Selenium alleviates pancreatic fibrosis in chickens caused by mercuric chloride: Involvement of the MAPK signaling pathway and selenoproteins.

Mercuric chloride (HgCl2) is a widespread inorganic mercury with digestive toxicity. The pancreas is an important digestive organ in animals, and pancreatic fibrosis (PF) is a major pathological feature of chronic pancreatitis, which can be caused by heavy metals. Selenium (Se) is an essential trace element for the animal organism, performing biological functions in the form of selenoproteins, as well as alleviating the toxicity of heavy metals. In this study, we explored the specific mechanisms underlying the protective effect of Se on HgCl2-induced pancreatic injury in chickens. Morphological observation and serum biochemical analysis showed that Se attenuated HgCl2-caused pancreatic tissue damage and elevated glucose concentration and α-amylase activity. Next, the expression of oxidative stress indicators such as MDA and GSH-Px as well as inflammation-related markers including IL-1ß, IL-6, and TNF-α were detected. Results showed that Se had an inhibitory effect on HgCl2-induced oxidative stress and inflammation. Furthermore, we found that Se alleviated HgCl2-induced PF by detecting the expression of markers related to PF including TGF-ß1, α-SMA, COL1A1, and FN1. Mechanistically, Se attenuated HgCl2-induced PF via the MAPK signaling pathway. Importantly, several selenoproteins, especially those with antioxidant activity, were involved in the protective effect of Se on HgCl2 toxicity. In conclusion, our findings demonstrated that Se inhibited HgCl2-induced oxidative stress and inflammation and alleviated chicken PF through the MAPK signaling pathway, in which some antioxidant selenoproteins were involved.

Tunable multifunctional terahertz metasurface based on an indium antimonide medium.

Active adjustable terahertz multifunctional devices are crucial for the application of terahertz technology. In this paper, we propose a composite metasurface structure based on an indium antimonide metal octagonal pattern, which achieves different functional switching by controlling the phase state of indium antimonide material under different ambient temperatures. When indium antimonide exhibits in the dielectric state, by stacking and encoding the unit cell, the designed metasurface has the functions of two-beam splitting beam superposition, vortex beam and quarter beam superposition, and dual vortex beam superposition for circularly polarized and linearly polarized wave incidence. When indium antimonide appears in the metallic state, the encoding metasurface alters the modulation function of incident circularly polarized and linearly polarized terahertz waves. This terahertz metasurface provides a new approach for the design of multifunctional devices that can flexibly regulate terahertz wave metasurfaces.

Alteration of soil pH induced by submerging/drainage and application of peanut straw biochar and its impact on Cd(II) availability in an acidic soil to indica-japonica rice varieties.

The effects of soil pH variations induced by submergence/drainage and biochar application on soil cadmium (Cd) availability to different rice (Oryza sativa L.) varieties are not well understood. This study aims to investigate the possible reasons for available Cd(II) reduction in paddy soil as influenced by biochar and to determine Cd(II) absorption and translocation rates in different parts of various rice varieties. A pot experiment in a greenhouse using four japonica and four indica rice varieties was conducted in Cd(II) contaminated paddy soil with peanut straw biochar. The results indicated that the submerging led to an increase in soil pH due to the consumption of protons (H+) by the reduction reactions of iron/manganese (Fe/Mn) oxides and sulfate (SO42-) and thus the decrease in soil available Cd(II) contents. However, the drainage decreased soil pH due to the release of protons during the oxidation of Fe2+, Mn2+, and S2- and thus the increase in soil available Cd(II) contents. Application of the biochar increased soil pH during soil submerging and inhibited the decline in soil pH during soil drainage, and thus decreased soil available Cd(II) contents under both submerging and drainage conditions. The indica rice varieties absorbed more Cd(II) in their roots and accumulated higher amounts of Cd(II) in their shoots and grains than the japonica rice varieties. The Cd(II) sensitive varieties exhibited a greater absorption and translocation rate of Cd(II) compared to the tolerant varieties of both indica and japonica rice. Biochar inhibited the absorption and accumulation of Cd(II) in the rice varieties, which ultimately lowered the Cd(II) contents in rice grains below the national food safety limit (0.2 mg kg-1). Overall, planting japonica rice varieties in Cd(II) polluted paddy soils combined with the use of biochar can effectively reduce Cd(II) content in rice grains which protects human health against Cd(II) toxicity.

