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Abstract Studies suggest that amyotrophic lateral sclerosis (ALS) compromises the integrity of white matter fiber tracts, primarily affecting motor fibers. However, it remains uncertain whether the integrity of these fibers influences the risk of ALS. We performed bidirectional two-sample Mendelian randomization (MR) and multivariable MR analyses to evaluate the associative relationships between the integrity of fiber tracts [including the corticospinal tract (CST) and corpus callosum (CC)] and the risk of ALS. Genetic instrumental variables for specific fiber tracts were obtained from published genome-wide association studies (GWASs), including 33,292 European individuals from five diffusion magnetic resonance imaging (dMRI) datasets. Summary-level GWAS data for ALS were derived from 27,205 ALS patients and 110,881 controls. The MR results suggested that an increase in the first principal component (PC1) of fractional anisotropy (FA) in the genu of the CC (GCC) was correlated with an increased risk of ALS (P FDR = 0.001, odds ratio = 1.363, 95% confidence interval 1.178–1.577). Although other neuroimaging phenotypes [mean diffusivity in the CST, radial diffusivity (RD) in the CST, FA in the GCC, PC1 in the body of the CC (BCC), PC1 in the CST, and RD in the GCC] did not pass correction, they were also considered to have suggestive associations with the risk of ALS. No evidence revealed that ALS caused changes in the integrity of fiber tracts. In summary, the results of this study provide genetic support for the potential association between the integrity of specific fiber tracts and the risk of ALS. Greater fiber integrity in the GCC and BCC may be a risk factor for ALS, while greater fiber integrity in the CST may have a protective effect on ALS. This study provides insights into ALS development.

Abstract Objective The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) was specifically designed as a self-reported measure of bulbar function. The purpose of this research was to validate the Chinese translation of the CNS-BFSC as an effective measurement for the Chinese population with ALS. Methods A total of 111 ALS patients were included in this study. The CNS-BFSC score, three bulbar function items from the ALSFRS-R, and visual analog scale (VAS) score for speech, swallowing and salivation were assessed in the present study. Forty-six ALS patients were retested on the same scale 5–10 days after the first evaluation. Results The CNS-BFSC sialorrhea, speech and swallowing subscores were separately correlated with the VAS subscores (p 0.05). The Cronbach’s α of the CNS-BFSC was 0.972. Conclusion The Chinese version of the CNS-BFSC has acceptable efficacy and reliability for the assessment of bulbar dysfunction in ALS patients.

Abstract Introduction Pseudobulbar palsy is a common symptom in patients with amyotrophic lateral sclerosis (ALS), but it is often underdiagnosed or misdiagnosed as other diseases. The Center for Neurologic Study Lability Scale (CNS-LS) is a self-report scale consisting of seven questions designed for evaluating pseudobulbar affect (PBA). The current study aimed to validate a Chinese version of the CNS-LS. Methods The Chinese version of the CNS-LS was obtained through a standardized forward–backward translation and cultural adaptation. A total of 105 patients with ALS were recruited from the ALS database of Peking University Third Hospital in Beijing, China, to complete the CNS-LS. The reliability of the Chinese version was determined by the test–retest method, and receiver operating characteristic (ROC) analysis was performed for criterion validity. Results Of 105 patients with ALS, 37 had symptoms of PBA and were diagnosed with that condition by neurologists. Forty-two patients completed the CNS-LS twice, and there was no statistically significant difference between the scores (Z = -0.896, p = 0.37). The Spearman correlation coefficient between the test and retest scores was 0.940 (p

