The beneficial effect of α-lipoic acid on spinal cord injury repair in rats is mediated through inhibition of oxidative stress: A transcriptomic analysis.

BACKGROUND: Oxidative stress is a crucial factor contributing to the occurrence and development of secondary damage in spinal cord injuries (SCI), ultimately impacting the recovery process. α-lipoic acid (ALA) exhibits potent antioxidant properties, effectively reducing secondary damage and providing neuroprotective benefits. However, the precise mechanism by which ALA plays its antioxidant role remains unknown. METHODS: We established a model of moderate spinal cord contusion in rats. Experimental rats were randomly divided into 3 distinct groups: the sham group, the model control group (SCI_Veh), and the ALA treatment group (SCI_ALA). The sham group rats were exposed only to the SC without contusion injury. Rats belonging to SCI_Veh group were not administered any treatment after SCI. Rats of SCI_ALA group were intraperitoneally injected with the corresponding volume of ALA according to body weight for three consecutive days after the surgery. Subsequently, three days after SCI, spinal cord samples were obtained from three groups of rats: the sham group, model control group, and administration group. Thereafter, total RNA was extracted from the samples and the expression of three sets of differential genes was analyzed by transcriptome sequencing technology. Real-time PCR was used to verify the sequencing results. The impact of ALA on oxidative stress in rats following SCI was assessed by measuring their total antioxidant capacity and hydrogen peroxide (H2O2) content. The effects of ALA on rat recovery following SCI was investigated through Beattie and Bresnahan (BBB) score and footprint analysis. RESULTS: The findings from the transcriptome sequencing analysis revealed that the model control group had 2975 genes with altered expression levels when compared to the ALA treatment group. Among these genes, 1583 were found to be upregulated while 1392 were down-regulated. Gene ontology (GO) displayed significant enrichment in terms of functionality, specifically in oxidative phosphorylation, oxidoreductase activity, and signaling receptor activity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway was enriched in oxidative phosphorylation, glutathione metabolism and cell cycle. ALA was found to have multiple benefits for rats after SCI, including increasing their antioxidant capacity and reducing H2O2 levels. Additionally, it was effective in improving motor function (such as 7 days after SCI, the BBB score for SCI_ALA was 8.400 ± 0.937 compared to 7.050 ± 1.141 for SCI_Veh) and promoting histological recovery after SCI (The results of HE demonstrated that the percentage of damage area in was 44.002 ± 6.680 in the SCI_ALA and 57.215 ± 3.964 in the SCI_Veh at the center of injury.). The sequence data from this study has been deposited into Sequence Read Archive (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242507). CONCLUSION: Overall, the findings of this study confirmed the beneficial effects of ALA on recovery in SCI rats through transcriptome sequencing, behavioral, as well histology analyses.

Axisymmetric Compression of a Circular Particle Raft Driven by the Diffusion of Surfactant.

Particle rafts are a new kind of soft matter formed by self-organization on the interface, which possesses mechanical properties between fluid and solid, and they have been widely used in many industrial fields. In the present study, the compression experiment of a circular particle raft is first performed, where an SDS (sodium dodecyl sulfate)-coated metal ring is placed around its periphery. When the surfactant diffuses, the particle raft shrinks, and its shrinkage ratio increases with the increase in the surfactant concentration, where the experimental results are consistent with the numerical simulation. Next, the relationship between the initial surface tension difference of SDS and the radius shrinkage of the particle raft is obtained by dimensional analysis. In what follows, the diffusion model is built to quantify the diffusion process of SDS at the liquid-gas interface, and then the analytical concentration solution of the concentration of SDS at the periphery of particle raft is given. The particle raft is viewed as an elastic circular plate under the action of the radial pressure, which originates from the surface tension difference, which has been verified by the experimental result. These explorations cast a new light on how to apply loads to measure mechanical properties of soft matter, which also provide some inspirations on the design of microsensors and microfluidics.

Exosomes derived from vMIP-II-Lamp2b gene-modified M2 cells provide neuroprotection by targeting the injured spinal cord, inhibiting chemokine signals and modulating microglia/macrophage polarization in mice.

