Microglia-derived exosomes modulate myelin regeneration via miR-615-5p/MYRF axis.

Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to 3'UTR of myelin regulator factor (MYRF), a crucial myelination transcription factor expressed in oligodendrocyte lineage cells. Mechanistically, exosomes from activated microglia transferred miR-615-5p to OPCs, which directly bound to MYRF and inhibited OPC maturation. Furthermore, an effect of AAV expressing miR-615-5p sponge in microglia was tested in experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ)-induced demyelination model, the classical mouse models of multiple sclerosis. miR-615-5p sponge effectively alleviated disease progression and promoted remyelination. This study identifies miR-615-5p/MYRF as a new target for the therapy of demyelinating diseases.

Electro-optically tunable optical delay on a lithium niobate photonic chip.

An approach for continuous tuning of on-chip optical delay with a microring resonator is proposed and demonstrated. By introducing an electro-optically tunable waveguide coupler, the bus waveguide to the resonance coupling can be effectively tuned from the under-coupling regime to the over-coupling regime. The optical delay is experimentally characterized by measuring the relative phase shift between lasers and shows a large dynamic range of delay from -600 to 600 ps and an efficient tuning of delay from -430 to -180 ps and from 40 to 240 ps by only a 5 V voltage.

Numerical analysis of on-chip acousto-optic modulators for visible wavelengths.

On-chip acousto-optic modulators that operate at an optical wavelength of 780 nm and a microwave frequency of 6.835 GHz are proposed. The modulators are based on a lithium-niobate-on-sapphire platform and efficiently excite surface acoustic waves and exhibit strong interactions with tightly confined optical modes in waveguides. In particular, a high-efficiency phase modulator and single-sideband mode converter are designed. We found that for both microwave and optical wavelengths below 1 µm, the interactions at the cross-sections of photonic waveguides are sensitive to the waveguide width and are significantly different from those in previous studies. Our designed devices have small footprints and high efficiencies, making them suitable for controlling rubidium atoms and realizing hybrid photonic-atomic chips. Furthermore, our devices have the potential to extend the acousto-optic modulators to other visible wavelengths for other atom transitions and for visible light applications, including imaging and sensing.

Omics analysis revealed the intestinal toxicity induced by aflatoxin B1 and aflatoxin M1.

Aflatoxin B1 (AFB1), a common mycotoxin, can occur in agricultural products. As a metabolite of AFB1, aflatoxin M1 (AFM1) mainly exist in dairy products. These two mycotoxins threaten human health, although it is unclear how they affect the function of the intestinal barrier. In this study, mice were exposed to AFB1 (0.3 mg/kg body b.w.) and AFM1(3.0 mg/kg b.w.) either individually or in combination for 28 days to explore the main differentially expressed proteins (DEPs) and the associated enriched pathways. These findings were preliminarily verified by the transcriptomic and proteomic analyses in differentiated Caco-2 cells. The results revealed that AFB1 and AFM1 exposure in mice disrupted the function of the intestinal barrier, and the combined toxicity was greater than that of each toxin alone. Further proteomic analysis in mice demonstrated that the mechanisms underlying these differences could be explained as follows: (i) lipid metabolism was enriched by AFB1-induced DEPs. (ii) protein export pathway was stimulated by AFM1-induced DEPs. (iii) cell metabolic ability was inhibited (as evidenced by changes in UDP-GT1, UDP-GT2, and Gatm6), apoptosis was induced (MAP4K3), and epithelial cell integrity was disrupted (Claudin7 and IQGAP2), resulting in more extensive intestinal damage after combined treatment. In conclusion, the hazardous impact of co-exposure to AFB1 and AFM1 from proteomic perspectives was demonstrated in the present study.

Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma.

BACKGROUND: Our clinical practice of laparoscopic liver resection (LLR) had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma (HCC) over open liver resection (OLR), but the underlying mechanisms are not clear. This study was to find out whether systemic inflammation plays an important role. METHODS: A total of 103 patients with early-stage HCC under liver resection were enrolled (LLR group, n = 53; OLR group, n = 50). The expression of 9 inflammatory cytokines in patients at preoperation, postoperative day 1 (POD1) and POD7 was quantified by Luminex Multiplex assay. The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR. RESULTS: Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels. Compared to OLR, the POD1 levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) in the LLR group were significantly lower. Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation. The levels of these cytokines were positively associated with postoperative liver injury, and the length of hospital stay. Importantly, a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection. CONCLUSIONS: Significantly lower level of GM-CSF, IL-6, IL-8, and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

Integration of Metal Catalysis and Organocatalysis in a Metal Nanocluster with Anchored Proline.