Selenium represses microRNA-202-5p/MICU1 aixs to attenuate mercuric chloride-induced kidney ferroptosis.

Mercuric chloride (HgCl2) is a nephrotoxic contaminant that is widely present in the environment. Selenium (Se) can effectively antagonize the biological toxicity caused by heavy metals. Here, in vivo and in vitro models of Se antagonism to HgCl2-induced nephrotoxicity in chickens were established, with the aim of exploring the specific mechanism. Morphological observation and kidney function analysis showed that Se alleviated HgCl2-induced kidney tissue injury and cytotoxicity. The results showed that ferroptosis was the primary mechanism for the toxicity of HgCl2, as indicated by iron overload and lipid peroxidation. On the one hand, Se significantly prevented HgCl2-induced iron overload. On the other hand, Se alleviated the intracellular reactive oxygen species (ROS) levels caused by HgCl2. Subsequently, we focused on the sources of ROS during HgCl2-induced ferroptosis. Mechanically, Se reduced ROS overproduction induced by HgCl2 through mitochondrial calcium uniporter (MCU)/mitochondrial calcium uptake 1 (MICU1)-mediated mitochondrial calcium ion (Ca2+) overload. Furthermore, a dual luciferase reporter assay demonstrated that MICU1 was the direct target of miR-202-5p. Overall, Se represses miR-202-5p/MICU1 axis to attenuate HgCl2-induced kidney ferroptosis.

When transition-metal catalysis meets electrosynthesis: a recent update.

While aiming at sustainable synthesis, organic electrosynthesis has attracted increasing attention in the past few years. In parallel, with a deeper understanding of catalyst and ligand design, 3d transition-metal catalysis allows the conception of more straightforward synthetic routes in a cost-effective fashion. Owing to their intrinsic advantages, the merger of organic electrosynthesis with 3d transition-metal catalysis has offered huge opportunities for conceptually novel transformations while limiting ecological footprint. This review summarizes the key advancements in this direction published in the recent two years, with specific focus placed on strategy design and mechanistic aspects.

Dietary Iron Overload Triggers Hepatic Metabolic Disorders and Inflammation in Laying Hen.

Iron, an essential trace element, is involved in various physiological processes; however, consumption of excessive iron possesses detrimental effects. In practical feed production, the iron content added to feeds often far exceeds the actual demand, resulting in an excess of iron in the body. The liver as a central regulator of iron homeostasis is susceptible to damage caused by disorders in iron metabolism. A model of hepatic iron overload in laying hens was developed in this study by incorporating iron into their diet, and the specific mechanisms underlying iron overload-induced hepatic injury were investigated. Firstly, this study revealed that a high-iron diet resulted in hepatic iron overload, accompanied by impaired liver function. Next, assessment of oxidative stress markers indicated a decrease in activities of T-SOD and CAT, coupled with an increase in MDA content, pointing to the iron-overloaded liver oxidative stress. Thirdly, the impact of iron overload on hepatic glycolipid and bile acid metabolism-related gene expressions were explored, including PPAR-α, GLUT2, and CYP7A1, highlighting disruptions in hepatic metabolism. Subsequently, analyses of inflammation-related genes such as iNOS and IL-1ß at both protein and mRNA levels demonstrated the presence of inflammation in the liver under conditions of dietary iron overload. Overall, this study provided comprehensive evidence that dietary iron overload contributed to disorders in glycolipid and bile acid metabolism, accompanied by inflammatory responses in laying hens. Further detailing the specific pathways involved and the implications of these findings could offer valuable insights for future research and practical applications in poultry nutrition.

Flexible manipulation terahertz beam based on an all-dielectric metasurface by utilizing addition and convolution algorithms.

The flexibly manipulated terahertz wave is currently a hot research topic. To address this challenge, we proposed an all-dielectric coding metasurface for shaping the terahertz wave including beam splitting, beam deflection, vortex beam generators, and a vortex beam and multi-beam splitting combination by combining addition with the convolution theorem. This work represents what we believe to be a new method of combining terahertz wave regulation with digital signal processing and opens up the versatile design ideas of multifunctional metadevices.

miR-15b-5p promotes HgCl2-induced chicken embryo kidney cells ferroptosis by targeting ß-TrCP-mediated ATF4 ubiquitin degradation.

