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RationaleFructose-1,6-bisphosphatase (FBP1) is a tumor suppressor and a key enzyme negatively regulating Warburg effect in cancer. However, regulation of FBP1 protein expression and its exact role in prostate cancer (PCa) is largely unclear. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumor suppressor genes in human PCa. However, the role of PTEN loss in aberrant Warburg effect in cancer remains poorly understood.MethodsExpression of PTEN and FBP1 was analyzed in several PCa cell lines and prostate tumor tissues in mice. Western blot (WB) and RT-PCR approaches were used to examine how PTEN regulates FBP1 expression. Co-immunoprecipitation (co-IP) and in vivo ubiquitination assays were used to define the regulatory mechanisms. A PCa xenograft model was employed to determine the impact of PTEN regulation of FBP1 on PCa growth in vivo.ResultWe demonstrated that in a manner dependent of PI3K/AKT signal pathway PTEN regulated FBP1 expression in various PCa cell lines and tumors in mice. We confirmed that this regulation took place at the protein level and was mediated by SKP2 E3 ubiquitin ligase. Mechanistically, we showed that serine 271 phosphorylation of FBP1 by cyclin-dependent kinases (CDKs) was essential for SKP2-mediated degradation of FBP1 protein induced by PTEN loss. Most importantly, we further showed that loss of PTEN expression enhanced Warburg effect and PCa growth in mice in a manner dependent, at least partially on FBP1 protein degradation.ConclusionsOur results reveal a novel tumor-suppressive feature of PTEN in restraining FBP1 degradation and the Warburg effect. These results also suggest that prohibiting FBP1 protein degradation could be a viable therapeutic strategy for PTEN-deficient PCa.

The antibacterial activity of royalisin, an antimicrobial peptide from the royal jelly produced by honeybees, has been addressed extensively. However, its mechanism of action remains unclear. In this study, a recombinant royalisin, RAcc-royalisin from the royal jelly of Asian honeybee Apis cerana cerana, was expressed by fusing with glutathione S-transferase (GST) in Escherichia coli BL21, isolated and purified. The agar dilution assays with inhibition zone showed that RAcc-royalisin, similar to nisin, inhibits the growth of Gram-positive bacteria. The antibacterial activity of RAcc-royalisin was associated with its concentration, and was weakened by heat treatment ranging from 55°C to 85°C for 15 min. Both RAcc-royalisin and nisin exhibited the minimum inhibitory concentrations (MIC) of 62.5 µg/ml, 125 µg/ml, and 250 µg/ml against Gram-positive bacterial strains, Bacillus subtilis and Micrococcus flavus and Staphyloccocus aureus in the microplate assay, respectively. However, RAcc-royalisin did not show antimicrobial activity against tested Gram-negative bacterial and fungal strains. The antibacterial activity of RAcc-royalisin agrees well with the decrease in bacterial cell hydrophobicity, the leakage of 260-nm absorbing materials, and the observation by transmission electron microscopy, all indicating that RAcc-royalisin induced the disruption and dysfunction of cell walls and membranes. This is the first report detailing the antibacterial mechanism of royalisin against Gram-positive bacteria, and provides insight into the application of recombinant royalisin in food and pharmaceutical industries as an antimicrobial agent.

