Zinc (Zn) is a trace element with a variety of anti-inflammatory and antioxidant effects. Zn deficiency is related to tissue fibrosis. The present study was designed to investigate the effect of Zn ...on renal fibrosis. Mouse models were successfully established by feeding mice diets with different concentrations of Zn. Zn deficiency induced a decrease in Zn levels in kidney tissue. The results also revealed renal vasodilation, hyperemia, and inflammatory cell infiltration, and the levels of creatinine and urea nitrogen were increased. Furthermore, the TUNEL results showed a large degree of renal cell necrosis caused by Zn deficiency. Meanwhile, the corresponding antioxidant and anti-inflammatory regulators (MT-1, MT-2, Nrf2, and TGF-β1) were detected by RT-PCR, showing that the expression of MT-1, MT-2, and Nrf2 decreased but that TGF-β1 expression increased. The results of Sirius red staining proved that the expression of collagen was increased by Zn deficiency. The immunohistochemical experiments found that the expression of α-smooth muscle actin (α-SMA) increased. ELISA showed that the expression of Collagen I, III, and IV; fibronectin (FN); and inflammatory factors (TNF-α and IL-1β) were remarkably increased. The expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-12, and TIMP-1, which are extracellular matrix-regulating molecules, was detected by RT-PCR. The results showed that the expression of TIMPs was increased but that the expression of MMPs was decreased. We also obtained consistent results in vivo. All the experimental results indicated that Zn deficiency could aggravate fibrosis by increasing inflammation in the kidney.
Bone-tissue defects affect millions of people worldwide. Despite being common treatment approaches, autologous and allogeneic bone grafting have not achieved the ideal therapeutic effect. This has ...prompted researchers to explore novel bone-regeneration methods. In recent decades, the development of bone tissue engineering (BTE) scaffolds has been leading the forefront of this field. As researchers have provided deep insights into bone physiology and the bone-healing mechanism, various biomimicking and bioinspired BTE scaffolds have been reported. Now it is necessary to review the progress of natural bone physiology and bone healing mechanism, which will provide more valuable enlightenments for researchers in this field. This work details the physiological microenvironment of the natural bone tissue, bone-healing process, and various biomolecules involved therein. Next, according to the bone physiological microenvironment and the delivery of bioactive factors based on the bone-healing mechanism, it elaborates the biomimetic design of a scaffold, highlighting the designing of BTE scaffolds according to bone biology and providing the rationale for designing next-generation BTE scaffolds that conform to natural bone healing and regeneration.
Bone-tissue engineering has become a promising treatment strategy for large bone defects. This work first introduces the advanced knowledge of bone biology, including the physiological microenvironment and healing process. Based on this concept, it further details the current biomimetic and bioactive bone-tissue engineering scaffolds promoting the healing process. Finally, it provides the future perspective in this field. Display omitted
•Elaborate the advanced knowledge of bone physiological microenvironment and healing process.•Summary the biomolecules involved in the natural bone healing process which could be applied to BTE materials and scaffolds.•Detail the current biomimetic and bioinspired scaffolds based on the bone physiological microenvironment.•Review the delivery of bioactive factors based on the bone healing mechanism.•Discuss the current limitations that still need to be solved, and the feasible improvement and outlooks are proposed.
Time-modulated array (TMA) has garnered significant interest in recent years as an alternative to phased arrays for certain applications. The TMA offer advantages such as simplicity and high accuracy ...when employed in scanning mode. However, a significant limitation of TMA is the constrained signal bandwidth, which must be lower than the modulation frequency to avoid aliasing. This constraint can impede progress in wideband range-Doppler (RD) estimation. To address this problem, this article proposes a TMA structure and signal processing method that integrates time, frequency, and time–frequency (TF) domains to extract information for RD estimation. The proposed methods effectively overcome the bandwidth limitation by utilizing TF filtering and data fusion techniques, thereby enhancing the performance of RD estimation in TMA. The simulation results validate the effectiveness of the proposed strategies.
Biothiols, such as glutathione (GSH), homocysteine (Hcy) and cysteine (Cys), are important biomarkers and play crucial roles in many physiological processes. Thus, the detection of biothiols is ...highly important for early diagnosis of diseases and evaluation of disease progression. Herein, new types of BODIPY-based fluorescent probes (probe 1, probe 2 and probe 3) capable of cysteine (Cys)/homocysteine (Hcy) sensing with high selectivity over other amino acids were developed. In addition, we further studied the influence of different electronegativity substituents on these probes to sensing Cys/Hcy. Ultimately, we concluded that the electron withdrawing group on probe 1 can accelerate the probe response to Cys/Hcy, and probe 1 was successfully applied for selective imaging Cys/Hcy in living cells.
