Celiac vagus nerve mediates expression of the acetylcholine receptor α7nAChR on monocytes in the spleen.

The spleen is required for the vagal cholinergic anti-inflammatory activity to maintain systemic immune homeostasis, but the underlying mechanism of this function is not fully understood yet. We hypothesized that vagus nerve mediates alpha 7 nicotinic acetylcholine receptor (α7nAChR) expression in monocytes, an essential regulator of cholinergic anti-inflammatory activity, and the spleen is essential site for this process. To verify this hypothesis, mice were subjected to splenectomy or celiac vagotomy. The level of α7nAChR expression in circulating monocytes was analyzed by real-time PCR. Impact of α7nAChR agonist PNU282987 on LPS-evoked release of TNF-α and IL-1ß from circulating monocytes was assessed by ELISA. The effect of norepinephrine (NE), acetylcholine (ACh) and neuregulin-1 (NRG-1) on α7nAChR expression was detected by real-time PCR. We found that splenectomy or celiac vagotomy abrogated α7nAChR expression in circulating monocytes. LPS-induced release of TNF-α and IL-1ß from these monocytes was not alleviated significantly by PNU282987 as compared with that of sham mice. NE and ACh addition fails to stimulate α7nAChR expression, but, NRG-1 treatment can significantly induce α7nAChR expression in these monocytes compared with untreated cells in vitro. Overall, our results reveal that celiac vagus nerve mediates α7nAChR expression in monocytes, and the spleen is indispensable site for this process.

Autophagy-deficiency in bone marrow mononuclear cells from patients with myasthenia gravis: a possible mechanism of pathogenesis.

Myasthenia gravis (MG) is a chronic autoimmune disorder resulting from autoantibodies against neuromuscular junction components. Research shows that this disease might be a primary bone marrow (BM) stem cell disorder. Autophagy protects the dynamics and homeostasis of the host cells by removing damaged mitochondria, protein aggregates and other intercellular materials. Dysfunctional autophagy is associated with autoimmune diseases. However, the autophagy activity and mechanisms in BM stem cell from MG patients remain largely uncharacterized. We evaluated the autophagy activity in bone marrow mononuclear cells (BM-MNCs) and the effects of autophagy on cell survival from patients with MG and healthy controls. Our results revealed that autophagy was significantly decreased in patients with MG before immunomodulation treatment compared with that in age-/sex-matched controls, and was lower in generalized MG (GMG) patients than in ocular MG (OMG) patients. Immunomodulatory treatment partially increased autophagy activity of BM-MNCs in MG patients and improved the symptoms. Furthermore, defective BM-MNCs differentiation, proliferation and apoptosis were observed due to dysfunctional autophagy. These findings suggest for the first time that BM-MNCs autophagy is impaired in patients with MG before immunomodulation therapy, and that autophagy is indispensable for the survival of BM-MNCs, implicating autophagy might be a potential pathogenic mechanism of MG and a novel therapeutic strategy for MG treatment.

Cognitive disorders in HIV-infected and AIDS patients in Guangxi, China.

The purposes of this study were to assess cognitive disorders in HIV/AIDS patients, identify the prevalence of HIV-associated neurocognitive disorders (HAND), provide evidence that may be used for early diagnosis and treatment, and establish a baseline for follow-up studies. The setting for this study was Guangxi, a culturally and economically underdeveloped province located in southwestern China with a large minority community. Due to the specific geographic and cultural environment, Guangxi has the second highest HIV incidence in China. There have been no research or large epidemiologic studies exploring cognitive disorders in HIV/AIDS patients in Guangxi; therefore, the prevalence of HAND in patients is unknown. Thirteen tests from 12 reliable and valid neuropsychological instruments (the digit symbol test, trail making test, arithmetic scores, digit span, wood puzzle, immediate visual memory, visual memory, Stroop test, vocabulary fluency, conceptual fluency, and the Wisconsin Card Sorting Test) were used to test and compare the cognitive functions and prevalence of HAND in 99 healthy individuals and 230 HIV/AIDS patients. Within the patient group, 114 were HIV-positive without cognitive impairment and 86 (37.39%) had HAND. Among them, 42 (18.27%) had HIV-related neurocognitive impairment (ANI), 25 (18.87%) had HIV-related mild neurocognitive disorder (MND), and 19 (8.26%) had HIV-associated dementia (HAD). These results may be used for future research, such as neuroimaging studies and risk factor analysis of HAND, and in the development of early diagnosis and treatment options for HAND patients.

Abortion outbreak in pregnant goats and cows with coinfection of 'Candidatus Mycoplasma haemobos' and HoBi-like pestivirus.