Mercuric chloride (HgCl2), a widespread environmental pollutant, induces ferroptosis in chicken embryonic kidney (CEK) cells. Whereas activating transcription factor 4 (ATF4), a critical mediator of oxidative homeostasis, plays a dual role in ferroptosis, but its precise mechanisms in HgCl2-induced ferroptosis remain elusive. This study aims to investigate the function and molecular mechanism of ATF4 in HgCl2-induced ferroptosis. Our results revealed that ATF4 was downregulated during HgCl2-induced ferroptosis in CEK cells. Surprisingly, HgCl2 exposure has no significant impact on ATF4 mRNA level. Further investigation indicated that HgCl2 enhanced the expression of the E3 ligase beta-transducin repeat-containing protein (ß-TrCP) and increased ATF4 ubiquitination. Subsequent findings identified that miR-15b-5p as an upstream modulator of ß-TrCP, with miR-15b-5p downregulation observed in HgCl2-exposed CEK cells. Importantly, miR-15b-5p mimics suppressed ß-TrCP expression and reversed HgCl2-induced cellular ferroptosis. Mechanistically, HgCl2 inhibited miR-15b-5p, and promoted ß-TrCP-mediated ubiquitin degradation of ATF4, thereby inhibited the expression of antioxidant-related target genes and promoted ferroptosis. In conclusion, our study highlighted the crucial role of the miR-15b-5p/ß-TrCP/ATF4 axis in HgCl2-induced nephrotoxicity, offering a new therapeutic target for understanding the mechanism of HgCl2 nephrotoxicity.

Persistent Hyperkeratotic Plaques on a Man's Genitogluteal Area.

A man in his 40s presented with a 10-year history of pruritic lesions on the scrotum and buttock. What is your diagnosis?

Segmental Skin Induration in a Boy.

An 11-year-old boy presented with progressive unilateral skin hardening on his right thigh and buttock for 7 years. What is your diagnosis?

Olmsted Syndrome.

This case report describes a 6-year-old girl who presented with symmetrical massive keratotic plaques on the palms, soles, and perioral area, as well as hair loss for 4 years.

Effect of carbon and nitrogen mineralization of chitosan and its composites with hematite/gibbsite on soil acidification of an Ultisol induced by urea.

Chitosan is a biodegradable polymer with a vast range of applications. Along with its metal composites, chitosan has been applied in the remediation of polluted soils as well as a biofertilizer. However, little attention has been given to the degradation of chitosan composites in soil and how they affect soil respiration rate and other physicochemical parameters. In this study, the degradation of chitosan and its composites with gibbsite and hematite in an acidic Ultisol and the effect on urea (200 mg N kg-1) transformation were investigated in a 70-d incubation experiment. The results showed that the change trends of soil pH, N forms, and CO2 emissions were similar for chitosan and its composites when applied at rates <5 g C kg-1. At a rate of 5 g C kg-1, the C and N mineralization trends suggested that the chitosan-gibbsite composite was more stable in soil and this stability was owed to the formation of a new chemical bond (CH-N-Al-Gibb) as observed in the Fourier-transform infrared spectrum at 1644 cm-1. The mineralization of the added materials significantly increased soil pH and decreased soil exchangeable acidity (P < 0.01). This played an important role in decreasing the amount of H+ produced during urea transformation in the soil. The soil's initial pH was an important factor influencing C and N mineralization trends. For instance, increasing the initial soil pH significantly increased the nitrification rate and chitosan decomposition trend (P < 0.01) and thus, the contribution of chitosan and its composites to increase soil pH and inhibit soil acidification during urea transformation was significantly decreased (P < 0.01). These findings suggest that to achieve long-term effects of chitosan in soils, applying it as a chitosan-gibbsite complex is a better option.

Anti-PD-1/PD-L1 therapy for colorectal cancer: Clinical implications and future considerations.

