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Background Kimura's disease (KD) is a rare chronic inflammatory condition characterized by nodules and lymphadenopathy in the head and neck region, exhibiting type II inflammation. Dupilumab is commonly used against type II inflammation. Aim To evaluate the efficacy and safety of dupilumab in KD patients. Design The real-world study was conducted in a hospital in China. Methods Six male patients with a mean age of 24.50 ± 15.47 years were treated with dupilumab following the same protocol as that for atopic dermatitis (AD). Clinical and laboratory indicators, such as maximum nodule diameter, blood eosinophil count, eosinophil percentage, and total serum IgE levels were assessed at baseline, Week 12 and Week 24. Adverse events were documented. Paired t -tests and one-way ANOVA were used for statistical analysis. Results The results showed significant reductions in the longest nodule diameter at Week 12 (P  =   0.006) and Week 24 (P  =   0.017) compared to baseline. Blood eosinophil count decreased by 57.95% (P  =   0.024) at Week 12 and 90.59% (P  =   0.030) at Week 24. Eosinophil percentage decreased by 58.44% (P  =   0.026) at Week 12 and 89.37% (P  =   0.013) at Week 24. Total serum IgE levels decreased by 78.02% (P  =   0.040) at Week 12 and 89.55% (P  =   0.031) at Week 24. The presence of AD did not affect the results. One patient experienced temporary facial erythema after 32 weeks of treatment, which resolved with topical treatment. No other adverse events were reported. Conclusion Dupilumab demonstrated effectiveness in treating KD without severe adverse events. [ABSTRACT FROM AUTHOR]

The anionic derivative of bis(azido)(tetraphenylporphinato)ferrate(III) was prepared and characterized using various techniques including crystal structure determination, temperature-dependent infrared spectroscopy and Mossbauer spectroscopy. In an effort to stabilize the six-coordinate anionic porphyrin and solubilize sodium azide crown ether 18C6 was used. A link between a high spin state and high temperature was also established.

An analysis of Mossbauer spectra from a model complex of known structure with an Fe(super 2+)(S1=2)-muOH-Cr(super 3+)(S2=3/2) center and of its Fe(super 3+)(S1=5/2)-muO-Cr(super 3+)(S2=3/2) analog reveals that effective S(super eff) = 1/2 and S(super eff) = 1 Hamiltonians successfully reproduce 4.2 K spectra, as antiferromagnetic spin coupling between Fe and Cr ions which results in S(super eff) = 1/2 and S(super eff) = 1 was confirmed. Analysis of the 4.2K spectra from the Fe(super 2+)(S1=2)-muOH-Cr(super 3+)(S2=3/2) center in terms of a spin Hamiltonian that includes the isotropic exchange and zero-field splittings was also conducted.

A bolter miner is a new type of mining machinery with cutting and anchoring functions. In order to study the best pick layout of bolter miner cutting head. Based on the constitutive relation of Holmquist-Johnson-Cook (HJC), three simulation models of different cutting heads were established, and the whole crushing process of coal-rock was simulated by finite element method (FEM). The influence of the cutting head on the cutting performance under the condition of different rotational speeds and pick layouts was intensively studied. The results show that the relationship of load fluctuation coefficient among the three pick layouts is as follows: sequential type > hybrid type I > checkerboard type. The circumferential pick layouts can reduce the load fluctuation coefficient of cutting head. The rotational speed from 20 to 40 r/min, the torque linearly decreases with the increase of rotational speed. The rotational speed increases from 40 to 50 r/min, the cutting torque is relatively stable. The specific energy of chessboard type is relatively higher than the other three cutting heads. The difference of specific energy between sequential type and hybrid type I is not more than 5.5%, and the reality of the simulation is verified by cutting experiments. The results were successfully applied to the first shield type bolter miner in China. [ABSTRACT FROM AUTHOR]

A labyrinth microstructure interconnected by micron and submicron acicular structures was successfully prepared by immersing nickel-aluminum bronze in 9 wt% FeCl3·6H2O solution at room temperature for 40 min. After being modified with 1H, 1H, 2H, 2H-perfluorodecyltriethoxysilane (FAS-17), the microstructure surface displays robustly low-adhesion superhydrophobicity, and the water contact angle is above 160 ° on it. In addition, the superhydrophobic surface exhibits excellent corrosion resistance and stability in 3.5wt % NaCl aqueous solution and corrosion solution with different pH values. [ABSTRACT FROM AUTHOR]