IntroductionAlthough acupuncture is recommended by chronic obstructive pulmonary disease (COPD) treatment guidelines owing to its effects on dyspnea, the underlying neurobiological mechanisms of these effects remain unclear. This study aims to evaluate the efficacy of acupuncture in patients with stable COPD and explore the possible involvement of specific brain regions.MethodsThis is a prospective, multicenter, single-blind, randomized controlled trial. A total of 90 participants will be recruited from three centers and will be randomly assigned in a 1:1 ratio to undergo acupuncture at acupoints on the disease-affected meridian (DAM) or non-acupoints on the non-affected meridian (NAM), in addition to routine pharmacological treatments. All participants will undergo 30 min of acupuncture three times a week for 8 weeks and will be followed up for 12 months. The primary outcome will be the severity of dyspnea, as measured using the Borg Dyspnea Scale and a visual analog scale at rest and after exercise. The secondary outcomes will include the multidimensional profile of dyspnea using Dyspnea-12, the modified Medical Research Council Dyspnea Scale, and the COPD assessment test; quality of life assessments using St George's Respiratory Questionnaire and the Hospital Anxiety and Depression Scale; and additional measurements of exacerbation frequency, pulmonary function, and the 6-min walking distance. Magnetic resonance imaging (MRI) will be performed before and after exercise to explore the potential neurobiological mechanisms of exertional dyspnea. Anxiety and depression will be measured and analyzed for their correlation with the activation of specific brain areas involved in dyspnea.DiscussionThis randomized controlled trial aims to use a multidimensional evaluation of the efficacy of acupuncture in relieving dyspnea in patients with COPD in terms of emotion and quality of life and explore the neurobiological mechanisms underlying the effects of acupuncture on dyspnea from an imaging perspective. It is expected to provide strong evidence to support the use of acupuncture in relieving dyspnea in patients with COPD and those with aother diseases involving dyspnea. Additionally, it provides novel insights into the central mechanisms of acupuncture intervention and dyspnea.Trial registrationChinese Clinical Trial Registry (https://www.chictr.org.cn/): ChiCTR2300071725.

BackgroundWilson's disease (WD) is an inherited disorder characterized by impaired biliary excretion of copper and excessive copper accumulation in multiple organs, primarily leading to hepatic, neurological, and psychiatric manifestations. The coexistence of WD and systemic lupus erythematosus (SLE) has rarely been reported, posing challenges in accurately diagnosing these two conditions because of overlapping clinical symptoms.Case presentationWe presented the case of a 17-year-old girl initially suspected of having SLE due to positive anti-nuclear antibodies and lupus anticoagulants, decreased platelet count, hypocomplementemia, and pleural effusion. However, the patient also exhibited an unusual manifestation of decompensated liver cirrhosis, which is not typical of SLE. Further investigation revealed low serum ceruloplasmin levels, high 24-h urine copper levels, the presence of Kayser–Fleischer rings, and a compound heterozygous mutation in the ATP7B gene, confirming the diagnosis of WD.ConclusionThe co-occurrence of WD and SLE poses a significant diagnostic challenge, often leading to misdiagnosis and delayed diagnosis. Therefore, in patients with well-controlled SLE presenting with unexplained liver fibrosis, neurological involvement, or psychiatric symptoms, it is crucial to consider the possibility of WD. However, further studies are required to elucidate the underlying pathophysiological mechanisms.

Abstract A reliable train‐to‐ground wireless communication system is proposed for the foundation of the safe operation of Hyperloop. The wireless channel characteristics of Hyperloops at millimetre‐wave (mmWave) bands are analysed based on the ray‐tracing method. Considering the reflection paths and line of sight path, the channel transfer function expression is derived for each multipath and then the channel impulse response is obtained. On this basis, the investigation and analysis of the large‐scale and small‐scale channel characteristics, including the path loss, shadow fading, delay spread, and angular spread of 4 different mmWave frequency carriers, that is, 28/38/45/60 GHz, are conducted. Simulation results show that the path loss increases as the frequency increases while the time delay spread and angular spread almost keep unchanged. The relevant research results will contribute to the design of future Hyperloop wireless communication systems.

Abstract Background Interstitial lung disease (ILD) may cause life-threatening complications of primary Sjogren’s syndrome (pSS), and has a poor prognosis in terms of survival and quality of life. To date, few studies have investigated the risk factors for ILD detected by high-resolution computed tomography (HRCT) in pSS patients with or without respiratory symptoms. Methods Data of 333 patients with newly diagnosed pSS were retrospectively analysed. Interstitial lung disease involvement was defined as typical abnormalities on HRCT and/or pulmonary function tests. Multivariate regression model was used to evaluate the association between interstitial lung disease and pSS characteristics. Results Sixty-six patients (19.82%) were diagnosed with pSS-ILD. Ground glass opacities (87.88%) and septal/sub pleural lines (81.82%) were most frequent. Based on pulmonary high-resolution computed tomography, patients were divided into nonspecific (n = 42), usual (n = 20), lymphocytic interstitial pneumonia (n = 3) and cryptogenic organising pneumonia (n = 1) groups. There was a strong association between erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) and the HRCT-score. Pulmonary function tests revealed impaired diffusion capacity for carbon monoxide and total lung capacity, and coexistence of small airway lesions in pSS-interstitial lung disease. On logistic regression analysis, age, Raynaud’s phenomenon, lymphopenia, cough, dyspnoea and rampant dental caries were risk factors associated with pSS-interstitial lung disease. Conclusions Interstitial lung disease involvement in pSS is a common clinical occurrence. The clinical manifestation is nonspecific and variable; Raynaud’s phenomenon and lymphopenia may predict its onset. pSS patients with advanced age, dry cough and dyspnoea should be systematically evaluated for ILD involvement and managed according to their symptoms.

