Inhibition of Prolactin Affects Epididymal Morphology by Decreasing the Secretion of Estradiol in Cashmere Bucks.

Yanshan Cashmere bucks are seasonal breeding animals and an important national genetic resource. This study aimed to investigate the involvement of prolactin (PRL) in the epididymal function of bucks. Twenty eleven-month-old Cashmere bucks were randomly divided into a control (CON) group and a bromocriptine (BCR, a prolactin inhibitor, 0.06 mg/kg body weight (BW)) treatment group. The experiment was conducted from September to October 2020 in Qinhuangdao City, China, and lasted for 30 days. Blood was collected on the last day before the BCR treatment (day 0) and on the 15th and 30th days after the BCR treatment (days 15 and 30). On the 30th day, all bucks were transported to the local slaughterhouse, where epididymal samples were collected immediately after slaughter. The left epididymis was preserved in 4% paraformaldehyde for histological observation, and the right epididymis was immediately preserved in liquid nitrogen for RNA sequencing (RNA-seq). The results show that the PRL inhibitor reduced the serum PRL and estradiol (E2) concentrations (p < 0.05) and tended to decrease luteinizing hormone (LH) concentrations (p = 0.052) by the 30th day, but no differences (p > 0.05) occurred by either day 0 or 15. There were no differences (p > 0.05) observed in the follicle-stimulating hormone (FSH), testosterone (T), and dihydrotestosterone (DHT) concentrations between the two groups. The PRL receptor (PRLR) protein was mainly located in the cytoplasm and intercellular substance of the epididymal epithelial cells. The PRL inhibitor decreased (p < 0.05) the expression of the PRLR protein in the epididymis. In the BCR group, the height of the epididymal epithelium in the caput and cauda increased, as did the diameter of the epididymal duct in the caput (p < 0.05). However, the diameter of the cauda epididymal duct decreased (p < 0.05). Thereafter, a total of 358 differentially expressed genes (DEGs) were identified in the epididymal tissues, among which 191 were upregulated and 167 were downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that ESR2, MAPK10, JUN, ACTL7A, and CALML4 were mainly enriched in the estrogen signaling pathway, steroid binding, calcium ion binding, the GnRH signaling pathway, the cAMP signaling pathway, and the chemical carcinogenesis-reactive oxygen species pathway, which are related to epididymal function. In conclusion, the inhibition of PRL may affect the structure of the epididymis by reducing the expression of the PRLR protein and the secretion of E2. ESR2, MAPK10, JUN, ACTL7A, and CALML4 could be the key genes of PRL in its regulation of epididymal reproductive function.

The Enhanced Performance of NiCuOOH/NiCu(OH)2 Electrode Using Pre-Conversion Treatment for the Electrochemical Oxidation of Ammonia.

Electrochemical oxidation of ammonia is an attractive process for wastewater treatment, hydrogen production, and ammonia fuel cells. However, the sluggish kinetics of the anode reaction has limited its applications, leading to a high demand for novel electrocatalysts. Herein, the electrode with the in situ growth of NiCu(OH)2 was partially transformed into the NiCuOOH phase by a pre-treatment using highly oxidative solutions. As revealed by SEM, XPS, and electrochemical analysis, such a strategy maintained the 3D structure, while inducing more active sites before the in situ generation of oxyhydroxide sites during the electrochemical reaction. The optimized NiCuOOH-1 sample exhibited the current density of 6.06 mA cm-2 at 0.5 V, which is 1.67 times higher than that of NiCu(OH)2 (3.63 mA cm-2). Moreover, the sample with a higher crystalline degree of the NiCuOOH phase exhibited lower performance, demonstrating the importance of a moderate treatment condition. In addition, the NiCuOOH-1 sample presented low selectivity (<20%) towards NO2- and stable activity during the long-term operation. The findings of this study would provide valuable insights into the development of transition metal electrocatalysts for ammonia oxidation.

Ethanol extract of Eclipta prostrata induces multiple myeloma ferroptosis via Keap1/Nrf2/HO-1 axis.

