The effects of cadmium on heme oxygenase-1 in HCT116 human colon epithelial cells with or without iron deficiency

Metals may have contrasting biological effects. Iron, a component of a variety of iron-containing proteins, plays an important role in maintaining a healthy human body. In contrast, cadmium, a contaminant and carcinogen, has been considered one of the most toxic elements in the environment. As a defending mechanism against the exposure to cadmium, cells increase expression of cytoprotective genes such as heme oxygenase-1 (HO-1). Although both the importance of iron and the toxicity of cadmium are well known, it is not clear whether iron is required for the defending mechanism (that is, the upregulation of HO-1) against the toxicity of cadmium. In my thesis project, the effects of cadmium on HO-1 in HCT116 human colon epithelial cells with or without iron deficiency were investigated. It was found that cadmium upregulated HO-1 mRNA and protein expression and enzyme activity, but these effects were decreased by desferoxamine (DFO), an iron chelator, suggesting iron plays a critical role in cadmium-induced upregulation of HO-1. This conclusion was supported by two other observations: 1) another iron chelator, 2',2'-dipyridyl (DPD), also decreased the upregulating effects of cadmium on HO-1 mRNA and protein expression; 2) iron sulfate, but not zinc sulfate and copper sulfate, restored the upregulating effects of cadmium on HO-1 mRNA and protein expression and enzyme activity in iron-deficient cells caused by the pretreatments with iron chelators, DFO or DPD. Further experiments were conducted to help explain the observations. There were two primary findings: 1) cadmium decreased intracellular glutathione levels, similar in the effects of glutathione inhibitors, ethacrynic acid (EA) and buthionine sulfoximine (BSO); however, only cadmium and EA, but not BSO, increased the expression of HO-1 mRNA and the nuclear expression of nuclear factor-E2-related factor-2 (Nrf-2), suggesting that cadmium may have the same effect as EA to directly react with intracellular glutathione; 2) being similar in effect to iron chelators, NADPH oxidase (NOX) inhibitors such as apocynin and diphenyleneiodonium (DPI), and superoxide scavenger, tiron, decreased the upregulating effects of cadmium on HO-1 mRNA and protein expression and enzyme activity. Compiled together, the results suggest that NOX-produced ROS play an important role in cadmium-induced HO-1 upregulation; cadmium induces intracellular accumulation of ROS by depleting intracellular glutathione, and increases nuclear Nrf-2 expression, which all lead to the upregulation of HO-1 expression. Moreover, it is possible that iron chelators, DFO and DPD, deplete iron contained in heme, a component of NOX, decreasing NOX-produced ROS, therefore decreasing the upregulating effect of cadmium on HO-1. In conclusion, the results imply that cadmium could be more toxic to iron-deficient cells than to iron-sufficient cells, suggesting that cadmium exposure could result in more severe consequences in an iron-deficient population than in a healthy population

SiamLST: Learning Spatial and Channel-wise Transform for Visual Tracking

Siamese network based trackers regard visual tracking as a similarity matching task between the target template and search region patches, and achieve a good balance between accuracy and speed in recent years. However, existing trackers do not effectively exploit the spatial and inter-channel cues, which lead to the redundancy of pre-trained model parameters. In this paper, we design a novel visual tracker based on a Learnable Spatial and Channel-wise Transform in Siamese network (SiamLST). The SiamLST tracker includes a powerful feature extraction backbone and an efficient cross-correlation method. The proposed algorithm takes full advantages of CNN and the learnable sparse transform module to represent the template and search patches, which effectively exploit the spatial and channel-wise correlations to deal with complicated scenarios, such as motion blur, in-plane rotation and partial occlusion. Experimental results conducted on multiple tracking benchmarks including OTB2015, VOT2016, GOT-10k and VOT2018 demonstrate that the proposed SiamLST has excellent tracking performances