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•A series of novel BODIPY-based fluorescent probes for cysteine and homocysteine were developed.•All three fluorescent probes have advantage of high sensitivity and selectivity.•Probe 1 was capable of detecting Cys/Hcy in living cells.
Early diagnosis is important for the clinical management of diseases caused by dengue virus (DENV) infections. We investigated the performance of three commercially available DENV nonstructural ...protein 1 (NS1) rapid diagnostic tests (RDTs) using 173 acute-phase sera collected from dengue fever-suspected patients during the 2012-2013 DENV outbreak in Taiwan. The results of the NS1 RDTs were compared with those of qRT-PCR to calculate the sensitivity and specificity of the NS1 RDTs. The anti-DENV IgM and IgG RDT results were included to increase the probability of detecting acute DENV infection. The anti-DENV IgM/IgG RDT results were also compared with those of IgM/IgG captured ELISA. The sera from DENV qRT-PCR-positive patients were subjected to NS1 RDTs, as well as IgM/IgG captured ELISA. These results suggested that there was no significant difference in the sensitivities of the three commercially available DNEV NS1 RDTs; the SD NS1 RDT results showed the highest agreement with the qRT-PCR reference results, followed in order by the Bio-Rad and CTK NS1 RDT results when the specificity was considered. Inclusion of the IgM or IgG RDT results increased the likelihood of diagnosing either a primary or secondary DENV infection. NS1 RDTs were more sensitive for the detection of primary infections than secondary infections, related to DENV viremia levels determined by qRT-PCR. These results suggested that anti-DENV antibodies reduced the sensitivity of NS1 rapid tests. We also analyzed the sensitivity for the detection of different DENV serotypes, and the results suggested that the NS1 RDTs used in this study were valuable for rapid screening of acute DENV infection with DENV-1, DENV-2 and DENV-3. Our results suggest that the NS1 RDT is a good alternative to qRT-PCR analysis for timely dengue disease management and prevention in dengue-endemic regions where medical resources are lacking or during large dengue outbreaks. However, the relatively low sensitivity for DENV-4 might miss the detection of DENV-4-infected cases.
Maintaining cellular Na+/K+ homeostasis is pivotal for plant survival in saline environments. However, knowledge about the molecular regulatory mechanisms of Na+/K+ homeostasis in plants under salt ...stress is largely lacking. In this report, the Arabidopsis double mutants atrbohD1/F1 and atrbohD2/F2, in which the AtrbohD and AtrbohF genes are disrupted and generation of reactive oxygen species (ROS) is pronouncedly inhibited, were found to be much more sensitive to NaCl treatments than wild-type (WT) and the single null mutant atrbohD1 and atrbohF1 plants. Furthermore, the two double mutant seedlings had significantly higher Na+ contents, lower K+ contents, and resultant greater Na+/K+ ratios than the WT, atrbohD1, and atrbohF1 under salt stress. Exogenous H2O2 can partially reverse the increased effects of NaCl on Na+/K+ ratios in the double mutant plants. Pre-treatments with diphenylene iodonium chloride, a widely used inhibitor of NADPH oxidase, clearly enhanced the Na+/K+ ratios in WT seedlings under salt stress. Moreover, NaCl-inhibited inward K+ currents were arrested, and NaCl-promoted increases in cytosolic Ca2+ and plasma membrane Ca2+ influx currents were markedly attenuated in atrbohD1/F1 plants. No significant differences in the sensitivity to osmotic or oxidative stress among the WT, atrbohD1, atrbohF1, atrbohD1/F1, and atrbohD2/F2 were observed. Taken together, these results strongly suggest that ROS produced by both AtrbohD and AtrbohF function as signal molecules to regulate Na+/K+ homeostasis, thus improving the salt tolerance of Arabidopsis.
Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of heart disease is uncertain. We ...performed a meta-analysis to investigate the link between radiotherapy and long-term cardiovascular morbidity and mortality in patients with breast cancer.