New emerging diseases, including 'Candidatus Mycoplasma haemobos' ('Ca. M. haemobos') and HoBi-like pestivirus in central China has been a huge challenge for ruminant production. From July to September 2022, an abortion outbreak affected 14 goat farms and 11 cattle farms in this area. To investigate whether the two pathogens are associated with the disease, samples were collected: Group 1 included 55 goat blood samples with foetal tissue samples and ticks on the skin; Group 2 included nine healthy goat blood samples; Group 3 included 36 cow blood samples with foetal tissue samples and ticks on the skin; and Group 4 included seven healthy cow blood samples. Then, these samples were analysed by serology, PCR, sequence analysis, and identification. A total of 339 Rhipicephalus (Boophilus) microplus and 61 Haemaphysalis longicornis ticks were identified in Group 1 and Group 3. By molecular detection, 32 'Ca. M. haemobos'-positive amplicons, and 27 HoBi-like pestivirus-positive amplicons were amplified from goats in Group 1; meanwhile, 20 'Ca. M. haemobos'-positive amplicons, and 18 HoBi-like pestivirus-positive amplicons were amplified from foetuses. Statistical significance (P = 0.002) and association (OR=7.556) between the 'Ca. M. haemobos' PCR results of foetus and goat samples were observed, and statistical significance (P = 0.017) and association (OR=4.271) between the HoBi-like pestivirus PCR results of foetus and goat samples were observed. These significances and associations were also observed in Group 3. In addition, coinfections were detected in Group 1 and Group 3. 'Ca. M. haemobos' was detected in both tick species. Further serological results revealed that the frequency of HoBi-like pestivirus was 20.0 % (11/55) in Group 1 % and 30.6 % (11/36) in Group 3 in central China. No ticks, pathogens, or neutralizing antibodies were observed in Group 2 or Group 4. This is the first molecular evidence of 'Ca. M. haemobos' and HoBi-like pestivirus natural coinfections in goats and cows with abortion in China. HoBi-like pestivirus and 'Ca. M. haemobos' can be transferred from goats/cows to their foetuses.

Novel Insight into the Mechanism of Metabolic Surgery Causing the Diversity in Glycemic Status in Type 2 Diabetes.

Metabolic surgery results in diverse glycemic status in patients with type 2 diabetes (T2D), including hyperglycemia without remission, significant amelioration of hyperglycemia with partial remission, complete restoration of euglycemia, or with prolonged remission, hyperglycemia recurrence in relapses after remission, or post-bariatric hypoglycemia. Unfortunately, it is not known how metabolic surgery leads to this diverse consequence. Here, we discuss the diversity of glycemic status associated with metabolic surgery and the potential mechanisms of T2D remission. We also highlight the relationship between the change in low-grade inflammation and T2D remission after metabolic surgery. We hypothesize that the level of inflammatory and anti-inflammatory cytokines controls the efficacy of metabolic surgery in patients with T2D. This hypothesis may provide further insight into the mechanism of the beneficial effects of metabolic surgery patients with T2D.

Molecular epidemiology, drug resistance, and virulence gene analysis of Streptococcus agalactiae isolates from dairy goats in backyard farms in China.

Streptococcus agalactiae infections may lead to clinical or subclinical mastitis in dairy animals when it invades the mammary gland. In this study, 51 S. agalactiae strains were isolated from 305 milk samples that were collected from goats with mastitis in 13 provinces of China. The antimicrobial resistance of S. agalactiae was determined by disk diffusion methods against 18 antibiotics from six classes. In addition, multilocus sequence typing (MLST), and the presence of resistance and virulence genes was determined by PCR analysis. Seven sequence types in five clonal complexes were identified according to MLST; CC103 and CC67 strains were predominant, with rates of 45.1% and 39.2%, respectively. All isolates (100%) were multiresistant to three or more antimicrobial agents. S. agalactiae isolates had a 100% resistance rate to penicillin, oxacillin, and amoxicillin, followed by doxycycline (82.4%), tetracycline (76.5%), and amikacin (74.5%). The lowest resistance was observed for ciprofloxacin (29.4%), which varied in five different regions. The detection rates of six classes of antimicrobial-related genes were calculated as follows: 33 (64.7%) for ß-lactam-related resistance gene, 12 (23.5%) for tetracyclines, 11 (21.6%) for quinolone-related resistance genes, 10 (19.6%) for aminoglycosides, 7 (13.7%) for macrolides (ermA, ermB, and mefA), and 3 (5.9%) for lincosamide (lnu(B)). Regarding virulence genes, profile 1 (bca cfb-cspA-cylE-hylB-bibA-pavA-fbsA-fbsB) was the most prevalent, with a detection rate of 54.9%. This work provides a primary source related to the molecular epidemiology of S. agalactiae in dairy goat herds in China and will aid in the clinical treatment, prevention, and control of mastitis.