Cellular Iron Depletion Weakens Induction of Heme Oxygenase-1 by Cadmium

Heme oxygenase-1 is an inducible cytoprotective gene, although its induction by environmental factors is not completely understood. This study aimed to ascertain if specific nutritive factors or related compounds influence heme oxygenase-1 expression. In HCT-116 cells, cadmium increased heme oxygenase-1 enzymatic activity. This effect of cadmium was weaker in cells made iron-deficient with the iron chelator, desferrioxamine, which was associated with repression of heme oxygenase-1 protein and mRNA expression. The repression by desferrioxamine of cadmium-induced heme oxygenase-1 upregulation was reversed upon iron replenishment of the cells. Additionally, it was found that thiol antioxidants inhibited the heme oxygenase-1 upregulation caused by cadmium and also by ethacrynic acid, which each decreased intracellular glutathione as did buthionine sulfoxamine. Interestingly, cadmium and ethacrynic acid increased nuclear translocation of Nrf2 and subsequent heme oxygenase-1 expression, but buthionine sulfoxamine did not. Furthermore, NADPH oxidase inhibitors (diphenyleneiodonium and apocynin, and a superoxide scavenger (Tiron) inhibited cadmium-induced upregulation of heme oxygenase-1. Diphenyleneiodonium was the most potent and inhibited NADPH-cytochrome P450 reductase as well, whereas apocynin and Tiron did not. It is concluded that adequate amounts of iron, which at the atomic level can serve as the pivotal element of heme in NADPH oxidase, must be present in cells to permit what appears to be thiol redox-sensitive, NADPH oxidase-dependent upregulation of heme oxygenase-1. Thus, these findings are significant because they suggest that cells without adequate iron would be unable to fully express the stress gene, heme oxygenase-1, when confronted with the toxic metal, cadmium

Detailed Analysis of a Contiguous 22-Mb Region of the Maize Genome

Most of our understanding of plant genome structure and evolution has come from the careful annotation of small (e.g., 100 kb) sequenced genomic regions or from automated annotation of complete genome sequences. Here, we sequenced and carefully annotated a contiguous 22 Mb region of maize chromosome 4 using an improved pseudomolecule for annotation. The sequence segment was comprehensively ordered, oriented, and confirmed using the maize optical map. Nearly 84% of the sequence is composed of transposable elements (TEs) that are mostly nested within each other, of which most families are low-copy. We identified 544 gene models using multiple levels of evidence, as well as five miRNA genes. Gene fragments, many captured by TEs, are prevalent within this region. Elimination of gene redundancy from a tetraploid maize ancestor that originated a few million years ago is responsible in this region for most disruptions of synteny with sorghum and rice. Consistent with other sub-genomic analyses in maize, small RNA mapping showed that many small RNAs match TEs and that most TEs match small RNAs. These results, performed on ∼1% of the maize genome, demonstrate the feasibility of refining the B73 RefGen_v1 genome assembly by incorporating optical map, high-resolution genetic map, and comparative genomic data sets. Such improvements, along with those of gene and repeat annotation, will serve to promote future functional genomic and phylogenomic research in maize and other grasses

Feasibility of electroacupuncture at Baihui (GV20) and Zusanli (ST36) on survival with a favorable neurological outcome in patients with postcardiac arrest syndrome after in-hospital cardiac arrest: study protocol for a pilot randomized controlled trial

Abstract Background At present, even the first-line medication epinephrine still shows no evidence of a favourable neurological outcome in patients with sudden cardiac arrest (SCA). The high mortality of patients with postcardiac arrest syndrome (PCAS) can be attributed to brain injury, myocardial dysfunction, systemic ischaemia/reperfusion response, and persistent precipitating pathology. Targeted temperature management, the only clinically proven method in the treatment of PCAS, is still associated with a series of problems that have not been completely resolved. Acupuncture is a crucial therapy in traditional Chinese medicine. On the basis of the results of previous studies, we hypothesize that electroacupuncture (EA) might provide therapeutic benefits in the treatment of PCAS. This study will explore the feasibility of EA on SCA patients. Methods This is a prospective pilot, randomized controlled clinical trial. Eligible patients with PCAS after in-hospital cardiac arrest (IHCA) admitted to our department will be randomly allocated to the control group or the EA group. Both groups will receive standard therapy according to American Heart Association guidelines for cardiopulmonary resuscitation. However, the EA group will also receive acupuncture at the Baihui acupoint (GV20) and Zusanli acupoint (ST36) with EA stimulation for 30 min using a dense-dispersed wave at frequencies of 20 and 100 Hz, a current intensity of less than 10 mA, and a pulse width of 0.5 ms. EA treatment will be administered for up to 14 days (until either discharge or death). The primary endpoint is survival with a favourable neurological outcome. The secondary endpoints are neurological scores, cardiac function parameters, and other clinical parameters, including Sequential Organ Failure Assessment (SOFA) scores and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, on days 0 to 28. Discussion This study will provide crucial clinical evidence on the efficacy of EA in PCAS when used as an adjunctive treatment with AHA standard therapy. Trial registration chictr.org.cn : ChiCTR2000040040. Registered on 19 November 2020. Retrospectively registered. http://www.chictr.org.cn/