Chiral metal nanoclusters have recently been attracting great attention. It is challenging to realize asymmetric catalysis via atomically precise metal nanoclusters. Herein, we report the synthesis and total structure determination of chiral clusters [Au7Ag8(dppf)3(l-/d-proline)6](BF4)2 (l-/d-Au7Ag8). Superatomic clusters l-/d-Au7Ag8 display intense and mirror-image Cotton effects in their CD spectra. Density functional theory (DFT) calculations were carried out to understand the correlation between electronic structures and the optical activity of the enantiomeric pair. Surprisingly, the incorporation of proline in a metal nanocluster can significantly promote the catalytic efficiency in asymmetric Aldol reactions. The increase of catalytic activity of Au7Ag8 in comparison with organocatalysis by proline is attributed to the cooperative effect of the metal core and prolines, showing the advantages of the integration of metal catalysis and organocatalysis in a metal nanocluster.

Oligodendrocyte lineage cells: Advances in development, disease, and heterogeneity.

Oligodendrocyte progenitor cells (OPCs) originate in the ventricular zone (VZ) of the brain and spinal cord, and their primary function is to differentiate into oligodendrocytes (OLs). Studies have shown that OPCs and OLs are pathologically and physiologically heterogeneous. Previous transcriptome analyses used Bulk RNA-seq, which compares average gene expression in cells and does not allow for heterogeneity. In recent years, the development of single-cell sequencing (scRNA-seq) and single-cell nuclear sequencing (snRNA-seq) has allowed us to study an individual cell. In this review, sc/snRNA-seq was used to study the different subpopulations of OL lineage cells, their developmental trajectories, and their applications in related diseases. These techniques can distinguish different subpopulations of cells, and identify differentially expressed genes in particular cell types under certain conditions, such as treatment or disease. It is of great significance to the study of the occurrence, prevention, and treatment of various diseases.

On the highest oxidation states of the actinoids in AnO4 molecules (An = Ac - Cm): A DMRG-CASSCF study.

Actinoid tetroxide molecules AnO4 (An = Ac - Cm) are investigated with the ab initio density matrix renormalization group (DMRG) approach. Natural orbital shapes are used to read out the oxidation state (OS) of the f-elements, and the atomic orbital energies and radii are used to explain the trends. The highest OSs reveal a "volcano"-type variation: For An = Ac - Np, the OSs are equal to the number of available valence electrons, that is, AcIII , ThIV , PaV , UVI , and NpVII . Starting with plutonium as the turning point, the highest OSs in the most stable AnO4 isomers then decrease as PuV , AmV , and CmIII , indicating that the 5f-electrons are hard to be fully oxidized off from Pu onward. The variations are related to the actinoid contraction and to the 5f-covalency characteristics. Combined with previous work on OSs, we review their general trends throughout the periodic table, providing fundamental understanding of OS-relevant phenomena.

Dissecting the Enantioselective Neurotoxicity of Isocarbophos: Chiral Insight from Cellular, Molecular, and Computational Investigations.

Chiral organophosphorus pollutants are found abundantly in the environment, but the neurotoxicity risks of these asymmetric chemicals to human health have not been fully assessed. Using cellular, molecular, and computational toxicology methods, this story is to explore the static and dynamic toxic actions and its stereoselective differences of chiral isocarbophos toward SH-SY5Y nerve cells mediated by acetylcholinesterase (AChE) and further dissect the microscopic basis of enantioselective neurotoxicity. Cell-based assays indicate that chiral isocarbophos exhibits strong enantioselectivity in the inhibition of the survival rates of SH-SY5Y cells and the intracellular AChE activity, and the cytotoxicity of (S)-isocarbophos is significantly greater than that of (R)-isocarbophos. The inhibitory effects of isocarbophos enantiomers on the intracellular AChE activity are dose-dependent, and the half-maximal inhibitory concentrations (IC50) of (R)-/(S)-isocarbophos are 6.179/1.753 µM, respectively. Molecular experiments explain the results of cellular assays, namely, the stereoselective toxic actions of isocarbophos enantiomers on SH-SY5Y cells are stemmed from the differences in bioaffinities between isocarbophos enantiomers and neuronal AChE. In the meantime, the modes of neurotoxic actions display that the key amino acid residues formed strong noncovalent interactions are obviously different, which are related closely to the molecular structural rigidity of chiral isocarbophos and the conformational dynamics and flexibility of the substrate binding domain in neuronal AChE. Still, we observed that the stable "sandwich-type π-π stacking" fashioned between isocarbophos enantiomers and aromatic Trp-86 and Tyr-337 residues is crucial, which notably reduces the van der Waals' contribution (ΔGvdW) in the AChE-(S)-isocarbophos complexes and induces the disparities in free energies during the enantioselective neurotoxic conjugations and thus elucidating that (S)-isocarbophos mediated by synaptic AChE has a strong toxic effect on SH-SY5Y neuronal cells. Clearly, this effort can provide experimental insights for evaluating the neurotoxicity risks of human exposure to chiral organophosphates from macroscopic to microscopic levels.

