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Abstract Objective Neuromyelitis optica (NMO) was a serious autoimmune inflammatory condition affecting the central nervous system. Currently, there was a lack of diagnostic biomarkers for AQP4‐IgG‐negative NMO patients. Methods A comparative proteomic analysis was conducted on the CSF of 10 patients with NMO and 10 patients with non‐inflammatory neurological disorders (NND) using tandem mass tagging technology. Differentially expressed proteins (DEPs) were analyzed using bioinformatic methods. The candidate proteins were then validated through ELISAs in a subsequent cohort of 160 samples, consisting of paired CSF and plasma samples from 50 NMO patients, CSF samples from 30 NND patients, and plasma samples from 30 healthy individuals. Results We identified 389 proteins via proteomics, screening 79 DEPs. NCAM1, SST and AHSG were selected as candidate molecules for further validation. Compared to NND patients, there were decreased levels of AHSG in CSF and increased levels of NCAM1 and SST in NMO patients. The ELISA results revealed significantly higher levels of AHSG, SST and NCAM1 in the CSF of the NMO group compared to the NND group. Similarly, the serum levels of these three proteins were also higher in the NMO group compared to the healthy control group. It was found that serum NCAM1 levels significantly decreased in patients with non‐relapsed NMO compared to patients with relapsed NMO and CSF NCAM1 level increased in patients with bilateral NMO compared to patients with unilateral NMO. Furthermore, CSF SST levels increased in AQP4 antibody‐positive NMO patients compared to AQP4 antibody‐negative patients. Interpretation CSF NCAM1, serum NCAM1 and serum SST may serve as potential biomarkers for NMO patients and aid in the diagnosis of AQP4 antibody‐negative NMO patients.

Abstract Aims We conducted a presentation on an 84‐year‐old male patient who has been diagnosed with TTRA81V (p. TTRA101V) hereditary transthyretin cardiac amyloidosis (hATTR‐CM). In order to establish its pathogenicity, we extensively investigated the biochemical and biophysical properties of the condition. Methods and results Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an increasingly acknowledged progressive infiltrative cardiomyopathy that leads to heart failure and potentially fatal arrhythmias. Gaining a comprehensive understanding of the biochemical and biophysical characteristics of genetically mutated TTR proteins serves as the fundamental cornerstone for delivering precise medical care to individuals affected by ATTR. Laboratory assessments indicated a brain natriuretic peptide of 200.12 ng/L (normal range: 0–100 ng/L) and high‐sensitivity cardiac troponin I of 0.189 μg/L (normal range: 0–0.1 μg/L). Echocardiography identified left atrial enlargement, symmetrical left ventricular hypertrophy (16 mm septal and 16 mm posterior wall), and a left ventricular ejection fraction of 56%. Cardiac‐enhanced magnetic resonance imaging revealed subendocardial late gadolinium enhancement. Tc‐99m‐PYP nuclear scintigraphy confirmed grade 3 myocardial uptake, showing an increased heart‐to‐contralateral ratio (H/CL = 2.33). Genetic testing revealed a heterozygous missense mutation in the TTR gene (c.302C>T), resulting in an alanine‐to‐valine residue change (p. Ala81Val, following the first 20 residues of signal sequence nomenclature). Biochemical analysis of this variant displayed compromised kinetic stability in both the TTRA81V:WT (wild‐type) heterozygote protein (half‐life, t1/2 = 21 h) and the TTRA81V homozygote protein (t1/2 = 17.5 h). The kinetic stability fell between that of the TTRWT (t1/2 = 42 h) and the early‐onset TTRL55P mutation (t1/2 = 4.4 h), indicating the patient's late‐onset condition. Kinetic stabilizers (Tafamidis, Diflunisal, and AG10) all exhibited the capacity to inhibit TTRA81V acid‐ and mechanical force‐induced fibril formation, albeit less effectively than with TTRWT. Chromatographic assessment of the patient's serum TTR tetramers indicated a slightly lower concentration (3.0 μM) before oral administration of Tafamidis compared with the normal range (3.6–7.2 μM). Conclusions We identified a patient with hATTR‐CM who possesses a rare TTRA81V mutation solely associated with cardiac complications. The slightly reduced kinetic stability of this mutation indicates its late‐onset nature and contributes to the gradual progression of the disease.

Straw return is an effective measure to increase soil sustainability. However, few studies have examined the effects of different straw return methods on soil structure, soil organic carbon content and maize yield or the potential relationships between those variables. Therefore, we developed a field orientation experiment to study the effects of different straw return methods on soil porosity, soil aggregate stability, the soil organic carbon content and maize yield. Four treatments were established: flat no-tillage with full straw mulching (FM), ridge no-tillage with full straw mulching (LM), rotary tillage with full straw incorporation (LX), and conventional tillage without straw (CK) as the control treatment. Compared with those of the CK treatment, the soil porosities (f) in the FM, LM and LX treatments significantly increased by 6.7%, 8.8% and 7.9%, respectively; the soil aggregate destruction rates (PAD) decreased by 17.3%, 34.3% and 16.9%, respectively. In addition, the FM, LM and LX treatments effectively increased the mean mass diameters (MWDs) of the soil aggregates and the soil organic carbon content. Compared with those in the CK treatment, the three-year average yields in the FM, LM and LX treatments significantly increased by 5.2%, 7.2% and 4.1%, respectively. Moreover, the f, MWD, soil organic carbon content and corn yield were positively correlated. Our study indicates that the LM treatment was most effective in improving soil structure and increasing soil organic carbon content with corn yield.

