Brucellosis is a zoonotic disease caused by a Gram-negative coccus a facultative intracellular pathogen. Neurobrucellosis has an incidence rate of 3-7% among all patients with brucellosis, while spinal cord involvement is rare and carries a significant mortality risk. This report describes a case of brucellosis myelitis in a 55-year-old male patient who presented with recurrent paralysis, incontinence, and damage to the visual and auditory nerves. The diagnosis of neurobrucellosis involves a serum tube agglutination test, cerebrospinal fluid analysis, a physical examination of the nervous system, and a comprehensive review of the patient\'s medical history. The presence of brucellosis was confirmed in cerebrospinal fluid using MetaCAP™ sequencing. Treatment with a combination of rifampicin, doxycycline, ceftriaxone sodium, amikacin, compound brain peptide ganglioside, and dexamethasone resulted in significant improvement of the patient\'s clinical symptoms and a decrease in the brucellosis sequence count in cerebrospinal fluid. For the first time, MetaCAP™ sequencing has been used to treat pathogenic microbial nucleic acids, which could be a valuable tool for early diagnosis and treatment of neurobrucellosis.

BACKGROUND: Alcohol use disorder is a chronic recurrent encephalopathy, and its pathogenesis has not been fully understood. Among possible explanations, neuroinflammation caused by the disorders of brain central immune signaling has been identified as one possible mechanism of alcohol use disorder. As the basic components of cells and important bioactive molecules, sphingolipids are essential in regulating many cellular activities. Recent studies have shown that sphingolipids-mediated neuroinflammation may be involved in the development of alcohol use disorder.
METHODS: PubMed databases were searched for literature on sphingolipids and alcohol use disorder (alcohol abuse, alcohol addiction, alcohol dependence, and alcohol misuse) including evidence of the relationship between sphingolipids-mediated neuroinflammation and alcohol use disorder (formation, withdrawal, treatment).
RESULTS: Disorders of sphingolipid metabolism, including the different types of sphingolipids and regulatory enzyme activity, have been found in patients with alcohol use disorder as well as animal models, which in turn cause neuro-inflammation in the central nervous system. Thus, these disorders may also be an important mechanism in the development of alcohol use disorder in patients. In addition, different sphingolipids may have different or even reverse effects on alcohol use disorder.
CONCLUSIONS: The sphingolipids-mediated neuroinflammation plays an important role in the development of alcohol use disorder. This review proposes a potential approach to prevent and treat alcohol use disorders by manipulating sphingolipid metabolism.

BACKGROUND: Acute myelitis (AM) can lead to sudden sensory, motor and autonomic nervous dysfunction, which negatively affects their daily activities and quality of life, so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.
OBJECTIVE: To investigate the effect of ganglioside (GM) combined with methylprednisolone sodium succinate (MPSS) on the curative effect and neurological function of patients with AM.
METHODS: First, we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality, with 52 patients receiving gamma globulin (GG) + MPSS and 56 patients receiving GM + MPSS, assigned to the control group (Con) and observation group (Obs), respectively. The therapeutic effect, neurological function (sensory and motor function scores), adverse events (AEs), recovery (time to sphincter function recovery, time to limb muscle strength recovery above grade 2, and time to ambulation), inflammatory factors (IFs) [interleukin (IL)-6, C-reactive protein (CRP), and tumor necrosis factor (TNF)-α] and other data of the two groups were collected for evaluation and comparison.
RESULTS: The Obs had: (1) A significantly higher response rate of treatment than the Con; (2) Higher scores of sensory and motor functions after treatment that were higher than the baseline (before treatment) and higher than the Con levels; (3) Lower incidence rates of skin rash, gastrointestinal discomfort, dyslipidemia, osteoporosis and other AEs; (4) Faster posttreatment recovery of sphincter function, limb muscle strength and ambulation; and (5) Markedly lower posttreatment IL-6, CRP and TNF-α levels than the baseline and the Con levels.
CONCLUSIONS: From the above, it can be seen that GM + MPSS is highly effective in treating AM, with a favorable safety profile comparable to that of GG + MPSS. It can significantly improve patients\' neurological function, speed up their recovery and inhibit serum IFs.