Undergraduate medical education in China has shifted from educator-centered learning to self-directed learning (SDL) over the past few decades. Careful design of public engagement activities can enable SDL and empower medical students to pioneer public health and patient safety education. In this study, we aimed to innovate nervous system education by implementing a public engagement model that empowers students to learn about the nervous system by teaching the public. Our goal was to generate greater interest in the nervous system at the undergraduate stage, inspire students’ enthusiasm to pursue a career in neurology, and ultimately, contribute to health promotion. During the nervous system module of the second year of the undergraduate curriculum, students were given the option to participate in the public engagement model. Participants were tasked with the creation of educational videos focusing on knowledge, attitudes, and behaviors associated with the prevention and management of neurological diseases and their complications. The videos were made accessible to the general public through the university’s official channel at the end of the semester. A total of 117 students (67.24% of all students) chose to participate in the public engagement model. Female students and those with higher Grade Point Averages in the present semester were more likely to participate. The model received strong positive feedback from participants, as students found the public engagement task helpful in learning about the nervous system module as well as in enhancing their public engagement skills. Despite the time and effort consumption, participating in the public engagement task did not affect students’ exam scores. The public engagement task is an innovative model in the nervous system curriculum and has the potential to be integrated into a broader range of undergraduate courses. It empowers medical students to pioneer public health and patient safety education.

Abstract Objectives Glioblastoma (GBM) is the most aggressive of intracranial gliomas. Despite the maximal treatment intervention, the median survival rate is still about 14–16 months. Nuclear receptor‐binding protein 1 (NRBP1) has a potential growth‐promoting role on biology function of cells. In this study, we investigated whether NRBP1 promotes GBM malignant phenotypes and the potential mechanisms. Methods The correlation between NRBP1 and glioma grade, prognosis in TCGA/CGGA databases and our clinical data were analyzed. Next, we conducted knockout and overexpression of NRBP1 on GBM cells to verify that NRBP1 promoted cell proliferation, invasion, and migration in vitro and in vivo. Finally, we detected the impact of NRBP1 on PI3K/Akt signaling pathway and EMT. Results There was a correlation between elevated NRBP1 expression and advanced stage glioma, as well as decreased overall and disease‐free survival. The suppression of proliferation, invasion, and migration of tumor cells was observed upon NRBP1 knockout, and in vitro studies also demonstrated the induction of apoptotic cell death. Whereas, its overexpression is associated with high multiplication rate, migration, invasion, and apoptotic escape. GO enrichment and KEGG analysis revealed that NRBP1 regulated differentially expressed gene clusters are involved in PI3K/Akt signaling pathway, as well as EMT mediated by this pathway. Moreover, the effects of NRBP1 knockdown and overexpression on GBM were mitigated by MK‐2206 and SC79, both of which respectively function as an inhibitor and an activator of the PI3K/Akt signaling pathway. Similarly, the suppression of NRBP1 led to a decrease in tumor growth, whereas its overexpression promoted tumor growth in a mouse model. Conclusions This study shows that NRBP1 promotes malignant phenotypes in GBM by activating PI3K/Akt pathway. Hence, it can function as both a predictive indicator and a new target for therapies in GBM treatment.

BackgroundUpper motor neuron-dominant ALS (UMND ALS) is recognized to have early onset and good prognosis, but may have a rapid decline in motor function due to gait instability in the early stage. We investigated changes in lower extremity function in UMND ALS, particularly UMND ALS patients accompanied with postural instability or repeated falls (UMND ALS plus).ResultsAmong the 2,353 ALS patients reviewed, 211 (9.0%) had UMND ALS. UMND ALS had a longer diagnosis delay and restricted symptoms. Although UMND ALS patients had better lower extremity function and strength than matched classic ALS patients on first evaluation, there was no difference in the time of needing assistance or not being able to walk after disease onset. In contrast, UMND ALS plus has severe UMN symptoms and a more rapid decline in motor function. The lower extremity function was no better than that in the matched classic ALS. The prognosis of UMND ALS and UMND ALS plus were significantly better than those of overall ALS.ConclusionUMND ALS has restricted symptoms but has a rapid decline in lower extremity function in the early stage of the disease. The motor function decline of UMND ALS plus is as fast as classic ALS. Whether these patients represent a distinct subgroup of ALS deserves further investigation.