Colorectal cancer (CRC) is the third most prevalent cancer in the world. The PD-1/PD-L1 pathway plays a crucial role in modulating immune response to cancer, and PD-L1 expression has been observed in tumor and immune cells within the tumor microenvironment of CRC. Thus, immunotherapy drugs, specifically checkpoint inhibitors, have been developed to target the PD-1/PD-L1 signaling pathway, thereby inhibiting the interaction between PD-1 and PD-L1 and restoring T-cell function in cancer cells. However, the emergence of resistance mechanisms can reduce the efficacy of these treatments. To counter this, monoclonal antibodies (mAbs) have been used to improve the efficacy of CRC treatments. mAbs such as nivolumab and pembrolizumab are currently approved for CRC treatment. These antibodies impede immune checkpoint receptors, including PD-1/PD-L1, and their combination therapy shows promise in the treatment of advanced CRC. This review presents a concise overview of the use of the PD-1/PD-L1 blockade as a therapeutic strategy for CRC using monoclonal antibodies and combination therapies. Additionally, this article outlines the function of PD-1/PD-L1 as an immune response suppressor in the CRC microenvironment as well as the potential advantages of administering inflammatory agents for CRC treatment. Finally, this review analyzes the outcomes of clinical trials to examine the challenges of anti-PD-1/PD-L1 therapeutic resistance.

Adrenocorticotropic hormone combined with magnesium sulfate therapy for infantile epileptic spasms syndrome: a real-world study.

BACKGROUND: Infantile epileptic spasms syndrome (IESS) is a serious disease in infants, and it usually evolves to other epilepsy types or syndromes, especially refractory or super-refractory focal epilepsies. Although adrenocorticotropic hormone (ACTH) is one of the first-line and effective treatment plans for IESS, it has serious side effects and is not sufficiently effective. METHODS: A retrospective study of the clinical outcomes of ACTH combined with magnesium sulfate (MgSO4) therapy for IESS in two hospital centers was conducted. The major outcome of the single and combined treatment was evaluated by changes in seizure frequency and improvements in hypsarrhythmia electroencephalography (EEG). To reduce the confounding bias between the two groups, we used SPSS for the propensity score matching (PSM) analysis. RESULTS: We initially recruited 1205 IESS patients from two Chinese hospitals and treated them with ACTH combined with MgSO4 and ACTH alone. Only 1005 patients were enrolled in the treatment (ACTH combined with MgSO4: 744, ACTH: 261), and both treatment plans had a more than 55% response rate. However, compared to patients treated with ACTH alone, those patients treated with ACTH combined with MgSO4 had better performance in terms of the seizure frequency and hypsarrhythmia EEG. After PSM, the two groups also showed significant differences in responder rate [70.8% (95% confidence interval, CI) = 66.7%-74.8%) vs. 53.8% (95% CI = 47.4%-60.2%), P < 0.001], seizure frequency (P < 0.001) and hypsarrhythmia EEG resolution (P < 0.001). Notably, multivariate analysis revealed that the lead time to treatment and the number of antiseizure medications taken before treatment were two factors that may affect the clinical outcome. Patients with less than 3 months of lead time responded to the treatment much better than those with > 3 months (P < 0.05). In addition, the overall incidence of adverse reactions in the ACTH combined with MgSO4 group was much lower than that in the ACTH group (31.4% vs. 63.1%, P < 0.001). During the treatment, only infection (P = 0.045) and hypertension (P = 0.025) were significantly different between the two groups, and no baby died. CONCLUSION: Our findings support that ACTH combined with MgSO4 is a more effective short-term treatment protocol for patients with IESS than ACTH alone, especially for those patients with short lead times to treatment. Video Abstract (MP4 533623 KB).

Reconfigurable three multi-mode terahertz metasurface.

We designed a three reconfigurable multi-mode terahertz metasurface based on a concentric elliptical ring structure. The proposed unit cell is a concentric elliptical ring composed of copper, vanadium oxide and photosensitive silicon from the inside ring to the outside ring. The conductivity of photosensitive silicon and vanadium oxide can be adjusted by changing the external operating temperature and pump light intensity. The same unit cell can reconstruct three kinds of states with different properties, and they have completely different transmission characteristics in various terahertz bands. By encoding the arrangement, through changing external stimulus and operating frequencies, the reconfigurable terahertz metasurface can achieve multiple functions including terahertz focusing with adjustable focal length, vortex beam with different topological charge, and near-field imaging with different patterns. It provides what we believe to be a new idea for the field of information security and the design of multifunctional and multifrequency terahertz devices.