Inflammation is one of the key injury factors for spinal cord injury (SCI). Exosomes (Exos) derived from M2 macrophages have been shown to inhibit inflammation and be beneficial in SCI animal models. However, lacking targetability restricts their application prospects. Considering that chemokine receptors increase dramatically after SCI, viral macrophage inflammatory protein II (vMIP-II) is a broad-spectrum chemokine receptor binding peptide, and lysosomal associated membrane protein 2b (Lamp2b) is the key membrane component of Exos, we speculated that vMIP-II-Lamp2b gene-modified M2 macrophage-derived Exos (vMIP-II-Lamp2b-M2-Exo) not only have anti-inflammatory properties, but also can target the injured area by vMIP-II. In this study, using a murine contusive SCI model, we revealed that vMIP-II-Lamp2b-M2-Exo could target the chemokine receptors which highly expressed in the injured spinal cords, inhibit some key chemokine receptor signaling pathways (such as MAPK and Akt), further inhibit proinflammatory factors (such as IL-1ß, IL-6, IL-17, IL-18, TNF-α, and iNOS), and promote anti-inflammatory factors (such as IL-4 and Arg1) productions, and the transformation of microglia/macrophages from M1 into M2. Moreover, the improved histological and functional recoveries were also found. Collectively, our results suggest that vMIP-II-Lamp2b-M2-Exo may provide neuroprotection by targeting the injured spinal cord, inhibiting some chemokine signals, reducing proinflammatory factor production and modulating microglia/macrophage polarization.

Optimized MLPA workflow for spinal muscular atrophy diagnosis: identification of a novel variant, NC_000005.10:g.(70919941_70927324)del in isolated exon 1 of SMN1 gene through long-range PCR.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare autosomal recessive hereditary neuromuscular disease caused by survival motor neuron 1 (SMN1) gene deletion or mutation. Homozygous deletions of exon 7 in SMN1 result in 95% of SMA cases, while the remaining 5% are caused by other pathogenic variants of SMN1. METHODS: We analyzed two SMA-suspected cases that were collected, with no SMN1 gene deletion and point mutation in whole-exome sequencing. Exon 1 deletion of the SMN gene was detected using Multiplex ligation-dependent probe amplification (MLPA) P021. We used long-range polymerase chain reaction (PCR) to isolate the SMN1 template, optimized-MLPA P021 for copy number variation (CNV) analysis within SMN1 only, and validated the findings via third-generation sequencing. RESULTS: Two unrelated families shared a genotype with one copy of exon 7 and a novel variant, g.70919941_70927324del, in isolated exon 1 of the SMN1 gene. Case F1-II.1 demonstrated no exon 1 but retained other exons, whereas F2-II.1 had an exon 1 deletion in a single SMN1 gene. The read coverage in the third-generation sequencing results of both F1-II.1 and F2-II.1 revealed a deletion of approximately 7.3 kb in the 5' region of SMN1. The first nucleotide in the sequence data aligned to the 7385 bp of NG_008691.1. CONCLUSION: Remarkably, two proband families demonstrated identical SMN1 exon 1 breakpoint sites, hinting at a potential novel mutation hotspot in Chinese SMA, expanding the variation spectrum of the SMN1 gene and corroborating the specificity of isolated exon 1 deletion in SMA pathogenesis. The optimized-MLPA P021 determined a novel variant (g.70919941_70927324del) in isolated exon 1 of the SMN1 gene based on long-range PCR, enabling efficient and affordable detection of SMN gene variations in patients with SMA, providing new insight into SMA diagnosis to SMN1 deficiency and an optimized workflow for single exon CNV testing of the SMN gene.

Review on the Role of IRF6 in the Pathogenesis of Non-syndromic Orofacial Clefts.

Non-syndromic orofacial clefts (NSOCs) are the most common craniofacial malformation. In the complex aetiology and pathogenesis of NSOCs, genetic factors play a crucial role and IRF6, located at chromosome 1q32.2, is the best documented NSOC susceptibility gene. IRF6 is a key factor in oral maxillofacial development and known to contribute the most in NSOCs. It is essential to conduct a complete review of the existing results on IRF6 to further understand its role in the pathogenesis of NSOCs. Thus, the present authors summarised the research progress on the mechanism of IRF6 in NSOCs from both genetic and functional perspectives in this review.