Seahorses are increasingly recognized for their nutritional potential, which underscores the necessity for comprehensive biochemical analyses. This study aims to investigate the fatty acid and amino acid compositions of eight seahorse species, including both genders of Hippocampus trimaculatus, Hippocampus kelloggi, Hippocampus abdominalis, and Hippocampus erectus, to evaluate their nutritional value. We employed Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC) to analyze the fatty acid and amino acid profiles of the seahorse species. GC-MS was used to detect 34 fatty acid methyl esters, while HPLC provided detailed amino acid profiles. GC-MS analysis demonstrated high precision with relative standard deviations (RSDs) generally below 2.53 %, satisfactory repeatability (RSDs from 6.55 % to 8.73 %), and stability (RSDs below 2.82 %). Recovery rates for major fatty acids ranged from 98.73 % to 109.12 %. HPLC analysis showed strong separation of amino acid profiles with theoretical plate numbers exceeding 5000. Precision tests yielded RSDs below 1.23 %, with reproducibility and stability tests showing RSDs below 2.73 % and 2.86 %, respectively. Amino acid recovery rates ranged from 97.58 % to 104.66 %. Nutritional analysis revealed significant variations in fatty acid content among the species. Female H. erectus showed higher levels of hexadecanoic acid and saturated fatty acids, while male H. abdominalis had lower concentrations of n-3 full cis 4,7,10,13,16,19-docosahexaenoic acid (DHA). Total lipid yields varied from 3.2491 % to 12.3175 %, with major fatty acids constituting 17.9717 %–74.6962 % of total lipids. In conclusion, this study provides essential insights into the fatty acid and amino acid composition of seahorses, supporting their potential as valuable dietary supplements. The differences between genders in specific fatty acids suggest a nuanced nutritional profile that could be exploited for targeted dietary applications. Further research is needed to explore the seasonal and environmental variations affecting seahorse biochemical composition.

Abstract Photochemical glycosylation has attracted considerable attention in carbohydrate chemistry. However, to the best of our knowledge, visible-light-promoted glycosylation via photoactive glycosyl donor has not been reported. In the study, we report a photosensitizer-free visible-light-mediated glycosylation approach using a photoactive 2-glycosyloxy tropone as the donor. This glycosylation reaction proceeds at ambient temperature to give a wide range of O-glycosides or oligosaccharides with yields up to 99%. This method is further applied in the stereoselective preparation of various functional glycosyl phosphates/phosphosaccharides, the construction of N-glycosides/nucleosides, and the late-stage glycosylation of natural products or pharmaceuticals on gram scales, and the iterative synthesis of hexasaccharide. The protocol features uncomplicated conditions, operational simplicity, wide substrate scope (58 examples), excellent compatibility with functional groups, scalability of products (7 examples), and high yields. It provides an efficient glycosylation method for accessing O/N-glycosides and glycans.

In paleobiology and macroevolution research, the spatial aggregation of fossil data can be influenced by the modifiable areal unit problem (MAUP), wherein the selection of different grid-cell sizes for data aggregation can lead to variations in statistical results. This study presents a case analysis focused on the spatial extent of marine bivalves and brachiopods over time across three Areas of Interest (AOIs) to evaluate the potential impact of the MAUP in grid-based fossil data processing. By employing rectangular grid matrices with cell sizes of 50, 100, 200, and 400 km, this research assesses the MAUP-related sensitivity of two commonly used grid-based proxies for species’ spatial distribution. The results reveal that the proxy based on the number of occupied grid cells (OGCs) is particularly sensitive to changes in cell size, whereas the proxy based on minimum-spanning-tree distance (MST distance) demonstrates greater robustness across varying grid scales. This study underscores that when constructing proxies for species’ spatial distribution ranges using grid matrices, the OGC method is more susceptible to MAUP effects than the MST distance method, warranting increased caution in studies employing the OGC approach.

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons. Early bilateral limb involvement significantly affects patients’ daily lives and may lead them to be confined to bed. However, the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear. To address this issue, we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022. A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis. We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients. Multiple factor analyses revealed that higher upper motor neuron scores (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.01–1.09, P = 0.018), onset in the left limb (HR = 0.72, 95% CI = 0.58–0.89, P = 0.002), and a horizontal pattern of progression (HR = 0.46, 95% CI = 0.37–0.58, P < 0.001) were risk factors for a shorter interval until bilateral limb involvement. The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients. These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