BACKGROUND: Multiple myeloma (MM) is an incurable hematological malignancy with limited therapeutic efficacy. Eclipta prostrata is a traditional Chinese medicinal plant reported to possess antitumor properties. However, the effects of E. prostrata in MM have not been explored. PURPOSE: The aim of this study was to define the mechanism of the ethanol extract of E. prostrata (EEEP) in treating MM and identify its major components. METHODS: The pro-ferroptotic effects of EEEP on cell death, cell proliferation, iron accumulation, lipid peroxidation, and mitochondrial morphology were determined in RPMI-8226 and U266 cells. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), kelch-like ECH-associated protein 1 (Keap1), heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), and 4-hydroxynonenal (4HNE) were detected using western blotting during EEEP-mediated ferroptosis regulation. The RPMI-8226 and U266 xenograft mouse models were used to explore the in vivo anticancer effects of EEEP. Finally, high performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry system (UPLC-Q/TOF-MS) were used to identify the major constituents of EEEP. RESULTS: EEEP inhibited MM cell growth and induced cell death in vitro and in vivo. By promoting malondialdehyde and Fe2+ accumulation, lipid peroxidation, and GSH suppression, EEEP triggers ferroptosis in MM. Mechanistically, EEEP regulates the Keap1/Nrf2/HO-1 axis and stimulates ferroptosis. EEEP-induced lipid peroxidation and malondialdehyde accumulation were blocked by the Nrf2 activator NK-252. In addition, HPLC and UPLC-Q/TOF-MS analysis elucidated the main components of EEEP, including demethylwedelolactone, wedelolactone, chlorogenic acid and apigenin, which may play important roles in the anti-tumor function of EEEP. CONCLUSION: In summary, EEEP exerts its anti-MM function by inducing MM cell death and inhibiting tumor growth in mice. We also showed that EEEP can induce lipid peroxidation and accumulation of ferrous irons in MM cells both in vivo and in vitro, leading to ferroptosis. In addition, this anti-tumor function may be achieved by the EEEP activation of Keap1/Nrf2/HO-1 axis. This is the first study to reveal that EEEP exerts anti-MM activity through the Keap1/Nrf2/HO-1-dependent ferroptosis regulatory axis, making it a promising candidate for MM treatment.

High-Throughput Acoustic Ejection Mass Spectrometry with Adjustable Signal Durations.

High-throughput mass spectrometry (MS) has witnessed rapid advancements and has found extensive applications across various disciplines. It enables the fast and accurate analysis of large sample sets, delivering a 10-fold or greater enhancement in analytical throughput when compared to conventional LC-MS methods. However, the signal duration in these high-throughput MS technologies is typically confined to a narrow range, presenting challenges for workflows demanding prolonged signal durations. In this study, we introduce a method that enables precise modulation of the signal duration on an acoustic ejection mass spectrometry (AEMS) system while ensuring high signal reproducibility. This flexibility allows for simultaneous and precise analysis of a significantly greater number of MS/MS transitions in high-throughput MS environments. Additionally, it offers a unique approach for parameter optimization and method development with minimal sample volume requirements. This advancement enhances the efficiency of MS-based analyses across diverse applications and facilitates broader utilization of MS technologies in high-throughput settings, including data-dependent acquisition (DDA) and data-independent acquisition (DIA).

When idiopathic multicentric Castleman disease meets COVID-19: a multicenter retrospective study from China.

Idiopathic multicentric Castleman disease (iMCD) is a rare and cytokine storm-driven inflammatory disorder. The exact cause of iMCD is still unknown, although several hypotheses have been proposed. However, regardless of the underlying cause, the ultimate result is the activation of the inflammatory pathway, which can lead to damage in multiple organs. Currently, there have been several reports highlighting the intricate link between coronavirus disease 2019 (COVID-19) and iMCD. To better understand the impact of COVID-19-induced immune storm on iMCD, we conducted a multicenter retrospective study in three hospitals in China. A total of 28 patients with iMCD were included, among whom 25 had confirmed COVID-19 infection, and we presented 4 cases that showed different disease progression after the infection of COVID-19, including 2 who did not receive any treatment for Castleman disease before. Our findings underscore the necessity of carefully monitoring iMCD patients with COVID-19 and promptly intervening to address any changes in their condition. Besides, this study also summarized the shared cytokines between COVID-19 and iMCD. Recent studies have shown promising results in treating severe COVID-19 and iMCD using tocilizumab, an interleukin-6 receptor antagonist. Therefore, it suggests that other potential cytokine storm therapy targets that have been effective in COVID-19 may also be explored for the treatment of iMCD.