Single-Cell RNA-Sequencing in Astrocyte Development, Heterogeneity, and Disease.

Astrocytes are the most plentiful cell type in the central nervous system (CNS) and perform complicated functions in health and disease. It is obvious that different astrocyte subpopulations, or activation states, are relevant with specific genomic programs and functions. In recent years, the emergence of new technologies such as single-cell RNA sequencing (scRNA-seq) has made substantial advance in the characterization of astrocyte heterogeneity, astrocyte developmental trajectory, and its role in CNS diseases which has had a significant impact on neuroscience. In this review, we present an overview of astrocyte development, heterogeneity, and its essential role in the physiological and pathological environments of the CNS. We focused on the critical role of single-cell sequencing in revealing astrocyte development, heterogeneity, and its role in different CNS diseases.

Thymosin ß4, a potential marker of malignancy and prognosis in hepatocellular carcinoma.

BACKGROUND: The lack of effective early diagnostic markers is an obstacle in clinical diagnosis and treatment of hepatocellular carcinoma (HCC). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an increasing popular approach for identification of clinically relevant parameters including biomarkers. PATIENTS AND METHODS: 540 subjects, including 274 HCC, 119 liver cirrhosis, 89 hepatitis, and 58 healthy volunteers were enrolled. MALDI-TOF MS was used to select potential novel biomarkers from serum of HCC patients. Its clinical application was evaluated by experiments and clinical data analysis. RESULTS: We identified Thymosin ß4 (Tß4) in serum by MALDI-TOF MS. The expression of Tß4 was detected up-regulating in HCC cells and tissues which enhanced motility of HCC cells. More important, the level of serum Tß4 was significantly elevated in HCC patients. The AUROC showed the optimum diagnostic cut-off was 1063.6 ng/mL, ROC and 95% CI of Tß4 (0.908; 0.880-0.935) were larger than that of serum AFP (0.712; 0.662-0.762; p < 0.001). The sensitivity (91.3% vs 83.1%) and specificity (81.2% vs 20.3%) of serum Tß4 were higher than alpha-fetoprotein (AFP). In AFP-negative HCC, the sensitivity could reach to 80.5%. ROC analysis showed serum Tß4 had a better performance compared with AFP in distinguishing early-stage and small HCC. Tß4 is correlated with TNM stage (p = 0.016) and vascular invasion (p = 0.005). Survival analysis indicated the survival time of Tß4 positive patients was shorter (p < 0.001). Cox analysis suggested Tß4 could be an independent factor for HCC prognosis. CONCLUSION: Tß4 may serve as a novel biomarker for HCC diagnosis and prognosis.

Performance and mechanism of a novel S-scheme heterojunction sonocatalyst CuS/BaWO4 for degradation of bisphenol A by ultrasonic activation.

A novel CuS/BaWO4 heterojunction catalyst was prepared and characterized. Taking bisphenol A as the target pollutant for catalytic degradation, the sonocatalytic activity of CuS/BaWO4 composite was evaluated, and the combination with persulfate improved the sonocatalytic degradation of bisphenol A. The results showed that CuS/BaWO4 composite had good sonocatalytic degradation activity for bisphenol A, and the degradation rate was 70.99% ± 1.46%. After combined with persulfate, the degradation rate was further increased to 95.34% ± 0.10%, and the reaction time was relatively shortened. The results of the trapping experiment and calculated energy band positions showed that the formation of S-scheme heterojunction and the formation of hydroxyl radicals and holes were the key to the catalytic degradation of bisphenol A by CuS/BaWO4 composite. In this study, a new CuS/BaWO4 heterojunction sonocatalyst was synthesized. The catalyst can efficiently remove bisphenol A from the water environment and can be used as a potential solution for endocrine disruptor pollution in the water environment.