Summary: Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that poses a worldwide public health challenge. A neuroimaging biomarker would significantly improve early diagnosis and intervention, ultimately enhancing the quality of life for affected individuals and reducing the burden on healthcare systems. Methods: Cross-sectional and longitudinal data (10,099 participants with 13,380 scans) from 12 independent datasets were used in the present study (this study was performed between September 1, 2021 and February 15, 2023). The Individual Brain-Related Abnormalities In Neurodegeneration (IBRAIN) score was developed via integrated regional- and network-based measures under an ensemble machine learning model based on structural MRI data. We systematically assessed whether IBRAIN could be a neuroimaging biomarker for AD. Findings: IBRAIN accurately differentiated individuals with AD from NCs (AUC = 0.92) and other neurodegenerative diseases, including Frontotemporal dementia (FTD), Parkinson's disease (PD), Vascular dementia (VaD) and Amyotrophic Lateral Sclerosis (ALS) (AUC = 0.92). IBRAIN was significantly correlated to clinical measures and gene expression, enriched in immune process and protein metabolism. The IBRAIN score exhibited a significant ability to reveal the distinct progression of prodromal AD (i.e., Mild cognitive impairment, MCI) (Hazard Ratio (HR) = 6.52 [95% CI: 4.42∼9.62], p

To investigate the differences in the quality of Huangguanyin oolong tea from different geographical origins, the aroma composition of Huangguanyin oolong tea produced in Yunxiao and Wuyishan was analyzed by using electronic nose and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS). The electronic nose data showed that orthogonal partial least squares-discriminant analysis (OPLS-DA) could distinguish Huangguanyin oolong tea from different geographical origins. By HS-SPME-GC-MS, a total of 79 aroma components were identified, of which 17 aroma components were found to be significantly different between the two production regions and therefore could be used to distinguish the geographical origin of Huangguanyin oolong tea. According to odor activity values (OAV), methyl jasmonate, indole, jasmonone, E-nerolidol and jasmonolacton contributed greatly to the floral aroma of Yunxiao Huangguanyin tea, while linalool, decanal, laurelene, isovaleraldehyde and hexanal contributed greatly to the floral and fruit aroma of Wuyi Huangguanyin tea. The results of geographical origin authentication showed that the discrimination accuracy of the support vector machine (SVM) model based on the 17 differential aroma compounds was only 83.33%, compared to 100% based on five important aroma components (linalool, E-lactone, jasmonolactone, methyl jasmonate and indole). Our results will provide useful information for elucidating the quality characteristics of Huangguanyin oolong tea from Yunxiao and Wuyishan.

Abstract This study aimed to determine whether regular recruitment maneuvers (RMs) are essential for obese patients (OPs) undergoing elective laparoscopic bariatric surgery (LBS) during intraoperative ventilation with individualized positive end‐expiratory pressure (PEEP). Patients were randomly assigned to two arms: the RM + PEEP−EIT arm consisted of individualized PEEP titrated by electrical impedance tomography (EIT) with two regular RMs and the PEEP−EIT arm consisted of individualized PEEP titrated by EIT without additional RMs. For these two arms together, EIT‐guided PEEP varied among individuals. The partial pressure of oxygen in arterial blood to fractional inspired oxygen (PaO2/FiO2) ratio in the RM + PEEP−EIT arm was higher than that in the PEEP−EIT arm at 1 h after pneumoperitoneum (p = 0.024) and at the end of surgery (p = 0.035). There was no great difference in the PaO2/FiO2 ratio between these two arms when measured 5 min prior to postanesthesia care unit (PACU) departure and on postoperative day 1. Compared with the PEEP−EIT arm, patients in the RM + PEEP−EIT arm had significantly higher intraoperative dynamic respiratory system compliance (p

BackgroundNeuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions and the GGC repeats in the 5'-untranslated region of NOTCH2NLC. The prevalent presence of high-intensity signal along the corticomedullary junction on diffusion-weighted imaging (DWI) helps to recognize this heterogeneous disease despite of highly variable clinical manifestations. However, patients without the typical sign on DWI are often misdiagnosed. Besides, there are no reports of NIID patients presenting with paroxysmal peripheral neuropathy-like onset to date.Case presentationWe present a patient with NIID who suffered recurrent transient numbness in arms for 17 months. Magnetic resonance imaging (MRI) showed diffuse, bilateral white matter lesions without typical subcortical DWI signals. Electrophysiological studies revealed mixed demyelinating and axonal sensorimotor polyneuropathies involving four extremities. After excluding differential diagnosis of peripheral neuropathy through body fluid tests and a sural nerve biopsy, NIID was confirmed by a skin biopsy and the genetic analysis of NOTCH2NLC.ConclusionThis case innovatively demonstrates that NIID could manifest as paroxysmal peripheral neuropathy-like onset, and addresses the electrophysiological characteristics of NIID in depth. We broaden the clinical spectrum of NIID and provide new insights into its differential diagnosis from the perspective of peripheral neuropathy.

ObjectiveThe purpose of this meta-analysis was to evaluate the effect of more intensive exercise training on the functional ability of patients with amyotrophic lateral sclerosis.MethodsRandomized controlled trials on exercise training in amyotrophic lateral sclerosis patients were retrieved from PubMed, Embase, Web of Science, Cochrane Library and other databases, and meta-analysis was conducted using a fixed effect model or random effect model. Sensitivity analysis was used as a means to study heterogeneity.ResultsA total of 8 randomized controlled trials involving 330 patients with amyotrophic lateral sclerosis were included in this study. The results showed that there was statistical significance in the influence of more intensive exercise training on amyotrophic lateral sclerosis Functional Rating Scale in the short term (0–4 months) and the medium term (5–8 months) (P < 0.05). There was no significant difference in the effect of the amyotrophic lateral sclerosis Functional Rating Scale-Revised in the short term (0–4 months) or long term (9–12 months) (P ≥ 0.05). In the medium term (5–8 months), there was statistical significance (P < 0.05). There was no significant difference in Forced vital capacity (FVC%) in the short term (0–4 months) (P > 0.05).ConclusionMore intensive exercise training may slow the decline in functional score of amyotrophic lateral sclerosis patients, and more studies should be carried out in the future to verify the effect of more intensive exercise training in patients with amyotrophic lateral sclerosis.

Plant-parasitic nematodes (PPNs) cause serious damage to agricultural production worldwide. Currently, because of a lack of effective and environmental-friendly chemical nematicides, the use of microbial nematicides has been proposed as an eco-friendly management strategy to control PPNs. A nematicidal bacterium GC-7 was originally isolated from the rice rhizosphere, and was identified as Pseudomonas rhodesiae. Treatment with the fermentation supernatant of GC-7 in vitro showed a highly lethal effect on second-stage juveniles of Meloidogyne graminicola, with the mortality rate increasing to 95.82% at 24 h and egg hatching significantly inhibited, with a hatch inhibition rate of 60.65% at 96 h. The bacterium significantly reduced the level of damage caused by M. graminicola infestations to rice (Oryza sativa) in greenhouse and field experiments. Under greenhouse conditions, the GC-7 culture efficiently reduced the gall index and nematode population in rice roots and soils, as well as inhibited nematode development compared to the control. Under field conditions, application of the GC-7 consistently showed a high biocontrol efficacy against M. graminicola (with a control efficiency of 58.85%) and promoted plant growth. In addition, the inoculation of GC-7 in M. graminicola-infested rice plant fields significantly suppressed final nematode populations in soil under natural conditions. Furthermore, activities of plant defense-related enzymes, peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase were remarkably increased in plant roots treated with GC-7 compared with roots that were challenge to M. graminicola. Moreover, quantitative real-time PCR analysis showed that GC-7 significantly enhanced the expression of defense genes (PR1a, WRKY45, JaMYB, AOS2, ERF1, and ACS1) related to salicylic acid, jasmonic acid, and ethylene signaling pathways in rice roots after inoculation with GC-7 at different levels. The results indicated that GC-7 could be an effective biological component in the integrated management of M. graminicola infecting rice.

