On the relation between the mass of Compact Massive Objects and their host galaxies

Supermassive black holes and/or very dense stellar clusters are found in the central regions of galaxies. Nuclear star clusters are present mainly in faint galaxies while upermassive black holes are common in galaxies with masses $\geq 10^{10}$ M$_\odot$. In the intermediate galactic mass range both types of central massive objects (CMOs) are found. Here we present our collection of a huge set of nuclear star cluster and massive black hole data that enlarges significantly already existing data bases useful to investigate for correlations of their absolute magnitudes, velocity dispersions and masses with structural parameters of their host galaxies. In particular, we directed our attention to some differences between the correlations of nuclear star clusters and massive black holes as subsets of CMOs with hosting galaxies. In this context, the mass-velocity dispersion relation plays a relevant role because it seems the one that shows a clearer difference between the supermassive black holes and nuclear star clusters. The $M_{MBH}-{\sigma}$ has a slope of $5.19\pm 0.28$ while $M_{NSC}-{\sigma}$ has the much smaller slope of $1.84\pm 0.64$. The slopes of the CMO mass- host galaxy B magnitude of the two types of CMOs are indistinguishable within the errors while that of the NSC mass-host galaxy mass relation is significantly smaller than for supermassive black holes. Another important result is the clear depauperation of the NSC population in bright galaxy hosts, which reflects also in a clear flattening of the NSC mass vs host galaxy mass at high host masses.Comment: 12 pages, 22 figures, 2 tables, accepted for publication in MNRA

Chlorobenzoxime inhibits respiratory syncytial virus infection in neonatal rats via up-regulation of IFN-γ in dendritic cells

Purpose: To investigate the effect of chlorobenzoxime on respiratory syncytial virus (RSV) infection in vitro in lung alveolar cells and in vivo in neonatal rats, as well as the mechanism of action involved. Methods: RSV infection in neonatal rats was induced via intranasal administration of 2 x 106PFU viral particles. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting were used for determination of changes in interleukin expression. Results: RSV infection in BEAS-2B cells caused significant reduction in viability and marked alteration in morphological appearance (p < 0.05). Exposure of RSV-infected BEAS-2B cells to chlorobenzoxime prevented viability reduction and changes in morphology, and led to reductions in RSV-mediated increases in levels of interleukin-6 and interleukin-8. Moreover, RSV infection significantly enhanced ROS levels in BEAS-2B cells, when compared to control cells (p < 0.05). Chlorobenzoxime at a concentration of 30 μM completely suppressed RSV-mediated generation of ROS in BEAS-2B cells. In neonatal rats, RSV-induced upregulation of interleukin-4, interleukin-13 and TNF-α, were suppressed in bronchoalveolar lavage fluid (BALF) and lung tissues by chlorobenzoxime. Moreover, the RSVmediated reduction in IFN-γ was maximally blocked by chlorobenzoxime at a dose of 10 mg/mL. Chlorobenzoxime enhanced the proportion of IFN-γ -producing cells in neonatal rat BALF. Conclusion: Chlorobenzoxime exhibits antiviral against RSV infection in neonatal rats via increase in dendritic cell population, leading to inhibition of cytokine production. Therefore, chlorobenzoxime is a potential therapeutic agent for RSV infection. Keywords: Respiratory syncytial virus, Cytokines, Dendritic cells, Lung aveolar cells, Morphology, Interleukin

Marked Variation Between Winter and Spring Gut Microbiota in Freeranging Tibetan Macaques (Macaca thibetana)

Variation in the availability and distribution of food resources is a strong selective pressure on wild primates. We explored variation in Tibetan macaque gut microbiota composition during winter and spring seasons. Our results showed that gut microbial composition and diversity varied by season. In winter, the genus Succinivibrio, which promotes the digestion of cellulose and hemicellulose, was significantly increased. In spring, the abundance of the genus Prevotella, which is associated with digestion of carbohydrates and simple sugars, was significantly increased. PICRUSt analysis revealed that the predicted metagenomes related to the glycan biosynthesis and metabolic pathway was significantly increased in winter samples, which would aid in the digestion of glycan extracted from cellulose and hemicellulose. The predicted metagenomes related to carbohydrate and energy metabolic pathways were significantly increased in spring samples, which could facilitate a monkey’s recovery from acute energy loss experienced during winter. We propose that shifts in the composition and function of the gut microbiota provide a buffer against seasonal fluctuations in energy and nutrient intake, thus enabling these primates to adapt to variations in food supply and quality