The milk fat globule membrane (MFGM) is a complex tri-layer membrane that wraps droplets of lipids in milk. In recent years, it has attracted widespread attention due to its excellent bioactive functions and nutritional value. MFGM contains a diverse array of bioactive lipids, including cholesterol, phospholipids, and sphingolipids, which play pivotal roles in mediating the bioactivity of the MFGM. We sequentially summarize the main lipid types in the MFGM in this comprehensive review and outline the characterization methods used to employ them. In this comprehensive review, we sequentially describe the types of major lipids found in the MFGM and outline the characterization methods employed to study them. Additionally, we compare the structural disparities among glycerophospholipids, sphingolipids, and gangliosides, while introducing the formation of lipid rafts facilitated by cholesterol. The focus of this review revolves around an extensive evaluation of the current research on lipid isolates from the MFGM, as well as products containing MFGM lipids, with respect to their impact on human health. Notably, we emphasize the clinical trials encompassing a large number of participants. The summarized bioactive functions of MFGM lipids encompass the regulation of human growth and development, influence on intestinal health, inhibition of cholesterol absorption, enhancement of exercise capacity, and anticancer effects. By offering a comprehensive overview, the aim of this review is to provide valuable insights into the diverse biologically active functions exhibited by lipids in the MFGM.

Respiratory support is required in 20-30% of patients with Guillain-Barré syndrome (GBS). We investigated clinical and biological risk factors for mechanical ventilation (MV) in northeast China through a retrospective GBS study. The Erasmus GBS Respiratory Insufficiency Score (EGRIS) is a prognostic model for MV in patients with GBS, and its usefulness has been validated in several countries but not in China. Therefore, we intended to validate the EGRIS model in our GBS cohort.
A total of 252 patients with GBS were included in this study from January 2013 to October 2017. Risk factors for MV were identified via multivariate logistic regression analysis. The prognostic value of the EGRIS was validated via receiver operating characteristic curve analysis.
Thirty-one patients (12.3%) required MV (mean age 54.19 years), with a majority being male (77.4%). The risk factors for MV were male sex [odds ratio (OR) 3.720, 95% confidence interval (CI) 1.155-11.985, p < 0.05], shorter interval from onset to admission (OR 0.830, 95% CI 0.711-0.970, p < 0.05), lower Medical Research Council sum score at admission (OR 0.942, 95% CI 0.911-0.973, p < 0.001), neutrophil-to-lymphocyte ratio at admission (OR 1.174, 95% CI 1.049-1.315, p < 0.01), and cranial nerve deficit (OR 3.805, 95% CI 1.373-10.541, p < 0.05). The EGRIS had a good predictive ability for MV (area under the receiver operating curve 0.861) in patients with GBS, and a high EGRIS was a predictor for MV (OR 8.778, 95% CI 3.432-22.448, p < 0.001). However, there was no significant difference in ganglioside administration between ventilated and nonventilated patients.
An elevated neutrophil-to-lymphocyte ratio at admission and a high EGRIS could serve as predictors for MV in our GBS cohort.

Objective: This study aimed to determine the diagnostic efficiency of a novel immunoblotting detection assay for anti-ganglioside antibodies (AGAs) in the Guillain-Barre syndrome (GBS). Method: Serum immunoglobulin (IgG and IgM) of AGAs were measured in 121 participants from a registered cohort study of immune-mediated neuropathies and 29 healthy controls by immunoblotting panel assay. Sensitivity, specificity, and positive predictive value (PPV) of the assay were compared to calculate the diagnostic accuracy. Result: In our cohort, any of the AGAs were positive in 42.4% of the GBS patients. The sensitivity and specificity of AGAs (both IgG and IgM) in the diagnosis of GSB were 42 and 76% while for IgG-AGAs were 35 and 87%. AGAs positivity had a significant association with the AMAN subtype (P = 0.0004), and the sensitivity, specificity of AGAs in AMAN were 86, 69%, respectively with high (AUC = 0.78, p = 0.002) discriminative powers. GM1-IgG AGA was more common and specific to AMAN patients than other GBS forms (p = 0.008). Conclusion: Our novel immunoblotting detection assay could complement GBS diagnosis. IgG-AGAs were more likely to be detected in GBS, and GM1-IgG AGA could assist AMAN diagnosis.

