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ObjectiveTo investigate atrophy patterns in hypothalamic subunits at different stages of ALS and examine correlations between hypothalamic subunit volume and clinical information.MethodsWe used the King’s clinical staging system to divide 91 consecutive ALS patients into the different disease stages. We investigated patterns of hypothalamic atrophy using a recently published automated segmentation method in ALS patients and in 97 healthy controls. We recorded all subjects’ demographic and clinical information.ResultsCompared with healthy controls, we found significant atrophy in the bilateral anterior–superior subunit and the superior tubular subunit, as well as a reduction in global hypothalamic volume in ALS patients. When we used the King’s clinical staging system to divide patients into the different disease stages, we found neither global nor specific subunit atrophy until King’s stage 3 in the hypothalamus. Moreover, specific subunit volumes were significantly associated with body mass index.ConclusionsIn a relatively large sample of Chinese patients with ALS, using a recently published automated segmentation method for the hypothalamus, we found the pattern of hypothalamic atrophy in ALS patients differed greatly across King’s clinical disease stages. Moreover, specific hypothalamic subunit atrophy may play an important role in energy metabolism in ALS patients. Thus, our findings suggest that hypothalamic atrophy may have potential phenotypic associations, and improved energy metabolism may become an important component of individualised therapy for ALS.

Background The exact relationship between 25-hydroxyvitamin D [25(OH) D] levels and small vessel disease (SVD) are not clear in China. The aim of this study was to determine such the association between 25(OH) D and SVD in China. Methods We retrospectively enrolled 106 patients with SVD and 115 controls between Jan 2017 and Dec 2017. All the subjects were categorized into three subgroups according to the level of 25 (OH) D: vitamin D deficiency (< 12 ng/ml), insufficiency (12–20 ng/ml) and sufficiency (> 20 ng/ml). Results Among 106 SVD patients, 80 (75.5%) were men and the mean age was 61.6 ± 13.2 years. The deficiency of 25(OH) D was observed in 76 (71.7%) of SVD patients and 47 (40.9%) of controls ( P  = 0.001). Compared with controls, patients with SVD were more likely to be male, a stroke history, smokers, with hyperlipidemia, higher systolic and diastolic blood pressure and low-density lipoprotein, and lower of 25(OH)D level ( P  < 0.05). Logistic regression analysis revealed the level of 25 (OH) D as an independent predictor of SVD ( OR 0.772, 95% CI 0.691–0.862, P  = 0.001). Compared with the sufficient 25 (OH) D group, the ORs of SVD in deficient and insufficient 25(OH)D group were 5.609 (95% CI 2.006–15.683) and 1.077 (95% CI : 0.338–3.428) after adjusting for potential confounders, respectively. In hypertensives with vitamin D deficient and insufficient group compared with sufficient group, the ORs of SVD increased to 9.738 (95% CI 2.398–39.540) and 1.108 (95% CI 0.232–5.280), respectively ( P interaction  = 0.001). Conclusion We found significant associations between SVD and 25(OH)D deficiency. The combined presence of hypertension and vitamin D deficiency increased the probability of developing SVD. Our findings will warrant further prospective studies in the future.

To examine selective atrophy patterns and resting‐state functional connectivity (FC) alterations in the amygdala at different stages of amyotrophic lateral sclerosis (ALS), and to explore any correlations between amygdala abnormalities and neuropsychiatric symptoms. We used the King's clinical staging system for ALS to divide 83 consecutive patients with ALS into comparable subgroups at different disease stages. We explored the pattern of selective amygdala subnucleus atrophy and amygdala‐based whole‐brain FC alteration in these patients and 94 healthy controls (HCs). Cognitive and emotional functions were also evaluated using a neuropsychological test battery. There were no significant differences between ALS patients at King's stage 1 and HCs for any amygdala subnucleus volumes. Compared with HCs, ALS patients at King's stage 2 had significantly lower left accessory basal nucleus and cortico‐amygdaloid transition volumes. Furthermore, ALS patients at King's stage 3 demonstrated significant reductions in most amygdala subnucleus volumes and global amygdala volumes compared with HCs. Notably, amygdala‐cuneus FC was increased in ALS patients at King's stage 3. Specific subnucleus volumes were significantly associated with Mini‐Mental State Examination scores and Hamilton Anxiety Rating Scale scores in ALS patients. In conclusions, our study provides a comprehensive profile of amygdala abnormalities in ALS patients. The pattern of amygdala abnormalities in ALS patients differed greatly across King's clinical disease stages, and amygdala abnormalities are an important feature of patients with ALS at relatively advanced stages. Moreover, our findings suggest that amygdala volume may play an important role in anxiety and cognitive dysfunction in ALS patients. Our study provides a comprehensive profile of amygdala abnormalities in ALS patients. The pattern of amygdala abnormalities in ALS patients differed greatly across King's clinical disease stages, and amygdala abnormalities are an important feature of patients with ALS at relatively advanced stages. Moreover, amygdala may play an important role in anxiety and cognitive dysfunction in ALS patients.