A case report of anti-GAD65 antibody-positive autoimmune encephalitis in children associated with autoimmune polyendocrine syndrome type-II and literature review

BackgroundGlutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extra limbic encephalitis. While there are few case reports and research on anti-GAD65 antibody-associated encephalitis in adults, such cases are extremely rare in pediatric cases.MethodsFor the first time, we report a case of anti-GAD65-positive autoimmune encephalitis associated with autoimmune polyendocrine syndrome (APS) type II. We reviewed previously published pediatric cases of anti-GAD65 autoimmune encephalitis to discuss their clinical features, laboratory tests, imaging findings, EEG patterns, and prognosis.Case presentationAn 8-year-old, male child presented to the outpatient department after experiencing generalized convulsions for twenty days. The child was admitted for epilepsy and had received oral sodium valproate (500 mg/day) in another center, where investigations such as USG abdomen and MRI brain revealed no abnormalities, however, had abnormal EEG with diffuse mixed activity in the left anterior middle prefrontal temporal region. On the follow-up day, a repeat blood test showed a very low serum drug concentration of sodium valproate hence the dose was increased to 750 mg/day. Then, the child experienced adverse effects including increased sleep, thirst, and poor appetite, prompting the parents to discontinue the medication. A repeat MRI showed increased signals on FLAIR sequences in the right hippocampus hence admitted for further management. The child's past history included a diagnosis of hypothyroidism at the age of 4, and receiving levothyroxine 75 mcg once daily. His parents are healthy with no history of any similar neurological, autoimmune, or genetic diseases, but his uncle had a history of epilepsy. At presentation, he had uncontrolled blood glucose levels with elevated HbA1c levels. Additionally, the serum and CSF autoantibodies were positive against the anti-GAD65 antibody with the titer of 1:100 and 1:32 respectively. The patient was managed with a mixed type of insulin regimen and received first-line immunotherapy (intravenous immunoglobulin, IVIG) for five consecutive days, followed by oral prednisone and sodium valproate as an antiepileptic drug. Upon achieving a favorable clinical outcome, the patient was discharged with oral medications.ResultsAmong the 15 pediatric patients reported in this literature, nine presented with limbic encephalitis (LE), three with extralimbic encephalitis (ELE), and three with a combination of limbic and extralimbic encephalitis. Most of these cases exhibited T2-W FLAIR hyperintensities primarily localized to the temporal lobes in the early phase, progressing to hippocampal sclerosis/atrophy in the later phase on MRI. EEG commonly showed slow or spike waves on frontotemporal lobes with epileptic discharges. Prognostic factors varied among patients, with some experiencing persistent refractory seizures, type-1 diabetes mellitus (T1DM), persistent memory impairment, persistent disability requiring full assistance, and, in severe cases, death.ConclusionOur findings suggest that anti-GAD65 antibody-positive autoimmune encephalitis patients may concurrently present with other APS. Our unique case presented with multiple endocrine syndromes and represents the first reported occurrence in children. Early diagnosis and timely initiation of immunotherapy are crucial for improving clinical symptoms and reducing the likelihood of relapses or permanent disabilities. Therefore, emphasis should be placed on prompt diagnosis and appropriate treatment implementation to achieve better patient outcomes

Case Report: Metagenomic next-generation sequencing applied in diagnosing psittacosis caused by Chlamydia psittaci infection