Increased functional connectivity within the salience network in patients with insomnia.

BACKGROUND: Insomnia is a common sleep disorder with significant negative impacts on emotional states; however, the underlying mechanism of insomnia with comorbid emotional dysregulation remains largely unknown. The salience network (SN) plays an important role in both sleep and emotional regulation. The study aimed to explore the specific alterations in functional connectivity (FC) within the SN in insomnia patients. METHODS: A total of 30 eligible patients with insomnia disorder (ID group) and 30 healthy controls (HC group) underwent resting-state functional magnetic resonance imaging (fMRI) scanning and psychometric assessments. Differences in FC within the SN were examined using seed-based region-to-region connectivity analysis. RESULTS: Compared with healthy controls, patients with insomnia showed increased FC within the SN, mainly between the anterior cingulate cortex (ACC) and right superior frontal gyrus (SFG), the right SFG and right supramarginal gyrus (SMG), and between the right insular (INS) and left SMG (P<0.05). Additionally, significant correlations were observed between increased FC and the Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), and Hamilton Anxiety Rating Scale (HAMA) scores (P<0.05, after Bonferroni correction). CONCLUSIONS: These results suggest that increased FC within the SN may be related to poor sleep quality and negative emotions, highlighting the importance of the SN in the pathophysiological mechanisms of insomnia with comorbid emotional dysregulation.

Abnormal alterations of regional spontaneous neuronal activity and functional connectivity in insomnia patients with difficulty falling asleep: a resting-state fMRI study.

BACKGROUND: Insomnia disorder (ID) seriously affects people's daily life. Difficulty falling asleep is the most commonly reported complaint in patients with ID. However, the mechanism of prolonged sleep latency (SL) is still obscure. The aim of our present study was to investigate the relationship between prolonged SL and alterations in spontaneous neural activity and brain functional connectivity (FC) in ID patients using functional magnetic resonance imaging (fMRI). METHODS: A total of 52 insomniacs with difficulty falling asleep and 30 matched healthy controls (HCs) underwent resting-state fMRI. The amplitude of low-frequency fluctuation (ALFF) was measured and group differences were compared. The peak areas with significantly different ALFF values were identified as the seed regions to calculate FC to the whole brain. SL was assessed by a wrist actigraphy device in ID patients. The Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Rating Scale (HAMA), and Hyperarousal Scale (HAS) were evaluated in both ID patients and HCs. Finally, correlation analyses were performed between the clinical features and FC/ALFF values. RESULTS: ID patients showed higher PSQI, HAMA, HAS scores than HCs. The functional MRI results indicated increased ALFF value in the left insula and right amygdala and decreased ALFF value in the right superior parietal lobe (SPL) in ID patients. The seed-based FC analysis demonstrated increased FC between the left insula and the bilateral precentral gyrus and FC between the right amygdala and the left posterior cingulate cortex (PCC) in patients with ID. Correlation analysis indicated that the increased FC value of the right amygdala-left PCC was positively correlated with SL measured by actigraphy. CONCLUSION: This study revealed abnormal regional spontaneous fluctuations in the right amygdala, left insula, and right SPL, as well as increased FC in the left insula-precentral and right amygdala-left PCC. Moreover, the prolonged SL was positively correlated with the abnormal FC in the right amygdala-left PCC in ID patients. The current study showed the correlation between prolonged SL and the abnormal function of emotion-related brain regions in ID patients, which may contribute to a better understanding of the neural mechanisms underlying difficulty falling asleep in patients with ID. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn ., ChiCTR1800015282. Registered on 20th March 2018.

[Apelin-13 promotes mitochondrial autophagy and improves rat myocardial ischemia-reperfusion injury by blocking PINK1/parkin signaling pathway].