Cognitive impairment of cerebral small vessel disease (CSVD) is one of the most common cognitive disorders. It has a high incidence and results in heavy social burden; thus, it is essential to provide reasonable diagnosis and treatment in clinical practice. Based on the results of clinical research and related reports, combined with the actual situation in China, we propose a diagnosis and treatment guideline for cognitive impairment of CSVD.

Hypoxic–ischemic injury increases neuroglobin (Ngb) expression in the brain. In our previous study, we have generated a transactivator-of-transcription protein-transduction domain-neuroglobin fusion protein (TAT PTD-Ngb) that successfully mediated exogenous Ngb expression in the primary neurons. In this study, we further investigated the role of TAT PTD-Ngb in protecting neurons against hypoxia-induced apoptosis and explored the possible mechanism. The primary cultured neurons were divided into four groups: (1) the normal group (no hypoxic injury); (2) the vehicle group (vehicle treatment and hypoxia injury); (3) the TAT PTD-Ngb group (TAT PTD-Ngb treatment and hypoxia injury); and (4) the Ngb group (Ngb treatment and hypoxia injury). Translocation of TAT PTD-Ngb into neurons was detected using fluorescent immunostaining against His-tag as early as 30 min after incubation. MTT assay showed that the TAT PTD-Ngb group had significantly increased cell viability compared to the vehicle or Ngb group after hypoxia. The result of transmission electron microscopy (TEM) also displayed rescued ultrastructure in TAT PTD-Ngb neurons compared to that of apoptotic neurons. In addition, TAT PTD-Ngb neurons showed significantly increased expression of anti-apoptotic Bcl-2 protein and decreased activities of caspase-3 and caspase-9 in response to hypoxia. These results suggest that TAT PTD-Ngb fusion protein protects primary cortical neurons against hypoxia-induced injury possibly through suppressing mitochondria apoptotic pathway.

The present study described the characteristics of three cases of Creutzfeldt-Jakob disease (CJD) in China and analyzed their clinical presentations. The clinical information of the three cases was collected and analyzed. Blood and cerebrospinal fluid (CSF) specimens of the patients were collected for detection of the prion protein (PRNP) gene and 14-3-3 protein levels. Dynamic changes of electroencephalograms (EEGs) and brain magnetic resonance images (MRIs) were also observed. All the three cases were sporadic CJD cases. They presented with symptoms including hyposthenia, progressive memory loss, truncal and limb ataxia, dysarthria, lowered vision acuity, bucking, language disorders, myoclonia and akinetic mutism state. One of the three cases was associated with a prolonged duration of >6 years. The EEG of two cases showed slow biphasic waves. The diffusion-weighted MRI sequence revealed abnormal hyperintensity and bilateral ribboning in the cortex. Two patients tested positive for the 14-3-3 protein in the CSF. All patients were of methionine homozygosity at codon 129 in the gene encoding PRNP protein and one patient had a mutation. The CJD cases showed differences in terms of symptoms and disease duration. Subacute onset was common and with attentive nursing and supportive treatments, one of the patients had a prolonged survival time of >6 years.

Background: The exact relationship between 25-hydroxyvitamin D 25(OH) D levels and small vessel disease (SVD) are not clear in China. The aim of this study was to determine such association between 25(OH) D and SVD in China. Methods: We retrospectively enrolled 106 patients with SVD and 115 controls between Jan 2017 and Dec 2017. All the subjects were categorized into three subgroups according to the level of 25(OH) D: vitamin D deficiency (<12 ng/ml), insufficiency (12-20 ng/ml) and sufficiency (>20 ng/ml). Results: Among 106 SVD patients, 80 (75.5%) were men and the mean age was 61.6±13.2 years. The deficiency of 25(OH) D was observed in 76 (71.7%) of SVD patients and 47 (40.9%) of controls (P=0.001). Compared with controls, patients with SVD were more likely to be male, a stroke history, smokers, with hyperlipidemia, higher systolic and diastolic blood pressure and low-density lipoprotein, and lower of 25(OH)D level (P<0.05). Logistic regression analysis revealed the level of 25(OH)D as an independent predictor of SVD (OR 0.772, 95% CI 0.691-0.862, P=0.001). Compared with the sufficient 25(OH)D group, the ORs of SVD in deficient and insufficient 25(OH)D group were 5.609 (95% CI 2.006-15.683) and 1.077 (95% CI: 0.338-3.428) after adjusting for potential confounders, respectively. In hypertensives with vitamin D deficient and insufficient group compared with sufficient group, the ORs of SVD increased to 9.738 (95% CI 2.398-39.540) and 1.108 (95% CI 0.232-5.280), respectively (Pinteraction=0.001). Conclusion: We found significant associations between SVD and 25(OH)D deficiency. The combined presence of hypertension and vitamin D deficiency increased the probability of developing SVD. Our findings will warrant further prospective studies in the future.