Aiming at the complex conditions of the first shielded bolter miner in the actual work, the mechanical model of bolter miner cutting head was established. Based on cutting mechanism of the conical pick and the cutting head, the cutting head load and torque analysis model under complex coal seam were established. The dynamic characteristics of load and torque in the process of cutting head are analyzed under three different working conditions of cutting roof-coal layers, coal-floor layers and coal seam by finite element method. The results show that when the damage variable D = 1, the coal-rock completely lacks the bearing capacity, and it forms arc-shaped crushing groove on the coal-rock. The large difference of torque between roof-coal layers and the roof-coal layers in the conical pick is 112 Nm, which indicates that the cutting head has the best performance with cutting the coal seam first and then cutting the rock. In the process of excavation, the load fluctuation coefficient of cutting the coal-floor layers and roof-coal layers is about 1.2 times of that of the coal seam. The results can provide a reference for the efficient cutting and performance evaluation of the bolter miner. [ABSTRACT FROM AUTHOR]

Background: Kimura's disease (KD) is a rare chronic inflammatory condition characterized by nodules and lymphadenopathy in the head and neck region, exhibiting type II inflammation. Dupilumab is commonly used against type II inflammation., Aim: To evaluate the efficacy and safety of dupilumab in KD patients., Design: The real-world study was conducted in a hospital in China., Methods: Six male patients with a mean age of 24.50 ± 15.47 years were treated with dupilumab following the same protocol as that for atopic dermatitis (AD). Clinical and laboratory indicators, such as maximum nodule diameter, blood eosinophil count, eosinophil percentage, and total serum IgE levels were assessed at baseline, Week 12 and Week 24. Adverse events were documented. Paired t-tests and one-way ANOVA were used for statistical analysis., Results: The results showed significant reductions in the longest nodule diameter at Week 12 (P = 0.006) and Week 24 (P = 0.017) compared to baseline. Blood eosinophil count decreased by 57.95% (P = 0.024) at Week 12 and 90.59% (P = 0.030) at Week 24. Eosinophil percentage decreased by 58.44% (P = 0.026) at Week 12 and 89.37% (P = 0.013) at Week 24. Total serum IgE levels decreased by 78.02% (P = 0.040) at Week 12 and 89.55% (P = 0.031) at Week 24. The presence of AD did not affect the results. One patient experienced temporary facial erythema after 32 weeks of treatment, which resolved with topical treatment. No other adverse events were reported., Conclusion: Dupilumab demonstrated effectiveness in treating KD without severe adverse events., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To analyze the role of oxycodone in acute lung injury(ALI) induced by lipopolysaccharide (LPS) in rats., Methods: Male SD rats were randomly allocated into 4 groups: control group, oxycodone group, LPS group, LPS+ oxycodone group. The effects of oxycodone on LPS-induced neutrophils influx, inflammatory cytokines release, pulmonary edema, apoptotic cell were examined. In addition, the toll-like receptor 4 (TLR4) in lung tissues was detected by Western blotting., Results: Oxycodone significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratio, was markedly decreased by oxycodone(5.60±0.24 vs 6.80±0.27, P<0.05 ). Moreover, oxycodone decreased the productions of the inflammatory cytokines including IL-1β, TNF-α, HMGB-1((1 208±18)pg/ml, (1 660±14) pg/ml, (61±4) pg/ml , all P<0.05). Oxycodone treatment also reduced the concentration of apoptosis in lung tissues(18.6%±0.5%, P<0.05). Furthermore, the expression of TLR4 was significantly suppressed by oxycodone treatment in lung tissues(1.20±0.15, P<0.05)., Conclusions: Oxycodone exerts protective effects on LPS-induced ALI in rats. The potential mechanism of this action may attribute partly to the inhibition of TLR4 activation.

Enzymatic glycerolysis of palm oil was studied in solid state with a lipase from Pseudomonus fluorescens as catalyst. The influences of molar ratio of glycerol to oil, reaction temperatures and temperature control on the accumulation of monoglyceriods in reaction mixtures were investigated. The suitable initial reaction temperature should be the minimum co-melting point of reactants. The monoglycerides contents in equilibrium state were approximately 30% at 48 degrees C or higher. An increment of 13% of monoglycerides content was obtained under the optimum temperature programming comparing with the normal equilibrium state.