Olfactory deficit: a potential functional marker across the Alzheimer's disease continuum.

Alzheimer's disease (AD) is a prevalent form of dementia that affects an estimated 32 million individuals globally. Identifying early indicators is vital for screening at-risk populations and implementing timely interventions. At present, there is an urgent need for early and sensitive biomarkers to screen individuals at risk of AD. Among all sensory biomarkers, olfaction is currently one of the most promising indicators for AD. Olfactory dysfunction signifies a decline in the ability to detect, identify, or remember odors. Within the spectrum of AD, impairment in olfactory identification precedes detectable cognitive impairments, including mild cognitive impairment (MCI) and even the stage of subjective cognitive decline (SCD), by several years. Olfactory impairment is closely linked to the clinical symptoms and neuropathological biomarkers of AD, accompanied by significant structural and functional abnormalities in the brain. Olfactory behavior examination can subjectively evaluate the abilities of olfactory identification, threshold, and discrimination. Olfactory functional magnetic resonance imaging (fMRI) can provide a relatively objective assessment of olfactory capabilities, with the potential to become a promising tool for exploring the neural mechanisms of olfactory damage in AD. Here, we provide a timely review of recent literature on the characteristics, neuropathology, and examination of olfactory dysfunction in the AD continuum. We focus on the early changes in olfactory indicators detected by behavioral and fMRI assessments and discuss the potential of these techniques in MCI and preclinical AD. Despite the challenges and limitations of existing research, olfactory dysfunction has demonstrated its value in assessing neurodegenerative diseases and may serve as an early indicator of AD in the future.

Quantitative and Qualitative Parameters of DCE-MRI Predict CDKN2A/B Homozygous Deletion in Gliomas.

RATIONALE AND OBJECTIVES: Homozygous deletion (HD) of CDKN2A/B holds important prognostic value in gliomas. This study aimed to explore the predictive potential of conventional MRI characteristics combined with dynamic contrast-enhanced MRI parameters in predicting CDKN2A/B HD status in gliomas. MATERIALS AND METHODS: Preoperative MRI data of 105 patients (69 without CDKN2A/B HD, and 36 with CDKN2A/B homozygous deletion) with gliomas were retrospectively collected. Conventional MRI features and dynamic contrast-enhanced-MRI qualitative parameter time-intensity curve type, quantitative parameters Ktrans, Kep, Ve, Vp, and iAUC were obtained. Logistic regression models for prediction of CDKN2A/B HD status were constructed in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. RESULTS: Multivariate analysis for all patients demonstrated that age (OR=1.103, p = 0.002) and Ktrans (OR=1.051, p < 0.001) independently predicted CDKN2A/B HD. In IDH-mutant subgroup, multivariate analysis results indicated that Ktrans (OR=1.098, p = 0.031) emerged as autonomous predictors of CDKN2A/B HD. In IDH-wild subgroup, age (OR=1.111, p = 0.002) and Ktrans (OR=1.032, p = 0.001) were independent predictors of CDKN2A/B HD according to the multivariate analysis. The areas under the receiver operating characteristic curve of the corresponding models were 0.90, 0.95 and 0.84, respectively. CONCLUSION: Ktrans can serve as valuable predictive parameters for identifying CDKN2A/B HD status in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. These findings provide a foundation for precise preoperative non-invasive diagnosis and personalized treatment approaches for glioma patients.

Optimization of water quality evaluation index using information sensitivity method and variable fuzzy model for the Guo River, China.

The more water quality evaluation indicators, the greater the amount of water quality evaluation calculation. Under the requirements of evaluation accuracy, the index screening method is usually used to optimize water quality evaluation index to reduce the calculation amount of water quality evaluation. Taking Mengcheng Gate of Guo River as an example, the information sensitivity index screening method was used to simplify the water quality evaluation index system from 17 to 12 indicators. The variable fuzzy comprehensive evaluation method was used to compare and evaluate the original index system and the optimal index system. The results showed that the water quality results of the optimal index system are consistent with the original index evaluation results. And the water quality of Mengcheng Gate is basically stable at class I level. The information sensitivity method reduced the number of indicators by 29.41%. The error between the water quality evaluation results based on the optimal indicators and the original indicators is less than 10%. The maximum error, minimum error, and average error are 8.92%, 0.08%, and 2.46%, respectively. It revealed that the information sensitivity method can eliminate the information redundancy while retaining the information of the original index system. It can also reduce the calculation amount of water quality evaluation in the future. The variable fuzzy comprehensive evaluation method can reasonably reflect the complex nonlinear relationship between water quality index and water quality category. This accuracy has practical significance for guiding the optimization of water quality evaluation index system, improving the efficiency of water quality evaluation. This model provides a scientific basis for indicator selection methods in similar river water quality evaluations.