Exosome-Derived MiRNAs as Biomarkers of the Development and Progression of Intracranial Aneurysms.

AIM: Exosome-derived microRNAs (miRNAs) are potential diagnostic biomarkers. However, little is known about their effectiveness as diagnostic biomarkers of intracranial aneurysms (IAs). This study aimed to explore miRNA levels in plasma exosomes of patients with IA to identify potential biomarkers that predict the development and progress of IA. METHODS: A total of 69 patients with IA and 30 healthy controls (HC) were recruited, among whom 30 had unruptured IA (UA), and 39 had ruptured IA (RA). The miRNA expression profiles of plasma exosomes in 12 IA patients (4 UA and 8 RA) and 4 HC were determined using next-generation sequencing. In addition, significantly differentially expressed miRNAs were further analyzed by Quantitative Real-Time PCR (qRT-PCR) in a validation cohort of 99 subjects. RESULTS: From the sequencing analysis, 181 miRNAs were identified to be differently (p＜0.05) expressed. Of these, 9 miRNAs were up-regulated, and 20 were down-regulated in patients with UA compared with HC. Also, 21 were up-regulated, and 10 were down-regulated in patients with RA compared with HC. In addition, compared with UA, 92 miRNAs were up-regulated in RA, whereas 29 were down-regulated. Furthermore, qRT-PCR analysis confirmed that miR-145-5p and miR-29a-3p were up-regulated in IA samples. To distinguish IA patients from controls, the area under the receiver operating characteristic curve was 0.791 for miR-29a-3p, while that of miRNA-145-5p was 0.773 in terms of discriminating whether the aneurysm was ruptured. CONCLUSIONS: Circulating exosomal miRNAs can serve as biomarkers of the development and progression of IA.

Otolith nucleus chemistry distinguishes Electrona antarctica in the westward-flowing Antarctic Slope Current and eastward-flowing Antarctic Circumpolar Current off East Antarctica.

Eastward transport in the Southern Ocean is concentrated in jets associated with fronts in the Antarctic Circumpolar Current (ACC), whereas flow along the Antarctic continental slope is strongly westward in the Antarctic Slope Current (ASC). The dominant mesopelagic fish endemic to the Southern Ocean, Electrona antarctica (Günther, 1878), has been linked to Circumpolar Deep Water (CDW) transported by the ACC, and a modified version of CDW associated with the ASC. In conjunction with a regional-scale hydrographic survey south of the Kerguelen Plateau, we sampled fish from the ACC and ASC across Princess Elizabeth Trough off East Antarctica, and examined their otolith chemistry. Material laid down in the nucleus during early life showed heterogeneity, arguing against a single homogeneous population. Instead, it suggested exposure to different environments after hatching, consistent with separate transport pathways along the ACC and ASC. Despite clear differences between stations documented in the survey, material laid down along the edge did not show heterogeneity, suggesting instead exposure to similar environments. Seasonal movement northward by ASC fish into the ACC may explain both these results, and potential physical mechanisms include circulation in the Australian-Antarctic Gyre; northward movement of slope waters along the eastern margin of Princess Elizabeth Trough; and seasonal extension of sea-ice into the ACC. Such meridional movement would expose fish to zonal flow, eastward in the ACC during winter and westward in the ASC during summer, promoting regional retention as well as creating opportunities for mixing with fish transported along the ACC.

Validity of the International HIV Dementia Scale as assessed in a socioeconomically underdeveloped region of Southern China: assessing the influence of educational attainment.

In 2012, more than 80,000 cases of HIV infection were recorded in the Southern Chinese minority autonomous region of Guangxi Zhuang, where the occurrence of HIV-associated dementia remains high. The International HIV Dementia Scale is a relatively simple-to-administer screening scale for HIV-associated neurocognitive disorders. However, clinical experience in utilizing the scale with large Chinese samples is currently lacking, especially among individuals with limited formal schooling. In this study, a full neuropsychological evaluation the gold standard was conducted to identify the incidence/prevalence of HIV-associated neurocognitive disorders in a socioeconomically underdeveloped region of Southern China and to locate the optimal cut-off scale value using receiver operating characteristic curves. The highest Youden index of the scale was 0.450, with a corresponding cut-off point of 7.25. The sensitivity and specificity were 0.737 and 0.713, respectively. These results suggest that the scale is an effective and feasible screening tool for HIV-associated neurocognitive disorders in poorer regions of China with fewer well-educated residents.