Selenium is an essential trace element for animals and humans. Selenium exerts its biological function largely through selenoproteins. Up to now nine selenoproteins' cDNAs have been cloned and sequenced, which are cellular glutathione peroxidase (cGPX), extracellular glutathine peroxidase(eGPX), phospholipid hydroperoxidase glutathione peroxidase(PHGPX), gastrointestinal glutathione peroxidase (GPX-GI), type I iodothyronine 5'-deiodinase (ID I), type 2 iodothyronine 5'-deiodinase(ID II), type III iodothyronine 5-deiodinase(ID III), selenoprotein P (Se-P) and selenoprotein W. In all these selenoproteins Se is incorporated into the protein molecule via the selenocysteinyl-tRNA which recognizes the specific UGA codons in mRNA to insert selenocysteine into the primary structure of selenoproteins.

Weanling Wistar rats were fed on diets prepared from grain from areas deficient in I and Se where Keshan disease in endemic. Rats were divided into four groups, each of twelve rats, and received a diet supplemented with: I, Se, I + Se or nothing. At 8 weeks after weaning, myocardial alpha-glycerophosphate dehydrogenase (EC 1.1.1.8; alpha-GPD) activity and indices of Se and thyroid hormone status were determined. The group supplemented with iodine had increased plasma thyroxine levels. There was no difference in plasma triiodothyronine concentration between the groups but triiodothyronine levels in heart were reduced in the Se-supplemented group. Se supplementation increased myocardial glutathione peroxidase activity (EC 1.11.1.9) and the type I 5'-deiodinase (EC 3.8.1.4) activity in rat liver, but no type I 5'-deiodinase activity was detected in heart. alpha-GDP activity in heart was increased in group supplemented with Se, I or both. There was a significant relationship (P < 0.05) between myocardial alpha-GDP activity and plasma thyroxine levels but not between alpha-GDP and myocardial glutathione peroxidase activity. The results indicate that iodine may be more important than Se in energy metabolism in the myocardium, which may give a new insight for the study of the aetiology of Keshan disease in areas where foodstuffs are deficient in both Se and I.

Selenomethionine (SeMet) reacted with cyanogen bromide (BrCN) quantitatively forms CH3SeCN. After extracted with CHCl3, the Se of CH3SeCN is acid-digested to Se(IV). Then 2,3-diaminonaphthalene is used to determine the fluorescent Se value of 4,5-benzopiaselenol. The determination limit of this method was 3 ng/g SeMet. The accuracy of 10-500 ng Se in SeMet standard was 91.8%-97.6%. RSD was 1.9%-6.3%. Recoveries for grain and blood were 92.3%-96.7%. RSD was 2.7%-5.1%. The RSD for samples was 2.7%-9.0%. Selenocystine, selenocystiene selenite and methionine did not interfere with the determination.

The human dietary selenium requirement in China has been estimated by various methods. The minimum dietary selenium requirement for the prevention of Keshan disease (KD) was found to be around 17 micrograms/d. On the other hand, an intake of 40 micrograms/d is required to maintain the plasma glutathione peroxidase (GPx) activity at plateau. Hence 40 micrograms/d is considered as the adequate dietary selenium requirement. Studies conducted in a chronic selenosis area indicate that the toxic dietary selenium intake (adverse effect level), which would maintain the characteristic fingernail changes, was approximately 1600 micrograms/d. The mean value of dietary selenium intakes, which enabled the five patients to recover from fingernail lesions, was found to be 819 +/- 126 micrograms/d. At a 95% confidence limit, the lower limit is around 600 micrograms/d. Therefore, 600 and 400 micrograms/d were suggested as the individual daily maximum safe selenium intake and the safe dietary selenium intake, respectively. The results were used in the prevention of Se-related endemic KD and Kashin-Beck disease (KBD).

Type I 5'-deiodinase is a Se-containing enzyme. If Se is deficient, the deiodinase activity would be inhibited, the level of circulation T4 will be elevated, and the concentration T3 in peripheral tissues will be decreased. Se deficiency will also accelerate the iodine depletion of thyroid and may even exacerbate some detrimental effects of iodine deficiency. Possibly Se deficiency is involved in the occurrence and development of iodine deficient disorders. Keshan disease, with Se deficiency as the major cause, was also observed a change of thyroid hormone metabolism. The change of respiratory enzyme activities in myocardium of Keshan disease is in the way somewhat like that of hypothyroidism caused by iodine deficiency. The metabolic change of thyroid hormone after Se deficiency or iodine deficiency may be related to the occurrence of Keshan disease.

