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Binary lithium silicides and germanides as well as ternary lithium phosphidotetrelates have been intensively investigated with regard to their suitability as anode materials for all‐solid‐state‐batteries. In this context we studied the ternary phase diagram Li/Tt/P on the phosphorus‐poor side. The phosphide tetrelides Li10.68(8)Si5P and Li10.1(2)Ge5P are ternary compounds in the respective phase systems so far uniquely featuring discrete building blocks, which were previously found exclusively in binary alkali metal tetrelides and phosphides. Li10.68(8)Si5P and Li10.1(2)Ge5P contain aromatic Tt5 pentagons with an environment of mostly ordered Li atoms and isolated P3− anions with a coordination environment of predominantly disordered Li atoms. The five‐membered ring subunits are stacked under formation of ∞1 [Li6Tt5] chains (Tt=Si, Ge). chains. The compounds crystallize in the space group Pnma (63) (Z=4) with cell parameters of a=10.2434(3) Å, b=4.2788(1) Å, c=23.9767(3) Å for Li10.68(8)Si5P and a=10.3599(11) Å, b=4.3072(2) Å, c=24.267(2) Å for Li10.1(2)Ge5P. The single crystal structure determination is supplemented by X‐ray powder diffraction experiments and 7Li, 29Si and 31P solid state MAS NMR spectroscopy. With respect to their electron count the compounds are placed between compounds comprising aromatic five‐membered rings such as the electron‐precise Zintl phase Li8MgSi6 and the non‐classical Zintl phase Li12Si7 having two extra electrons. [ABSTRACT FROM AUTHOR]

Objective: Obesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes., Methods: The expression of the NPY/melanocortin receptors' levels was assessed in the visceral AT of individuals with obesity and altered metabolism. Protein levels of these receptors were evaluated in cultured adipocytes incubated with ghrelin (30 and 100 ng/mL) and leptin (1 and 10 nM) and in the AT of an animal model with a mutation in the leptin receptor (ZSF1 rat), to understand their regulation by leptin and ghrelin. The vertical sleeve gastrectomy animal model was used to evaluate the putative therapeutic potential of the NPY/melanocortin system., Results: In this study, we unravelled that leptin (1 nM and 10 nM) selectively reduced the levels of NPY5R and MC3R but no other NPYR/MCRs in cultured adipocytes. In turn, acylated ghrelin (100 ng/mL) significantly increased NPY1R, but the inhibition of its receptor also abrogates MC3R levels. However, in the Lepr-deficient ZSF1 rat, both NPY5R and MC3R levels were reduced, along with other NPYRs and MCRs, suggesting that leptin resistance negatively affects NPY and melanocortin signalling. In human adipose tissue, we found a downregulation of genes encoding the NPY and melanocortin receptors in the visceral AT of individuals with obesity and insulin resistance, being correlated with genes regulating metabolic activity. Additionally, diabetic obese rats submitted to vertical sleeve gastrectomy showed increased levels of NPY, melanocortin, ghrelin, and leptin receptors in the AT, including MC3R, suggesting it may constitute a therapeutic target in obesity., Conclusions: Our results suggest that the AT NPY/melanocortin system, particularly the MC3R, may be involved in the neuroendocrine regulation of adipocyte metabolism. Altogether, our work shows MC3R is under the control of the ghrelin/leptin duo, is reduced in patients with obesity and prediabetes, and may constitute a therapeutic target in obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Dopamine directly acts in the liver and white adipose tissue (WAT) to regulate insulin signaling, glucose uptake, and catabolic activity. Given that dopamine is secreted by the gut and regulates insulin secretion in the pancreas, we aimed to determine its regulation by nutritional cues and its role in regulating glucagon-like peptide 1 (GLP-1) action in WAT. Solutions with different nutrients were administered to Wistar rats and postprandial dopamine levels showed elevations following a mixed meal and glucose intake. In high-fat diet-fed diabetic Goto-Kakizaki rats, sleeve gastrectomy upregulated dopaminergic machinery, showing the role of the gut in dopamine signaling in WAT. Bromocriptine treatment in the same model increased GLP-1R in WAT, showing the role of dopamine in regulating GLP-1R. By contrast, treatment with the GLP-1 receptor agonist Liraglutide had no impact on dopamine receptors. GLP-1 and dopamine crosstalk was shown in rat WAT explants, since dopamine upregulated GLP-1-induced AMPK activity in mesenteric WAT in the presence of the D2R and D3R inhibitor Domperidone. In human WAT, dopamine receptor 1 ( D1DR ) and GLP-1R expression were correlated. Our results point out a dietary and gut regulation of plasma dopamine, acting in the WAT to regulate GLP-1 action. Together with the known dopamine action in the pancreas, such results may identify new therapeutic opportunities to improve metabolic control in metabolic disorders.