Anterior column realignment via a minimally invasive hybrid approach in adult spinal deformity surgery: a short-term retrospective study.

BACKGROUND: Anterior column realignment (ACR) is a novel surgical method for correcting spinal sagittal balance. meanwhile, oblique lumbar interbody fusion (OLIF) and anterior lumbar interbody fusion (ALIF) are considered minimally invasive surgical methods through natural anatomical space. This study aimed to explore the corrective effects and clinical outcomes of OLIF or ALIF combined with ACR technology in patients with adult spinal deformity (ASD). METHODS: We retrospectively analyzed patients with sagittal imbalance who received OLIF and/or ALIF and ACR treatment from 2018 to 2021. Surgical time and intraoperative bleeding volume are recorded, the corrective effect is determined by the intervertebral space angle (IVA), lumbar lordosis (LL), the sagittal vertical axis (SVA), clinical outcome is evaluated by preoperative and final follow-up visual analog pain score (VAS), Japanese orthopedic association scores (JOA) and complications. RESULTS: Sixty-four patients were enrolled in the study, average age of 65.1(range, 47-82) years. All patients completed 173 fusion segments, for 150 segments of ACR surgery. The operation time of ALIF-ACR was 50.4 ± 22.1 min; The intraoperative bleeding volume was 50.2 ± 23.6 ml. The operation time and intraoperative bleeding volume of single-segment OLIF-ACR was 66.2 ± 19.4 min and 70.2 ± 31.6 ml. At the follow-up of 6 months after surgery, the intervertebral space angle correction for OLIF-ACR and ALIF-ACR is 9.2° and 12.2°, the preoperative and postoperative lumbar lordosis were 16.7° ± 6.4°and 47.1° ± 3.6° (p < 0.001), VAS and JOA scores were improved from 6.8 to 1.8 and 7.8 to 22.1 respectively, statistically significant differences were observed in these parameters. The incidence of surgical related complications is 29.69%, but without serious complications. CONCLUSION: ACR via a minimally invasive hybrid approach for ASD has significant advantages in restoring local intervertebral space angulation and correcting the overall sagittal balance. Simultaneously, it can achieve good clinical outcomes and fewer surgical complications.

The coexistence of aflatoxin M1 and ochratoxin A induced intestinal barrier disruption via the regulation of key differentially expressed microRNAs and long non-coding RNAs in BALB/c mice.

Food safety can be seriously threatened by the existence of both aflatoxin M1 (AFM1) and ochratoxin A (OTA) in milk and corresponding products. The importance of intestine integrity in preserving human health is widely understood in vitro, but the fundamental processes by which AFM1 and OTA cause disruption of the intestinal barrier are as yet unknown, especially in vivo. Based on the analysis of the whole transcriptome of BALB/c mice, the competing endogenous RNA (ceRNA) regulation network was obtained in the current study. Each of 12 mice were separated into five treatments: saline solution treatment, 1.0% DMSO vehicle control treatment, 3.0 mg/kg b.w. individual AFM1 treatment (AFM1), 3.0 mg/kg b.w. individual OTA treatment (OTA), and combined mycotoxins treatment (AFM1 +OTA). The study period lasted 28 days. The jejunum tissue was collected for the histological assessment and whole transcriptome analysis, and the whole blood was collected, and determination of serum biochemical indicators. The phenotypic results demonstrated that AFM1 and OTA caused intestinal barrier disruption via an increased apoptosis level and decreased expression of tight junction (TJ) proteins. The ceRNA network demonstrated that AFM1 and OTA induced cell apoptosis through activating the expression of DUSP9 and suppressing the expression of PLA2G2D, which were regulated by differentially expressed microRNAs (DEmiRNAs) (miR-124-y, miR-194-z, miR-224-x, and miR-452-x) and differentially expressed long non-coding RNAs (DElncRNAs) (FUT8 and GPR31C). And AFM1 and OTA decreased TJ proteins via inhibiting the expression of PAK6, which was regulated by several important DEmiRNAs and DElncRNAs. These DE RNAs in intestinal integrity were involved in MAPK and Ras signaling pathway. Overall, our findings expand the current knowledge regarding the potential mechanisms of intestinal integrity disruption brought on by AFM1 and OTA in vivo.