A recent report from this laboratory (Zhang, J.-H., Kurtz, D.M., Jr., Xia, Y.-M. and Debrunner, P.G. (1991) Biochemistry 30, 583-589) described a procedure for reconstitution of a functional di-iron site in the octameric, non-heme iron O2-carrying protein, hemerythrin by addition of ferrous salts to apoprotein, followed by slow dilution of the denaturant. Although the resulting protein contained its full complement of iron, i.e., 2 Fe per subunit, about 30% of the iron was found to remain ferrous under ambient O2, i.e., this iron was incapable of forming an O2 adduct. In this report a method is described for obtaining essentially fully functional hemerythrin by passage of the freshly reconstituted protein through an [oxy/30% non-functional----met----deoxy----oxy redox cycle. UV/vis absorption and 57Fe Mössbauer spectroscopies show that little or no non-functional iron remains in the reconstituted oxyhemerythrin after the redox cycle. Quantitations of protein and diiron sites show that, during the first step of the redox cycle, the non-functional iron is converted to a form that is spectroscopically indistinguishable from that of native methemerythrin. Far-UV circular dichroism shows that the secondary structure of this reconstituted methemerythrin is essentially identical to that of native protein. Non-denaturing polyacrylamide gel electrophoresis shows that the size and charge of the native and reconstituted proteins before and after redox cycling are essentially identical. These results indicate that the non-functional iron is converted to a functional form by the redox cycling, and that the key step in this conversion is the [oxy/30% non-functional]----met transformation.

The first reconstitutions of functional diiron sites in the nonheme O2-carrying proteins hemerythrin (Hr) and myohemerythrin (myoHr) have been achieved. Both proteins are reconstituted under anaerobic conditions, and the procedure consists of (i) denaturation of the native met form with 6 M guanidinium chloride in the presence of sodium dithionite and 2,2'-dipyridyl, (ii) separation of the apoprotein from the other reagents and products, (iii) addition of an iron(II) stock solution to the apoprotein in the presence of 2-mercaptoethanol, and (iv) several cycles of slow dilution and reconcentration by ultrafiltration to remove excess reagents. Iron analyses indicate that the apoproteins have been essentially completely freed of iron and that reconstituted Hr contains its full complement of iron, i.e., approximately 2 Fe/subunit. Ferrous rather than ferric iron appears to be necessary for recovery of the native structures for both myoHr and Hr. In the case of Hr, reconstitution was successful only when iron(II) was added to apoHr prior to removal of denaturant. ApoHr is essentially insoluble at pH 7 in the absence of denaturants but remains soluble when denaturant is removed in the presence of ferrous iron, which leads to recovery of the octameric structure containing all of its diiron sites. Iron(II) apparently stabilizes the native or a nearly native structure during reconstitution. OxymyoHr and oxyHr are the major initial products of reconstitution. The yield of oxymyoHr from apomyoHr was approximately 87%. In contrast to reconstituted oxymyoHr, where essentially all of the iron appears to be functional, approximately 30% of the diiron sites in the reconstituted oxyHr are unable to bind O2 at ambient p(O2).(ABSTRACT TRUNCATED AT 250 WORDS)

Selenium deficiency is necessary for the development of the cardiomyopathy known as Keshan disease. Healthy boys and men (19-22 per group) from a low selenium area (Dechang County) and from an area where sodium selenite was added to salt (Mianning County) were studied. Keshan disease was endemic in Dechang but occurred rarely in Mianning. After an initial blood sampling, each subject received daily selenium supplements (100 micrograms selenium for boys and 200 micrograms for men) as sodium selenate for 14 d. Blood was sampled again at 7 and 14 d. Boys from Dechang had blood selenium levels similar to levels reported for patients with Keshan disease. Plasma glutathione peroxidase activity in boys and men from Dechang was 33 and 43%, respectively, of values from the corresponding groups in Mianning. Comparison of plasma selenium concentrations in boys and men from Dechang gave values of 33 and 38%, respectively, of the corresponding groups in Mianning. Selenium status did not affect red blood cell superoxide dismutase or catalase activities. Plasma vitamin E concentration was below the normal range in all groups but was unaffected by selenium status. Measurements of plasma malondialdehyde revealed no difference between subjects from Dechang and subjects from Mianning. Selenium supplementation raised plasma glutathione peroxidase activity and plasma selenium concentration in all groups. Groups with higher plasma selenium concentration had relatively smaller increases in glutathione peroxidase activity than in selenium concentration. These results characterize the selenium deficiency in subjects at risk for developing Keshan disease. The results obtained with supplementation of selenium indicate the presence of additional plasma forms of selenium besides glutathione peroxidase.

