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Purpose: Much progress has been made by directing against the adrogen receptor (AR) pathway in the treatment of prostate cancer in past decades. However, AR-interactors related metastatic castration resistant prostate cancer eventually developed. Here, we aimed to characterize the aberrations and therapeutic implication in advanced disease. Materials and Methods: STRING database, UALCAN web portal and cBioPortal platform was used to analyze the AR interaction network, gene alterations, as well as the prognostic significance. GO and KEEG analysis was performed to characterize the functional enrichment of the identified AR-interactors. Results: Ten first shell AR-interactors were identified, among of which FOXA1 and PELP1 was significantly up-regulated, while CCND1, CTNNB1, NCOA4 and HSP90AA1 exhibited a significantly decreased pattern. The median survival period of altered group (n = 227) was 70 months (95% CI, 60-105M), while that of non-altered group (n = 545) was 141 months (95% CI, 115.13-NA, P < 0.001). GO and KEGG enrichment showed that the identified AR-interactors were particularly enriched in prostate cancer and thyroid hormone signaling pathway, as well as endocrine resistance. Conclusion: The AR-interactors might be useful markers for prostate cancer diagnosis and prognosis, and provide a new sight for revealing the molecular mechanism of CRPC progression. [ABSTRACT FROM AUTHOR]

Objective: Illumination of the integrative effects of herbs in a formula is a bottleneck that limits the development of traditional Chinese medicine (TCM). In the present study, we developed a transcriptome-based multi-scale network pharmacology model to explore the combined effects of different herbs. Materials and Methods: First, we curated gene signatures at different biological scales, from the molecular to higher tissue levels, including tissues, cells, pathological processes, biological processes, pathways, and targets. Second, using the Xiexin Tang (XXT) formula as an example, we collected transcriptomic data in response to the treatment of XXT or its three compositive herbs on Michigan cancer foundation7 cells. Third, we linked each herbal drug to different biological scales by calculating the correlation scores between herb-induced gene expression profiles and gene signatures. Finally, the combined mechanisms of the three constituent herbs in XXT were deciphered by comparing their multi-scale effects with those of the formula. Results: The results showed that although XXT or single herbs regulated a large number of signatures on each biological scale, the phenotypic effects of these herbal drugs are concentrated onto the “Blood” tissue, types of hemocytes, and hemorrhagic injury-related pathological processes. At the molecular level, these herbs consistently regulate processes such as the cell cycle and blood coagulation-related pathways, as well as protein targets related to the immunoinflammatory response and blood coagulation, such as proteinase-activated receptor 2, integrin beta-3, inhibitor of nuclear factor kappa-B kinase subunit beta, and coagulation factor XII. The analysis of the combinational modes demonstrated that different herbs can cooperate by acting on the same objects and/or regulating different objects in related functions, and cooperative behaviors change at different biological scales. Conclusions: Our model can dissect the combined effects of herbal formulae from a multi-scale perspective and should be beneficial for the development and exploitation of TCM.

Purpose: Chromosome 7 open reading frame 61 (C7orf 61) was a testis-specific gene, and may be involved in the process of spermatogenesis. This study aimed to investigate the expression of C7orf61 in the testis and determine its role in spermatogenesis. Materials and Methods: Reverse transcription–quantitative polymerase chain reaction, Western blot and immunofluorescence were performed to evaluate the expression characteristics of C7orf61 in mice and humans. In vitro fertilization assay was used to determine the role of the C7ORF61 protein in sperm-egg fusion. Results: The results demonstrated that C7orf61 was a testis-specific gene; the C7ofr61 mRNA expression level sharply increased in the fourth postnatal week and gradually increased until the adult stage. The C7ORF61 protein was located throughout the subacrosomal area and close to the nucleus in both mouse and human sperm. The incubation with the C7ORF61 antibody significantly decreased the fertilization rate of mouse eggs. Conclusion: The present findings suggested that the C7ORF61 protein might be involved in sperm–egg fusion, and could serve as a useful target for contraceptives. However, further research is still needed to know the detailed molecular mechanism of its role. [ABSTRACT FROM AUTHOR]