Medium and long-term radiographic and clinical outcomes of Dynesys dynamic stabilization versus instrumented fusion for degenerative lumbar spine diseases.

BACKGROUND: Dynesys stabilization (DS) is utilized to preserve mobility at the instrumental segments and prevent adjacent segment pathology in clinical practice. However, the advantages of DS method in medium and long-term follow-up remain controversial. OBJECTIVE: To compare the radiographic and clinical outcomes between DS and instrumented fusion in the treatment of degenerative lumbar spine disease with or without grade I spondylolisthesis with a minimum follow-up period of 2 years. METHODS: We conducted a comprehensive search of PubMed, EMBASE, Cochrane, and Web of Science databases, Chinese National Knowledge Databases, and Wanfang Database for potentially eligible articles. Clinical outcomes were assessed in terms of VAS and ODI scores, screw loosening and breakage, and surgical revision. Radiographic outcomes were assessed in terms of postoperative range of movement (ROM) and disc heigh. Moreover, adjacent segment degeneration (ASDeg) and adjacent segment disease (ASDis) were evaluated. RESULTS: Seventeen studies with 1296 patients were included in the meta-analysis. The DS group was associated with significantly lower postoperative VAS scores for low-back and leg pain, and lower rate of surgical revision than the fusion group. Moreover, the Dynesys group showed significantly less ASDeg than the fusion group but showed no significant advantage over the fusion group in terms of preventing ASDis. Additionally, the ROM at the stabilized segments of the fusion group decreased significantly and that at the adjacent segments increased significantly compared with those of the DS group. CONCLUSION: DS showed comparable clinical outcomes and provided benefits in preserving the motion at the stabilized segments, thus limiting the hypermobility at the adjacent segments and preventing ASDeg compared with the fusion method in degenerative disease with or without grade I spondylolisthesis.

A Lysosome-Targeting Self-Condensation Prodrug-Nanoplatform System for Addressing Drug Resistance of Cancer.

Lysosome-targeting self-assembling prodrugs had emerged as an attractive approach to overcome the acquisition of resistance to chemotherapeutics by inhibiting lysosomal sequestration. Taking advantage of lysosomal acidification induced intracellular hydrolytic condensation, we developed a lysosomal-targeting self-condensation prodrug-nanoplatform (LTSPN) system for overcoming lysosome-mediated drug resistance. Briefly, the designed hydroxycamptothecine (HCPT)-silane conjugates self-assembled into silane-based nanoparticles, which were taken up into lysosomes by tumor cells. Subsequently, the integrity of the lysosomal membrane was destructed because of the acid-triggered release of alcohol, wherein the nanoparticles self-condensed into silicon particles outside the lysosome through intracellular hydrolytic condensation. Significantly, the LTSPN system reduced the half-maximal inhibitory concentration (IC50) of HCPT by approximately 4 times. Furthermore, the LTSPN system realized improved control of large established tumors and reduced regrowth of residual tumors in several drug-resistant tumor models. Our findings suggested that target destructing the integrity of the lysosomal membrane may improve the therapeutic effects of chemotherapeutics, providing a potent treatment strategy for malignancies.

The Essential Role of H2S-ABA Crosstalk in Maize Thermotolerance through the ROS-Scavenging System.

Hydrogen sulfide (H2S) and abscisic acid (ABA), as a signaling molecule and stress hormone, their crosstalk-induced thermotolerance in maize seedlings and its underlying mechanism were elusive. In this paper, H2S and ABA crosstalk as well as the underlying mechanism of crosstalk-induced thermotolerance in maize seedlings were investigated. The data show that endogenous levels of H2S and ABA in maize seedlings could be mutually induced by regulating their metabolic enzyme activity and gene expression under non-heat stress (non-HS) and HS conditions. Furthermore, H2S and ABA alone or in combination significantly increase thermotolerance in maize seedlings by improving the survival rate (SR) and mitigating biomembrane damage. Similarly, the activity of the reactive oxygen species (ROS)-scavenging system, including enzymatic antioxidants catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (POD), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and superoxide dismutase (SOD), as well as the non-enzymatic antioxidants reduced ascorbic acid (AsA), carotenoids (CAR), flavone (FLA), and total phenols (TP), was enhanced by H2S and ABA alone or in combination in maize seedlings. Conversely, the ROS level (mainly hydrogen peroxide and superoxide radical) was weakened by H2S and ABA alone or in combination in maize seedlings under non-HS and HS conditions. These data imply that the ROS-scavenging system played an essential role in H2S-ABA crosstalk-induced thermotolerance in maize seedlings.