The environmental impact assessment of materials is usually based on laboratory tests, mostly in combination with models describing the longterm fate of the substances of interest in the targeted environmental compartment. Thus, laboratory tests are the fundamental link to achieve appropriate assessment conclusions which makes it essential to generate consistent results. This just as applies to the leaching of cementitious materials. In Europe, the leaching behavior of monolithic building materials is tested in the Dynamic Surface Leaching Test following the specification CEN/TS 16637-2. An interlaboratory comparison on European level regarding this technical specification showed relatively high intra- and interlaboratory variations for the tested materials (monolithic copper slag and cement stabilized coal fly ash). Therefore the German Committee for Structural Concrete (DAfStb) framed a guideline to specify additional testing conditions for cementitious materials. To assess the possible improvement by this guidelines measures, a round robin test with 11 participants from Germany and the Netherlands was conducted. This work aims to provide insight into the factors to be considered in the testing of alkaline materials, including sample preparation, and highlights crucial procedures and their manifestation in the results. All evaluated parameters showed improved results compared to the earlier round robin test. The relative standard deviations for repeatability (RSD r ) and reproducibility (RSD R ) of the elements calcium, barium, antimony, chromium, molybdenum and vanadium, which are the parameters evaluated in both round robin tests, were RSD r  = 4%, 4%, 2%, 5%, 5%, and 5% respectively (4% in average) for this work, in comparison to the European round robin test with an average RSD r of 29% (17%, 17%, 20%, 40%, 36%, and 42%). The RSD R improved from 41% (30%, 36%, 29%, 57%, 40%, and 56%) to 14% (12%, 8%, 6%, 28%, 15%, and 12%). CO 2 ingress during testing and the inaccuracy of eluate analytics for concentrations close to the determination limits were identified as the main sources of error., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Simulator arthroscopy training has gained popularity in recent years. However, it remains unclear what level of competency surgeons may achieve in what time frame using virtual training. It was hypothesized that 10 h of training would be sufficient to reach the target level defined by experts based on the Diagnostic Arthroscopic Skill Score (DASS)., Methods: The training concept was developed by ten instructors affiliated with the German-speaking Society of Arthroscopy and Joint Surgery (AGA). The programme teaches the basics of performing arthroscopy; the main focus is on learning and practicing manual skills using a simulator. The training was based on a structured programme of exercises designed to help users reach defined learning goals. Initially, camera posture, horizon adjustment and control of the direction of view were taught in a virtual room. Based on these skills, further training was performed with a knee model. The learning progress was assessed by quantifying the exercise time, camera path length and instrument path length for selected tasks. At the end of the course, the learners' performance in diagnostic arthroscopy was evaluated using DASS. Participants were classified as novice or competent based on the number of arthroscopies performed prior to the assessment., Results: Except for one surgeon, 131 orthopaedic residents and surgeons (29 women, 102 men) who participated in the seven courses agreed to anonymous data analysis. Fifty-eight of them were competents with more than ten independently performed arthroscopies, and 73 were novices, with fewer than ten independently performed arthroscopies. There were significant reductions in exercise time, camera path length and instrument path length for all participants after the training, indicating a rapid increase in performance. No difference in camera handling between the dominant and non-dominant sides was found in either group. The competents performed better than the novices in various tasks and achieved significantly better DASS values on the final performance test., Conclusions: Our data have demonstrated that arthroscopic skills can be taught effectively on a simulator, but