Umbilical cord blood-derived neutrophils possess higher viability than peripheral blood derived neutrophils.

Neutrophils, a primary type of immune cell, play critical roles in numerous biological processes. Both umbilical cord blood (UCB) and peripheral blood are rich in neutrophils. UCB is more abundant than peripheral blood, with cells generally at a more immature stage. However, comparative data between these two cell sources is lacking. This study aims to elucidate differences between UCB-derived neutrophils (UCBN) and peripheral blood-derived neutrophils (PBN). UCBN and PBN were isolated from fresh human umbilical cord blood and peripheral blood, respectively. Transcriptomic profiling was performed and compared against neutrophil RNA from three different donors. Bioinformatics analysis was employed to compare cell phenotypes. A cytokine cocktail (IFN-ß, IFN-γ, and LPS) was used to activate UCBN and PBN in vitro. A united multi-omic approach, combining transcriptomic and proteomic analysis, was followed by experimental validation through flow cytometry, cell killing assays, and proteome profiler array to verify cell functions. Transcriptomic analysis revealed that the most upregulated genes in freshly isolated umbilical cord blood neutrophils (UCBN) compared to peripheral blood neutrophils (PBN) predominantly involve neutrophil activation and cell-killing functions. Validation through flow cytometry and cell-killing experiments demonstrated that highly viable UCBN exhibited significantly stronger ovarian tumor cell-killing activity in vitro compared to PBN. Both transcriptomic and proteomic analyses indicated that the primary upregulated genes in activated UCBN are chiefly involved in biological processes related to the regulation of cytokine secretion. Integrative multi-omic analysis, including a proteome profiler array, confirmed that UCBN indeed secrete elevated levels of cytokines. In conclusion: UCBN shows higher viability and cellular activity compared with PBN, particularly in tumor cell-killing and cytokine secretion.

In Silico Study on a Binding Mechanism of ssDNA Aptamers Targeting Glycosidic Bond-Containing Small Molecules.

Aptamer-based detection targeting glycoconjugates has attracted significant attention for its remarkable potential in identifying structural changes in saccharides in different stages of various diseases. However, the challenges in screening aptamers for small carbohydrates or glycoconjugates, which contain highly flexible and diverse glycosidic bonds, have hindered their application and commercialization. In this study, we investigated the binding conformations between three glycosidic bond-containing small molecules (GlySMs; glucose, N-acetylneuraminic acid, and neomycin) and their corresponding aptamers in silico, and analyzed factors contributing to their binding affinities. Based on the findings, a novel binding mechanism was proposed, highlighting the central role of the stem structure of the aptamer in binding and recognizing GlySMs and the auxiliary role of the mismatched bases in the adjacent loop. Guided by this binding mechanism, an aptamer with a higher 6'-sialyllactose binding affinity was designed, achieving a KD value of 4.54 ± 0.64 µM in vitro through a single shear and one mutation. The binding mechanism offers crucial guidance for designing high-affinity aptamers, enhancing the virtual screening efficiency for GlySMs. This streamlined workflow filters out ineffective binding sites, accelerating aptamer development and providing novel insights into glycan-nucleic acid interactions.

The mechanism of action and experimental verification of Gan-song Yin on renal clear cell carcinoma based on network pharmacology and bioinformatics.