Effects of lavender essential oil inhalation aromatherapy on depression and sleep quality in stroke patients: A single-blind randomized controlled trial.

BACKGROUND AND PURPOSE: Post-stroke depression (PSD) has major implications for rehabilitation, motor recovery, activities of daily living, social and interpersonal functioning, and mortality. In view of the side effects of antidepressants, aromatherapy, a widely used non-pharmacological therapy, has received growing attention in recent years for its benefits of reduced complications, accessibility, and effectiveness. This study was designed to assess the effects of inhalation aromatherapy with lavender essential oil on depression and sleep quality in patients with PSD. MATERIALS AND METHODS: Forty patients with PSD were enrolled and randomized into experimental and placebo groups. Experimental-group patients inhaled microencapsulated lavender essential oil every night at bedtime over a period of 4 weeks. A nonwoven bag containing 2.3 g of microcapsules with about 1.5 g of lavender essential oil was placed on or under the patient's pillow, depending on the patient's scent sensitivity. Placebo-group patients used the empty nonwoven bags for the same period as the experimental group. The 17-item Hamilton Rating Scale for Depression (HAMD-17), the Zung Self-Rating Depression Scale (SDS), and the Pittsburgh Sleep Quality Index (PSQI) were used to measure outcomes. RESULTS: The HAMD-17 score, SDS score, and PSQI score showed statistically significant differences between both groups before and after intervention (P ≤ 0.01). The improvement in the experimental group was more marked than in the placebo group (P < 0.05). CONCLUSION: Lavender essential oil inhalation aromatherapy may help reduce depression and improve sleep quality in patients with PSD.

[Determination of furosine in liquid milk by high performance liquid chromatography-quadrupole time-of-flight mass spectrometry].

Furosine is often used both domestically and internationally as an indicator of the degree of heating to evaluate milk quality. However, in actual detection, the complexity of the milk matrix may lead to the inaccurate quantification of furosine in liquid milk. Therefore, in this study, an efficient and accurate method based on high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS) was established to determine furosine in liquid milk. A 2.00 mL milk sample was hydrolyzed with 5 mL 12.00 mol/L hydrochloric acid solution and 1 mL water at 110 ℃ for 12 h. After hydrolysis, vortex-mixing and filtration were performed. The filtrate was diluted six times with 6.00 g/L ammonium acetate solution and then analyzed. Gradient elution was performed with 0.20% formic acid aqueous solution and acetonitrile solution as mobile phases, followed by chromatographic separation on an AQ-C18 column (150 mm×3.5 mm, 5 µm). The data were collected by Q-TOF/MS with an electrospray ionization source operated in positive-ion mode. The accuracy of the quantification of furosine in milk was assessed by investigating the effects of the hydrochloric acid concentration (0.30, 1.25, and 3.00 mol/L) in the furosine solution on the MS response. The results showed that high hydrochloric acid concentrations inhibited the response signals. A good linear relationship was obtained in the mass concentration range of 0.05-2.00 mg/L, with a correlation coefficient (r) of 0.994. The limit of detection of the method was 0.50 mg/100 g, which meets the requirements of actual sample detection. The average recoveries of furosine ranged from 79.9% to 119.7% at three spiked levels of 1.52, 3.03, and 15.17 mg/100 g, with relative standard deviations of 1.4%-2.6%. The method was applied to detect 303 samples from 101 batches of pasteurized milk sold in the market, and the contents of furosine in these samples ranged from 5.1 to 11.9 mg/100 g. The proposed method is characterized with high efficiency, recovery, sensitivity, and accuracy. Thus, it can be used for the determination of large quantities of samples and provides technical support for the continuous promotion of the high-quality development of the whole dairy industry chain.