a 10-h course is not sufficient to reach the target level set by experienced arthroscopists. However, learning progress can be monitored more objectively during simulator training than in the operating room, and simulation may partially replace the current practice of arthroscopic training., Level of Evidence: III., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Purpose: To develop and validate a novel score to more objectively assess the performance of diagnostic knee arthroscopy using a simulator., Methods: A Diagnostic Arthroscopy Skill Score (DASS) was developed by ten AGA (AGA-Society for Arthroscopy and Joint-Surgery) instructors for the assessment of arthroscopic skills. DASS consists of two parts: the evaluation of standardized diagnostic knee arthroscopy (DASS part1 ) and the evaluation of manual dexterity, including ambidexterity and triangulation, using objective measurement parameters (DASS part2 ). Content validity was determined by the Delphi method. One hundred and eleven videos of diagnostic knee arthroscopies were recorded during simulator training courses and evaluated by six specially trained instructors using DASS. Construct validity, measurement error calculated by the minimum detectable change (MDC), internal consistency using Cronbach's alpha and interrater and intrarater reliability were assessed. The Bland-Altman method was used to calculate the intrarater agreement., Results: Six skill domains were identified and evaluated for each knee compartment. DASS, DASS part1, and DASS part2 showed construct validity, with experts achieving significantly higher scores than competents and novices. MDC was 4.5 ± 1.7 points for DASS part1 . There was high internal consistency for all domains in each compartment from 0.78 to 0.86. The interrater reliability showed high agreement between the six raters (ICC = 0.94). The evaluation of intrarater reliability demonstrated good and excellent agreement for five raters (ICC > 0.80) and moderate agreement for one rater (ICC = 0.68). The Bland-Altman comparison showed no difference between the first and second evaluations in five out of six raters. Precision, estimated by the regression analysis and comparison with the method of Bland and Altman, was excellent for four raters and moderate for two raters., Conclusions: The results of this study indicate good validity and reliability of DASS for the assessment of the surgical performance of diagnostic knee arthroscopy during simulator training. Standardized training is recommended before arthroscopy surgery is considered in patients., Level of Evidence: II., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Methylglyoxal was shown to impair adipose tissue capillarization and insulin sensitivity in obese models. We hypothesized that glyoxalase-1 (GLO-1) activity could be diminished in the adipose tissue of type 2 diabetic obese patients. Moreover, we assessed whether such activity could be increased by GLP-1-based therapies in order to improve adipose tissue capillarization and insulin sensitivity. GLO-1 activity was assessed in visceral adipose tissue of a cohort of obese patients. The role of GLP-1 in modulating GLO-1 was assessed in type 2 diabetic GK rats submitted to sleeve gastrectomy or Liraglutide treatment, in the adipose tissue angiogenesis assay and in the HUVEC cell line. Glyoxalase-1 activity was decreased in visceral adipose tissue of pre-diabetic and diabetic obese patients, together with other markers of adipose tissue dysfunction and correlated with increased HbA1c levels. Decreased adipose tissue GLO-1 levels in GK rats were increased by sleeve gastrectomy and Liraglutide, being associated with overexpression of angiogenic and vasoactive factors, as well as insulin receptor phosphorylation (Tyr1161). Moreover, GLP-1 increased adipose tissue capillarization and HUVEC proliferation in a glyoxalase-dependent manner. Lower adipose tissue GLO-1 activity was observed in dysmetabolic patients, being a target for GLP-1 in improving adipose tissue capillarization and insulin sensitivity., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The spatial gap between cochlear implants (CIs) and the auditory nerve limits frequency selectivity as large populations of spiral ganglion neurons (SGNs) are electrically stimulated synchronously. To improve CI performance, a possible