Abstract Aims To evaluate the effect of antibiotic prophylaxis(AP) in the prognosis of Post-neurosurgical meningitis(PNM) patients. Methods A cohort analysis was performed using the clinical database in Beijing Tiantan Hospital and Capital Medical University. Data were collected on patients with the diagnosis of PNM (n = 3931) during 2012.01 to 2022.04. The microbial distribution, types of AP, and 42 and 90 days survival analysis of AP patients were evaluated using probable statistical methods. Independent risk factors for mortality were established by constructing a logistic regression analysis. Result A total of 1,190 patients were included in this study, Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus occupied the highest proportion. Of them, 929 cases received AP, cefuroxime and ceftriaxone are the most frequent used antibiotics. In addition, We found that PNM patients without AP significantly increased the 42 days and 90 days all-cause mortality rates. The use of different levels of AP did not improve patient outcomes, and ICU admission and assisted mechanical ventilation (AMV) were identified as independent mortality risk factors for PNM patient received AP. Conclusions AP plays an important role in the prognosis of PNM patients and has a significant function in improving prognosis. The prevention of PNM with antibiotics prior to neurosurgery should be emphasized in clinical practice, and appropriate selection of antibiotics is necessary to prevent the occurrence of infection and inhibit the emergence of antibiotic-resistant bacteria.

The accumulation, processing and toxicity of Aβ can be affected by interacting with transthyretin (TTR). We obtained 31 compounds with different structures by virtual screening based on protein structure. Among them, compound 11 inhibited acid-induced TTR protein amyloid fibrils by 75.57 ​± ​11.27%, inhibited Aβ amyloid fibrils by 68.55 ​± ​0.81%, and promoted depolymerization of Aβ fibrils by 109.2 ​± ​7.9%. Surprisingly, this molecule, as a pharmacological chaperone of TTR/Aβ, bound to TTR and Aβ to form a ternary complex that promoted Aβ phagocytosis by microglia and attenuated Aβ neurotoxicity. These results together suggest that formation of the ternary complex [TTR+11] +Aβ may become a viable therapeutic approach for AD treatment.

ObjectivesTo analyze the differences in laboratory data between patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD).MethodsThe study included 26 MOGAD patients who visited Beijing Tiantan Hospital from 2018 to 2021. MS and NMOSD patients who visited the clinic during the same period were selected as controls. Relevant indicators were compared between the MOGAD group and the MS/NMOSD groups, and the diagnostic performance of meaningful markers was assessed.ResultsThe MOGAD group showed a slight female preponderance of 57.7%, with an average onset age of 29.8 years. The absolute and relative counts of neutrophils were higher in the MOGAD group than in the MS group, while the proportion of lymphocytes was lower. The cerebrospinal fluid (CSF) IgG level, IgG index, 24-h IgG synthesis rate, and positive rate of oligoclonal bands (OCB) were lower in MOGAD patients than in the MS group. The area under ROC curve (AUC) was 0.939 when combining the relative lymphocyte count and IgG index. Compared to the NMOSD group, the MOGAD group had higher levels of serum complement C4 and lower levels of serum IgG. The AUC of serum C4 combined with FT4 was 0.783.ConclusionStatistically significant markers were observed in the laboratory data of MOGAD patients compared to MS/NMOSD patients. The relative lymphocyte count combined with IgG index had excellent diagnostic efficacy for MOGAD and MS, while serum C4 combined with FT4 had better diagnostic efficacy for MOGAD and NMOSD.

BackgroundGuillain–Barré syndrome (GBS) is the most common severe acute paralytic neuropathy, with a mortality rate of 5% and permanent sequelae rate of 10%. Currently, the cause of GBS remains unclear. Therefore, we sought to determine potential predictors for GBS and its severity.MethodsA case–control study was performed at Tiantan Hospital in Beijing from January 2017 to December 2021. Laboratory and clinical characteristics were assessed in recruited GBS patients and healthy control individuals (matched by sex and age). The potential risk factors for GBS and severe GBS were assessed using a logistic regression analysis. The mRNA levels of toll-like receptor 4 (TLR4), toll-like receptor 2 (TLR2) and nuclear factor κB (NF-κB) in GBS patients and control PBMCs were detected by fluorescence quantitative PCR. THP-1 cells were costimulated with LPS and free cholesterol to demonstrate the effect of free cholesterol on monocyte activation.ResultsA total of 147 GBS patients and 153 healthy individuals were included in the study. Logistic regression analyses showed that preceding infection, alcohol consumption, remnant cholesterol, homocysteine and the dyslipidemia index were correlated with a higher risk of GBS. In contrast, increased HDL cholesterol was correlated with a lower risk of GBS. Moreover, remnant cholesterol and the dyslipidemia index were significantly correlated with severe GBS. The mRNA levels of TLR4, TLR2 and NF-κB in the PBMCs of GBS patients were significantly higher than those of healthy individuals. LPS activated THP-1 cells, and free cholesterol treatment increased the expression of TLR4, TLR2, NF-κB and IL-1β mRNA in LPS-activated THP-1 cells.ConclusionDyslipidemia was correlated with the risk of GBS and severe GBS. Remnant cholesterol may promote the activation of monocytes in GBS patients. It may be valuable to control lipid levels in the prevention of GBS and severe GBS.

