RATIONALE: The thiosuccinimide linker is widely used in the synthesis of bioconjugates. However, it is susceptible to hydrolysis and is transformed into its hydrolyzed and/or the isobaric thiazine forms, the latter of which is a fairly common product in a conjugate that contains a cysteinyl peptide. MALDI-MS and MS/MS are useful for differentiating these isobaric species. METHODS: Four cross-linked peptides with thiosuccinimide linkers were synthesized. Analogs with the linker that were transformed into thiazine and/or the hydrolyzed thiosuccinimide linkers were then generated by incubating the samples at neutral or basic pH. All of the cross-linked peptides were purified by rp-HPLC and differentiated by MALDI-MS, -MS/MS and UVPD. RESULTS: A cysteinyl peptide-containing conjugate, the thiosuccinimide form, was largely transformed into the hydrolyzed or thiazine forms after incubation at neutral or basic pH. MALDI-MS allowed the three forms to be differentiated: the thiosuccinimide and its hydrolysis product gave two constituent peptides after reductive cleavage between the Cys and succinimide moieties; no fragment ions were produced from the thiazine form. In addition, MALDI-MS/MS of the thiosuccinimide form yielded two pairs of complementary fragment ions via 1,4-elimination: Cys-SH and maleimide, and dehydro-alanine and thiosuccinimide, which are different from those produced via reductive cleavage in MALDI-MS. The thiazine form gave fragment ions resulting from the cleavage of the newly formed amide bond in the linker that arose from thiazine formation. CONCLUSIONS: The thiosuccinimide (but not thiazine) form of the cross-linked peptide yielded individual constituent peptides in MALDI-MS; MALDI-MS/MS showing specific 1,4-elimination for the thiosuccinimide form and cleavage at the newly formed peptide bond via transcyclisation for the thiazine form.
IntroductionA volvulus occurs when a segment of intestine, usually part of the colon, twists around its mesentery. Following this rotation, initially venous return is disturbed and causes ischemia caused by venous stasis. With the prolongation of obstruction in the mesenteric vessels, along with the distention of the twisted segment of the intestine due to the progressive production of gas by the bacteria inside it, the arterial input is also disturbed, and the mucosal ischemia gradually progresses towards the muscular and serous layers, leading to perforation of the entire thickness of the intestineSigmoid volvulus accounts for 2% to 5% of colonic obstructions in Western countries and 20% to 50% of colonic obstructions in Eastern countries (1). This occurs mostly in patients with lack of mobility and a history of chronic constipation, where the sigmoid colon becomes chronically distended and redundant.Undescended testis (UDT) is defined as one or both testicles absent in scrotal sac when descending processes become disturbed and testis remains inside the peritoneal cavity (2). There are some very known complications of a undescendent intra-abdominal testicle such as cancer, ischemia and infertility(3); But the rotation of the colon around the spermatic cord of one UDT, it is a very rare phenomenon that there is no similar report.In this article, we introduce a 67-year-old man who underwent laparotomy with the diagnosis of sigmoid volvulus, and the intraoperative findings were surprising.
Metformin hydrochloride, an antihyperglycemic agent, and sulindac, a nonsteroidal anti-inflammatory drug, are FDA-approved drugs known to exert anticancer effects. Previous studies demonstrated sulindac and metformin’s anticancer properties through mitochondrial dysfunction and inhibition of mitochondrial electron transport chain (ETC) complex I, as well as key signaling pathways. In this study, various drugs were adminsitered to A549 lung cancer cells, and results revealed that a combination of sulindac and metformin enhanced cell death compared to administration of the drugs separately. To measure superoxide production over time, we employed a time-lapse fluorescence imaging technique using mitochondrial-targeted hydroethidine. Fluorescence microscopy data showed largest increases in superoxide production in the combination treatment of metformin and sulindac. Results showed significant differences between the combined drug treatment and control groups, as well as between the positive control and control groups. This approach can be utilized to quantify anticancer efficacy of drugs, creating possibilities for additional therapeutic options.
Transition metal-catalyzed asymmetric transfer hydrogenation has been proved to be a powerful approach for the synthesis of chiral alcohols. Herein, A highly efficient and enantioselective transfer hydrogenation of dibenzoheptaheterocyclic ketones catalyzed by an arene-tethered TsDPEN-based Rh(III) catalyst has been successfully developed, and a variety of dibenzoheptaheterocyclic ketones were reduced by a 1/1 mixture of formic acid and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) with high yields and enantioselectivities. With this method, the asymmetric reduction of 7,8-difluorodibenzo[b,e]thiepin-11(6H)-one has been realized, providing the key intermediate of baloxavir marboxil with >99% yield and >99% ee at a substrate/catalyst molar ratio of 1000.