strategy is to promote neurite outgrowth toward the CI, thereby allowing a discrete stimulation of small SGN subpopulations. Brain-derived neurotrophic factor (BDNF) is effective to stimulate neurite outgrowth from SGNs., Method: TrkB (tropomyosin receptor kinase B) agonists, BDNF, and five known small-molecule BDNF mimetics were tested for their efficacy in stimulating neurite outgrowth in postnatal SGN explants. To modulate Trk receptor-mediated effects, TrkB and TrkC ligands were scavenged by an excess of recombinant receptor proteins. The pan-Trk inhibitor K252a was used to block Trk receptor actions., Results: THF (7,8,3'-trihydroxyflavone) partly reproduced the BDNF effect in postnatal day 7 (P7) mouse cochlear spiral ganglion explants (SGEs), but failed to show effectiveness in P4 SGEs. During the same postnatal period, spontaneous and BDNF-stimulated neurite outgrowth increased. The increased neurite outgrowth in P7 SGEs was not caused by the TrkB/TrkC ligands, BDNF and neurotrophin-3 (NT-3)., Conclusions: The age-dependency of induction of neurite outgrowth in SGEs was very likely dependent on presently unidentified factors and/or molecular mechanisms which may also be decisive for the age-dependent efficacy of the small-molecule TrkB receptor agonist THF.

Solid electrolytes with superionic conductivity are required as a main component for all-solid-state batteries. Here we present a novel solid electrolyte with three-dimensional conducting pathways based on "lithium-rich" phosphidosilicates with ionic conductivity of σ > 10 -3 S cm -1 at room temperature and activation energy of 30-32 kJ mol -1 expanding the recently introduced family of lithium phosphidotetrelates. Aiming toward higher lithium ion conductivities, systematic investigations of lithium phosphidosilicates gave access to the so far lithium-richest compound within this class of materials. The crystalline material (space group Fm 3 m ), which shows reversible thermal phase transitions, can be readily obtained by ball mill synthesis from the elements followed by moderate thermal treatment of the mixture. Lithium diffusion pathways via both tetrahedral and octahedral voids are analyzed by temperature-dependent powder neutron diffraction measurements in combination with maximum entropy method and DFT calculations. Moreover, the lithium ion mobility structurally indicated by a disordered Li/Si occupancy in the tetrahedral voids plus partially filled octahedral voids is studied by temperature-dependent impedance and 7 Li NMR spectroscopy.

Introduction: Metabolic surgery has become an accepted option for the treatment of obesity and associated metabolic diseases like hypertension and type 2 diabetes. Adipose tissue dysfunction and ectopic storage of excess lipids are thought to be involved in the underlying pathophysiological process., Objectives: The present study aims to clarify the effect of sleeve gastrectomy (SG) on adipose tissue microvasculature and health in an animal model of adipose type 2 diabetes., Methods: After weaning, diabetic Goto-Kakizaki rats were either fed on standard rat chow or high-calorie diet. At 4 months, animals on high-calorie diet were randomized to SG, sham surgery, or control group. Non-diabetic Wistar rats served as further controls. At 6 months, glucose and lipid metabolisms were studied in vivo. After sacrifice, periepididymal adipose tissue was collected for histology and analysis of parameters of adipose tissue metabolism and insulin sensitivity., Results: SG decreased body and adipose tissue weight and improved glycemic and lipid profiles. Fasting glycemia, area under the curve after intraperitoneal insulin tolerance test, and insulin resistance were decreased in operated animals. SG also reduced circulating triglycerides and cholesterol while increasing serum adiponectin and adipose tissue peroxisome proliferator-activated receptor γ (PPAR-γ) and perilipin A. Additionally, surgery improved adipose tissue vascular function and markedly increased vascular endothelial growth factor, cluster of differentiation 31, and endothelial nitric oxide synthase., Conclusions: In our obese animal model of type 2 diabetes, SG significantly improved adipose tissue health and angiogenesis while reducing insulin resistance, involving PPAR-γ and markers of sprouting angiogenesis and endothelial function.