Objective To investigate the effect of adipocytokine Apelin-13 (AP13) on mitochondrial autophagy in myocardial ischemia reperfusion injury (MIRI) and its mechanism. Methods MIRI model was established by ligating the coronary artery branches of rats. The rats are divided into sham group, AP13-treated sham group, MIRI group and AP13-treated MIRI group. 24 h after the establishment of MIRI model, serum creatine kinase (CK), lactate dehydrogenase (LDH) and cardiac troponin I (cTnI) levels were detected by ELISA, and the size of myocardial infarction was detected by 2, 3, 5-triphenyltetrazole chloride (TTC) staining. Terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) was used to detect the apoptosis of myocardial cells in MIRI myocardium, and transmission electron microscopy (TEM) was employed to observe the mitochondrial damage of myocardial cells and the formation of autophagosomes in the damaged myocardium. Western blot analysis was used to detect the microtubule-associated protein 1 light chain 3 II (LC3 II)/LC3 I ratio and protein expression level of the ubiquitin-binding protein (P62), phosphatase and tensin homologous (PTEN)-induced kinase 1 (PINK1), E3 ubiquitin ligase parkin and cleaved-caspase-3(c-caspase-3)in myocardial infarction tissues of rats in each group. The myocardial cells isolated from myocardial infarction area of rats were infected with adenovirus carrying GFP-LC3, and the co-localization of translocase of outer mitochondrial membrane 20 (TOM20) and LC3 was observed by immunofluorescence cytochemical staining. Results Compared with sham operation group or AP13-treated sham group, serum CK, LDH, cTnI, myocardial infarction area and apoptosis rate of MIRI group or AP13-treated MIRI rats were significantly increased, and there was no significant difference between the first two groups. Compared with MIRI group, the above changes were significantly decreased in AP13-treated MIRI rats. The integrity of mitochondrial structure in cardiomyocytes was significantly damaged, and a large number of autophagosomes enclosing mitochondria appeared in MIRI group and AP13-treated MIRI group compared with the sham group or AP13-treated sham group. However, compared with MIRI group, mitochondrial damage of myocardial cells in AP13-treated MIRI group was significantly reduced, and the number of autophagosomes was significantly increased. LC3 II/LC3 I ratio, PINK1, parkin and c-caspase-3 protein expression were significantly increased, while the expression level of P62 was significantly decreased in MIRI group or AP13-treated MIRI group compared with the other two groups. The change trend of above protein levels in AP13-treated MIRI group was significantly decreased compared with MIRI group. LC3 and TOM20 were co-located in the mitochondria of cardiomyocytes after MIRI modeling, and the expression intensity of LC3 in AP13-treated MIRI group was significantly increased compared with that in MIRI group. Conclusion Aplein-13 may promote the level of mitochondrial autophagy through PINK1/parkin signaling pathway, which can effectively reduce the size of myocardial infarction caused by I/R and reduce the rate of apoptosis.

Bispecific antibody treatment of multiple myeloma: latest updates from the 2022 ASH annual meeting.

Background: Effective novel therapies for multiple myeloma (MM) patients who are unresponsive to conventional treatments (triple-class refractory) are an urgent need. Bispecific antibodies (BsAbs) offer a promising new approach to stimulate T cells and induce tumor cell death by targeting molecules on the surface of malignant plasma cells and CD3 on the surface of T cells. Objectives: Addressing the issue of improving the prognosis of triple-class refractory MM patients has become a significant clinical challenge. Design: This is a brief report. Methods: This article summarizes the latest updates of BsAbs treatment of MM from the 2022 ASH annual meeting. Results: BsAbs that target B-cell maturation antigen and G protein-coupled receptor family C group 5 memberD have demonstrated remarkable clinical activity and favorable safety profiles. Many potential targets for myeloma cells are currently undergoing phase I/II clinical trials, and these off-the-shelf bispecific molecules are likely to become a critical part of the MM treatment landscape. Conclusion: This article provides an overview of the latest advances in BsAbs immunotherapy for refractory and relapsed MM and highlights significant findings from the 2022 ASH annual meeting.

Prolactin inhibitor changes testosterone production, testicular morphology, and related genes expression in cashmere goats.