BACKGROUND: Gan-song Yin (GSY) is originated from the scripture "Gan-song Pills", a medical work of the Ningxia ethnic minorities, and its treatment of kidney diseases has good results. Its method of treating Renal clear cell carcinoma (KIRC) is still unknown, nevertheless. METHODS: Firstly, utilizing a network pharmacology strategy to screen GSY for active components and targets and looking up KIRC-related targets in GeneCards and GEO databases. Secondly, protein interaction networks were constructed and analyzed for GO and KEGG enrichment. Molecular docking was then performed and clinical and other correlations of the network pharmacology results were analyzed using bioinformatic analysis methods. Finally, we performed in vitro cellular experiments with 786-O cells and ACHN cells to validate the results of network pharmacology and bioinformatic analysis. RESULTS: With the help of network pharmacological analysis, six hub targets were eliminated. Bioinformatics study revealed that the hub targets has clinically significant clinical guiding importance. The results showed that GSY inhibited the proliferation of 786-O cells and ACHN cells, induced cell apoptosis, blocked cell cycle, and reduced cell colony formation ability. qRT-PCR results showed that GSY promoted the expression of ALB and CASP3 genes, and inhibited the expression of EGFR, JUN, MYC and VEGFA genes. Western blot results showed that GSY could promote the expression of ALB and CASP3 protein, and inhibit the expression of EGFR, JUN, MYC and VEGFA protein. CONCLUSIONS: Network pharmacology and bioinformatics analysis showed that GSY could act on multiple targets through a variety of components to achieve the effect of treating KIRC. In this study, we confirmed that GSY inhibits KIRC by regulating the expression of core targets through in vitro cellular experiments, thus providing a reference for subsequent related studies.

Rhegmatogenous retinal detachment in highly myopic eyes with implantable collamer lens.

AIM: To investigate the clinical characteristics, treatment methods and outcomes of rhegmatogenous retinal detachment (RRD) in highly myopic eyes with implantable collamer lens (ICL). METHODS: High myopia patients who received treatment for nontraumatic RRD after ICL implantation surgery at the Retinal Department of Zhongshan Ophthalmic Center from Jan 2018 to Dec 2022 were reviewed. Comprehensive ophthalmologic examinations including visual acuity measurement and digital fundus photography were performed in each patient. RESULTS: A total of nine RRD eyes from nine patients who received V4c-ICL implantation were included. The mean time from ICL implantation surgery to the diagnosis of RRD was 32.44±22.56mo (range, 1-60mo). At the initial visit for RRD, giant retinal tear (GRT), horseshoe tear, simple round hole, and horseshoe tear combined with round hole were detected in 3, 3, 2, and 1 eye(s), respectively, with macula-off in eyes. Eight patients received surgical treatment, and one patient was treated by retinal laser photocoagulation alone. The ICL was preserved in 7 eyes. At the last follow-up, the mean best corrected visual acuity (BCVA) improved significantly from 1.76±1.06 logMAR at presentation to 0.81±1.01 logMAR (P=0.035), and no case of recurrent retinal detachment was found. CONCLUSION: The morphological presentation of retinal breaks is diverse in this study. The ICL can be preserved in most cases during the course of retinal detachment repair surgery in our data, companied with acceptable visual and anatomical outcomes.

Structurally manipulated antioxidant peptides derived from wheat bran: Preparation and identification.

Bioactive peptide's development is facing two challenges in terms of its lower yield and limited understanding of structurally orientated functionality. Therefore, peptides were prepared from wheat bran via a cocktail enzyme for achieving a higher level of hydrophobic amino acids than traditional method. The obtained peptides exhibited great antioxidant activities against H2O2-induced oxidative stress in HepG2 cells. Among them, 91 bioactive peptides were selected through the virtual screening, and their N-terminal and C-terminal contained many hydrophobic amino acids. Then the peptides with capacity to interact with Keap1 were identified by in silico simulation, because Keap1 acts as a sensor of redox insults. The results revealed that peptides DLDW and DLGL demonstrated the highest binding affinities, and a bridge was formed between Asp of DLGL and Arg415 of Klech domain, contributing to interfering Keap1-Nrf2 interaction. These findings implied a potential application of wheat bran peptides as nutraceuticals and health-promoting ingredients.

The Plastic Deformation Mechanism in Nano-Polycrystalline Al/Mg Layered Composites: A Molecular Dynamics Study.