The Hopkinson tension bar technique is widely used and is the only method utilized to measure the mechanical behaviors of materials under a high strain rate; however, many fundamental problems still exist that need to be made clear, which directly link to measurement accuracy. In this work, these problems are elaborately investigated theoretically and experimentally, with the aid of a novelly designed integrated Hopkinson tension bar. Firstly, the calibration for the dynamical mechanical parameters of the bar is theoretically proposed and experimentally obtained by the one-dimension stress wave method, and verified by the integrated Hopkinson tension bar. Then, the stress wave theory is introduced to reconstruct the initial loading process of the Hopkinson bar technique for quantitatively assessing the stress inequilibrium influence on measurement accuracy at small strain. The results indicate that the elastic modulus under high strain rate loading can be determined using the Hopkinson tension bar technique, for the influence of stress inequilibrium is little even when the loading time is over 2.2 characteristic times. The traditional dynamic tension specimens are fixed to the bar ends by gluing plate specimens and screwing the screwed dogbone specimen. The joint contacts are assessed experimentally and analyzed with the integrated Hopkinson tension bar as a reference, as it requires a perfect contacting condition from the specimen to the bar ends. Finally, the involved influences are also explained to elucidate the intrinsic factors, in the hope of offering some reference for potential experiments. Comparison investigations are also conducted with the aim of simulation work, and it is found that the measurement accuracy is distinctly influenced by the transition zone, whereas the influence can be compensated by selecting a specimen with a gauge length around double that of the diametric size. [ABSTRACT FROM AUTHOR]

Abstract Continuous monitoring of cardiac motions has been expected to provide essential cardiac physiology information on cardiovascular functioning. A fiber-optic micro-vibration sensing system (FO-MVSS) makes it promising. This study aimed to explore the correlation between Ballistocardiography (BCG) waveforms, measured using an FO-MVSS, and myocardial valve activity during the systolic and diastolic phases of the cardiac cycle in participants with normal cardiac function and patients with congestive heart failure (CHF). A high-sensitivity FO-MVSS acquired continuous BCG recordings. The simultaneous recordings of BCG and electrocardiogram (ECG) signals were obtained from 101 participants to examine their correlation. BCG, ECG, and intracavitary pressure signals were collected from 6 patients undergoing cardiac catheter intervention to investigate BCG waveforms and cardiac cycle phases. Tissue Doppler imaging (TDI) measured cardiac time intervals in 51 participants correlated with BCG intervals. The BCG recordings were further validated in 61 CHF patients to assess cardiac parameters by BCG. For heart failure evaluation machine learning was used to analyze BCG-derived cardiac parameters. Significant correlations were observed between cardiac physiology parameters and BCG's parameters. Furthermore, a linear relationship was found betwen IJ amplitude and cardiac output (r = 0.923, R2 = 0.926, p

AIM: To evaluate the efficacy of Ahmed glaucoma valve implanting through the ciliary sulcus in the treatment of intraocular lens(IOL)glaucoma.METHODS: Retrospective case series study. The clinical data of 18 patients(18 eyes)with IOL glaucoma from February 2020 to February 2022 in Liuzhou Red Cross Hospital were collected. All patients underwent Ahmed glaucoma valve implanting through the ciliary sulcus. The visual acuity, intraocular pressure, corneal endothelial cell density, corneal endothelial cell loss rate and complications were observed before operation and 1, 3, 6 and 12mo after operation.RESULTS: The mean intraocular pressure before operation was 43.41±5.33 mmHg. The mean intraocular pressure at 1, 3, 6 and 12mo after operation were 12.11±3.26, 13.82±4.12, 13.54±3.83 and 15.80±4.35 mmHg respectively. The mean intraocular pressure at each follow-up point after operation was significantly lower than that before operation(F=203.40, P0.05). Furthermore, the overall surgery success rate was 83%.CONCLUSIONS: Ahmed glaucoma valve implanting through the ciliary sulcus is safe and effective in the treatment of IOL glaucoma, and the damage to corneal endothelial cells is mild. The corneal endothelial cells density doesn't decrease with time after surgery.

Abstract Background Brain-derived neurotrophic factor (BDNF) is one of the proteins that contributes to the survival, growth, maintenance of neurons, and plays important roles in the pathophysiology of depression. It has been reported that depression is closely associated with the pathogenesis of acne vulgaris disease. But, there is no report of serum BDNF levels in patients with acne vulgaris. The study aimed to determine the potential association between BDNF and depressive symptoms in young adults with acne vulgaris. Methods In this analytical cross-sectional study, the serum BDNF levels were measured in peripheral blood samples of 20 consecutive acne vulgaris patients with depression and 98 consecutive acne vulgaris patients without depression and also compared it with a 59 healthy control group by using a ELISA. The potential correlation between the BDNF levels, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and depressive symptoms such as nine-item patient health questionnaire (PHQ-9) and Athens insomnia scale (AIS) were evaluated with multivariate logistic regression analysis. Results Our results showed that levels of BDNF expression were lower in consecutive acne vulgaris patients when compared with healthy control (P 0.05). Similarly, the overall area under the curve of receiver operating characteristic was 0.82, indicating the highly conserving of serum BDNF levels as an biomarker for screening of depression in young adults with acne vulgaris (72% sensitivity and 85% specificity). Conclusion Serum BDNF levels were decreased and negatively associated with depressive symptoms in young Chinese adults with acne vulgaris.