With the increasing interest in the application of electrochromism to flexible and wearable electronics in recent years, flexible electrochromic devices (ECDs) that can function at extreme temperatures are required. However, the functionalities of flexible ECDs are severely hampered by the inadequate choice of electrolytes, which might ultimately result in performance fading during low‐ and high‐temperature operations. Here, we develop a deep eutectic solvent (DES)‐based gel electrolyte that can maintain its optical, electrical, and mechanical properties over a wide range of temperatures (−40 to 150°C), exhibiting an extremely high visible‐range transmittance over 90%, ion conductivity of 0.63 mS cm−1, and fracture strain exceeding 2000%. Owing to the excellent processability of the DES‐based electrolytes, provided by dynamic interactions such as the lithium and hydrogen bonding between the DES and polymer matrix, a directly written patterning in ECDs is realized for the first time. The fabricated ECDs exhibit an excellent electrochromic behavior superior to the behavior of the ECDs fabricated with traditional gel electrolytes. The introduction of such DES‐based electrolytes is expected to pave the way for a widespread application of electrochromic products. The gel electrolyte constructed with deep eutectic solvent (DES) and acrylate‐based copolymer enables a direct writing electrolyte layer for patterning in flexible electrochromic devices (ECDs), which can maintain its excellent optical transparency, electrical, and mechanical properties over a wide span of temperature ranging from −40 to 150°C.

The Enterobacter cloacae complex (ECC), a member of the genus Enterobacter within the family Enterobacteriaceae, is an important opportunistic pathogen associated with nosocomial infections. Colistin is considered a last-resort antimicrobial for multidrug-resistant Gram-negative infections; however, the emergence and dissemination of plasmid-mediated colistin resistance genes, particularly mcr variants, have raised significant public health concerns. Among these, mcr-10 has been increasingly detected in ECC isolates from diverse clinical and environmental sources, underscoring the importance of genomic surveillance to elucidate its genetic context and transmission potential. Swab samples were collected from a kitchen sink and cultured for bacterial isolation, followed by species identification using MALDI-TOF MS. Antimicrobial susceptibility was determined by the broth microdilution method, with results interpreted according to EUCAST and CLSI guidelines. Whole-genome sequencing was performed using a hybrid approach combining Illumina short-read and Oxford Nanopore long-read sequencing. Genome annotation and antimicrobial resistance gene detection were conducted using RAST and ResFinder, respectively. Multilocus sequence typing and plasmid replicon typing were performed using the MLST and PlasmidFinder tools. Comparative plasmid analysis was carried out with EasyFig and BLAST Ring Image Generator, while phylogenetic relationships were inferred using a core-genome-based phylogenetic analysis, and the resulting tree was visualized with iTOL. Enterobacter kobei JX24083 was resistant to cefazolin, cefoxitin, and fosfomycin. Consistently, the isolate harbored the resistance genes bla and fosA on the chromosome. The colistin resistance gene mcr-10.1 was identified on an IncFIB plasmid in the isolate; however, the isolate remained susceptible to colistin (MIC = 1 mg/L). Exposure to subinhibitory concentrations of colistin upregulated mcr-10.1 expression in vitro. Comparative sequence analysis revealed a conserved xerC-mcr-10 genetic context among Enterobacter kobei isolates harboring plasmid-borne mcr-10. Phylogenetic analysis of JX24083 together with 46 mcr-10-carrying ECC isolates from GenBank showed that several dominant sequence types, including ST681, ST125, and ST1, were distributed across different hosts and countries, indicating the potential for international dissemination. The first report of an E. kobei isolate from a domestic kitchen sink in China carrying a conserved xerC-mcr-10 plasmid backbone, yet remaining susceptible to colistin, highlights the potential for silent dissemination of mcr-10 within the Enterobacter cloacae complex (ECC) and underscores the need for continuous One Health-oriented surveillance of environmental reservoirs.

Esophageal squamous cell carcinoma (ESCC) is a common digestive cancer with high mortality rate due to late diagnosis and drug resistance. It is important to identify new molecular target and develop new anticancer strategy. ML323 is a novel USP1 inhibitor and exhibits anticancer activity against several cancers. Herein, we investigated whether ML323 has some cytotoxity effect on ESCC cells and explored the underlying mechanisms. Results revealed that ML323 impeded esophageal cancer cell viability and colony formation. Meanwhile, ML323 blocked cells at G0/G1 phase concomitant with the reduced protein level of c-Myc, cyclin D1, CDK4 and CDK6. ML323 treatment also triggered DNA damage and active p53. Then, ML323 induced apoptosis by p53-Noxa. Additionally, it stimulated protective autophagy. Co-treatment with CQ or BafA1, two classical autophagy inhibitors, enhanced the cytotoxity of ML323. These findings suggested that USP1 inhibitor (ML323) could be used as a viable anti-ESCC approach.