Understanding plastic deformation behaviour is key to optimising the mechanical properties of nano-polycrystalline layered composites. This study employs the molecular dynamics (MD) simulation to comprehensively investigate the effects of various factors, such as grain sizes, strain rates, and the interlayer thicknesses of the intermetallic compounds (IMCs), on the plastic deformation behaviour of nano-polycrystalline Al/Mg layered composites. Our findings reveal that the influence of grain size on deformation behaviour is governed by the strain rate, and an increase in grain size is inversely proportional to yield stress at low strain rates, whereas it is positively proportional to tensile stress at high strain rates. Moreover, an optimal thickness of the intermediate layer contributes to enhanced composite strength, whereas an excessive thickness leads to reduced tensile strength due to the fewer grain boundaries (GBs) available for accommodating dislocations. The reinforcing impact of the intermediate IMCs layer diminishes at excessive strain rates, as the grains struggle to accommodate substantial large strains within a limited timeframe encountered at high strain rates. The insights into grain sizes, strain rates, and interlayer thicknesses obtained from this study enable the tailored development of nanocomposites with optimal mechanical characteristics.

Harmonic and anharmonic studies on THz spectra of two vanillin polymorphs.

Polymorphism commonly exists in organic molecular crystals. The fingerprint features in low-frequency vibrational range are important information reflecting different intermolecular interactions of polymorphs. Interpreting these features is very helpful to understand vibrational property of polymorphs and reveal the thermodynamic stability. In this work, the low-frequency vibrations of form I and II of vanillin are investigated using terahertz time-domain spectroscopy. Static DFT calculation and ab initio molecular dynamics (AIMD) are employed to interpret their low-frequency vibrations of both forms in harmonic and anharmonic ways, respectively. Their low-frequency vibration characteristics in harmonic calculations are discussed, and anharmonic mode couplings between OH bond stretch and the stretching and bending motion of hydrogen bonds are uncovered. Moreover, the thermodynamic energies including electronic potential energy and vibrational/kinetic energy arising from nuclear motions are calculated. The result reveals that the stability order of the two forms is mainly dependent on their electric potential energy difference.

Posterior Approximate Clustering-Based Sensitivity Matrix Decomposition for Electrical Impedance Tomography.

This paper introduces a sensitivity matrix decomposition regularization (SMDR) method for electric impedance tomography (EIT). Using k-means clustering, the EIT-reconstructed image can be divided into four clusters, derived based on image features, representing posterior information. The sensitivity matrix is then decomposed into distinct work areas based on these clusters. The elimination of smooth edge effects is achieved through differentiation of the images from the decomposed sensitivity matrix and further post-processing reliant on image features. The algorithm ensures low computational complexity and avoids introducing extra parameters. Numerical simulations and experimental data verification highlight the effectiveness of SMDR. The proposed SMDR algorithm demonstrates higher accuracy and robustness compared to the typical Tikhonov regularization and the iterative penalty term-based regularization method (with an improvement of up to 0.1156 in correlation coefficient). Moreover, SMDR achieves a harmonious balance between image fidelity and sparsity, effectively addressing practical application requirements.

Changes of FGF23 and hearing in chronic renal failure and their correlation analysis.

BACKGROUND: To explore the association between fibroblast growth factor 23 (FGF23) and hearing in chronic renal failure (CRF). METHODS: Pure tone audiometry was used to detect the hearing of patients with CRF; the level of serum FGF23, creatinine, blood urea nitrogen (BUN), parathyroid hormone (PTH), and mean binaural hearing threshold were compared to the control group (people without kidney disease). The rat model of renal failure was established by 5/6 nephrectomy, and the auditory brainstem response (ABR) of rats after modeling was detected by the Tucker Davis Technologies (TDT) system; the expression level of FGF23 in the peripheral blood, renal and cochlear tissue was also detected. RESULTS: The incidence of hearing loss (HL) and serum FGF23 were higher in CRF patients than the control group; the sFGF23 was positively correlated with the mean binaural hearing threshold. Animal studies showed that the ABR threshold, creatinine, FGF23, BUN, and PTH increased after modeling; although, an increase in FGF23 was observed earlier than other indicators. The HL of rats with renal failure was significantly correlated with BUN, phosphate, PTH, sFGF23, kFGF23/ß-actin, eFGF23/ß-actin, weight, and modeling cycle. CONCLUSIONS: Both CRF patients and rat models showed high-frequency HL. FGF23 was highly expressed in the serum of HL renal failure patients and rats, as well as in the renal tissue and cochlea of renal failure rats. Therefore, FGF23 may be involved in the occurrence and development of HL caused by CRF.