We performed a literature search using MEDLINE (January 1966 to January 2015) and EMBASE (January 1980 to January 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95%CIs for the associations of interest were included. Pooled effect estimates were obtained by using random-effects meta-analysis. Thirty-nine studies involving 1 191 371 participants were identified. Patients who received left-sided radiotherapy, as compared with those receiving right-sided radiotherapy, experienced increased risks of developing coronary heart disease (RR 1.29, 95%CI 1.13-1.48), cardiac death (RR 1.22, 95%CI 1.08-1.37) and death from any cause (RR 1.05, 95%CI 1.01-1.10). In a comparison of patients with radiotherapy and without radiotherapy, the RRs were 1.30 (95%CI 1.13-1.49) for coronary heart disease and 1.38 (95%CI 1.18-1.62) for cardiac mortality. Radiotherapy for breast cancer was associated with an absolute risk increase of 76.4 (95%CI 36.8-130.5) cases of coronary heart disease and 125.5 (95%CI 98.8-157.9) cases of cardiac death per 100 000 person-years. The risk started to increase within the first decade for coronary heart disease and from the second decade for cardiac mortality.
Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent risk of coronary heart disease and cardiac mortality.
The therapeutic options for thrombocytopenia in non-severe aplastic anaemia (NSAA) are limited. Avatrombopag (AVA) is prescribed for thrombocytopenic diseases but not for NSAA.
Herein, we conducted a ...phase 2, non-randomized, single-arm trial to explore the efficacy and safety of AVA in refractory/relapsed/intolerant NSAA. AVA dose was initiated at 20 mg/d and titrated to a maximum of 60 mg/d. The primary endpoint was the haematological response at 3 months.
Twenty-five patients were analyzed. The overall response rate (ORR) at 3 months was 56% (14/25), with 12% (3/25) achieving a complete response (CR). At a median follow-up of 7 (3-10) months, the OR and CR rates were 52% and 20%, respectively. Responders had a shorter duration of diagnosis of AVA administration than non-responders (10 (6-80) vs 37 (6-480) months, p = 0.027) and belonged to the relapsed/intolerant NSAA type (71% vs 27%, p = 0.047); 44% (8/18) patients previously treated with eltrombopag before enrollment responded at 3 months, with an average prior eltrombopag dose of median 72.5 (50-100) mg/d and an average AVA dose for a response of median 43.5 (20-60) mg/d. 3-month ORR had no significant correlation with eltrombopag exposure (p = 0.09), prior eltrombopag length (R
2
=0.11), or cumulative eltrombopag dose (R
2
=0.30). Only one patient relapsed after stopping AVA for 1 month. No serious AVA-related side effects or clone evolution were detected.
AVA is effective and well-tolerated in NSAA patients who are refractory, relapsed, or intolerant to CsA/tacrolimus ± eltrombopag. Earlier treatment and relapsed/intolerant AA may show a better short-term response rate. More studies are needed to define the optimal dose and the long-term efficacy (NCT04728789).
Nutrient excess, a major driver of obesity, diminishes hypothalamic responses to exogenously administered leptin, a critical hormone of energy balance. Here, we aimed to identify a physiological ...signal that arises from excess caloric intake and negatively controls hypothalamic leptin action. We found that deficiency of the gastric inhibitory polypeptide receptor (Gipr) for the gut-derived incretin hormone GIP protected against diet-induced neural leptin resistance. Furthermore, a centrally administered antibody that neutralizes GIPR had remarkable antiobesity effects in diet-induced obese mice, including reduced body weight and adiposity, and a decreased hypothalamic level of SOCS3, an inhibitor of leptin actions. In contrast, centrally administered GIP diminished hypothalamic sensitivity to leptin and increased hypothalamic levels of Socs3. Finally, we show that GIP increased the active form of the small GTPase Rap1 in the brain and that its activation was required for the central actions of GIP. Altogether, our results identify GIPR/Rap1 signaling in the brain as a molecular pathway linking overnutrition to the control of neural leptin actions.
With the progress of "more electric aircraft," introducing active power filter (APF) technology into the aircraft power system to improve its quality and reliability catches growing interest. In this ...paper, based on the analysis and modeling of the shunt APF with close-loop control, a feedforward compensation path of load current is proposed to improve the dynamic performance of the APF. The two H-bridge cascaded inverter is selected for the aeronautical APF (AAPF). Justifications for topology choosing and corresponding system control method are given. Furthermore, the global framework and operation principle of the proposed AAPF are presented in detail. A prototype with the load power of 7.2 kVA is built and tested in the laboratory. Experimental results verify the feasibility of the proposed AAPF and the high performance of the control strategy during steady-state and dynamic operations.
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