Precessing jet nozzle connecting to a spinning black hole in M87.

The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole1-4. The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity5. With a baseline of 17 years of observations, there was a shift in the jet's transverse position, possibly arising from an 8- to 10-year quasi-periodicity3. However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense-Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation.

Recurrent myocardial injury in a de novo SON mutation ZTTK syndrome patient: a case report.

BACKGROUND: Zhu-Tokita-Takenouchi-Kim syndrome (ZTTK syndrome) is a severe multi-systemic developmental disorder, caused by variants in the SON gene. A patient diagnosed with ZTTK syndrome who carried a de novo SON mutation and exhibited recurrent myocardial injury was described in this case. CASE PRESENTATION: A 7-year-old girl was admitted to the Cardiology Department of Beijing Children's Hospital in November 2019 due to myocardial injury following respiratory infection. She displayed elevated myocardial enzymes and severe T-wave changes on electrocardiogram. Over the past three years, she had experienced myocardial injury on three occasions. Additionally, she exhibited intellectual disability, congenital amblyopia, and dysmorphic facial features. Genetic analysis revealed a de novo heterozygous mutation c.3852_3856delGGTAT in the SON gene, which was confirmed by Sanger sequencing of her parents. She received anti-infection treatment and was administered metoprolol orally. Her condition was stable at the time of discharge. Over a 42-month follow-up period at the outpatient clinic, she complained intermittent fatigue and palpitation. CONCLUSIONS: The identified SON mutation, which plays a crucial role in heart development and mitochondrial function, may be associated with an increased susceptibility to myocardial injury or cardiomyopathy. This case report contributes novel insights into this rare condition and suggests the expansion of the ZTTK syndrome phenotype.

Tanshinone IIA alleviates brain damage in a mouse model of neuromyelitis optica spectrum disorder by inducing neutrophil apoptosis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathic disease associated with the anti-aquaporin-4 (AQP4) antibody, is characterized by extensive necrotic lesions primarily located on the optic nerves and spinal cord. Tanshinone IIA (TSA), an active natural compound extracted from Salvia miltiorrhiza Bunge, has profound immunosuppressive effects on neutrophils. OBJECTIVE: The present study aimed to evaluate the effect of TSA on NMOSD mice and explore the underlying mechanisms. Mice were initially administered TSA (pre-TSA group, n = 20) or vehicle (vehicle group, n = 20) every 8 h for 3 days, and then NMOSD model was induced by intracerebral injection of NMOSD-immunoglobulin G (NMO-IgG) and human complement (hC). In addition, post-TSA mice (n = 10) were administered equal dose of TSA at 8 h and 16 h after model induction. At 24 h after intracerebral injection, histological analysis was performed to assess the inhibitory effects of TSA on astrocyte damage, demyelination, and neuroinflammation in NMOSD mice, and western blotting was conducted to clarify the effect of TSA on the NF-κB and MAPK signaling pathways. Furthermore, flow cytometry and western blotting were conducted to verify the proapoptotic effects of TSA on neutrophils in vitro. RESULTS: There was a profound reduction in astrocyte damage and demyelination in the pre-TSA group and post-TSA group. However, prophylactic administration of TSA induced a better effect than therapeutic treatment. The number of infiltrated neutrophils was also decreased in the lesions of NMOSD mice that were pretreated with TSA. We confirmed that prophylactic administration of TSA significantly promoted neutrophil apoptosis in NMOSD lesions in vivo, and this proapoptotic effect was mediated by modulating the caspase pathway in the presence of inflammatory stimuli in vitro. In addition, TSA restricted activation of the NF-κB signaling pathway in vivo. CONCLUSION: Our data provide evidence that TSA can act as a prophylactic agent that reduces NMO-IgG-induced damage in the mouse brain by enhancing the resolution of inflammation by inducing neutrophil apoptosis, and TSA may serve as a promising therapeutic agent for neutrophil-associated inflammatory disorders, such as NMOSD.

14-3-3 Proteins Are on the Crossroads of Cancer, Aging, and Age-Related Neurodegenerative Disease.

