was presented. The main purpose of this paper is to investigate the application of the EMI technique for interlayer slide detection using piezoceramic smart aggregates (SAs). In the experimental study, three small landslide specimens with a weak interlayer in the middle were fabricated. For each specimen, three piezoceramic SAs were post-embedded at specific positions, which were located above the weak interlayer inside the structure. The specimens were subjected to a compressive test to initiate an interlayer slide along the weak layer. The whole loading process was monitored with a precision impedance analyzer by measuring the admittance (reciprocal of impedance) of the SAs over time. The statistic metrics, including root mean square deviation (RMSD) and mean absolute percentage deviation (MAPD), were introduced to quantify the variations in admittance signatures due to interlayer slide damage. It was found that the admittance signatures and statistic metrics were sensitive to the interlayer slide damage. The experimental results verify the feasibility and practicality of using EMI technique to detect the interlayer slide.

Amenability of coarse spaces and K -algebras.

In this article we analyze the notions of amenability and paradoxical decomposition from an algebraic perspective. We consider this dichotomy for locally finite extended metric spaces and for general algebras over fields. In the context of algebras we also study the relation of amenability with proper infiniteness. We apply our general analysis to two important classes of algebras: the unital Leavitt path algebras and the translation algebras on locally finite extended metric spaces. In particular, we show that the amenability of a metric space is equivalent to the algebraic amenability of the corresponding translation algebra.

[A pilot study on the accuracy of digital model reconstructed by cone beam CT].

PURPOSE: To study the feasibility of digital model produced by cone beam CT. METHODS: Ten patients seeking orthodontic treatment with congested lower incisors were enrolled in this study. Plaster models of the lower arch were made using routing method. Digital model was reconstructed from these plaster models by NewTom 3G cone beam CT with 6 inch model. Linear measurements including right first premolar width, arch width, arch length, right first incisor width, all incisors and canines width, were done on the lower arch on plaster models with calipers. The same measurements on digital model were made using software Simplant Pro11.04. Linear measurements were repeated one week later on both plaster and digital model. Paired t test was used to determine the difference between the linear measurements on both models. The absolute measurements errors of two models were compared using paired t test. All statistical analysis was performed using SPSS13.0 software package. RESULTS: The linear measurements of the digital model slightly underestimated the real plaster model, but no significant difference of the linear measurements was seen between the plaster model and the digital model. The value of all of the lower incisors and canines width of plaster models was significantly higher than that of digital model. Mean absolute difference of different measurement of digital model was not significant from that of plaster model. CONCLUSION: Digital model using CBCT is feasible for the linear measurement and storage.

Trinuclear and mononuclear copper(II) complexes incorporating tetradentate 2,2'-[1,1'-(ethylenedioxydinitrilo)diethylidyne]diphenol ligand: Syntheses, crystal structures, spectral and thermal behaviors.

Mononuclear and trinuclear Cu(II) complexes with chemical formula [CuL].CH3OH (1) and [{(Cu(mu-L))2(OAc)2}Cu] (2), where H2L = 2,2'-[1,1'-(ethylenedioxydinitrilo)diethylidyne]diphenol, have been synthesized and characterized by elemental analyses, 1H NMR, IR and UV-vis spectra et al. Crystallographic data of complex 1 reveal the formation of an asymmetric mononuclear structure and a slight distortion toward tetrahedral geometry from the square planar structure, in which the introduction of the non-coordinated methanol molecule lead to the assembly of the 1D chains by hydrogen bonding, Cu...pi and pi...pi interactions. Complex 2 have the elongated square pyramidal geometries for the two terminal Cu(II) ions and an octahedral coordinated geometry for the central Cu(II) ion. In complex 2, two acetate ions coordinate to three Cu(II) ions adopting a familiar syn-syn (muM-O-C-O-M) coordinated fashion. The central Cu(II) ion sits in a crystallographic inversion centre. Therefore, the whole molecule of complex 2 is rigorously centrosymmetric, and forms a 3D supramolecular networks through intermolecular C-H...O and C-H..pi interactions.

4-Bromo-2-({4-[(hy-droxy-imino)-meth-yl]phen-yl}imino-meth-yl)phenol.

In the title compound, C(14)H(11)BrN(2)O(2), the mean planes of the two benzene rings are almost parallel to each other, making a dihedral angle of 4.09 (1)°. An intra-molecular O-H⋯N hydrogen bond occurs. In the crystal, inter-molecular O-H⋯N and C-H⋯O hydrogen bonds link the mol-ecules into a chain-like supra-molecular structure.

Bis{(E)-2-[(2-chloro-3-pyrid-yl)imino-meth-yl]-6-meth-oxy-phenolato-κN,O}copper(II).

In the title mononuclear copper(II) complex, [Cu(C(13)H(10)ClN(2)O(2))(2)], the Cu(II) ion, lying on an inversion center, is four-coordinated in a trans-CuN(2)O(2) square-planar geometry by two phenolate O and two imino N atoms from two symmetry-related N,O-bidentate Schiff base ligands. The shortest Cu⋯Cu distance is 7.5743 (9) Å. However, there are weak intra-molecular electrostatic inter-actions between the Cu atom and the Cl atom of the ligand, with a Cu⋯Cl distance of 3.3845 (9) Å.