Abstract Glioblastoma multiforme (GBM) is a life-threatening brain tumor. This study aimed to identify potential targets of the long noncoding RNA (lncRNA) HULC that promoted the progression of GBM. Two U87 cell lines were constructed: HULC-siRNA and negative control (NC). Quantitative real-time PCR (qRT-PCR) was performed to validate the transfection efficiency of HULC silencing vector. Mass spectrometry (MS) was used to generate proteomic profiles for the two cell lines. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to distinguish HULC-related genes and pathway mapping. Colony formation, Transwell, and wound-healing assays were used to investigate the functional effects of HULC knockdown on GBM. We identified 112 up-regulated proteins and 24 down-regulated proteins from a total of 4360 quantified proteins. GO enrichment illustrated that these proteins were mainly involved in organelle structure, catalysis, cell movement, and material metabolism. KEGG pathway analysis indicated that some of these proteins were significantly enriched in tight junction, metabolic pathways, and arachidonic acid metabolism. In vitro experiments demonstrated that HULC knockdown inhibited GBM cell proliferation, invasion, and migration. Our KEGG analyses revealed that PLA2G4A was a shared protein in several enriched pathways. HULC silencing significantly down-regulated the expression of PLA2G4A. Knockdown of HULC changed the proteomic characteristics of GBM and altered the behaviors of GBM cells. Specifically, we identified PLA2G4A as an HULC target in GBM. This study provides a new perspective on the mechanisms and potential drug targets of GBM treatment.

Attention deficit hyperactivity disorder (ADHD) has a complex etiology, and its specific causal factors remain to be elucidated. Aberration of nitric oxide synthase (nNOS) and inflammation, together with astrocytic and microglial cells have been continually associated with several neurological disorders, including ADHD. Using spontaneously hypertensive rat (SHR), we investigated the changes in nNOS, inflammatory, microglial and astrocytic markers in the frontal cortex and hippocampus at three different ages: onset of hypertension stage (i.e., 6 weeks after birth of SHR), established hypertension stage (i.e., 12 weeks after birth of SHR) and senescent stage (i.e., 12 months after birth of SHR), and compared with its age-matched normotensive control, Wistar-Kyoto (WKY) rats. A significant upregulation of Iba-1 expression in the senescent stage of SHR was observed. Further, we observed an upregulated nNOS expression in both onset and established stages of SHR, and a downregulated nNOS in the senescent stage. Our study showed an age-related increment of astrogliosis in the cortex and hippocampi of aged SHR. On the basis of our results, alterations in the nNOS and Iba-1 expressions, as well as age-related astrogliosis, may contribute to ADHD pathogenesis.

Abstract Weight loss is common in patients with Amyotrophic lateral sclerosis (ALS), and associated with disease progression. Loss of appetite has been shown to be a contributor to weight loss in patients with amyotrophic lateral sclerosis (ALS). However, the reason of loss of appetite is not clear. The Council on Nutrition appetite questionnaire (CNAQ) and the simplified nutritional appetite questionnaire (SNAQ) are short and simple appetite assessment tools, which were using in ALS patients. In our study, the CNAQ and SNAQ were translated into Chinese, and their reliability and validity were tested. The Chinese version of the CNAQ (CNAQ-C) presented more appropriate reliability and validity than the SNAQ. Among the 94 ALS patients, 50 patients (53.2%) had loss of appetite, and we found that anxiety and/or depression contributed to the loss of appetite in the ALS patients. We reconfirmed that loss of appetite was associated with greater weight loss but not with clinical features of ALS. The loss of appetite caused by emotional problems in ALS patients should be taken seriously, and early intervention should be implemented to reduce weight loss.

Abstract Background While the influence of meteorology on carbon monoxide (CO) poisoning has been reported, few data are available on the association between air pollutants and the prediction of CO poisoning. Our objective is to explore meteorological and pollutant patterns associated with CO poisoning and to establish a predictive model. Results CO poisoning was found to be significantly associated with meteorological and pollutant patterns: low temperatures, low wind speeds, low air concentrations of sulfur dioxide (SO2) and ozone (O38h), and high daily temperature changes and ambient CO (r absolute value range: 0.079 to 0.232, all P values