Redox/Near-Infrared Dual-Responsive Hollow Mesoporous Organosilica Nanoparticles for Pesticide Smart Delivery.

Extremely inefficient utilization of pesticides has prompted a study of low-cost, sustainable, and smart application systems. Herein, as a promising pesticide nanocarrier, hollow mesoporous organosilica nanoparticles (HMONs) were first synthesized by using inexpensive CaCO3 nanoparticles as the hollow templates. A redox/near-infrared light dual-triggered pesticide release system was further achieved via loading avermectin (AVM) into the HMONs and coating a layer of polydopamine (PDA). The as-prepared AVM@HMONs@PDA displays a favorable pesticide load capability (24.8 wt %), outstanding photothermal performance, and high adhesion to leaves. In addition, with glutathione (GSH), the AVM cumulative release from AVM@HMONs@PDA was 3.5 times higher than that without GSH. Under ultraviolet light irradiation, the half-life of AVM@HMONs@PDA was prolonged by 17.0-fold compared to that of the AVM technical. At day 21 after treatment in the insecticidal activity, the median lethal concentrations (LC50) values displayed that the toxicity of AVM@HMONs@PDA for Panonychus citri (McGregor) was enhanced 4.0-fold compared with the commercial emulsifiable concentrate. In the field trial, at day 28 after spraying, AVM@HMONs@PDA was significantly more control effective than AVM-EC in controlling the P. citri (McGregor), even at a 50% reduced dosage. Moreover, HMONs@PDA was safe for crops. This research presents a novel preparation approach for HMONs, and it also offers a promising nanoplatform for the precise release of pesticides.

Diagnosis and Treatment of X-Linked Creatine Transporter Deficiency: Case Report and Literature Review.

(1) Background: X-linked creatine transporter deficiency (CTD) (OMIM 300036) is a rare group of inherited metabolic disorders characterized by global developmental delay/intellectual disability (GDD/ID), seizures, autistic behavior, and movement disorders. Pathogenic variants in the SLC6A8 gene, located at Xq28, are causative of the disease, leading to impaired creatine transport into the brain. Supplementation with creatine and its precursors, glycine and arginine, has been attempted, yet the treatment efficacy remains controversial. (2) Methods: Here we report a de novo SLC6A8 variant in a boy aged 3 years 9 months presenting with GDD, autistic behavior, and epilepsy. Elevated urinary creatine/creatinine ratio and diminished creatine peak on brain MR spectroscopy suggested the diagnosis of CTD. Genetic sequencing revealed a de novo hemizygous frameshift variant (NM_005629: c.1136_1137del, p. Glu379ValfsTer85). Creatine supplementation therapy was initiated after definitive diagnosis. Electroencephalography and MR spectroscopy were monitored during follow-up in concurrence with neuropsychological evaluations. The clinical phenotype and treatment response of CTD were summarized by systematic view of the literature. (3) Results: In silico analysis showed this variant to be deleterious, probably interfering with substrate binding and conformational changes during creatine transport. Creatine supplementation therapy led to seizure cessation and modest cognitive improvement after half-year's treatment. (4) Conclusions: This case highlights the importance of MR spectroscopy and metabolic screening in males with GDD/ID, allowing for early diagnosis and therapeutic intervention. Mechanistic understanding and case-per-se analysis are required to enable precision treatment for the patients.