The lithium phosphidosilicates Li 10 Si 2 P 6 and Li 3 Si 3 P 7 are obtained by high-temperature reactions of the elements or including binary Li-P precursors. Li 10 Si 2 P 6 (P2 1 /n, Z = 2, a = 7.2051(4) Å, b = 6.5808(4) Å, c = 11.6405(7) Å, β = 90.580(4)°) features edge-sharing SiP 4 double tetrahedra forming [Si 2 P 6 ] 10- units with a crystal structure isotypic to Na 10 Si 2 P 6 and Na 10 Ge 2 P 6 . Li 3 Si 3 P 7 (P2 1 /m, Z = 2, a = 6.3356(4) Å, b = 7.2198(4) Å, c = 10.6176(6) Å, β = 102.941(6)°) crystallizes in a new structure type, wherein SiP 4 tetrahedra are linked via common vertices and which are further connected by polyphosphide chains to form unique ∞ 2 [Si 3 P 7 ] 3- double layers. The two-dimensional Si-P slabs that are separated by Li atoms can be regarded as three covalently linked atoms layers: a defect α-arsenic type layer of P atoms sandwiched between two defect wurzite-type Si 3 P 4 layers. The single crystal and powder X-ray structure solutions are supported by solid-state 7 Li, 29 Si, and 31 P magic-angle spinning NMR measurements.

Food intake and energy expenditure are closely regulated by several mechanisms which involve peripheral organs and nervous system, in order to maintain energy homeostasis.Short-term and long-term signals express the size and composition of ingested nutrients and the amount of body fat, respectively. Ingested nutrients trigger mechanical forces and gastrointestinal peptide secretion which provide signals to the brain through neuronal and endocrine pathways. Pancreatic hormones also play a role in energy balance exerting a short-acting control regulating the start, end, and composition of a meal. In addition, insulin and leptin derived from adipose tissue are involved in long-acting adiposity signals and regulate body weigh as well as the amount of energy stored as fat over time.This chapter focuses on the gastrointestinal-, pancreatic-, and adipose tissue-derived signals which are integrated in selective orexigenic and anorexigenic brain areas that, in turn, regulate food intake, energy expenditure, and peripheral metabolism.

In moderately or morbidly obese patients, bariatric surgery has been proven to be an effective therapeutic approach to control body weight and comorbidities. Surgery-mediated modulation of brain function via modified postoperative secretion of gut peptides and vagal nerve stimulation was identified as an underlying mechanism in weight loss and improvement of weight-related diseases. Increased basal and postprandial plasma levels of gastrointestinal hormones like glucagon-like peptide 1 and peptide YY that act on specific areas of the hypothalamus to reduce food intake, either directly or mediated by the vagus nerve, are observed after surgery while suppression of meal-induced ghrelin release is increased. Hormones released from the adipose tissue like leptin and adiponectin are also affected and leptin plasma levels are reduced in treated patients. Besides homeostatic control of body weight, surgery also changes hedonistic behavior in regard to food intake and cognitive performance involving the limbic system and prefrontal areas.

Liquid cell transmission electron microscopy (LCTEM) provides a unique insight into the dynamics of nanomaterials in solution. Controlling the addition of multiple solutions to the liquid cell remains a key hurdle in our ability to increase throughput and to study processes dependent on solution mixing including chemical reactions. Here, we report that a piezo dispensing technique allows for mixing of multiple solutions directly within the viewing area. This technique permits deposition of 50 pL droplets of various aqueous solutions onto the liquid cell window, before assembly of the cell in a fully controlled manner. This proof-of-concept study highlights the great potential of picoliter dispensing in combination with LCTEM for observing nanoparticle mixing in the solution phase and the creation of chemical gradients.