Background Evidence has demonstrated that puerarin is a potential medicine for the treatment of cardiac hypertrophy. However, the precise underlying molecular mechanisms of the protective effect of puerarin are still unclear. Here, we aimed to explore the regulatory mechanisms of lncRNAs/mRNAs co-expression network in a cardiac hypertrophy mouse model after puerarin treatment. Methods A mouse model of cardiac hypertrophy was established by transverse aortic constriction (TAC). The echocardiography, tissue staining and western blot were used to examine the protective effect of puerarin. Then RNA sequencing (RNA-seq) was carried out to analyze systematically mRNAs and lncRNAs expression. The target lncRNA were confirmed using qRT-PCR. Moreover, a coding/non-coding gene co-expression network were established to find the interaction of lncRNA and mRNAs. The biological process, cellular component, molecular function and pathways of different expression mRNAs targeted by lncRNA were explored using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis. Results Puerarin exhibited an obvious inhibitory effect in cardiac hypertrophy in TAC model. RNA-seq analysis was performed to investigate the lncRNAs and mRNAs expression patterns of cardiomyocytes in sham and TAC groups treated with or without puerarin. RNA-seq identified that TAC downregulated four lncRNAs, which could be revised by puerarin treatment (|log2 Fold change| > 2 and FDR < 0.05). Among them, expression alterations of lncRNA Airn (antisense of Igf2r non-protein coding RNA) was confirmed by qRT-PCR. Pearson’s correlation coefficients of co-expression levels suggested that there was an interactive relationship between Airn and 2,387 mRNAs (r > 0.95 or r < −0.95). Those co-expressed mRNAs were enriched in some important biological processes such as translational initiation, cell proliferation, insulin-like growth factor binding and poly(A) RNA binding. KEGG analyses suggested that those Airn-interacted mRNAs were enriched in endocytosis, signaling pathways regulating pluripotency of stem cells and the Jak-STAT pathway. Conclusion Puerarin may exert beneficial effects on cardiac hypertrophy through regulating the lncRNAs/mRNAs co-expression network.

Background and ObjectiveIn amyotrophic lateral sclerosis (ALS), progressive weakness significantly limits the ability to exercise. However, measurements of the impaired exercise function and their practical value to assess disease progression in ALS are scarce. Cardiopulmonary exercise testing (CPET) is a non-invasive accurate method used to comprehensively quantify exercise physiology in a variety of diseases. This study aimed to evaluate the clinical value of CPET and to explore its association with disease severity and prognosis prediction in ALS.MethodsA total of 319 participants were enrolled in this 3-year prospective study. After strict quality control, 109 patients with ALS and 150 age- and sex-matched healthy controls were included with comprehensive clinical assessment and follow-ups. The incremental ramp protocol for symptom-limited CPET was applied in both groups. The exercise physiology during peak effort exercise was systematically measured, including the overall aerobic capacity of exercise (VO2 peak) and the respective capacity of the exercise-involved organs [cardiac response (heart rate peak—HR peak), ventilatory efficiency (VE/VCO2 slope), breathing economy (VE/VO2 peak), and other relevant parameters]. Disease severity and progression were evaluated using recognized scales. Survival was monitored with regular follow-ups every 6 months.ResultsDecreased exercise capacity (VO2 peak < 16 ml/kg/min) occurred more frequently in patients with ALS than in controls (44.95% vs. 9.33%, p < 0.01). In patients with ALS, the average VO2 peak (16.16 ± 5.43 ml/kg/min) and HR peak [135 (112–153) bpm] were significantly lower (p < 0.01) than in controls [22.26 ± 7.09 ml/kg/min; 148 (135–164) bpm], but the VE/VCO2 slope was significantly higher [28.05 (25.03–32.16) vs. 26.72 (24.37–29.58); p = 0.03]. In patients with ALS, the VO2 peak and HR peak were significantly correlated with disease severity and progression scores (p < 0.05). Survival analyses revealed the VO2 peak and HR peak as protective indicators while the VE/VO2 peak as a detrimental indicator for the prognostic prediction in ALS (HR = 0.839, p = 0.001; HR = 0.967, p < 0.001; HR = 1.137, p = 0.028, respectively).ConclusionOur prospective study quantified the significantly decreased exercise capacity in ALS through non-invasive CPET. The impaired VO2 peak and HR peak closely correlated with disease severity and independently predicted a worse prognosis. Our findings identified the clinical value of CPET as an objective indicator of disease progression in ALS.