Treatment with anacardic acid modulates dendritic cell activation and alleviates the disease development of autoimmune neuroinflammation in mice.

Anacardic acid (AA) is a phenolic acid extract found in a number of plants, crops, and fruits. It exhibits a wide range of biological activities. This study displayed that AA effectively alleviated EAE, a classical mouse model of multiple sclerosis. AA administered to the EAE greatly decreased inflammatory cell infiltration to the CNS and protected the myelin integrity in the white matter of the spinal cord. AA could block lipopolysaccharide-induced DC activation. inhibited the polarization of 2D2 mice-derived T cells by inhibiting the DCs activity. Immunoblot results indicated that the phosphorylation of NF-κB is significantly suppressed in AA-treated DCs. This work displayed that AA possessed a potential anti-inflammatory therapeutic effect for the treatment of autoimmune disease.

The detection of up-regulated anti-thyroid antibodies and autoimmune thyroid diseases in patients with autoimmune encephalitis: a retrospective study of 221 patients.

OBJECTIVE: To investigate the potential detection rate of anti-thyroid antibodies' (ATAbs) positivity, thyroid dysfunctions, and autoimmune thyroid diseases (AITDs) in autoimmune encephalitis (AE) and to analyze whether thyroid autoimmunity/dysfunction can affect the clinical course of AE. METHODS: Two hundred twenty-one AE patients and 229 age- and sex-matched controls were included in this study. We measured the levels of ATAbs (anti-thyroglobulin antibodies [TgAb], anti-thyroid peroxidase anti-bodies [TPOAb]) and thyroid hormones in all the individuals. In addition, the association of thyroid autoimmunity/dysfunctions with functional outcomes of AE was identified by using logistic regression and Kaplan-Meier analyses. RESULTS: The prevalence of TPOAb-positive and TgAb-positive was significantly higher in AE patients (16.3% and 16.7%, respectively) as compared with controls (9.6% and 7.4%, respectively; P = 0.034 and P = 0.002, respectively). In addition, the free triiodothyronine (fT3) level was significantly lower in AE patients as compared to the controls (P < 0.001). However, the frequency of AITDs (Hashimoto's thyroiditis and Graves' disease) did not significantly differ between AE patients and control subjects. Importantly, low fT3 was found to be associated with poor functional outcomes at the 3-month follow-up in AE. Adjustment of potential confounders did not change the association. However, the presence of ATAbs did not significantly alert the disease course of AE. CONCLUSIONS: ATAbs-positive and/or AITD patients with symptomatic encephalopathy should undergo proper surveillance for AE. Moreover, low fT3 could serve as a possible predictor of poor short-term outcome in AE, thereby suggesting that monitoring of thyroid function in AE may be necessary.

Impact of the COVID-19 pandemic on career intention amongst undergraduate medical students: a single-centre cross-sectional study conducted in Hubei Province.

BACKGROUND: Undergraduate medical (UM) students faced the difficulties inherent in medical careers due to the coronavirus (COVID-19) outbreak. Thus, imperative containment measures might affect UM students' career intentions. Information on the factors that may be associated with these students' career change intentions is limited. METHODS: We conducted a cross-sectional survey in August 2020 to investigate the impact of the COVID-19 pandemic on career intention and the associated factors in UM students. Univariate analyses and logistic regression analysis were performed to identify said factors. RESULTS: A total of 2040 medical students from the Hubei University of Medicine were surveyed. Univariate analyses showed that grade, attitude towards healthcare, and the degree of the COVID-19 pandemic's impact on the students' lives were associated with changes in career choice (P<0.05). Logistic regression analysis showed that Grade 2, Grade 5, attitude towards a medical career, and having relatives with a medical background were associated with changes in career choice. The degree of the COVID-19 pandemic's impact was a common and significant factor associated with career preference, career perspective, and ideal workplace. CONCLUSIONS: Changes in career intentions were particularly influenced by grade, attitude towards being a health worker, and the degree of COVID-19's impact on the participants' lives. Treating large-scale public health emergencies rationally, setting up correct views of occupation choice, and building reasonable career planning may reduce the loss of medical talent.