Design and Analysis of 5-DOF Compact Electromagnetic Levitation Actuator for Lens Control of Laser Cutting Machine.

In laser beam processing, the angle or offset between the auxiliary gas and the laser beam axis have been proved to be two new process optimization parameters for improving cutting speed and quality. However, a traditional electromechanical actuator cannot achieve high-speed and high-precision motion control with a compact structure. This paper proposes a magnetic levitation actuator which could realize the 5-DOF motion control of a lens using six groups of differential electromagnets. At first, the nonlinear characteristic of a magnetic driving force was analyzed by establishing an analytical model and finite element calculation. Then, the dynamic model of the magnetic levitation actuator was established using the Taylor series. And the mathematical relationship between the detected distance and five-degree-of-freedom was determined. Next, the centralized control system based on PID control was designed. Finally, a driving test was carried out to verify the five-degrees-of-freedom motion of the proposed electromagnetic levitation actuator. The results show it can achieve a stable levitation and precision positioning with a desired command motion. It also proves that the proposed magnetic levitation actuator has the potential application in an off-axis laser cutting machine tool.

Phase separation of S-RNase promotes self-incompatibility in Petunia hybrida.

Self-incompatibility (SI) is an intraspecific reproductive barrier widely present in angiosperms. The SI system with the broadest occurrence in angiosperms is based on an S-RNase linked to a cluster of multiple S-locus F-box (SLF) genes found in the Solanaceae, Plantaginaceae, Rosaceae, and Rutaceae. Recent studies reveal that non-self S-RNase is degraded by the Skip Cullin F-box (SCF)SLF -mediated ubiquitin-proteasome system in a collaborative manner in Petunia, but how self-RNase functions largely remains mysterious. Here, we show that S-RNases form S-RNase condensates (SRCs) in the self-pollen tube cytoplasm through phase separation and the disruption of SRC formation breaks SI in self-incompatible Petunia hybrida. We further find that the pistil SI factors of a small asparagine-rich protein HT-B and thioredoxin h together with a reduced state of the pollen tube all promote the expansion of SRCs, which then sequester several actin-binding proteins, including the actin polymerization factor PhABRACL, the actin polymerization activity of which is reduced by S-RNase in vitro. Meanwhile, we find that S-RNase variants lacking condensation ability fail to recruit PhABRACL and are unable to induce actin foci formation required for pollen tube growth inhibition. Taken together, our results demonstrate that phase separation of S-RNase promotes SI response in P. hybrida, revealing a new mode of S-RNase action.

Calcium dobesilate-induced hyperpyrexia: A case report.

RATIONALE: Calcium dobesilate, a vasoprotective and antioxidant agent, is gradually being used for the treatment of chronic kidney disease. Calcium dobesilate-induced hyperpyrexia is a rare clinical event, and few studies have reported it. PATIENT CONCERNS: The patient took calcium dobesilate, which caused high fever. After stopping calcium dobesilate, his body temperature returned to normal. DIAGNOSES: Based on the medical history, symptoms and signs, the patient was diagnosed with drug fever caused by calcium dobesilate. INTERVENTIONS: Calcium dobesilate was stopped, and supportive treatment was given at the same time. OUTCOMES: The present case was initially misdiagnosed as a fever caused by a bacterial infection, but treatment with the antibiotic moxifloxacin was ineffective. Based on the patient's medical history, laboratory and examination results, body temperature changes, and Naranjo Advanced Drug Response Scale, calcium dobesilate-induced hyperpyrexia was diagnosed. After discontinuation of calcium dobesilate, the patient's body temperature normalized, and no additional episode of fever was observed at follow-up. LESSON: Moreover, misdiagnosis and mistreatment of this condition can deteriorate the patient's condition. Herein, we report a case of calcium dobesilate-induced hyperpyrexia that occurred during the treatment of chronic renal insufficiency. Subsequently, a systematic analysis of the patient's diagnosis and treatment was reviewed. If unexplained high fever develops during the use of calcium dobesilate, calcium dobesilate-induced hyperpyrexia should be considered. Accordingly, calcium dobesilate should be discontinued.