Prolactin has multifaceted roles in lactation, growth, metabolism, osmoregulation, behavior, and the reproduction of animals. This study aimed to investigate the involvement of prolactin in testicular function in cashmere goats. Twenty cashmere goats were randomly assigned to either the control group (CON) or the bromocriptine treatment group (BCR, bromocriptine, prolactin inhibitor). Blood and testis samples collected for analysis after 30 days of treatment. The results indicated that, compared with the CON group, BCR significantly decreased (p < 0.05) the serum concentrations of prolactin, and significantly increased (p < 0.05) the levels of testosterone and luteinizing hormone (LH) on day 30. The serum level of the follicle-stimulating hormone (FSH) was not affected (p > 0.05) by the treatment. The mean seminiferous tubule diameter and spermatogenic epithelium thickness were increased (p < 0.05) in the BCR group. Subsequently, we performed RNA sequencing and bioinformatics analysis to identify the key genes and pathways associated with the regulation of spermatogenesis or testosterone secretion function. A total of 142 differentially expressed genes (DEGs) were identified (91 were upregulated, 51 were downregulated). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the DEGs were mainly involved in the extracellular matrix (ECM), hippo, and steroid hormone biosynthesis, which are related to testicular function. The expression of the genes SULT2B1, CYP3A24, and CYP3A74 in the steroid hormone biosynthesis pathway significantly increased (p < 0.05) in the BCR group, which was validated by qRT-PCR. These results provide a basis for understanding the mechanisms underlying the regulation of testicular function by prolactin in cashmere goats.

[Tiaoshen acupuncture for primary insomnia: a pilot randomized controlled trial].

OBJECTIVE: To observe the effects of Tiaoshen (regulating the spirit) acupuncture on cognitive function and sleep quality in patients with primary insomnia (PI). METHODS: Sixty patients with PI were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases dropped off, 1 case was excluded). The patients in the observation group were treated with acupuncture at Baihui (GV 20), Shenting (GV 24), Sishencong (EX-HN 1), and bilateral Benshen (GB 13), Shenmen (HT 7), Neiguan (PC 6), Sanyinjiao (SP 6). The patients in the control group were treated with shallow needling at non-effective points. Each treatment was provided for 30 min, once every other day, 3 treatments per week for 4 weeks. The Montreal cognitive assessment (MoCA), digit span test (DST), trail making test (TMT)-A, Pittsburgh sleep quality index (PSQI), and fatigue scale-14 (FS-14) were used to assess cognitive function and sleep quality before and after treatment, as well as in follow-up of 4-week after treatment completion. Correlation analysis was conducted between the differences in PSQI scores and differences in MoCA scores before and after treatment in the observation group. RESULTS: Compared with before treatment, the total score, visuospatial and executive function score and delayed memory score of MoCA as well as DST backward score were increased (P<0.01), while TMT-A time, PSQI and FS-14 scores were significantly reduced (P<0.01) after treatment and in follow-up in the observation group. Compared with before treatment, the PSQI score in the control group was reduced (P<0.01, P<0.05). After treatment and in follow-up, the observation group had significantly higher total score, visuospatial and executive function score, delayed memory score of MoCA, and DST backward score compared to the control group (P<0.05, P<0.01). In the observation group, the TMT-A time was significantly shorter than that in the control group (P<0.05, P<0.01), and the PSQI and FS-14 scores were significantly lower than those in the control group (P<0.01). In the observation group, there was a negative correlation between the difference in PSQI scores (post-treatment minus pre-treatment) and the difference in MoCA scores (post-treatment minus pre-treatment) (r=-0.481, P<0.01). A similar negative correlation was found between the difference in PSQI scores (follow-up minus pre-treatment) and the difference in MoCA scores (follow-up minus pre-treatment) (r=-0.282, P<0.05). CONCLUSION: Tiaoshen acupuncture could improve cognitive function, enhance sleep quality, and alleviate daytime fatigue in patients with PI. The improvement in cognitive function in patients with PI is correlated with the improvement in sleep quality.

MALAT1 regulates network of microRNA-15a/16-VEGFA to promote tumorigenesis and angiogenesis in multiple myeloma.

MALAT1 is one of the most hopeful members implicated in angiogenesis in a variety of non-malignant diseases. In multiple myeloma (MM), MALAT1 is recognized as the most highly expressed long non-coding RNA. However, the functional roles of MALAT1 in angiogenesis and the responsible mechanisms have not yet been explored. Herein, we discovered a novel regulatory network dependent on MALAT1 in relation to MM tumorigenesis and angiogenesis. We observed that MALAT1 was upregulated in MM and significantly associated with poor overall survival. MALAT1 knockdown suppressed MM cell proliferation and promoted apoptosis, while restricting endothelial cells angiogenesis. Moreover, MALAT1 directly targeted microRNA-15a/16, and microRNA-15a/16 suppression partly reverted the effects of MALAT1 deletion on MM cells in vitro as well as tumor growth and angiogenesis in vivo. In addition, further study indicated that MALAT1 functioned as a competing endogenous RNA for microRNA-15a/16 to regulate vascular endothelial growth factor A (VEGFA) expression. Our results suggest that MALAT1 plays an important role in the regulatory axis of microRNA-15a/16-VEGFA to promote tumorigenicity and angiogenesis in MM. Consequently, MALAT1 could serve as a novel promising biomarker and a potential antiangiogenic target against MM.