Metal-Organic Framework-Based Insecticide and dsRNA Codelivery System for Insecticide Resistance Management.

Targeted silencing of resistance-associated genes by specific double-stranded RNA (dsRNA) is an attractive strategy for overcoming insecticide resistance in insect pests. However, silencing target genes of insect pests by feeding on dsRNA transported via plants remains challenging. Herein, a codelivery system of insecticide and dsRNA is designed by encapsulating imidacloprid and dsNlCYP6ER1 within zeolitic imidazolate framework-8 (ZIF-8) nanoparticles to improve the susceptibility of Nilaparvata lugens (Stål) to imidacloprid. With an average particle size of 195 nm and a positive surface charge, the derived imidacloprid/dsNlCYP6ER1@ZIF-8 demonstrates good monodispersity. Survival curve results showed that the survival rates of N. lugens treated with imidacloprid and imidacloprid@ZIF-8 were 82 and 62%, respectively, whereas, in the imidacloprid/dsNlCYP6ER1@ZIF-8 treatment group, the survival rate of N. lugens is only 8%. Pot experiments demonstrate that the survival rate in the imidacloprid/dsNlCYP6ER1@ZIF-8 treatment group was much lower than that in the imidacloprid treatment group, decreasing from 54 to 24%. The identification of NlCYP6ER1 expression and the fluorescence tracking of ZIF-8 demonstrate that ZIF-8 can codeliver dsRNA and insecticide to insects via rice. Safety evaluation results showed that the dsNlCYP6ER1@ZIF-8 nanoparticle had desirable biocompatibility and biosafety to silkworm. This dsRNA and insecticide codelivery system may be extended to additional insecticides with potential resistance problems in the future, greatly enhancing the development of pest resistance management.

Genome-Wide Identification and Expression Analysis of the SWEET Gene Family in Annual Alfalfa (Medicago polymorpha).

SWEET (Sugars will eventually be exported transporter) proteins are a group of sugar transporters that are involved in sugar efflux, phloem loading, reproductive development, plant senescence, and stress responses. In this study, 23 SWEET transporter members were identified in the Medicago polymorpha genome, heterogeneously distributed on seven chromosomes. These MpSWEET genes were divided into four subfamilies, which showed similar gene structure and motif composition within the same subfamily. Seventeen MpSWEET genes encode seven transmembrane helices (TMHs), and all MpSWEET proteins possess conserved membrane domains and putative serine phosphorylation sites. Four and three pairs of MpSWEET genes were predicted to be segmentally and tandemly duplicated, respectively, which may have contributed to their evolution of M. polymorpha. The results of microarray and RNA-Seq data showed that some MpSWEET genes were specifically expressed in disparate developmental stages (including seedling stage, early flowering stage, and late flowering stage) or tissues such as flower and large pod. Based on protein network interaction and expression patterns of MpSWEET genes, six MpSWEET genes were selected for further quantitative real-time PCR validation in different stress treatments. qRT-PCR results showed that MpSWEET05, MpSWEET07, MpSWEET12, MpSWEET15, and MpSWEET21 were significantly upregulated for at least two of the three abiotic stress treatments. These findings provide new insights into the complex transcriptional regulation of MpSWEET genes, which facilitates future research to elucidate the function of MpSWEET genes in M. polymorpha and other legume crops.

A pH-responsive MOF-functionalized hollow mesoporous silica controlled herbicide delivery system exhibits enhanced activity against ACCase-herbicide-resistant weeds.