Removal of Ciprofloxacin from Water by a Potassium Carbonate-Activated Sycamore Floc-Based Carbonaceous Adsorbent: Adsorption Behavior and Mechanism.

In this study, a porous carbonaceous adsorbent was prepared from sycamore flocs by pyrolysis method and K2CO3 activation. The effects of preparative conditions of the material on its adsorptive property were explored. The optimal material (SFB2-900) was obtained with a K2CO3/biochar mass ratio of 2:1 at an activation temperature of 900 °C, possessing a huge surface specific area (1651.27 m2/g). The largest adsorption capacity for ciprofloxacin on SFB2-900 was up to 430.25 mg/g. The adsorption behavior was well described by the pseudo-second-order kinetic model and the Langmuir isothermal model. Meanwhile, this process was spontaneous and exothermic. The obtained material showed excellent adsorption performance in the conditions of diverse pH range, ionic strength, and water quality of the solution. The optimum adsorption conditions (pH = 7.01, dosage = 0.6 g/L, and C0 = 52.94 mg/L) determined based on the response surface methodology were in accordance with the practical validation consequences. The good regeneration effect of SFB2-900 manifested that this material had great practical application potential. Combining the experimental results and density functional theory calculation results, the adsorption mechanisms mainly included pore filling, π-π EDA interactions, electrostatic interactions, and H-bonds. The material could be regarded as a novel and high-efficiency adsorbent for antibiotics. Additionally, these findings also provide reference for the reuse of waste biomass in water treatment.

Performance and mechanism of sycamore flock based biochar in removing oxytetracycline hydrochloride.

In this study, sycamore flocs (SF), which caused environmental and health problems, were utilized to prepare biochar. SFB2-900 obtained under the conditions of activation agent K2CO3, pyrolysis temperature 900℃ and m(K2CO3):m(BC) 2 had the strongest adsorption capacity (730 mg/g) for oxytetracycline hydrochloride (OTC-HCl). The pseudo-second-order kinetic model and Langmuir model described the adsorption kinetics and isotherms best. SFB2-900 exhibited high OTC-HCl adsorption capacity in both higher ionic strength and wide pH range. The theoretical simulation indicated that the closest interaction distance between OTC-HCl and SFB2-900 was 2.44 Å via π-π stacking configuration. Pore filling, π-π electron donor acceptor (EDA) interaction, H-bonding and electrostatic interactions were also involved in the process of OTC-HCl removal. SFB2-900 showed great removal efficiency for OTC-HCl in different water matrices and good regeneration ability. This study solved the problems caused by SF, realized waste biomass recycling, and achieved preparing high-efficient adsorbent for antibiotic.

Origin, loss, and regain of self-incompatibility in angiosperms.

The self-incompatibility (SI) system with the broadest taxonomic distribution in angiosperms is based on multiple S-locus F-box genes (SLFs) tightly linked to an S-RNase termed type-1. Multiple SLFs collaborate to detoxify nonself S-RNases while being unable to detoxify self S-RNases. However, it is unclear how such a system evolved, because in an ancestral system with a single SLF, many nonself S-RNases would not be detoxified, giving low cross-fertilization rates. In addition, how the system has been maintained in the face of whole-genome duplications (WGDs) or lost in other lineages remains unclear. Here we show that SLFs from a broad range of species can detoxify S-RNases from Petunia with a high detoxification probability, suggestive of an ancestral feature enabling cross-fertilization and subsequently modified as additional SLFs evolved. We further show, based on its genomic signatures, that type-1 was likely maintained in many lineages, despite WGD, through deletion of duplicate S-loci. In other lineages, SI was lost either through S-locus deletions or by retaining duplications. Two deletion lineages regained SI through type-2 (Brassicaceae) or type-4 (Primulaceae), and one duplication lineage through type-3 (Papaveraceae) mechanisms. Thus, our results reveal a highly dynamic process behind the origin, maintenance, loss, and regain of SI.

Enantioselective γ-Addition-Driven Cascade of ß,γ-Unsaturated Ketones by Ion-Pair Catalysis: Access to Chiral 1,3-Dioxolochroman Scaffolds.