Delivery of functional proteins into cells may help us understand how specific protein influences cell behavior as well as treat diseases caused by protein deficiency or loss-of-function mutations. However, protein cannot enter cells by diffusion. In this work, a novel cell biology tool for delivering recombinant proteins into mammalian cells was developed. We hijacked the intracellular transport routes used by the cholera toxin and took advantage of recent development on split intein that is compatible with denatured conditions and shows an exceptional splicing activity to deliver a protein of interest into mammalian cells. Here, we used green fluorescent protein and apoptin as proofs-of-concept. The results demonstrate that the cholera toxin B subunit alone could deliver other recombinant proteins into cells through either covalent conjugation or noncovalent interaction. Our method offers more than 10-fold better delivery efficiency than the tat cell-penetrating peptide and is selective for ganglioside-rich cells. This study adds a useful tool to the receptor-mediated intracellular targeting toolkit and opens possibility for the selective delivery of therapeutic proteins into ganglioside-rich cells.

OBJECTIVE: This study was intended to evaluate the effects of gangliosides combined with mouse nerve growth factor (NGF) on the expression of serum hypoxia-inducible factor-1α (HIF-1α), neuron-specific enolase (NSE), and soluble intercellular adhesion molecule-1 (sICAM-1) levels in neonates with ischemic-hypoxic encephalopathy (HIE).
METHODS: One hundred and thirty neonates with HIE admitted to our hospital from May 2017 to April 2019 were grouped into two groups according to the protocol of a randomized controlled trial, with 65 cases in each group. The control group received ganglioside treatment, while the combined group was treated with ganglioside + NGF for 2 weeks.
RESULTS: The total effective rate of treatment was higher in the combined group (90.77%) than in the control group (76.92%). The recovery time of sucking, consciousness, muscle tone and primitive reflexes was shorter in the combined group than in the control group, and the incidence of neurological sequelae was lower after 1 year in the combined group (4.62%) than in the control group (15.38%) (P < 0.05).
CONCLUSIONS: Gangliosides combined with NGF can promote the recovery of muscle tone and reduce neurological sequelae, which may possibly be achieved by repairing damaged neuronal cells, enhancing antioxidant enzyme activity, and promoting the regression of inflammation.

Sea urchin gangliosides (SU-GLSs) are well acknowledged for their nerve regeneration activity and neuroprotective property. The present study sought to characterize and semi-quantitate different SU-GLS subclasses in three sea urchin species, including Strongylocentrotus nudus, Hemicentrotus pulcherrimus, and Glyptocidaris crenularis. A total of 14 SU-GLS subclasses were identified by a hydrophilic interaction liquid chromatography-Q-Exactive tandem mass spectrometry method. Three sialic acid (Sia) structures, including Neu5Ac, Neu5Gc, and KDN, were identified in SU-GLSs, of which Neu5Ac and Neu5Gc had their corresponding sulfated forms. The linkage among Sias was determined to be 2-8. Additionally, KDN2-6Glc1-1Cer, KDN2-8Neu5Gc2-6Glc1-1Cer, and KDN2-8Neu5Gc2-8Neu5Gc2-6Glc-1Cer were speculated to be novel SU-GLS structures. Furthermore, the total SU-GLS content was 2.0-7.3 mg/g in the three sea urchin species. These results will provide useful data for developing a SU-GLS database of aquatic products. Besides, this study will provide a theoretical basis to explore the nutritional values of seafood products further.

Four potent native human monoclonal antibodies (mAbs) targeting distinct epitopes on tetanus toxin (TeNT) are isolated with neutralization potency ranging from approximately 17 mg to 6 mg each that are equivalent to 250 IU of human anti-TeNT immunoglobulin. TT0170 binds fragment B, and TT0069 and TT0155 bind fragment AB. mAb TT0067 binds fragment C and blocks the binding of TeNT to gangliosides. The co-crystal structure of TT0067 with fragment C of TeNT at a 2.0-Å resolution demonstrates that mAb TT0067 directly occupies the W pocket of one of the receptor binding sites on TeNT, resulting in blocking the binding of TeNT to ganglioside on the surface of host cells. This study reveals at the atomic level the mechanism of action by the TeNT neutralizing antibody. The key neutralization epitope on the fragment C of TeNT identified in our work provides the critical information for the development of fragment C of TeNT as a better and safer tetanus vaccine.