Abstract Background Osteoporosis is a major public health concern for the elderly population and is characterized by fatigue load resulting in bone microdamage. The ability of bone mesenchymal stem cells (BMSCs) to repair bone microdamage diminishes with age, and the accumulation of bone microdamage increases the risk of osteoporotic fracture. There is a lack of effective means to promote the repair of bone microdamage in aged patients with osteoporosis. Exosomes have been shown to be related to the osteogenic differentiation of BMSCs. Here, we aimed to evaluate the changes in the osteogenic differentiation capacity of BMSCs in aged osteoporotic rats after fatigue loading and the treatment potential of serum exosomes from young rats. Methods The tibias of six aged osteoporotic rats were subjected to fatigue loading in vivo for 2 weeks, and the bone microdamage, microstructures, and mechanical properties were assessed. Subsequently, BMSCs were extracted to evaluate their proliferation and osteogenic differentiation abilities. In addition, the BMSCs of aged osteoporotic rats after fatigue loading were treated with serum exosomes from young rats under osteogenic induction conditions, and the expression of osteogenic-related miRNAs was quantified. The osteogenetic effects of miRNA-19b-3p in exosomes and the possible target protein PTEN was detected. Results Obvious bone microdamage at the fatigue load stress point, the bone microstructure and biomechanical properties were not obviously changed. A decreased osteogenic differentiation ability of BMSCs was observed after fatigue loading, while serum exosomes from young rats highly expressing miRNA-19b-3p improved the decreased osteogenic differentiation ability of BMSCs. Transfection with miRNA-19b-3p mimic could promote osteoblastic differentiation of BMSCs and decreased the expression of PTEN. After transfection of miRNA-19b-3p inhibitor, the promotional effect of exosomes on bone differentiation was weakened. Treatment with transfected exosomes increased the expression of PTEN. Conclusion Serum exosomes derived from young rats can improve the decreased osteogenic differentiation ability of BMSCs in aged rats with osteoporosis after fatigue loading and can provide a new treatment strategy for the repair of bone microdamage and prevention of fractures.

Introduction Increasing numbers of patients with non-haematological diseases are infected with invasive pulmonary aspergillosis (IPA), with a high mortality reported which is mainly due to delayed diagnosis. The diagnostic capability of mycological tests for IPA including galactomannan test, (1,3)-β-D-glucan test, lateral flow assay, lateral flow device and PCR for the non-haematological patients remains unknown. This protocol aims to conduct a systematic review and meta-analysis of the diagnostic performance of mycological tests to facilitate the early diagnosis and treatments of IPA in non-haematological diseases.Methods and analysis Database including PubMed, CENTRAL and EMBASE will be searched from 2002 until the publication of results. Cohort or cross-sectional studies that assessing the diagnostic capability of mycological tests for IPA in patients with non-haematological diseases will be included. The true-positive, false-positive, true-negative and false-negative of each test will be extracted and pooled in bivariate random-effects model, by which the sensitivity and specificity will be calculated with 95% CI. The second outcomes will include positive (negative) likelihood ratio, area under the receiver operating characteristic curve and diagnostic OR will also be computed in the bivariate model. When applicable, subgroup analysis will be performed with several prespecified covariates to explore potential sources of heterogeneity. Factors that may impact the diagnostic effects of mycological tests will be examined by sensitivity analysis. The risk of bias will be appraised by the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2).Ethics and dissemination This protocol is not involved with ethics approval, and the results will be peer-reviewed and disseminated on a recognised journal.PROSPERO registration number CRD42021241820.