14-3-3 proteins are a family of conserved regulatory adaptor molecules which are expressed in all eukaryotic cells. These proteins participate in a variety of intracellular processes by recognizing specific phosphorylation motifs and interacting with hundreds of target proteins. Also, 14-3-3 proteins act as molecular chaperones, preventing the aggregation of unfolded proteins under conditions of cellular stress. Furthermore, 14-3-3 proteins have been shown to have similar expression patterns in tumors, aging, and neurodegenerative diseases. Therefore, we put forward the idea that the adaptor activity and chaperone-like activity of 14-3-3 proteins might play a substantial role in the above-mentioned conditions. Interestingly, 14-3-3 proteins are considered to be standing at the crossroads of cancer, aging, and age-related neurodegenerative diseases. There are great possibilities to improve the above-mentioned diseases and conditions through intervention in the activity of the 14-3-3 protein family.

[Correlation analysis between foliar endophytic fungi of Salvia miltiorrhiza and effective components].

The aim of this study was to comprehensively investigate the correlations between foliar fungal endophyte communities and effective components accumulations in Salvia miltiorrhiza. Foliar samples of S. miltiorrhiza were collected in 5 different areas. Their fungal endophyte communities and effective component contents were determined by denaturing gradient gel electrophoresis (DGGE) and high performance liquid chromatography (HPLC), respectively. The results showed that, for characteristics of foliar fungal endophyte communities and effective component contents, there were both similarities and differences among the five samples. Correlation analysis of DGGEs' band and 24 effective components revealed a significant correlations (P < 0.01). For examples, 4 bands (15, 18, 23 and 26) were all significantly correlated with the accumulations of caffeic acid, salvianolic acid B, salvianolic acid C and dihydrotanshinone I.

Performance of two interferon-gamma release assays for tuberculosis infection screening in Kawasaki children before immunosuppressive therapy.

Objective: We aimed to compare QuantiFERON-TB Gold In-Tube (QFT-GIT) and X.DOT-TB for screening latent tuberculosis infection (LTBI) in kawasaki patients, and to identify the risk factors associated with indeterminate IGRA results. Methods: We conducted a retrospective study on children with KD, who were screened for mycobacterium tuberculosis (Mtb) infection by either ELISA-based QFT-GIT or ELISPOT-based X.DOT-TB tests, admitted in Department of Cardiology, Beijing Children's Hospital from July 2019 to April 2022. Results: A total of 1327 cases were included. Among them, 932 cases were tested by QFT-GIT and 395 cases by X.DOT-TB. The positive rate of children was 0.1% and 0.2%, and the indeterminate rate was 68.2% and 6.1% for QFT-GIT and X.DOT-TB, respectively. Patients with hypoproteinemia had a higher risk of indeterminate X.DOT-TB result. Female, critical ill, shock or hypoproteinemia presented statistically significant associations with an increased risk of indeterminate QFT-GIT result. High-dose of IVIG inhibited the release of IFN-γ by more than 90%, which might account for the high indeterminate incidence. Conclusion: It is recommended to perform X.DOT-TB rather than QFT-GIT to screen LTBI in patients with high level of the mitogen that can inhibit IFN-γ release. For KD children with positive IGRA results, it has a higher risk of activation TB infection when treated with immunosuppressive therapy in the future. Children with KD aged <5 years old had higher frequency of indeterminate IGRA results.

Transseptal approach for catheter ablation of left-sided accessory pathways in children with Marfan syndrome: A case report.

BACKGROUND: Left-sided accessory pathways (APs) can be accessed with either a transaortic (TA) or transseptal approach (TS). For children with Marfan syndrome (MFS) who have aortic disease, the use of TA can aggravate the disease, making TS the best choice for these patients. CASE SUMMARY: A 10-year-old girl was hospitalized because of intermittent heart palpitations and chest tightness. She was diagnosed with MFS, supraventricular tachycardia, Wolff-Parkinson-White syndrome, and left-sided AP was detected by cardiac electrophysiological. Catheter ablation was successfully performed via TS under the guidance of the Ensite system. During the follow-up, no recurrence or complications occurred. CONCLUSION: The TS for catheter ablation of left-sided APs can be considered in children with MFS. Adequate evaluation and selection of the appropriate puncture site are particularly important.