Rituximab-bortezomib-dexamethasone induce high response rates in iMCD in clinical practice.

Treatment options for idiopathic multicentric Castleman disease (iMCD) are currently limited, especially for patients who do not respond or are resistant to interleukin-6 inhibitors. For the first time, we innovatively designed a protocol using rituximab-bortezomib-dexamethasone (RVD) as first-line consolidation therapy in patients newly diagnosed with iMCD. Furthermore, we adopted a no-maintenance treatment strategy to simplify post-remission care. Five patients with iMCD were enrolled (including one with TAFRO syndrome) and underwent the RVD regimen, all of whom achieved partial response (PR) or better. After four cycles of RVD, three (60%) patients achieved PR, while one (20%) achieved a complete response. These five patients, who achieved PR or better, discontinued treatment but remained stable for a median follow-up of 11 months, with a duration of response of 7, 7, 10, 12 and 13 months, respectively. None of the patients experienced grade ≥3 adverse events during the observation period. Collectively, these findings demonstrated that the RVD regimen may be a promising treatment option for patients with iMCD. It was a safe and effective approach that resulted in lasting responses without the need for ongoing maintenance therapy.

Trends in mortality from infection among patients with hematologic malignancies: differences according to hematologic malignancy subtype.

Background: Infection is the most important cause of non-relapse mortality in hematologic malignancy patients, leading to increased costs and prolonged hospitalization times. However, comprehensive and comparable reports on infection-specific mortality (ISM) trends in hematologic malignancy patients are lacking. Objectives: We aimed to provide updated ISM trends and factors associated with ISM among hematologic malignancy patients. Design: This is a retrospective study. Methods: Patients diagnosed with the five most common hematologic malignancies from 1983 to 2016 from the Surveillance, Epidemiology, and End Results database were included. Joinpoint regression was used to analyze mortality trends. Results: ISM decreased beginning in 1983, 1988, and 1994, with yearly decreases of -2.1% for acute leukemia (AL), -1.3% for Hodgkin lymphoma (HL), and -14.3% for non-Hodgkin lymphoma (NHL). In contrast, ISM in patients with chronic leukemia (CL) and multiple myeloma (MM) increased dramatically beginning in 2000, with yearly increases of 2.8% and 3.3%, respectively. ISM rates were higher in males than in females across all hematologic malignancy subtypes. The mortality trends significantly differed according to race, age, sex, and stage, which could help in further etiological investigations. Moreover, male sex, older age at diagnosis, black race, and unmarried status were poor prognostic factors for ISM across all hematologic malignancy subtypes. Conclusion: A promising downward trend in ISM in recent years occurred in patients with AL, HL, and NHL; however, ISM increased dramatically in patients with CL and MM. Our data suggest that risk assessment and careful infection monitoring are recommended for hematologic malignancy patients, particularly those with CL and MM.

The increased functional connectivity between the locus coeruleus and supramarginal gyrus in insomnia disorder with acupuncture modulation.

Background: Insomnia disorder (ID) seriously affects the quality of people's daily life, and acupuncture is an effective therapy for it. As an essential component of the upward activation system, the locus coeruleus (LC) plays a crucial role in sleep-wake regulation, its aberrant functional connectivity (FC) is found to be involved in ID. The purpose of this study was to explore the modulation effect of acupuncture on the resting state FC of LC in ID patients. Methods: 60 ID patients were recruited and randomly assigned to real acupuncture (RA) or sham acupuncture (SA) treatment. Resting-state functional magnetic resonance imaging (fMRI) data were collected before and after the treatment. With LC as the region of interest, the FC method was adopted to examine acupuncture-related modulation of intrinsic connectivity in ID patients. The Pittsburgh Sleep Quality Index (PSQI), Hyperarousal Scale (HAS), and actigraphy were used to assess sleep quality and cortical hyperarousal states. Associations between clinical outcomes and FC features were calculated using Pearson's correlation analysis. Results: The improvement in sleep quality and hyperarousal in the RA group was greater than that in the SA group. After treatment, the FC between the LC and left inferior frontal gyrus (IFG) decreased in the RA group. The FC between the LC and left insula and supramarginal gyrus (SMG) was higher in the RA group. The change of LC FC values with the SMG was negatively associated with the change in PSQI scores. Conclusion: Acupuncture can modulate FC between the LC and IFG, insular gyrus, and SMG. This may imply the potential mechanism of acupuncture treatment for insomnia.