FBXL19 promotes malignant behaviours by activating MAPK signalling and negatively correlates with prognosis in hepatocellular carcinoma.

FBXL19 is a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases and is linked to a variety of vital biological processes, such as cell proliferation, migration, and differentiation. Previous studies have identified it as an oncogene in breast cancer and glioma. However, its role in hepatocellular carcinoma (HCC) remains unclear. To comprehensively elucidate its role in tumour biology and its underlying mechanisms, a variety of sophisticated methods, including bioinformatics analysis, RNA-sequencing technique, and in vitro cell biology experiments, were used. Here, we found that FBXL19 was upregulated in patients with HCC and correlated with poor prognosis. In in vitro experiments, the specific targeting of short hairpin RNAs via lentiviruses successfully induced the knockdown of FBXL19, resulting in notable inhibition of the proliferation, migration, and invasion of HCC cells. Furthermore, FBXL19 downregulation resulted in significant induction of G0/G1 phase cell cycle arrest. Importantly, FBXL19 knockdown inhibited tumour malignant behaviour primarily by inactivating extracellular signal-regulated protein kinase 1/2 and p38 mitogen-activated protein kinases. In conclusion, this study revealed that FBXL19 was upregulated in patients with HCC, and that its expression was negatively correlated with prognosis. Thus, FBXL19 displays oncogenic properties in HCC by activating mitogen-activated protein kinase signalling.

Understanding the Workplace-Violence-Related Perceptions and Coping Strategies of Nurses in Emergency Rooms.

BACKGROUND: Workplace violence (WPV) is a well-known and serious issue in most countries, and WPV against healthcare providers is of particular concern, especially among nurses working in emergency rooms (ERs). PURPOSE: We aimed to develop a deeper understanding of nurses' perceptions and coping strategies related to WPV that took place over a 1-year period from the perspective of nursing victims still working in ERs in southern Taiwan. METHODS: This is a qualitative study with in-depth and semistructured interviews. Nineteen ER nurse victims were recruited from six hospitals in southern Taiwan from June 2015 to April 2016. All of the interview recordings were analyzed using content analysis. RESULTS: The content analysis identified two themes of perceptions and two themes of coping strategies toward WPV. The two themes of perceptions were "adversity" and "dilemma," with the former covering the three subthemes of "misunderstanding of health policy," "unsafe environment," and "nursing shortage" and the latter covering the two subthemes of "burnout" and "keeping or quitting the job." The two themes of coping strategies were "adjustment" and "resilience," with the former covering the three subthemes of "acceptance of the reality of WPV," "self-regulation," and "culture and belief" and the latter covering the two subthemes of "living with WPV" and "problem solving." CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings revealed that ER nurse victims of WPV experienced a complicated journey after encountering WPV. Their coping strategies may be referenced by other ER nurses to better prevent and manage violent events in ERs. To prevent and manage violence in ERs, hospital managers should create a safe working environment through, for example, assigning sufficient security personnel and staff; provide relevant training to ER nurses in communications and other skills; and implement support systems to strengthen nurse resilience.

Transcriptome sequencing and metabolome analysis reveal the metabolic reprogramming of partial hepatectomy and extended hepatectomy.

Surgical resection remains a critical treatment option for many patients with primary and secondary hepatic neoplasms. Extended hepatectomy (eHx) may be required for some patients with large tumors, which may cause liver failure and death. Partial hepatectomy (pHx) and eHx mouse models were constructed, liver tissues were sampled at 18, 36, and 72 h posthepatectomy. Transcriptome and metabolome analyses were employed to explore the different potential mechanisms in regeneration and injury between pHx and eHx. The results showed that eHx was associated with more severe liver injury and lower survival rates than pHx. Transcriptomics data showed there were 1842, 2129, and 1277 differentially expressed genes (DEGs) in eHx and 962, 1305, and 732 DEGs in pHx at 18, 36, and 72 h posthepatectomy, respectively, compared with the those in the sham groups. Compared with pHx, the number of DEGs in the eHx group reached a maximum of 230 at 18 h after surgery and decreased sequentially to 87 and 43 at 36 and 72 h. Metabolomics analysis identified a total of 1399 metabolites, and 48 significant differentially produced metabolites (DPMs) were screened between eHx and pHx. Combined analysis of DEGs and DPMs indicated that cholesterol metabolism and insulin resistance may be two important pathways for liver regeneration and mouse survival postextended hepatectomy. Our results showed the global influence of pHx and eHx on the transcriptome and metabolome in mouse liver, and revealed cholesterol metabolism and insulin resistance pathways might be involved in regeneration post-pHx and -eHx.