A highly enantioselective γ-addition-driven cascade of ß,γ-unsaturated carbonyl compounds by bifunctional ion-pair catalysis has been developed. With this protocol, a range of functionalized chiral 1,3-dioxolochroman derivatives were prepared in high yields with superior stereoselectivities (>99% ee and >20:1 dr). The utility of this method was demonstrated by one-pot synthesis, scaled-up preparation, and facile transformation. Moreover, mechanistic investigations provided insights into the reaction pathway and the origin of chiral induction.

Regio- and Stereoselective Cascade of ß,γ-Unsaturated Ketones by Dipeptided Phosphonium Salt Catalysis: Stereospecific Construction of Dihydrofuro-Fused [2,3-b] Skeletons.

Chiral (dihydro)furo-fused heterocycles are significant structural motifs in numerous natural products, functional materials and pharmaceuticals. Therefore, developing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein, we develop an effective, modular method by a dipeptide-phosphonium salt-catalyzed regio- and stereoselective cascade reaction of readily available linear ß,γ-unsaturated ketones with aromatic alkenes, affording a wide variety of structurally fused heterocyclic molecules in high yields with excellent stereoselectivities. Moreover, mechanistic investigations revealed that the bifunctional phosphonium salt controlled the regio- and stereoselectivities of this cascade reaction, particularly proceeding through the initial ketone α-addition followed by O-participated substitution; and the multiple hydrogen-bonding interactions between Brønsted acid moieties of catalyst and nitro group of aromatic alkene were crucial in asymmetric induction. Given the generality, versatility, and high efficiency of this method, we anticipate that it will have broad synthetic utilities.

Enantiodivergent Kinetic Resolution of 1,1'-Biaryl-2,2'-Diols and Amino Alcohols by Dipeptide-Phosphonium Salt Catalysis Inspired by the Atherton-Todd Reaction.

A highly enantiodivergent organocatalytic method is disclosed for the synthesis of atropisomeric biaryls via kinetic resolution inspired by a dipeptide-phosphonium salt-catalyzed Atherton-Todd (A-T) reaction. This flexible approach led to both R- and S-enantiomers by fine-tuning of bifunctional phosphonium with excellent selectivity factors (s) of up to 1057 and 525, respectively. The potential of newly synthesized O-phosphorylated biaryl diols was illustrated by the synthesis of axially chiral organophosphorus compounds. Mechanistic investigations suggest that the bifunctional phosphonium halide catalyst differentiates between the in-situ-generated P-species in the A-T process, mainly involving phosphoryl chloride and phosphoric anhydride, thus leading to highly enantiodivergent O-phosphorylation reactions. Furthermore hydrogen bonding interactions between the catalysts and phosphorus molecules were crucial in asymmetric induction.

Catalyst-Free Synthesis of α-Functionalized 2H-Chromenes in Water: A Tandem Self-Promoted pseudo-Substitution and Decarboxylation Process.

A catalyst-free decarboxylative reaction between ß-keto acids and 2H-chromene acetals in water was developed. This reaction featured a broad substrate scope and easily obtainable starting materials to afford α-functionalized 2H-chromenes in high yields. The synthetic value of this protocol was also demonstrated by the scale-up synthesis and versatile conversions of the title product into other useful compounds. In addition, control experiments indicated that water was essential for the reactivity. Mechanistic studies further revealed that the reaction proceeded through a self-promoted tandem pseudo-substitution and decarboxylation process.

Highly Enantioselective Synthesis of Fused Tri- and Tetrasubstituted Aziridines: aza-Darzens Reaction of Cyclic Imines with α-Halogenated Ketones Catalyzed by Bifunctional Phosphonium Salt.

The first enantioselective aza-Darzens reaction of cyclic imines with α-halogenated ketones was realized under mild reaction conditions by using amino-acid-derived bifunctional phosphonium salts as phase-transfer promoters. A variety of structurally dense tri- and tetrasubstituted aziridine derivatives, containing benzofused heterocycles as well as spiro-structures, were readily synthesized in high yields with excellent diastereo- and enantioselectivities (up to >20:1 d.r. and >99.9 % ee). The highly functionalized aziridine products could be easily transformed into different classes of biologically active compounds.