Background: Accumulating evidence has revealed that coronavirus disease 2019 (COVID-19) patients may be complicated with myocardial injury during hospitalization. However, data regarding persistent cardiac involvement in patients who recovered from COVID-19 are limited. Our goal is to further explore the sustained impact of COVID-19 during follow-up, focusing on the cardiac involvement in the recovered patients.Methods: In this prospective observational follow-up study, we enrolled a total of 40 COVID-19 patients (20 with and 20 without cardiac injury during hospitalization) who were discharged from Zhongnan Hospital of Wuhan University for more than 6 months, and 27 patients (13 with and 14 without cardiac injury during hospitalization) were finally included in the analysis. Clinical information including self-reported symptoms, medications, laboratory findings, Short Form 36-item scores, 6-min walk test, clinical events, electrocardiogram assessment, echocardiography measurement, and cardiac magnetic resonance imaging was collected and analyzed.Results: Among 27 patients finally included, none of patients reported any obvious cardiopulmonary symptoms at the 6-month follow-up. There were no statistically significant differences in terms of the quality of life and exercise capacity between the patients with and without cardiac injury. No significant abnormalities were detected in electrocardiogram manifestations in both groups, except for nonspecific ST-T changes, premature beats, sinus tachycardia/bradycardia, PR interval prolongation, and bundle-branch block. All patients showed normal cardiac structure and function, without any statistical differences between patients with and without cardiac injury by echocardiography. Compared with patients without cardiac injury, patients with cardiac injury exhibited a significantly higher positive proportion in late gadolinium enhancement sequences [7/13 (53.8%) vs. 1/14 (7.1%), p = 0.013], accompanied by the elevation of circulating ST2 level [median (interquartile range) = 16.6 (12.1, 22.5) vs. 12.5 (9.5, 16.7); p = 0.044]. Patients with cardiac injury presented higher levels of aspartate aminotransferase, creatinine, high-sensitivity troponin I, lactate dehydrogenase, and N-terminal pro–B-type natriuretic peptide than those without cardiac injury, although these indexes were within the normal range for all recovered patients at the 6-month follow-up. Among patients with cardiac injury, patients with positive late gadolinium enhancement presented higher cardiac biomarker (high-sensitivity troponin I) and inflammatory factor (high-sensitivity C-reactive protein) on admission than the late gadolinium enhancement–negative subgroup.Conclusions: Our preliminary 6-month follow-up study with a limited number of patients revealed persistent cardiac involvement in 29.6% (8/27) of recovered patients from COVID-19 after discharge. Patients with cardiac injury during hospitalization were more prone to develop cardiac fibrosis during their recovery. Among patients with cardiac injury, those with relatively higher cardiac biomarkers and inflammatory factors on admission appeared more likely to have cardiac involvement in the convalescence phase.

TRAF6 is a ubiquitin E3 ligase regulating a number of biological processes. Here the authors show that ROS, generated during pathological cardiac stress, induces TRAF6 auto-ubiquitination and activation, promoting its interaction with and ubiquitination of TAK1 that contributes to development of cardiac hypertrophy.

Abstract Although pathological cardiac hypertrophy represents a leading cause of morbidity and mortality worldwide, our understanding of the molecular mechanisms underlying this disease is still poor. Here, we demonstrate that suppressor of IKKɛ (SIKE), a negative regulator of the interferon pathway, attenuates pathological cardiac hypertrophy in rodents and non-human primates in a TANK-binding kinase 1 (TBK1)/AKT-dependent manner. Sike-deficient mice develop cardiac hypertrophy and heart failure, whereas Sike-overexpressing transgenic (Sike-TG) mice are protected from hypertrophic stimuli. Mechanistically, SIKE directly interacts with TBK1 to inhibit the TBK1-AKT signalling pathway, thereby achieving its anti-hypertrophic action. The suppression of cardiac remodelling by SIKE is further validated in rats and monkeys. Collectively, these findings identify SIKE as a negative regulator of cardiac remodelling in multiple animal species due to its inhibitory regulation of the TBK1/AKT axis, suggesting that SIKE may represent a therapeutic target for the treatment of cardiac hypertrophy and heart failure.