ObjectiveHere, we aimed to identify protein biomarkers that could rapidly and accurately diagnose multiple sclerosis (MS) using a highly sensitive proteomic immunoassay.MethodsTandem mass tag (TMT) quantitative proteomic analysis was performed to determine the differentially expressed proteins (DEPs) in cerebrospinal fluid (CSF) samples collected from 10 patients with MS and 10 non-inflammatory neurological controls (NINCs). The DEPs were analyzed using bioinformatics tools, and the candidate proteins were validated using the ELISA method in another cohort comprising 160 samples (paired CSF and plasma of 40 patients with MS, CSF of 40 NINCs, and plasma of 40 healthy individuals). Receiver operating characteristic (ROC) curves were used to determine the diagnostic potential of this method.ResultsCompared to NINCs, we identified 83 CSF-specific DEPs out of a total of 343 proteins in MS patients. Gene ontology (GO) enrichment analysis revealed that these DEPs are mainly involved in platelet degranulation, negative regulation of proteolysis, and post-translational protein modification. Pathway enrichment analysis revealed that the complement and coagulation cascades, Ras signaling pathway, and PI3K-Akt signaling pathway are the main components. Insulin-like growth factor-binding protein 7 (IGFBP7), insulin-like growth factor 2 (IGF2), and somatostatin (SST) were identified as the potential proteins with high scores, degree, and centrality in the protein-protein interaction (PPI) network. We validated the expression of these three proteins using ELISA. Compared to NINCs, the level of CSF IGFBP7 was significantly upregulated, and the level of CSF SST was significantly downregulated in the MS group.ConclusionOur results suggest that SST and IGFBP7 might be associated with the pathogenesis of MS and would be helpful in diagnosing MS. Since IGFBP7 was used to classify relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients, therefore, it may act as a potential key marker and therapeutic target in MS.

Genetically modified pigs have become a popular model system in fundamental research, agricultural and biomedical applications. However, random integration often result in unstable expression of transgene and unpredictable phenotypes. The Rosa26 locus has been widely used to produce genetic modified animals with high and consistent expressing of transgene in mouse, human and rat, as it can be targeted efficiently and is not subject to gene-silencing effects. Recently, the first case of reporter gene targeting pigs in porcine Rosa26 (pRosa26) locus was reported. In the study, full sequence of pRosa26 locus was further characterized, and the pRosa26 promoter (pR26) was cloned and we evidenced that the new porcine endogenous promoter is suitable for driving transgene expression in a high and stable manner by avoiding DNA methylation. Furthermore, elongation factor 1a promoter (EF1a) -driven GFP reporter and Myostatin promoter (MyoP)-driven Follistatin (Fst) were successfully targeted into the pRosa26 locusby traditional homologous recombination (HR) strategy. EF1a showed high activity and hypomethylation at the locus. And, muscle-specific promoter MyoP was activated strictly in muscle of the pRosa26 targeted pigs, indicating Rosa26 locus supports tissue-specific promoter driving transgene expression in its own manner. The study provided further demonstration on biomedical and agricultural applications of porcine Rosa26 promoter and locus.

On-Road Sensor Networks (ORSNs) play an important role in capturing traffic flow data for predicting short-term traffic patterns, driving assistance and self-driving vehicles. However, this kind of network is prone to large-scale communication failure if a few sensors physically fail. In this paper, to ensure that the network works normally, an effective fault-tolerance mechanism for ORSNs which mainly consists of backup on-road sensor deployment, redundant cluster head deployment and an adaptive failure detection and recovery method is proposed. Firstly, based on the N − x principle and the sensors’ failure rate, this paper formulates the backup sensor deployment problem in the form of a two-objective optimization, which explains the trade-off between the cost and fault resumption. In consideration of improving the network resilience further, this paper introduces a redundant cluster head deployment model according to the coverage constraint. Then a common solving method combining integer-continuing and sequential quadratic programming is explored to determine the optimal location of these two deployment problems. Moreover, an Adaptive Detection and Resume (ADR) protocol is deigned to recover the system communication through route and cluster adjustment if there is a backup on-road sensor mismatch. The final experiments show that our proposed mechanism can achieve an average 90% recovery rate and reduce the average number of failed sensors at most by 35.7%.