[Genetic diversity and volatile components of Asarum sieboldii in Qin-ba region].

OBJECTIVE: To analyze the genetic diversity and the volatile components of Asarum sieboldii from seven habitats in Qin-ba region. METHODS: The genetic diversity of the herb was analyzed by ISSR (inter simple sequence repeat) markers; The relative content volatile components of the herb were dectected by head space solid-phase microextraction gas chromatogrphy-mass spectrometry (HS-SPME-GC-MS). The contents of the 3 main components were analyzed by steam distillation gas chromatography-mass spectrometry (GC-MS). RESULTS: 57 bands were amplified from 7 populations by 6 reliable primers, 51 of which were polymorphic (89.47% of the total). The cluster analysis presented that these resources were divided into two main groups. There were differences in the chemical components and the contents of Asarum sieboldii from the 6 wild habitats. Except for some same components, many unique components were identified in them respectively. In addition, some components could be detected only in some populations which had smaller genetic distance. CONCLUSION: Cluster analysis shows no direct correlation between genetic distance and geographic distance of Asarum sieboldii in Qin-ba region. The accumulations of some volatile components of Asarum sieboldii are possibly related to genetic diversity.

Transseptal Approach Versus Transaortic Approach for Catheter Ablation of Left-Sided Accessory Pathways in Children.

Background: Catheter ablation is recommended to eradicate supraventricular tachycardia caused by left-sided accessory pathways (APs) in children. This study aims to compare the safety and efficacy of the transseptal approach (TS) and aortic approach (TA) for catheter ablation of left-sided APs in a pediatric cohort. Methods: Patients < 18 years of age with left-sided APs who had undergone ablation at Beijing Children's Hospital between 13 January 2018 and 7 January 2020 were included and randomly categorized into either TS or TA group (follow-up for 22 months). In all, 60 patients in TS group and 41 patients in TA group were included in this study. Principal endpoints were success rate, recurrence rate, complications, procedure time, and radiation dose. Results: For TS group versus TA group, success rate was observed in 100 versus 97.56% (p = 0.402). The procedure time was 27.0 (32.0-23.0) versus 29.0 (38.0-24.5) min (p = 0.092). The rate of success or the procedure time was similar, but for the patients with Aps located in left posterior septum (LPS) or left posterior lateral (LPL), the TS group had a shorter procedure time compared with TA group (p < 0.01). The radiation dose was 28.0 (20.0-41.75) versus 0 mGy (p < 0.001). After successful ablation, no recurrence and complication were observed in either group. Conclusion: Both TS and TA for catheter ablation of left-sided Aps were shown to be safe and effective in children. Zero radiation and ease of mastery make TA the preferred choice. TS is recommended to be used by properly trained medical professionals, especially for patient with AP localized in the LPL or LPS. However, TS is a good alternative where patients have aortic lesions or when TA fails.

[The volatile components of three radix et rhizoma asari].

OBJECTIVE: To analyze and compare the volatile components of Asarum sieboldii Miq, Asarum himalaicum Hook. F. et Thoms and Asarum. debile Franch in the same area. METHODS: The volatile components were extracted from three Radix et Rhizoma Asari by solid-phrase microextraction and their contents were analyzed by gas chromatography-mass spectrometry (GC-MS). RESULTS: 59, 99 and 85 volatile components were identified from Asarum sieboldii Miq, Asarum himalaicum Hook. F. et Thoms and Asarum debile Franch, representing the ralative content of 82.75% - 99.43% of the volatile oil. 16 of same components were identified in the three Radix et Rhizoma Asari, and the contents of the same components were different among them. In addition, some unique components were identified in them respectively. CONCLUSION: There were differences among the chemical components and the contents of the volatile oil of the three Radix et Rhizoma Asari. The results could give certain reference value for the medicine whether Asarum himalaicum Hook. F. et Thoms and Asarum debile Franch can replace Asarum sieboldii Miq.

Tanshinone IIA Ameliorates CNS Autoimmunity by Promoting the Differentiation of Regulatory T Cells.