BackgroundChlamydia psittaci is the causative agent of psittacosis in humans, while its rapid identification is hampered due to the lack of specificity of laboratory testing methods.Case presentationThis study reports four cases of C. psittaci infection after contact with a domestic parrot, all belonging to the same family. Common manifestations like fever, cough, headache, nausea, and hypodynamia appeared in the patients. Metagenomic next-generation sequencing (mNGS) aided the etiological diagnosis of psittacosis, revealing 58318 and 7 sequence reads corresponding to C. psittaci in two cases. The detected C. psittaci was typed as ST100001 in the Multilocus-sequence typing (MLST) system, a novel strain initially reported. Based on the results of pathogenic identification by mNGS, the four patients were individually, treated with different antibiotics, and discharged with favorable outcomes.ConclusionIn diagnosing psittacosis caused by a rare C. psittaci agent, mNGS provides rapid etiological identification, contributing to targeted antibiotic therapy and favorable outcomes. This study also reminds clinicians to raise awareness of psittacosis when encountering family members with a fever of unknown origin

Population genomics of wild Chinese rhesus macaques reveals a dynamic demographic history and local adaptation, with implications for biomedical research

Background The rhesus macaque (RM, Macaca mulatta) is the most important nonhuman primate model in biomedical research. We present the first genomic survey of wild RMs, sequencing 81 geo-referenced individuals of five subspecies from 17 locations in China, a large fraction of the species’ natural distribution. Results Populations were structured into five genetic lineages on the mainland and Hainan Island, recapitulating current subspecies designations. These subspecies are estimated to have diverged 125.8 to 51.3 thousand years ago, but feature recent gene flow. Consistent with the expectation of a larger body size in colder climates and smaller body size in warmer climates (Bergman's rule), the northernmost RM lineage (M. m. tcheliensis), possessing the largest body size of all Chinese RMs, and the southernmost lineage (M. m. brevicaudus), with the smallest body size of all Chinese RMs, feature positively selected genes responsible for skeletal development. Further, two candidate selected genes (Fbp1, Fbp2) found in M. m. tcheliensis are involved in gluconeogenesis, potentially maintaining stable blood glucose levels during starvation when food resources are scarce in winter. The tropical subspecies M. m. brevicaudus showed positively selected genes related to cardiovascular function and response to temperature stimuli, potentially involved in tropical adaptation. We found 118 single-nucleotide polymorphisms matching human disease-causing variants with 82 being subspecies specific. Conclusions These data provide a resource for selection of RMs in biomedical experiments. The demographic history of Chinese RMs and their history of local adaption offer new insights into their evolution and provide valuable baseline information for biomedical investigation

Polypharmacology of Berberine Based on Multi-Target Binding Motifs

Background: Polypharmacology is emerging as the next paradigm in drug discovery. However, considerable challenges still exist for polypharmacology modeling. In this study, we developed a rational design to identify highly potential targets (HPTs) for polypharmacological drugs, such as berberine.Methods and Results: All the proven co-crystal structures locate berberine in the active cavities of a redundancy of aromatic, aliphatic, and acidic residues. The side chains from residues provide hydrophobic and electronic interactions to aid in neutralization for the positive charge of berberine. Accordingly, we generated multi-target binding motifs (MBM) for berberine, and established a new mathematical model to identify HPTs based on MBM. Remarkably, the berberine MBM was embodied in 13 HPTs, including beta-secretase 1 (BACE1) and amyloid-β1-42 (Aβ1-42). Further study indicated that berberine acted as a high-affinity BACE1 inhibitor and prevented Aβ1-42 aggregation to delay the pathological process of Alzheimer’s disease.Conclusion: Here, we proposed a MBM-based drug-target space model to analyze the underlying mechanism of multi-target drugs against polypharmacological profiles, and demonstrated the role of berberine in Alzheimer’s disease. This approach can be useful in derivation of rules, which will illuminate our understanding of drug action in diseases

The comparison of manual and mechanical anastomosis after total pharyngolaryngoesophagectomy