Will China-Africa trade increase Africa's carbon emissions?

In order to explore whether China-Africa exchange will influence on the African environment. This paper selects four paths of China-Africa exchanges and explores the impact of each path on the African environment under the influence of different factors. We found that construction income and Africa's exports to China will increase Africa's carbon emissions. Foreign direct investment and China's exports to Africa will lead to a reduction in carbon emissions in Africa. The resource moderation will reduce the significance of the environmental impact of each path on Africa. Based on the above conclusions, several suggestions are made on the policies and actual operations in the path of China-Africa exchanges.

Terahertz Bessel beam generator.

The Bessel beam has broad application prospects in wireless energy transmission and high-speed communications. The traditional Bessel beam generation method has the problems of large volume, low efficiency, and complex manufacturing. To solve the above problems, we present a terahertz Bessel beam generator based on the reflective metasurface, which is composed of a metal pattern, dielectric layer, and bottom metal plate. Under the incidence of right circularly polarized (RCP) wave, the zero-order Bessel beam and zero-order symmetric double Bessel beam are generated. It can be found that the bottom angle of the axicon of the first-order Bessel beam is inversely proportional to the propagation distance of the Bessel beam. Comparing the electric field intensity distribution, phase distribution, and mode purity of the second-order Bessel beam and the second-order vortex beam in different observation planes, it can be seen that the energy of the higher-order Bessel beam is more concentrated and the field distribution is more stable than those of the ordinary vortex beam. The reflective terahertz Bessel beam generator has potential application value in terahertz wireless communications, measurement, radar detection, and imaging.

Frequency regulated transmission-reflection integration modes of a terahertz metasurface.

The conventional transmission and reflection operating mode switching metasurface depends on phase change materials, which are often difficult to integrate with metasurface devices and work in real time. Here, we propose an integration of a transmission-reflection metasurface that can dynamically control beam direction and functions in both transmission and reflection modes by varying the frequency of the incident wave. Remarkably, the transmission and reflection modes of terahertz beam manipulation can be obtained by illuminating only the transmission side of the metasurface. The full-wave simulation results are in good agreement with the theoretically calculated results, which verifies the terahertz wave manipulation capability of the proposed structure. This metasurface provides a design method for full-space terahertz beam regulation devices.

Selenoprotein K knockdown induces apoptosis in skeletal muscle satellite cells via calcium dyshomeostasis-mediated endoplasmic reticulum stress.

Skeletal muscle satellite cells (SMSCs), known as muscle stem cells, play an important role in muscle embryonic development, post-birth growth, and regeneration after injury. Selenoprotein K (SELENOK), an endoplasmic reticulum (ER) resident selenoprotein, is known to regulate calcium ion (Ca2+) flux and ER stress (ERS). SELENOK deficiency is involved in dietary selenium deficiency-induced muscle injury, but the regulatory mechanisms of SELENOK in SMSCs development remain poorly explored in chicken. Here, we established a SELENOK deficient model to explore the role of SELENOK in SMSCs. SELENOK knockdown inhibited SMSCs proliferation and differentiation by regulating the protein levels of paired box 7 (Pax7), myogenic factor 5 (Myf5), CyclinD1, myogenic differentiation (MyoD), and Myf6. Further analysis exhibited that SELENOK knockdown markedly activated the ERS signaling pathways, which ultimately induced apoptosis in SMSCs. SELENOK knockdown-induced ERS is related with ER Ca2+ ([Ca2+]ER) overload via decreasing the protein levels of STIM2, Orai1, palmitoylation of inositol 1,4,5-trisphosphate receptor 1 (IP3R1), phospholamban (PLN), and plasma membrane Ca2+-ATPase (PMCA) while increasing the protein levels of sarco/endoplasmic Ca2+-ATPase 1 (SERCA1) and Na+/Ca2+ exchanger 1 (NCX1). Moreover, thimerosal, an activator of IP3R1, reversed the overload of [Ca2+]ER, ERS, and subsequent apoptosis caused by SELENOK knockdown. These findings indicated that SELENOK knockdown triggered ERS driven by intracellular Ca2+ dyshomeostasis and further induced apoptosis, which ultimately inhibited SMSCs proliferation and differentiation.