Acupuncture at Zusanli (ST36) for Experimental Sepsis: A Systematic Review

Background. Sepsis is a global major health problem with high mortality rates. More effective therapy is needed for treating sepsis. Acupuncture has been used for various diseases, including severe infection, in China for more than 2,000 years. Previous studies reported that acupuncture at Zusanli (ST36) might be effective in treating sepsis, but the efficacy and the quality of evidence remain unclear since there is no systematic review on acupuncture at ST36 for sepsis. Methods. Seven databases were searched from the inception of each database up to May 2019. Ultimately, 54 studies using acupuncture at ST36 for the treatment of experimental sepsis were identified in both English and Chinese literature with systematic review procedures. Results. Acupuncture might be useful in reducing injuries induced by sepsis in cardiac, lung, kidney, liver, gastrointestinal tract, and immune system. Its potential mechanisms for antisepsis might include reducing oxidative stress and inflammation, improving microcirculatory disturbance, and maintaining the immune balance mediated by dopamine. However, the positive findings should be interpreted with caution due to poor methodological quality and publication bias. Conclusion. Acupuncture at ST36 might be a promising complementary strategy for controlling sepsis inflammation, yet further studies are needed

Robust Dual Spatial Weighted Sparse Unmixing for Remotely Sensed Hyperspectral Imagery

Sparse unmixing plays a crucial role in the field of hyperspectral image unmixing technology, leveraging the availability of pre-existing endmember spectral libraries. In recent years, there has been a growing trend in incorporating spatial information from hyperspectral images into sparse unmixing models. There is a strong spatial correlation between pixels in hyperspectral images (that is, the spatial information is very rich), and many sparse unmixing algorithms take advantage of this to improve the sparse unmixing effect. Since hyperspectral images are susceptible to noise, the feature separability of ground objects is reduced, which makes most sparse unmixing methods and models face the risk of degradation or even failure. To address this challenge, a novel robust dual spatial weighted sparse unmixing algorithm (RDSWSU) has been proposed for hyperspectral image unmixing. This algorithm effectively utilizes the spatial information present in the hyperspectral images to mitigate the impact of noise during the unmixing process. For the proposed RDSWSU algorithm, which is based on ℓ1 sparse unmixing framework, a pre-calculated superpixel spatial weighting factor is used to smooth the noise, so as to maintain the original spatial structure of hyperspectral images. The RDSWSU algorithm, which builds upon the ℓ1 sparse unmixing framework, employs a pre-calculated spatial weighting factor at the superpixel level. This factor aids in noise smoothing and helps preserve the inherent spatial structure of hyperspectral images throughout the unmixing process. Additionally, another spatial weighting factor is utilized in the RDSWSU algorithm to capture the local smoothness of abundance maps at the sub-region level. This factor helps enhance the representation of piecewise smooth variations within different regions of the hyperspectral image. Specifically, the combination of these two spatial weighting factors in the RDSWSU algorithm results in an enhanced sparsity of the abundance matrix. The RDSWSU algorithm, which is a sparse unmixing model, offers an effective solution using the alternating direction method of multiplier (ADMM) with reduced requirements for tuning the regularization parameter. The proposed RDSWSU method outperforms other advanced sparse unmixing algorithms in terms of unmixing performance, as demonstrated by the experimental results on synthetic and real hyperspectral datasets

Rechargeable Solid‐State Na‐Metal Battery Operating at −20 °C

Abstract Achieving satisfactory performance for a solid‐state Na‐metal battery (SSNMB) with an inorganic solid electrolyte (SE), especially under freezing temperatures, poses a challenge for stabilizing a Na‐metal anode. Herein, this challenge is addressed by utilizing a Natrium super ionic conductor (NASICON) NASICON‐type solid electrolyte, enabling the operation of a rechargeable SSNMB over a wide temperature range from −20 to 45 °C. The interfacial resistance at the Na metal/SE interface is only 0.4 Ω cm2 at 45 °C and remains below 110 Ω cm2 even at −20 °C. Remarkably, long‐term Na‐metal plating/stripping cycles lasting over 2000 h at −20 °C are achieved with minimal polarization voltages at 0.1 mA cm−2. Further analysis reveals the formation of a uniform Na3−xCaxPO4 interphase layer at the interface, which significantly contributes to the exceptional interfacial performance observed. By employing a Na3V1.5Al0.5(PO4)3 cathode, the full battery system demonstrates excellent adaptability to low temperatures, exhibiting a capacity of 80 mA h g−1 at −20 °C over 50 cycles and retaining a capacity of 108 mAh g−1 (88.5% of the capacity at 45 °C) at 0 °C over 275 cycles. This research significantly reduces the temperature threshold for SSNMB operation and paves the way toward solid‐state batteries suitable for all‐season applications