Circ-C16orf62 Regulates Oxidized low-density Lipoprotein-induced Apoptosis, Inflammation, Oxidative Stress and Cholesterol Accumulation of Macrophages via Mediating RAB22A Expression by Targeting miR-377.

Atherosclerosis (AS) is one of the most common and important vascular diseases. It is believed that the abnormal expression of circular RNAs (circRNAs) plays an important role in AS. Hence, we investigate the function and mechanism of circ-C16orf62 in AS development.In this study, oxidized low-density lipoprotein (ox-LDL)-treated human macrophages (THP-1) were used as pathological conditions of AS in vitro. The expression of circ-C16orf62, miR-377 and Ras-related protein (RAB22A) mRNA was detected by real-time quantitative polymerase chain reaction (RT-qPCR) or western blot. Cell viability or cell apoptosis was assessed by cell counting kit-8 (CCK-8) assay or flow cytometry assay. The releases of proinflammatory factors were investigated using enzyme-linked immunosorbent assay (ELISA). The production of malondialdehyde (MDA) and superoxide dismutase (SOD) was examined to assess oxidative stress. Total cholesterol (T-CHO) level was detected, and cholesterol efflux level was tested using a liquid scintillation counter. The putative relationship between miR-377 and circ-C16orf62 or RAB22A was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.circ-C16orf62 expression was elevated in AS serum samples and ox-LDL-treated THP-1 cells. Apoptosis, inflammation, oxidative stress and cholesterol accumulation induced by ox-LDL were suppressed by circ-C16orf62 knockdown. Circ-C16orf62 could bind to miR-377 and thus increased the expression level of RAB22A. Rescued experiments showed that circ-C16orf62 knockdown alleviated ox-LDL-induced THP-1 cell injuries by increasing miR-377 expression, and miR-377 overexpression lessened ox-LDL-induced THP-1 cell injuries by degrading RAB22A level.In conclusion, circ-C16orf62 played a crucial role in the regulation of apoptosis, inflammation, oxidative stress and cholesterol accumulation in ox-LDL-treated human macrophages via mediating the miR-377/RAB22A axis, hinting that circ-C16orf62 might be involved in AS progression.

Average Daily Gain in Lambs Weaned at 60 Days of Age Is Correlated with Rumen and Rectum Microbiota.

Colonization of gastrointestinal microbiota in mammals during early life is vital to host health. The objective of this study was to investigate whether lambs with high and low ADG have a different rumen and rectum microbial community. Thus, we investigated potential relationships between rumen and rectum microbiota and average daily gain (ADG) in weaned lambs. Sixteen lambs with similar body weights (7.63 ± 1.18 kg) were selected at 30 days of age. At 60 days of age, lambs were weaned, and ADG was calculated from 60 to 90 days. Then, two groups were generated: higher ADG (HG, 134.17 ± 13.48 g/day) and lower ADG (LG, 47.50 ± 19.51 g/day). Microbiota was evaluated at 30, 60, and 90 days of age. The final live weight and ADG at 90 days of age was higher (p < 0.05) in the HG group compared to the LG group. The maturity of bacterial and fungal communities was increased (p < 0.05) in the HG group for the 30 days vs. 90 days comparison and 60 days vs. 90 days comparison. Linear discriminant analysis effect size (LEfSe) analysis revealed a total of 18 bacterial biomarkers that are ADG-specific in the rumen and 35 bacterial biomarkers in the rectum. Meanwhile, 15 fungal biomarkers were found in the rumen and 8 biomarkers were found in the rectum. Our findings indicated that ADG is related to the rumen and rectum microbiota in lambs.

At What Point Are Long-Term (>5 Years) Survivors of APL Safe? A Study from the SEER Database.