BACKGROUND: Weeds grow aggressively in agricultural fields, leading to reduced crop yields and an inability to meet the growing demand for food. Herbicides are currently the most effective method for weed control. However, the overuse of herbicides has resulted in the evolution of resistance mutants and has caused environmental pollution. Therefore, new technologies are urgently required to address this global challenge. RESULTS: We report a copper-benzene-1,4-dicarboxylate metal organic framework (Cu-BDC MOF)-functionalized carboxyl hollow mesoporous silica (HMS-COOH) delivery system for the pH-controlled release of the acetyl-CoA carboxylase (ACCase)-inhibiting herbicide quizalofop-p-ethyl (QE). The delivery system (QE@HMS@Cu-BDC) enabled the efficient control of barnyard grasses that are susceptible and resistant to ACCase-inhibiting herbicides, which showed 93.33% and 88.33% FW control efficacy at 67.5 g ha-1 , respectively. With the lowest pH value (3), QE and copper ion were released slowly to total 70.30% and 78.55% levels (respectively) from QE@HMS@Cu-BDC after 89 h. QE@HMS@Cu-BDC showed better absorption, conduction, transportation and ACCase activity inhibition performance than that of QE emulsifiable concentrate (EC) in both susceptible and ACCase-herbicide resistant barnyard grasses. In addition, with the safener effect of carrier HMS@Cu-BDC and the aid of the safener fenchlorazole-ethyl (FE), the application of QE@HMS@Cu-BDC was shown to mitigate the damage caused by QE to rice plants. CONCLUSION: This work found that the new material HMS-COOH@Cu-BDC can be used to mitigate herbicide-induced oxidative stress and improve rice plant safety. Futhermore, the QE@HMS-COOH@Cu-BDC constructed in this research might be used as an efficient nanopesticide formulation for weed controls in paddy rice fields. © 2023 Society of Chemical Industry.

Redox and Near-Infrared Light-Responsive Nanoplatform for Enhanced Pesticide Delivery and Pest Control in Rice: Construction, Efficacy, and Potential Mechanisms.

The brown planthopper, Nilaparvata lugens (Stål), is a major rice pest in various Asian countries, causing significant negative impacts on rice yield and quality. In this study, we developed a novel nanoplatform (NIT@MON@CuS) for pesticide delivery that responds to redox and near-infrared light stimuli. The nanoplatform consisted of CuS nanoparticles with mesoporous organic silica (MON), loaded with nitenpyram (NIT). With an average size of 190 nm and a loading efficiency of 22%, NIT@MON@CuS exhibited remarkable thermal response in the near-infrared region, demonstrating excellent photothermal conversion ability and stability. In vitro release kinetics demonstrated the rapid release of nitenpyram under near-infrared light and glutathione conditions, facilitating a satisfactory temperature increase and accelerated drug release. The NIT@MON@CuS-treated group exhibited a higher mortality of N. lugens, increasing from 62 to 88% compared to the group treated with nitenpyram technical after 96 h. Bioassay revealed that NIT@MON@CuS significantly enhanced nitenpyram toxicity by more than 1.4-fold against both laboratory insecticide-resistant and field strains of N. lugens. Furthermore, RT-qPCR results demonstrated that MON@CuS had the capability to reduce P450 gene expression, thereby improving the sensitivity of N. lugens to insecticides. These findings suggest that MON@CuS holds great potential as an intelligent pest control platform, offering a sustainable and efficient approach to protect crops against pests.

In Silico Selection and Validation of High-Affinity ssDNA Aptamers Targeting Paromomycin.

Glycans are promising for disease diagnosis since glycan biosynthesis is significantly affected by disease states, and glycosylation changes are probably more pronounced than protein expression during the transformation to the diseased condition. Glycan-specific aptamers can be developed for challenging applications such as cancer targeting; however, the high flexibility of glycosidic bonds and scarcity of studies on glycan-aptamer binding mechanisms increased the difficulty of screening. In this work, the model of interactions between glycans and ssDNA aptamers synthesized based on the sequence of rRNA genes was developed. Our simulation-based approach revealed that paromomycin as a representative example of glycans is preferred to bind base-restricted stem structures of aptamers because they are more critical in stabilizing the flexible structures of glycans. Combined experiments and simulations have identified two optimal mutant aptamers. Our work would provide a potential strategy that the glycan-binding rRNA genes could act as the initial aptamer pools to accelerate aptamer screening. In addition, this in silico workflow would be potentially applied in the more extensive in vitro development and application of RNA-templated ssDNA aptamers targeting glycans.