Furans bearing alkynyl substituents are highly useful in organic synthesis. However, the methodologies to access these important furan derivatives are rather limited. We herein report an efficient synthesis of alkynylated furan derivatives based on Pd-catalyzed oxidative cross-coupling reaction between allenyl ketones and terminal alkynes. This novel synthesis of alkynylated furans with wide substrate scope is operationally simple and tolerates various functional groups. Mechanistically, the formation of the palladium carbene through cycloisomerization and the subsequent alkynyl migratory insertion are proposed as the key steps in the transformation. The reaction reported in this manuscript further demonstrates the generality of the carbene-based cross coupling.
In recent years, environmental DNA (eDNA) has received attention from biologists due to its sensitivity, convenience, labor and material efficiency, and lack of damage to organisms. The extensive application of eDNA has opened avenues for the monitoring and biodiversity assessment of amphibians, which are frequently small and difficult to observe in the field, in areas such as biodiversity survey assessment and detection of specific, rare and endangered, or alien invasive species. However, the accuracy of eDNA can be influenced by factors such as ambient temperature, pH, and false positives or false negatives, which makes eDNA an adjunctive tool rather than a replacement for traditional surveys. This review provides a concise overview of the eDNA method and its workflow, summarizes the differences between applying eDNA for detecting amphibians and other organisms, reviews the research progress in eDNA technology for amphibian monitoring, identifies factors influencing detection efficiency, and discusses the challenges and prospects of eDNA. It aims to serve as a reference for future research on the application of eDNA in amphibian detection.
INTRODUCTIONTakotsubo syndrome is an acute heart disease that mimics the typical features of acute coronary syndrome (ACS) . Although takotsubo syndrome has an uncertain prevalence in the general population, in women with suspected ACS, the prevalence is estimated to be around 5-6% . The annual incidence is very low and is approximately 0.02% .Unlike ACS, TS is reversible and the heart often heals within four to eight changes weeks. The syndrome is characterised by transient systolic and diastolic left ventricular dysfunction with wall motion abnormalities . This condition, which was first described by Dote et al. in Japan in 1990 , usually affects postmenopausal women who have experienced some physical or psychological stress. However, it can also occur in the absence of these triggers .The prevalence of saccular aneurysms in the general population is estimated at 3.2%. Approximately 20 to 30% of cases present in the form of multiple aneurysms . Intracranial aneurysms are generally diagnosed after episodes of subarachnoid haemorrhage (SAH), which causes a high rate of morbidity and mortality . Rupture of an aneurysm is believed to be responsible for 0.4 to 0.6% of all aneurysm deaths, and approximately 10% of patients die before arriving at the hospital. Takotsubo syndrome is generally reported to have an incidence of 0.8-17% in patients with SAH caused by ruptured aneurysm . However, this case report is relevant for the clinical and pathophysiological observation of the possible association between aneurysms of the internal carotid arteries (ICA) and TS, with the latter being able to serve as an alert for possible aneurysms and thus allow for intervention prior to disruption.
IntroductionTinea capitis is a common infection of the scalp and hair caused by dermatophyte fungi that principally affects children1. It is an uncommon infection in adults and generally occurs in postmenopausal women and immunocompromised patients. Adult tinea capitis may have atypical clinical presentations2 34. The causative pathogens in children and adults belong to two genera: Trichophyton andMicrosporum 5. The clinical manifestations characterized by an erythematous and scaly plaques, itching, suppurative swelling with purulent discharge, areas of alopecia and regional lymphadenopathy. It is often misdiagnosed as a bacterial infection, leading to unnecessary antibiotic prescription or surgical intervention. Treatment delay may result in permanent hair loss6 7. The diagnosis of tinea capitis is made by fungal culture (gold standard), microscopy, wood’s lamp and trichoscopy5 8.
This study aims to green synthesize and full characterize CdO nanoparticles by means of an environmentally friendly synthesis using Crocus sativus in its reaction with cadmium ions. The CdO nanoparticles were characterized and their purity was confirmed by XRD and UV.-Vis. spectroscopy. Moreover, scanning electron microscopy (SEM) showed that the prepared cadmium oxide nanoparticles were polymorphic. Furthermore, cadmium oxide nanoparticles were cast in the gas storage (H 2) study. The hydrogen storage results prove that the maximum H 2 uptake was equal to 2.85 Wt.%H 2 at a pressure of 69 bar at 77 K with ∆H=0.62607 KJ/mol H 2 and ∆S=3.35697 J/mol H 2. K. Moreover, the thermodynamic studies under four different temperatures proves that the maximum H 2 uptake could be recorded at a pressure limit of 69-86.2 bar.
Here, we report a cobalt-catalyzed sequential dehydrogenative Heck silylation/hydroamination of styrenes with hydrosilane and diazo compound to access 1-amino-2-silyl compounds with excellent regioselectivity. This difunctionalization reaction could undergo smoothly using 1 mol% catalyst loading with good functional group tolerance. Not only di- and tri-substituted hydrosilanes, but also alkoxysilane are suitable, which does explore the scope of the family of 1-amino-2-silyl compounds. The ligand relay phenomenon between neutral tridentate NNN ligand and anionic NNN ligand is observed for the first time via absorption spectra analysis in this one-pot, two-step transformations. The primary mechanism has been proposed based on the control experiments.