Methylene Blue Attenuates Diabetic Retinopathy by Inhibiting NLRP3 Inflammasome Activation in STZ-Induced Diabetic Rats.

Purpose: This study aimed to investigate the regulatory effects of methylene blue (MB) on diabetic retinopathy (DR) and explored the molecular mechanisms of MB as a retina protection agent. Methods: The thicknesses of retinal layers and permeability of the blood-retinal barrier (BRB) were measured by histology analysis, and the expression levels of NLRP3, ASC, procaspase-1, caspase-1, IL-1ß, and IL-18 were measured by western blotting. Lentivirus-based knockdown of NLRP3 gene was used to confirm the role of NLRP3 inflammasome. Results: MB treatment attenuates DR supported by the increase of relative thicknesses of retinal layers and the reduction of BRB permeability when compared with the untreated diabetic group. Further, MB significantly downregulated the levels of all detected inflammation mediators and showed inhibition on NLRP3 inflammasome activation similar to NLRP3 gene silencing. Conclusions: This study revealed a novel mechanism underlying the protection role of MB in the pathogenesis of DR.

d-Glucosamine production from chitosan hydrolyzation over a glucose-derived solid acid catalyst.

A glucose-based solid acid catalyst (GSA) was synthesized by hydrothermal carbonization and its physicochemical properties were explored by various characterization techniques including IR, TG and SEM. In addition, its catalytic performance towards d-glucosamine formation from the hydrolysis of chitosan was extensively investigated to determine the effects of reaction parameters, such as reaction temperature, time and mass ratio of catalyst and reactants. The experimental results revealed that the yield of targeted product d-glucosamine could reach as high as 98.1% under optimal conditions (temperature: 110 °C; time: 6 h). After six catalytic cycles, no evident deactivation was observed, suggesting the satisfactory stability of the investigated solid acid catalyst. This might provide insight on the development of suitable catalyst systems for d-glucosamine formation to replace homogeneous catalysts.

Induction of Autophagic Death in Cancer Cells by Agonizing TR3 and Attenuating Akt2 Activity.

Apoptotic resistance is becoming a significant obstacle for cancer therapy as the majority of treatment takes the route of apoptotic induction. It is of great importance to develop an alternative strategy to induce cancer cell death. We previously reported that autophagic cell death mediated by nuclear receptor TR3 and driven by a chemical agonist, 1-(3,4,5-trihydroxyphenyl)nonan-1-one (THPN), is highly effective in the therapy of melanoma but not any other cancer types. Here, we discovered that the insensitivity of cancer cells to THPN originated from a high cellular Akt2 activity. Akt2 phosphorylation interferes with TR3 export to cytoplasm and targeting to mitochondria, which lead to the autophagic induction. Therefore, the TR3-mediated autophagy could be effectively induced in the otherwise insensitive cells by downregulating Akt2 activity. Highly effective antineoplastic compounds are developed through optimizing the structure of THPN. This study implicates a general strategy for cancer therapy by the induction of autophagic cell death.

Cyclosporine nanomicelle eye drop: a novel medication for corneal graft transplantation treatment.

Corneal transplantation has been used to treat severe eye disease for decades, but the therapeutic effect of the operation is highly compromised by immunological allograft rejection. To improve the success rate of corneal transplantation, we studied the protective effects of cyclosporine nanomicelle eye drops (CNED) on immune rejection after high-risk corneal transplantation and its underlying mechanisms. The therapeutic effects against immune rejection of both conventional cyclosporine eye drop (CCED) and CNED in different concentrations were assessed and compared using animal models of corneal transplantation. In addition, the expression of nuclear factor-κ-gene binding (NF-κB) as well as its target intracellular adhesion molecule 1 (ICAM-1) in the corneal samples obtained from recipients treated with either CCED or CNED was also screened. The results showed that the CNED displayed significantly better effects at suppressing the immune response induced by corneal transplantation compared to CCED. CNED also significantly down-regulated the NF-κB and ICAM-1 expressions, indicating NF-κB might play an important role in the initiation of an immune response against the allograft. Our study demonstrates CNED may suppress the NF-κB pathway to attenuate the immune response, which highlights the possible therapeutic applications of cyclosporine nanomicelle eye drops in corneal transplantation.