Genome-Wide Identification and Expression Analysis of the Dof Transcription Factor in Annual Alfalfa Medicago polymorpha.

The Dof transcription factor is a plant-specific transcription gene family that plays various biological functions in plant development and stress response. However, no relevant research has been conducted on Medicago polymorpha. Here, 36 MpDof genes were identified in the M. polymorpha genome and further divided into 10 groups based on the comparative phylogenetic analysis. The essential information of MpDof genes, such as chromosomal localization, gene structure, conserved motifs, and selective pressures were systematically analyzed. All 36 MpDof genes were predicted to contain more cis-acting elements related to hormone response. MpDof24 and MpDof25 were predicted to interact with MpDof11 and MpDof26 to involve in the photoperiod blooms process. The MpDof genes showed a diverse expression pattern in different tissues. Notably, MpDof29 and MpDof31 were specifically expressed in the large pod and root, respectively, suggesting their crucial role in the pod and root development. qRT-PCR analysis indicated that the expression levels of MpDof10, MpDof25, MpDof26, and MpDof29 were obviously up-regulated under drought, salt, and cold stress. Collectively, genome-wide identification, evolutionary, and expression analysis of the Dof transcription gene family in M. polymorpha will provide new information to further understand and utilize the function of these Dof genes in Medicago plants.

L-Tyrosine Limits Mycobacterial Survival in Tuberculous Granuloma.

Caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb), tuberculosis (TB) remains a massive global public health issue. A well-known and key TB trait is caseous necrotic granuloma, which allows mycobacteria to reactivate and disseminate, thus confounding TB eradication programs. Amino acid (AA) metabolism is key to regulating immune responses in Mtb infections; however, it is currently unclear if AAs can be used to treat tuberculous granulomas. Here, we screened 20 proteinogenic AAs using a Mycobacterium marinum-infected zebrafish granuloma model. Only L-tyrosine simultaneously reduced Mycobacterium marinum (M. marinum) levels in zebrafish larvae and adults and inhibited intracellular pathogen survival levels. Mechanistically, L-tyrosine significantly upregulated interferon-γ (IFN-γ) expression in M. marinum -infected zebrafish adults but not in larvae. Using N-acetylcysteine (NAC) to inhibit reactive oxygen species (ROS), L-tyrosine appeared to inhibit Mtb intracellular survival by promoting ROS production. Thus, L-tyrosine as a non-essential AA may reduce mycobacterial survival in both macrophages and tuberculous granulomas. Our research provides a platform for the clinical development of AAs for active or latent TB patients infected with drug-sensitive or drug-resistant Mtb.

Predictive value of serum d-serine level for hearing impairment in uremic patients.

OBJECTIVE: To investigate the predictive value of serum d-serine level for hearing impairment (HI) in uremic patients. METHODS: In this study, 30 uremic patients with HI and 30 with normal hearing were selected. The basic conditions, biochemical indicators, and serum serine levels of the two groups were compared to analyze the influencing factors of HI. RESULTS: The age and d-serine levels were higher in the HI group, while the l-serine level was lower than uremia in the normal hearing group. Logistic regression analysis showed that d-serine level ≥10 µM and older age increased the risk of HI. The area of the receiver operating characteristic (ROC) curve drawn by the prediction probability of HI was 0.838, indicating that age, d-serine, and l-serine had predictive diagnostic values for HI (p < .001). Among these, the ROC curve area of d-serine in predicting HI in uremic patients was 0.822 (p < .001). CONCLUSIONS: Increased d-serine and age are two risk factors for HI, while l-serine is a protective factor. d-Serine level has a predictive value for HI in uremic patients. Uremic patients are recommended hearing assessment, estimation of d-serine levels, and early intervention.