Background: Dental stem cells in combination with implant materials may become an alternative to autologous bone transplants. For tissue engineering different types of soft and rigid implant materials are available, but little is known about the viability and the osteogenic differentiation of dental stem cells on these different types of materials. According to previous studies we proposed that rigid bone substitute materials are superior to soft materials for dental tissue engineering., Methods: We evaluated the proliferation, the induction of apoptosis and the osteogenic differentiation of dental stem/progenitor cells on a synthetic bone-like material and on an allograft product. The soft materials silicone and polyacrylamide (PA) were used for comparison. Precursor cells from the dental follicle (DFCs) and progenitor cells from the dental apical papilla of retained third molar tooth (dNC-PCs) were applied as dental stem cells in our study., Results: Both dental cell types attached and grew on rigid bone substitute materials, but they did not grow on soft materials. Moreover, rigid bone substitute materials only sustained the osteogenic differentiation of dental stem cells, although the allograft product induced apoptosis in both dental cell types. Remarkably, PA, silicone and the synthetic bone substitute material did not induce the apoptosis in dental cells., Conclusions: Our work supports the hypothesis that bone substitute materials are suitable for dental stem cell tissue engineering. Furthermore, we also suggest that the induction of apoptosis by bone substitute materials may not impair the proliferation and the differentiation of dental stem cells.

Fungal infections are a leading cause of morbidity and death for hospitalized patients, mainly because they remain difficult to diagnose and to treat. Diseases range from widespread superficial infections such as vulvovaginal infections to life-threatening systemic candidiasis. For systemic mycoses, only a restricted arsenal of antifungal agents is available. Commonly used classes of antifungal compounds include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapies, significant side effects, and high costs for several antifungals, there is a need for new antifungals in the clinic. In order to expand the arsenal of compounds with antifungal activity, we previously screened a compound library using a cell-based screening assay. A set of novel benzimidazole derivatives, including (S)-2-(1-aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole (EMC120B12), showed high antifungal activity against several species of pathogenic yeasts, including Candida glabrata and Candida krusei (species that are highly resistant to antifungals). In this study, comparative analysis of EMC120B12 versus fluconazole and nocodazole, using transcriptional profiling and sterol analysis, strongly suggested that EMC120B12 targets Erg11p in the ergosterol biosynthesis pathway and not microtubules, like other benzimidazoles. In addition to the marker sterol 14-methylergosta-8,24(28)-dien-3β,6α-diol, indicating Erg11p inhibition, related sterols that were hitherto unknown accumulated in the cells during EMC120B12 treatment. The novel sterols have a 3β,6α-diol structure. In addition to the identification of novel sterols, this is the first time that a benzimidazole structure has been shown to result in a block of the ergosterol pathway., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Background: Pathophysiology of type 2 diabetes (T2D) includes insulin resistance (IR) and insufficient insulin secretion. Remission in obese patients can be achieved through surgically induced weight loss. Sleeve gastrectomy is a novel technique for the treatment of morbid obesity, and its effects on the metabolic syndrome and T2D have not yet been fully understood., Methods: From February 2008 to July 2010, sleeve gastrectomy as stand-alone treatment for severe or morbid obesity was performed in 23 patients with T2D or impaired fasting glucose (IFG). No postoperative complications occurred and patients were dismissed from hospital on day 2 after surgery. Body mass index (BMI), fasting blood glucose (FBG) and fasting insulin were determined before and up to 24 months after surgery. IR and beta cell function were calculated using the modified homeostasis model assessment (HOMA2)., Results: BMI, FBG and fasting insulin improved significantly as early as 3 months after surgery. Threefold increased preoperative insulin resistance (3.05) decreased to near-normal values (1.14) during the same period. Interestingly, overall beta cell function diminished at 12 months of follow-up (79.6 %), in comparison with preoperative values (117.8 %). Patients with a markedly reduced preoperative beta cell function (<40 %) did not achieve a complete remission after surgery., Conclusions: In obese patients with T2D and IFG, commonly characterized by an augmented beta cell function and an increased insulin resistance, sleeve gastrectomy induces remission through reduction of insulin resistance. Preoperative IR and beta cell function calculated by HOMA2 deserve further studies in patients undergoing metabolic surgery.