Construction of Zr-Metal-Organic Frameworks-Based Composite Materials toward Anhydrous Proton Conduction and Photocatalytic CO2 Reduction.

Metal-organic frameworks constructed from Zr usually possess excellent chemical and physical stability. Therefore, they have become attractive platforms in various fields. In this work, two families of hybrid materials based on ZrSQU have been designed and synthesized, named Im@ZrSQU and Cu@ZrSQU, respectively. Im@ZrSQU was prepared through the impregnation method and employed for proton conduction. Im@ZrSQU exhibited terrific proton conduction performance in an anhydrous environment, with the highest proton conduction value of 3.6 × 10-2 S cm-1 at 110 °C. In addition, Cu@ZrSQU was synthesized via the photoinduction method for the photoreduction of CO2, which successfully promoted the conversion of CO2 into CO and achieved the CO generation rate of up to 12.4 µmol g-1 h-1. The photocatalytic performance of Cu@ZrSQU is derived from the synergistic effect of Cu NPs and ZrSQU. Based on an in-depth study and discussion toward ZrSQU, we provide a versatile platform with applications in the field of proton conduction and photocatalysis, which will guide researchers in their further studies.

Escherichia coli-Based In Situ Triggerable Probe as an Amplifier for Sensitive Diagnosis and Penetrated Therapy of Cancer.

Escherichia coli (E. coli) was used for cancer therapy due to the tumor-targeting, catalytic, and surface-reducing properties. Effective diagnosis combined with treatment of cancer based on E. coli, however, was rarely demonstrated. In this study, E. coli was used to surface reduce HAuCl4 and as a carrier to modify riboflavin (Rf) and luminol (E-Au@Rf@Lum). After targeted delivery to tumor, the E-Au@Rf@Lum probe could actively emit 425 nm blue-violet chemiluminescence (CL) to achieve cell imaging for cancer diagnosis. Furthermore, this light could in situ trigger the photosensitizer (Rf) through CL resonance energy transfer, which produces reactive oxygen species (ROS) for accurate photodynamic therapy. In return, the excessive ROS enhanced the blue-violet light which was further absorbed by Rf, and ROS production was cyclically amplified. Abundant ROS broke down the dense extracellular matrix network and penetrated deep into tumors. Besides, E. coli with excellent catalytic property could decompose H2O2 to O2 to relieve tumor hypoxia for a long time and enhance the photosensitized process of Rf. By self-illumination, effective penetration, and tumor hypoxia relief, this work opens a self-amplified therapy modality to tumor.

Configuration Evolution of a Particle Raft with a Preprepared Crack Driven by the Diffusion of a Surfactant.

In the present study, the morphology evolution of a particle raft with a preprepared crack, which is caused by injecting the surfactant sodium dodecyl sulfate (SDS) into water, is demonstrated. Experimental results on the process of crack closure and configuration evolution are captured and are in excellent agreement with the numerical simulations. Then a surface diffusion model on SDS is proposed to quantify the detailed physical scenario. The surface diffusion factor is determined through the shooting method based on the experimental result of dynamic surface tension. As a result, the analytical solution for the SDS concentration distribution is given. The theoretical result on the dependence relationship between the profile shrinkage ratio and the time variable is consistent with the experimental result. At last, the relation between the initial surface tension difference of SDS and the profile shrinkage ratio is obtained in the light of experiments and dimensional analysis, and the two results are very close. These analyses provide a comprehensive understanding of the coupling between chemicals and mechanical behaviors of soft matter, and the modulation of defects in the particle raft provides some inspiration for engineering new devices at the microscale.