Abstract Background A consensus has been reached that carbapenem-resistant Enterobacteriaceae (CRE) screening in immunosuppressed individuals can reduce the incidence of CRE bloodstream infection (BSI). Methods We retrospectively studied the clinical data of 395 consecutive HSCT patients from September 2017 to April 2019. From September 2017 to June 2018 (period 1), 200 patients received single CRE screening before transplantation. From July 2018 to April 2019 (period 2), 195 patients received continuous weekly CRE screening after admission. For patients colonized with CRE, targeted managements were received: (1) contact precautions and (2) preemptive CRE-targeted treatment if necessary. Results During period 1, 3 patients with CRE colonization were detected (1.5%). The CRE BSI rate was 2.0% (4 patients), and the related 30-day mortality was 50.0% (2 out of 4 patients). During period 2, 21 patients with CRE colonization were detected, and the detection rate was significantly higher than that in period 1 (P

Background: Increasing evidence has shown that amyotrophic lateral sclerosis (ALS) can result in abnormal energy metabolism and sleep disorders, even before motor dysfunction. Although the hypothalamus and thalamus are important structures in these processes, few ALS studies have reported abnormal MRI structural findings in the hypothalamus and thalamus.Purpose: We aimed to investigate volumetric changes in the thalamus and hypothalamus by using the automatic brain structure volumetry tool AccuBrain®.Methods: 3D T1-weighted magnetization-prepared gradient echo imaging (MPRAGE) scans were acquired from 16 patients with ALS with normal cognitive scores and 16 age-, sex- and education-matched healthy controls. Brain tissue and structure volumes were automatically calculated using AccuBrain®.Results: There were no significant differences in bilateral thalamic (F = 1.31, p = 0.287) or hypothalamic volumes (F = 1.65, p = 0.213) between the ALS and control groups by multivariate analysis of covariance (MANCOVA). Left and right hypothalamic volumes were correlated with whole-brain volume in patients with ALS (t = 3.19, p = 0.036; t = 3.03, p = 0.044), while the correlation between age and bilateral thalamic volumes tended to be significant after Bonferroni correction (t = 2.76, p = 0.068; t = 2.83, p = 0.06). In the control group, left and right thalamic volumes were correlated with whole-brain volume (t = 4.26, p = 0.004; t = 4.52, p = 0.004).Conclusion: Thalamic and hypothalamic volumes did not show differences between patients with normal frontotemporal function ALS and healthy controls, but further studies are still needed.

Maintenance activities mostly depend on the specific conditions of individual equipment, being defined as personalized businesses. In order to improve the efficiency of maintenance activities for complex equipment in lots, the thinking of mass customization is used. After the modular technology used for generic maintenance model, the product/service was divided into mandatory and optional modules, which can form multiple optional maintenance service solutions. Considering the characteristics of maintenance activities and customers’ personalized maintenance requirements, configuration optimization is used to find the most satisfied maintenance solution under different objectives. This paper aims to provide the configuration optimization ideas and solutions for complex equipment maintenance services. A multi-objective optimization model was established, and an algorithm based on Non-Dominated Sorting Genetic Algorithms (NSGA-II) was proposed to solve this configuration optimization model. Finally, the maintenance service of the Electric Multiple Units (EMU) bogie was taken as an example to verify the feasibility of the model and the algorithm.

Herein, the convenient one-step electrochemical bromination of glycals using Bu4NBr as the brominating source under metal-catalyst-free and oxidant-free reaction conditions was described. A series of 2-bromoglycals bearing different electron-withdrawing or electron-donating protective groups were successfully synthesized in moderate to excellent yields. The coupling of tri-O-benzyl-2-bromogalactal with phenylacetylene, potassium phenyltrifluoroborate, or a 6-OH acceptor was achieved to afford 2C-branched carbohydrates and disaccharides via Sonogashira coupling, Suzuki coupling, and Ferrier rearrangement reactions with high efficiency. The radical trapping and cyclic voltammetry experiments indicated that bromine radicals may be involved in the reaction process.