BackgroundTotal pharyngolaryngoesophagectomy (TPLE) is considered as a curative treatment for hypopharynx cancer and cervical esophageal carcinomas (HPCECs). Traditional pharyngo-gastric anastomosis is usually performed manually, and postoperative complications are common. The aim of this study was to introduce a new technique for mechanical anastomosis and to evaluate perioperative outcomes and prognosis.MethodsFrom May 1995 to Nov 2021, a series of 75 consecutive patients who received TPLE for a pathological diagnosis of HPCECs at Sun Yat-sen Memorial Hospital were evaluated. Mechanical anastomosis was performed in 28 cases and manual anastomosis was performed in 47 cases. The data from these patients were retrospectively analyzed.ResultsThe mean age was 57.6 years, and 20% of the patients were female. The rate of anastomotic fistula and wound infection in the mechanical group were significantly lower than that in the manual group. The operation time, intraoperative blood loss and postoperative hospital stays were significantly higher in the manual group than that in the mechanical group. The R0 resection rate and the tumor characteristics were not significantly different between groups. There was no significant difference in overall survival and disease-free survival between the two groups.ConclusionThe mechanical anastomosis technology adopted by this study was shown to be a safer and more effective procedure with similar survival comparable to that of manual anastomosis for the HPCECs patients

QSYQ Attenuates Oxidative Stress and Apoptosis Induced Heart Remodeling Rats through Different Subtypes of NADPH-Oxidase

We aim to investigate the therapeutic effects of QSYQ, a drug of heart failure (HF) in clinical practice in China, on a rat heart failure (HF) model. 3 groups were divided: HF model group (LAD ligation), QSYQ group (LAD ligation and treated with QSYQ), and sham-operated group. After 4 weeks, rats were sacrificed for cardiac injury measurements. Rats with HF showed obvious histological changes including necrosis and inflammation foci, elevated ventricular remodeling markers levels(matrix metalloproteinases-2, MMP-2), deregulated ejection fraction (EF) value, increased formation of oxidative stress (Malondialdehyde, MDA), and up-regulated levels of apoptotic cells (caspase-3, p53 and tunnel) in myocardial tissue. Treatment of QSYQ improved cardiac remodeling through counter-acting those events. The improvement of QSYQ was accompanied with a restoration of NADPH oxidase 4 (NOX4) and NADPH oxidase 2 (NOX2) pathways in different patterns. Administration of QSYQ could attenuate LAD-induced HF, and AngII-NOX2-ROS-MMPs pathway seemed to be the critical potential targets for QSYQ to reduce the remodeling. Moreover, NOX4 was another key targets to inhibit the p53 and Caspase3, thus to reduce the hypertrophy and apoptosis, and eventually provide a synergetic cardiac protective effect

Pro-angiogenic Role of Danqi Pill Through Activating Fatty Acids Oxidation Pathway Against Coronary Artery Disease

Coronary artery disease (CAD) is one of the leading causes of deaths worldwide. Energy metabolism disorders, including a reduction in fatty acids oxidation and upregulation of glycolysis pathway, are involved in the process of CAD. Therapeutic angiogenesis has become a promising treatment for CAD. Traditional Chinese medicines, such as Danqi Pill (DQP), have been proven to be effective in treating CAD in China for many years. However, the pro-angiogenic effects of DQP based on fatty acids oxidation are still unknown and the mechanism is worthy of investigation. In this study, left anterior descending (LAD) coronary artery was ligated to induce the CAD models in vivo, and cardiac functions were examined using echocardiography. Human umbilical vein endothelial cells (HUVEC) were subjected to H2O2-induced oxidative stress in vitro. The effects of DQP on CAD rat models and in vitro HUVEC were detected. Our results showed that DQP had cardio-protective effects in rat model. The intensity of capillaries in the marginal area of infarction of the rat heart was increased remarkably in DQP group, and the expression of PPARα and VEGF-2 were increased. The key enzymes involved in the transportation and intake of fatty acids, including CPT1A and CD36, both increased. In H2O2-induced endothelial cells injury models, DQP also showed protective roles and promoted capillary-like tube formation. DQP up-regulated key enzymes in fatty acids oxidation in H2O2-treated HUVEC. In addition, inhibition of CPT1A compromised the pro-angiogenic effects of DQP. In conclusion, fatty acids oxidation axis PPARα-CD36-CPT1A was involved in the pro-angiogenic roles of DQP against CAD. Cardiac CPT1A may serve as a target in therapeutic angiogenesis in clinics