INTRODUCTION:Ramsay-Hunt syndrome is a disease caused by reactivation of latent varicella zoster virus in the geniculate ganglia. It involves facial nerve paralysis and it is usually associated with a rash on the auricle and/or external ear . Sometimes the blisters are not very noticeable and can be overlooked by the inspector. Other accompanying symptoms may be ache and fullness of the ear (78%), vertigo/dizziness (51%), hearing loss (45%), nausea, vomiting, tinnitus and hyperacusia .The diagnosis is mainly based on the history, clinical findings and neurological examination. Polymerase chain reaction assays may be useful by detecting DNA of the virus in exudates from ear scraping or cerebrospinal fluid (CSF) .It represents 7% of all peripheral facial paralysis and recovery rates are lower in this group [4,5]. Early treatment with a combination of acyclovir and prednisone is reported to be effective [6-8].
A single-mode-fiber (SMF)-multimode-fiber (MMF)-tri-core-fiber (TCF) Michelson probe structure is proposed for trace detection of canine distemper virus (CDV). One end of the TCF is cut flat and fused with the multimode fiber, and the other end is coated with a silver film to enhance the reflection, and an optic-fiber sensing probe with SMF-MMF-TCF structure is obtained. The (PDDA/PSS) 3 multilayer film is modified on the surface of the fiber by layer-by-layer self-assembly method as a polyelectrolyte binder to immobilize CDV antibodies to form a (PDDA/PSS) 3/CDV antibody composite membrane for specific detection of CDV antigens. The response-recovery test of the sensor is performed to verify its repeatability. The detection limit, the sensitivity, and the linear fitting degree for CDV antigen are 0.1236 pg/ml, 1.1776 dB/(pg/ml), and 0.9899, respectively. At the same time, the stability, selectivity, and clinical samples of the sensors were also verified.
Children fast-map new words to their referents early on but do not show robust retention until much later. This paper examines whether children’s interest in a natural category relates to retention of newly learned words in that category. German-speaking 24-month-olds and 38-month-olds (n = 88, 41 female) were trained on novel word-object-associations from different categories. Pupillary arousal and parental reports served as indices of interest in the objects and categories presented. Recognition and retention were tested directly after exposure, five minutes later, and 24 hours later. Both younger and older children showed successful word-object recognition and retention. Furthermore, interest in the category modulates young children’s recognition and retention of newly learned word-object associations from semantic categories across ages.
Herein we report a condition-controlled divergent synthesis of spiro indene-2,1’-isoindolinones and spiro isochroman-3,1’-isoindolinones through cobalt-catalyzed formal [4 + 1] and [4 + 1 + 1] spirocyclization of aromatic amides with 2-diazo-1H-indene-1,3(2H)-dione. When the reaction is carried out under air in ethyl acetate, spiro indene-2,1’-isoindolinones are formed through Co(II)-catalyzed C−H/N−H [4 + 1] spirocyclization. When the reaction is run under O2 in CH3CN, on the other hand, spiro isochroman-3,1’-isoindolinones are generated through Baeyer-Villiger oxidation of the in situ formed spiro indene-2,1’-isoindolinones with O2 as a cheaper and environmental-friendly oxygen source. In general, these protocols have advantages such as using non-precious and earth-abundant metal catalyst, no extra additive, high efficiency and regioselectivity. A gram-scale synthesis and the removal of the directing group further highlight its utility.
In order to treat persons suffering from narcissistic personality disorder (NPD) it is necessary to agree on therapeutic goals and om tasks to undertake in order to meet them. This is difficult with NPD, as they have difficulties finding meaningful goals to strive for, other than the quest for status. Moreover, in order to change they need to expose themselves to experience painful feelings such as shame, guilt or fear, feelings that they automatically tend to keep at bay. Finally, they have problems forming a benevolent image of their therapists and to harken to it in order to cooperate towards mutually agreed goals and tasks. As a consequence, NPD patients ask for change but hardly engage themselves in the work necessary to achieve it. Therapists therefore need to pay the uttermost attention to drafting, negotiating and continuously updating a reasonable and realistic therapeutic contract. In this paper we describe the story of a man in his thirties with NPD who was ridden with depression, guilt, envy and anger and did not find ways to pursue the healthy and adaptive behaviors he would need to pursue in order to leave a richer social life. The therapist overcame ruptures in the therapeutic alliance and then involved the patient in a process where they set the steps to follow, making sure the patient was convinced they made sense. After a contract was reached progress became possible. Implications for the role of the therapeutic contract in NPD treatment are discussed.