Selenium deficiency has been implicated as a cause of the cardiomyopathy known as Keshan disease in China. Selenium is an essential constituent of glutathione peroxidase, an enzyme that destroys hydroperoxides by using the reducing equivalents of reduced glutathione (GSH). We studied glutathione-dependent hydroperoxide metabolism in isolated perfused rat hearts. Hearts from selenium-deficient rats contained 5% of the glutathione peroxidase activity found in control hearts. Glutathione reductase activity and glutathione content were not affected by selenium deficiency. Infusion of t-butylhydroperoxide into control hearts caused an increase in heart glutathione disulfide (GSSG) concentration proportional to the rate of hydroperoxide infusion up to 200 nmol/(g heart X min). GSSG was released into the perfusate in proportion to the hydroperoxide infusion rate up to 150 nmol/(g heart X min), but GSSG release did not increase further with higher infusion rates. Thus, GSSG release by the heart is saturable. It had a maximum rate of about 14 nmol GSH equivalents/(g heart X min) when stimulated by t-butylhydroperoxide infusion. This indicates that GSSG release by the heart is carrier-mediated and is not due to passive diffusion. Infusion of hydroperoxide into selenium-deficient hearts failed to cause increases in heart GSSG concentration and in GSSG release. This indicates that selenium-deficient heart cannot metabolize hydroperoxides through glutathione-dependent pathways. We suggest that selenium deficiency might predispose the heart to injury from oxidant stress.

Nitric oxide forms adducts with the binuclear iron site of hemerythrin (Hr) at [Fe(II),Fe(II)]deoxy and [Fe(II),Fe(III)]semimet oxidation levels. With deoxyHr our results establish that (i) NO binds reversibly, forming a complex which we label deoxyHrNO, (ii) NO forms a similar but distinct complex in the presence of fluoride, which we label deoxyHrFNO, (iii) NO is directly coordinated to one iron atom of the binuclear pair in these adducts, most likely in a bent end-on fashion, and (iv) the iron atoms in the binuclear sites of both deoxyHrNO and deoxyHrFNO are antiferromagnetically coupled, thereby generating unique electron paramagnetic resonance (EPR) detectable species. The novel EPR signal of deoxyHrNO (deoxyHrFNO) with g[[ = 2.77 (2.58) and g = 1.84 (1.80) is explained by the magnetic interaction of the Fe(II) (S' = 2) and [FeNO]7 (S = 3/2) centers observed by Mössbauer spectroscopy. Antiferromagnetic coupling leads to a ground state of Seff = 1/2. Analysis of the EPR parameters using the isotropic spin-exchange Hamiltonian, Hex = 2JS3/2.S2, and including zero-field splitting leads to a coupling constant, -J approximately 23 cm-1, for deoxyHrNO. The resonance Raman spectrum of deoxyHrNO shows features at 433 and 421 cm-1 that shift downward with 15N16O and that are assigned to stretching and bending modes, respectively, of the [FeNO]7 unit. Sensitivity of the bending mode to D2O suggests that bound NO participates in hydrogen bonding. We propose that the terminal oxygen atom of NO is hydrogen bonded to the proton of the mu-hydroxo bridge in the Fe-(OH)-Fe unit. A bent Fe-N-O geometry is supported by spectroscopic and structural comparisons to synthetic complexes and is consistent with a limiting [FeII,FeIIINO-] formulation for deoxyHrNO. Reversibility of NO binding to deoxyHr is demonstrated by bleaching of the optical and EPR spectra of deoxyHrNO upon additions of excess N3- or CNO-. DeoxyHrNO undergoes autoxidation under anaerobic conditions over the course of several hours. The product of this autoxidation appears to be an EPR-silent NO adduct of semimetHr. The formal one-electron oxidations of the binuclear iron site of deoxyHr by NO and by HNO2 can conceivably occur with no net change in charge on the iron site. In contrast, autoxidation of oxy- to metHr requires a change in net charge on the iron site, which may provide a kinetic barrier.