Impeding the interaction between Nur77 and p38 reduces LPS-induced inflammation.

Sepsis, a hyperinflammatory response that can result in multiple organ dysfunctions, is a leading cause of mortality from infection. Here, we show that orphan nuclear receptor Nur77 (also known as TR3) can enhance resistance to lipopolysaccharide (LPS)-induced sepsis in mice by inhibiting NF-κB activity and suppressing aberrant cytokine production. Nur77 directly associates with p65 to block its binding to the κB element. However, this function of Nur77 is countered by the LPS-activated p38α phosphorylation of Nur77. Dampening the interaction between Nur77 and p38α would favor Nur77 suppression of the hyperinflammatory response. A compound, n-pentyl 2-[3,5-dihydroxy-2-(1-nonanoyl) phenyl]acetate, screened from a Nur77-biased library, blocked the Nur77-p38α interaction by targeting the ligand-binding domain of Nur77 and restored the suppression of the hyperinflammatory response through Nur77 inhibition of NF-κB. This study associates the nuclear receptor with immune homeostasis and implicates a new therapeutic strategy to treat hyperinflammatory responses by targeting a p38α substrate to modulate p38α-regulated functions.

Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway.

Autophagy is linked to cell death, yet the associated mechanisms are largely undercharacterized. We discovered that melanoma, which is generally resistant to drug-induced apoptosis, can undergo autophagic cell death with the participation of orphan nuclear receptor TR3. A sequence of molecular events leading to cellular demise is launched by a specific chemical compound, 1-(3,4,5-trihydroxyphenyl)nonan-1-one, newly acquired from screening a library of TR3-targeting compounds. The autophagic cascade comprises TR3 translocation to mitochondria through interaction with the mitochondrial outer membrane protein Nix, crossing into the mitochondrial inner membrane through Tom40 and Tom70 channel proteins, dissipation of mitochondrial membrane potential by the permeability transition pore complex ANT1-VDAC1 and induction of autophagy. This process leads to excessive mitochondria clearance and irreversible cell death. It implicates a new approach to melanoma therapy through activation of a mitochondrial signaling pathway that integrates a nuclear receptor with autophagy for cell death.

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A.

A concise enantioselective synthesis of the advanced intermediate 5 for the synthesis of pumiliotoxins (Gallagher's intermediate) is described. The synthesis started from the regio- and trans-diastereoselective (dr = 98:2) reductive 3-butenylation of (R)-3-(tert-butyldimethylsilyloxy)glutarimide 14. After O-desilylation and Dess-Martin oxidation, the resulting keto-lactam 10 was subjected to a highly trans-stereoselective addition of the methylmagnesium iodide to give carbinol 11 as sole diastereomer. An efficient ring closure procedure consisting of ozonolysis and reductive dehydroxylation provided the indolizidine derivative 5, which completed the formal enantioselective total synthesis of pumiliotoxins 251D and 237A.

Enantioselective total syntheses of (-)-FR901483 and (+)-8-epi-FR901483.

The enantioselective total syntheses of the potent immunosuppressant FR901483 (1) and its 8-epimer (47) have been accomplished. Our approach features the use of building block 6 as the chiron, the application of the one-pot amide reductive bis-alkylation method to construct the chiral aza-quaternary center (dr = 9:1), regio- and diastereoselective intramolecular aldol reaction to build the bridged ring, and RCM to form the 3-pyrrolin-2-one ring.

A formal enantioselective total synthesis of FR901483.

A formal enantioselective total synthesis of the potent immunosuppressant FR901483 (1) has been accomplished. Our approach features the use of chiron 6 as the starting material, the application of the one-pot amide reductive bisalkylation method to construct the chiral aza-quaternary center (dr = 9:1), regio- and diastereoselective intramolecular aldol reaction to build the bridged ring, and ring closing metathesis to form the 3-pyrrolin-2-one ring.