BACKGROUND: Acute promyelocytic leukemia (APL) is a highly curable cancer, but it is not clear whether it is also necessary to monitor long-term toxicity in "cured" patients who survive for more than five years, which is critical to ensuring maximum survival in APL patients. METHODS: A total of 1952 APL 5-year survivors and 5973 non-APL acute myeloid leukemia (AML) 5-year survivors were included from the Surveillance, Epidemiology, and End Results (SEER) database. The standardized mortality ratio (SMR) was calculated to measure the risk of death. Cumulative mortality is calculated as the incidence of specific causes of death under competing risk events. RESULTS: The SMR of all causes of death in >5-year survivors of APL was higher than that of the general population only at 60-119 months (SMR, 1.41). This was mainly because a significant increase in mortality from AML (SMR, 87.67) and second malignant neoplasms (SMNs) (SMR, 1.56) was found only at 60-119 months. However, there was no higher risk of death from non-cancer-related disease in >5-year survivors of APL than that of the general population (SMR, 0.89). The SMR of all-cause deaths in >5-year survivors of non-APL AML decreased year by year and was no higher than that of the general population until after 216 months. The cumulative incidence of AML-related death, SMN-related death, and non-cancer-related death was significantly lower in APL patients than in non-APL AML patients throughout the follow-up period. CONCLUSIONS: Compared with the general population, the risk of death of patients with APL was higher within 5 to 10 years but not higher over 10 years. Therefore, we believe that long-term survivors of APL are safe after 10 years.

Long-Term Performance of Nitrogen Removal and Microbial Analysis in an Anammox MBBR Reactor with Internal Circulation to Provide Low Concentration DO.

The anammox process is considered as a revolutionary new denitrification technology. In this study, the anammox process was started in a single-stage moving bed biofilm reactor (MBBR) and the mechanism of excess removal of ammonia nitrogen was studied. At stage I (day 0-51), anammox bacteria (AnAOB) was enriched by feeding synthetic sewage without adding organic carbon. The removal rate of ammonia nitrogen was maintained at about 54% and the removal rate of total inorganic nitrogen was maintained at about 62%. At stage II (day 52-91), internal circulation was added into the MBBR. After adding internal circulation, the ammonium removal efficiency reached about 96% (at day 56) and the total nitrogen removal efficiency reached about 86%. At day 90, the biofilm sample was drowned out for high-throughput sequencing. The results showed that the relative abundance of AnAOB was 23.23%. The dominant anammox genus was Candidatus Brocadia. The relative abundance of Nitrosomonas (ammonia oxidizing bacteria, AOB) was 0.63%. The excess ammonia nitrogen was removed by AOB and AnAOB through the partial nitrification and anammox (PNA) process.

Role of Radiation Therapy in Mortality among Adolescents and Young Adults with Lymphoma: Differences According to Cause of Death.

BACKGROUND: Despite its efficacy, emerging concerns exist regarding radiation therapy (RT)-associated toxicity in adolescent and young adult (AYA) lymphoma patients. Few long-term follow-up studies have examined the association between RT and outcomes. METHODS: Lymphoma patients aged 15-39 years were identified in the Surveillance, Epidemiology and End Results (SEER) database from 1992 to 2016. Mortality was assessed by comparing those with and without RT using the Fine-Gray competing risk model. Standardized mortality ratios (SMRs) were used to assess the relative risk of death compared with the general U.S. RESULTS: In total, 29,686 patients were included; 10,708 (36.07%) received RT. Cause-specific mortality was compared between patients with and without RT while considering other competing events, including death due to index cancer, second malignant neoplasms (SMNs), and noncancer causes. Patients with RT had a lower probability of death and crude 5-year cumulative incidence of death. Moreover, there were significantly lower SMRs in patients with RT than in patients without RT. Differences between the two groups were greatest for mortality due to hematological malignancies and infections. Additionally, in the RT cohort, the SMR for index-cancer-related death was highest in the first year after diagnosis and gradually decreased. Hematological malignancies and infections were the most common specific SMN and noncancer causes of death, respectively. CONCLUSIONS: RT did not increase mortality from index cancer, SMNs, or noncancer causes in AYA patients with lymphoid malignancies. The current analysis may serve as a reference for healthcare providers monitoring RT application for AYA lymphoid malignancy survivors.