Hyperloop is envisioned as the next generation of railway transportation mode, which can proceed at a speed of more than 1000 km/h. The safe operation of the Hyperloop depends heavily on the support of a stable communication system. In this paper, we propose a 3D channel model in vacuum tube scenarios based on the ray-tracing method. The reflection paths and line of sight (LoS) paths are considered. We derive the channel transfer function (CTF) expression for each multipath, and then the channel impulse response (CIR) is obtained. On this basis, the large-scale and small-scale channel characteristics, including path loss, shadow fading, correlation coefficient, delay spread, and angular spread, are investigated and analyzed. Simulation results show that the proposed channel model can characterize the wireless channel in the Hyperloop scenarios in detail, and the results maintain a high level of symmetry between the range of 0–250 m and 250–500 m. The relevant research results will contribute to the design of future Hyperloop wireless communication systems.

Abstract Background Marsdenia tenacissima extract (MTE) is a phytochemical widely used as complementary therapy in cancer care. This systematic review was conducted to investigate the anticancer and detoxification effects of MTE, as an adjuvant therapy to chemotherapy, for treating gastric cancer. Methods Ten databases were searched to identify randomized controlled trials (RCTs) comparing oral or injectable MTE plus chemotherapy versus chemotherapy alone for treating gastric cancer up to May 1, 2019. In meta-analyses, proportional odds ratios (PORs) with 95% confidence intervals (CIs) were pooled for the ordinal outcomes using the generalized linear model, and risk ratios (RRs) with 95% CIs were pooled for dichotomous outcomes using the Mantel-Haenszel method. Results Seventeen RCTs with 1329 individuals were included, with a moderate to high risk of selection and performance bias. Compared to chemotherapy alone, MTE adjuvant therapy significantly improved the response to anticancer treatment (POR 2.01, 95% CI 1.60–2.53) and patients’ performance status (POR 3.15, 95% CI 2.22–4.48) and reduce the incidences of chemotherapy-induced leukopenia (RR 0.66, 95% CI 0.56–0.78), thrombocytopenia (RR 0.64, 95% CI 0.48–0.86), anemia (RR 0.89, 95% CI 0.72–1.10), nausea/vomiting (RR 0.79, 95% CI 0.69–0.91), hepatic injury (RR 0.77, 95% CI 0.61–0.96), and peripheral neurotoxicity (RR 0.77, 95% CI 0.59–1.01). However, MTE did not significantly alleviate anemia, diarrhea, constipation, kidney injury, and oral mucosal lesions after chemotherapy. Incidence of nausea/vomiting was lower in patients receiving oral MTE than those receiving injectable MTE (RR 0.47 vs. 0.82, interaction P = 0.04). Heterogeneity was generally low among these outcomes. Three out of five RCTs that reported survival data supported the effects of MTE for prolonging progression-free and/or overall survival. No studies reported safety outcomes of MTE. Conclusions The current evidence with limitations of risk of selection and performance bias suggests that MTE, as an adjuvant therapy to chemotherapy, is effective for inhibiting cancer growth and reducing incidences of multiple chemotherapy side effects. Oral MTE may be a better choice. Uncertainty remains regarding the effects of MTE on survival endpoints and the subgroup differences between acute and chronic use of MTE and between different chemotherapy regimens.

Cellulose acetate CAbased nanocomposites with various contents of neat multiwalled carbon nanotube MWCNT or acidtreated one MWCNTCOOH are prepared via meltcompounding method and investigated their morphology, thermal stability, mechanical, and electrical properties. SEM microphotographs reveal that MWCNTCOOHs are dispersed uniformly in the CA matrix, compared with neat MWCNTs. FTIR spectra support that there exists a specific interaction between carboxyl groups of MWCNTCOOHs and ester groups of CA, indicating good interfacial adhesion between MWCNTCOOHs and CA matrix. Accordingly, thermal stability and dynamic mechanical properties of CAMWCNTCOOH nanocomposites were higher than those of CAMWCNT composites. On the contrary, electrical volume resistivities of CAMWCNTCOOH nanocomposites are found to be somewhat higher than those of CAMWCNT composites, which is because of the deterioration of graphene structures for MWCNTCOOHs and the good dispersion of MWCNTCOOHs in the CA matrix. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [ABSTRACT FROM AUTHOR]