Regulatory Effect and Mechanism of Erythroblastic Island Macrophages on Anemia in Patients with Newly Diagnosed Multiple Myeloma.

Objective: To examine the clinical characteristics and anemia-related factors in patients with newly diagnosed multiple myeloma (NDMM), as well as the effect and mechanism of erythroblastic islands (EBIs) and EBI macrophages in NDMM patients with anemia. Methods: We collected and analyzed clinical data to find anemia-related factors. Using flow cytometry, the numbers and ratios of erythroblasts and EBI macrophages were determined. RNA sequencing (RNA-seq) was used to determine the differences of EBI macrophages in NDMM patients with or without anemia. Results: Based on the clinical characteristics of NDMM patients with anemia, MCV, abnormal levels of albumin, osteolytic lesions, and Durie-Salmon (DS) stage are risk factors for anemia. Patients with anemia have fewer erythroblasts, erythroblastic islands (EBIs), and EBI macrophages in their bone marrow than patients without anemia. RNA-seq analysis of EBI macrophages from the bone marrow of patients with and without anemia revealed that macrophages from patients with anemia are impaired and tend to promote the production of interleukin-6, which has been demonstrated to be an essential survival factor of myeloma cells and protects them from apoptosis. Conclusion: In NDMM patients with anemia, EBI macrophages are impaired, which causes anemia in those patients. Our finding highlights the significance of EBI macrophages in anemia in NDMM patients and provides a new strategy for recovery from anemia in these patients.

The Alterations of Gut Microbiome and Lipid Metabolism in Patients with Spinal Muscular Atrophy.

INTRODUCTION: Spinal muscular atrophy (SMA) can cause multiple system dysfunction, especially lipid metabolic disorders, for which management strategies are currently lacking. Microbes are related to metabolism and the pathogenesis of neurological diseases. This study aimed to preliminarily explore the alterations in the gut microbiota in SMA and the potential relationship between altered microbiota and lipid metabolic disorders. METHODS: Fifteen patients with SMA and 17 gender- and age-matched healthy controls were enrolled in the study. Feces and fasting plasma samples were collected. 16S ribosomal RNA sequencing and nontargeted metabolomics analysis were performed to explore the correlation between microbiota and differential lipid metabolites. RESULTS: No significant difference was found in microbial diversity (α- and ß-diversity) between the SMA and control groups, with both groups having a relatively similar community structure. However, compared to the control group, the SMA group showed an increased relative abundance of the genera Ruminiclostridium, Gordonibacter, Enorma, Lawsonella, Frisingicoccus, and Anaerofilum and a decreased abundance of the genera Catabacter, Howardella, Marine_Methylotrophic_Group_3, and Lachnospiraceae_AC2044_group. The concurrent metabolomic analysis showed that the SMA group had 56 different kinds of lipid metabolite levels than did the control group. Additionally, the Spearman correlation suggested a correlation between the altered differential lipid metabolites and the above-mentioned altered microbiota. CONCLUSIONS: The gut microbiome and lipid metabolites differed between the patients with SMA and the control subjects. The altered microbiota may be related with the lipid metabolic disorders in SMA. However, further study is necessary to clarify the mechanism of lipid metabolic disorders and develop management strategies to improve the related complications in SMA.

Unraveling different influences of the fraction of the tetragonal phase in oxide films on the corrosion resistance of Zr alloys from the phase transition mechanism.

The mechanism of Sn and Nb influence on the fraction of tetragonal ZrO2 in oxide films on Zr alloys and their influence mechanism on corrosion resistance of Zr alloys, despite decades of research, are ambiguous due to the lack of kinetic knowledge of phase evolution of ZrO2 with doping. Using stochastic surface walking and density functional theory calculations, we investigate the influence of Nb and Sn on the stability of tetragonal (t) and monoclinic (m) ZrO2, and t-m phase transition in oxide films. We found that though Nb and Sn result in similar apparent variation trends in the t-phase fraction in oxide films, their influences on t-m phase transition differ significantly, which is the underlying origin of different influences of the t-phase fraction in oxide films on the corrosion resistance of Zr alloys with Sn and Nb alloying. These results clarify an important aspect of the relationship between the microstructure and corrosion resistance of Zr alloys.