Tanshinone IIA (TSA), an important natural lipophilic diterpene compound from the traditional Chinese herb Salvia miltiorrhiza Bunge, has long been widely used for the prevention and treatment of various diseases because of its anti-inflammatory activities; however, the anti-inflammatory mechanism remains unknown. In the present work, we examined the effects of TSA on experimental autoimmune encephalomyelitis (EAE), a model of autoreactive T/B cell-mediated central nervous system (CNS) autoimmunity. The data showed that TSA significantly attenuates the severity of EAE when administered at the pre-onset and peak of clinical disease. In vivo, the protective effects of TSA on EAE mice are correlated with diminished inflammatory infiltration, demyelination, and GM-CSF-producing CD4+ T cells in the spinal cord and selectively increased regulatory T (Treg) cell frequencies in both the spinal cord and spleen. We further confirm that TSA can promote the polarization of naïve CD4+ T cells into Treg cells both by targeting dendritic cells (DCs) to drive transforming growth factor ß1 (TGF-ß1) upregulation and by directly targeting naïve CD4+ T cells in vitro. Most importantly, we showed that TSA-induced Treg cells display an effective suppressive activity at a level comparable to TGF-ß1-polarized Treg Cells in vitro and in vivo. Taken together, our data provide evidence that TSA can promote Treg cell differentiation, and TSA may have a promising application as a therapeutic agent for the treatment of neuroinflammatory diseases.

Deubiquitinase USP7 regulates Drosophila aging through ubiquitination and autophagy.

Ubiquitination-mediated protein degradation is the selective degradation of diverse forms of damaged proteins that are tagged with ubiquitin, while deubiquitinating enzymes reverse ubiquitination-mediated protein degradation by removing the ubiquitin chain from the target protein. The interactions of ubiquitinating and deubiquitinating enzymes are required to maintain protein homeostasis. The ubiquitin-specific protease USP7 is a deubiquitinating enzyme that indirectly plays a role in repairing DNA damage and development. However, the mechanism of its participation in aging has not been fully explored. Regarding this issue, we found that USP7 was necessary to maintain the normal lifespan of Drosophila melanogaster, and knockdown of dusp7 shortened the lifespan and reduced the ability of Drosophila to cope with starvation, oxidative stress and heat stress. Furthermore, we showed that the ability of USP7 to regulate aging depends on the autophagy and ubiquitin signaling pathways. Furthermore, 2,5-dimethyl-celecoxib (DMC), a derivative of celecoxib, can partially restore the shortened lifespan and aberrant phenotypes caused by dusp7 knockdown. Our results suggest that USP7 is an important factor involved in the regulation of aging, and related components in this regulatory pathway may become new targets for anti-aging treatments.

CASQ2 variants in Chinese children with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Biallelic variants of the CASQ2 are known to cause the autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited disease that predisposes young individuals to syncope and sudden cardiac death. To date, only about 24 CASQ2 variants have been reported in association with CPVT pathogenesis; furthermore, studies in Asians, especially in the Chinese population, are relatively rare. The aim of this study was to detect CASQ2 variants in Chinese patients with CPVT. METHODS: We used targeted next-generation sequencing (NGS) to identify CASQ2 variants in Chinese patients with CPVT. A screening process was performed to prioritize rare variants of potential functional significance. Sanger sequencing was conducted to conform the candidate variants and determine the parental origin. RESULTS: We identified seven different CASQ2 variants, of which three (c.1074_1075delinsC, c.1175_1178delACAG, and c.838+1G>A) have not been previously reported. The variants exhibited autosomal recessive inheritance, and were detected in four unrelated Chinese families with CPVT. They included a nonsense variant c.97C>T (p.R33*) and a missense variant c.748C>T (p.R250C) in Family 1 with three CPVT patients; two heterozygous frameshift variants, c.1074_1075delinsC (p.G359Afs*12) and c.1175_1178delACAG (p.D392Vfs*84), in Family 2 with one CPVT patient; one pathogenic homozygous variant c.98G>A (p.R33Q) of CASQ2 in the CPVT patient of Family 3; and two heterozygous splicing variants, (c.532+1G>A) and (c.838+1G>A), in Family 4 with one CPVT patient. CONCLUSION: To our knowledge, this is the first systematic study of Chinese children with CASQ2 variants. Our work further expands the genetic spectrum of CASQ2-associated CPVT.