Towards dynamically configured databases for CIFs: the new modulated structures open database at the Bilbao Crystallographic Server.

This article presents a web-based framework to build a database without in-depth programming knowledge given a set of CIF dictionaries and a collection of CIFs. The framework consists of two main elements: the public site that displays the information contained in the CIFs in an ordered manner, and the restricted administrative site which defines how that information is stored, processed and, eventually, displayed. Thus, the web application allows users to easily explore, filter and access the data, download the original CIFs, and visualize the structures via JSmol. The modulated structures open database B-IncStrDB, the official International Union of Crystallography repository for this type of material and available through the Bilbao Crystallographic Server, has been re-implemented following the proposed framework.

SUBGROUPS: a computer tool at the Bilbao Crystallographic Server for the study of pseudo-symmetric or distorted structures.

SUBGROUPS is a free online program at the Bilbao Crystallographic Server (https://www.cryst.ehu.es/). It permits the exploration of all possible symmetries resulting from the distortion of a higher-symmetry parent structure, provided that the relation between the lattices of the distorted and parent structures is known. The program calculates all the subgroups of the parent space group which comply with this relation. The required minimal input is the space-group information of the parent structure and the relation of the unit cell of the distorted or pseudo-symmetric structure with that of the parent structure. Alternatively, the wavevector(s) observed in the diffraction data characterizing the distortion can be introduced. Additional conditions can be added, including filters related to space-group representations. The program provides very detailed information on all the subgroups, including group-subgroup hierarchy graphs. If a Crystallographic Information Framework (CIF) file of the parent high-symmetry structure is uploaded, the program generates CIF files of the parent structure described under each of the chosen lower symmetries. These CIF files may then be used as starting points for the refinement of the distorted structure under these possible symmetries. They can also be used for density functional theory calculations or for any other type of analysis. The power and efficiency of the program are illustrated with a few examples.

Revisiting the nature and pharmacodynamics of tacrolimus metabolites.

The toxicity of tacrolimus metabolites and their potential pharmacodynamic (PD) interactions with tacrolimus might respectively explain the surprising combination of higher toxicity and lower efficacy of tacrolimus despite normal blood concentrations, described in extensive metabolizers. To evaluate such interactions, we produced tacrolimus metabolites in vitro and characterized them by high resolution mass spectrometry (HRMS, for all) and nuclear magnetic resonance (NMR, for the most abundant, M-I). We quantified tacrolimus metabolites and checked their structure in patient whole blood and peripheral blood mononuclear cells (PBMC). We explored the interactions of M-I with tacrolimus in silico, in vitro and ex vivo. In vitro metabolization produced isoforms of tacrolimus and of its metabolites M-I and M-III, whose HRMS fragmentation suggested an open-ring structure. M-I and M-III open-ring isomers were also observed in patient blood. By contrast, NMR could not detect these open-ring forms. Transplant patients expressing CYP3A5 exhibited higher M-I/TAC ratios in blood and PBMC than non-expressers. Molecular Dynamics simulations showed that: all possible tacrolimus metabolites and isomers bind FKPB12; and the hypothetical open-ring structures induce looser binding between FKBP12 and calcineurins, leading to lower CN inhibition. In vitro, tacrolimus bound FKPB12 with more affinity than purified M-I, and the pool of tacrolimus metabolites and purified M-I had only weak inhibitory activity on IL2 secretion and not at all on NFAT nuclear translocation. M-I showed no competitive effect with tacrolimus on either test. Finally, M-I or the metabolite pool did not significantly interact with tacrolimus MLR suppression, thus eliminating a pharmacodynamic interaction.

Cohomogeneity one solitons for the isometric flow of G 2 -structures.

We consider the existence of cohomogeneity one solitons for the isometric flow of G 2 -structures on the following classes of torsion-free G 2 -manifolds: the Euclidean R 7 with its standard G 2 -structure, metric cylinders over Calabi-Yau 3-folds, metric cones over nearly Kähler 6-manifolds, and the Bryant-Salamon G 2 -manifolds. In all cases we establish existence of global solutions to the isometric soliton equations, and determine the asymptotic behaviour of the torsion. In particular, existence of shrinking isometric solitons on R 7 is proved, giving support to the likely existence of type I singularities for the isometric flow. In each case, the study of the soliton equation reduces to a particular nonlinear ODE with a regular singular point, for which we provide a careful analysis. Finally, to simplify the derivation of the relevant equations in each case, we first establish several useful Riemannian geometric formulas for a general class of cohomogeneity one metrics on total spaces of vector bundles which should have much wider application, as such metrics arise often as explicit examples of special holonomy metrics.

The actin-binding protein palladin associates with the respiratory syncytial virus matrix protein.

The respiratory syncytial virus (RSV) matrix (M) protein plays an important role in infection as it can interact with viral components as well as the host cell actin microfilaments. The M-actin interaction may play a role in facilitating the transportation of virion components to the apical surface, where RSV is released. We show that M protein's association with actin is facilitated by palladin, an actin-binding protein. Cells were infected with RSV or transfected to express full-length M as a green fluorescent protein (GFP)-tagged protein, followed by removal of nuclear and cytosolic proteins to enrich for cytoskeleton and its associated proteins. M protein was present in inclusion bodies tethered to microfilaments in infected cells. In transfected cells, GFP-M was presented close to microfilaments, without association, suggesting the possible involvement of an additional protein in this interaction. As palladin can bind to proteins that also bind actin, we investigated its interaction with M. Cells were co-transfected to express GFP-M and palladin as an mCherry fluorescent-tagged protein, followed by cytoskeleton enrichment. M and palladin were observed to colocalize towards microfilaments, suggesting that palladin is involved in the M-actin interaction. In co-immunoprecipitation studies, M was found to associate with two isoforms of palladin, of 140 and 37 kDa. Interestingly, siRNA downregulation of palladin resulted in reduced titer of released RSV, while cell associated RSV titer increased, suggesting a role for palladin in virus release. Together, our data show that the M-actin interaction mediated by palladin is important for RSV budding and release.IMPORTANCERespiratory syncytial virus is responsible for severe lower respiratory tract infections in young children under 5 years old, the elderly, and the immunosuppressed. The interaction of the respiratory syncytial virus matrix protein with the host actin cytoskeleton is important in infection but has not been investigated in depth. In this study, we show that the respiratory syncytial virus matrix protein associates with actin microfilaments and the actin-binding protein palladin, suggesting a role for palladin in respiratory syncytial virus release. This study provides new insight into the role of the actin cytoskeleton in respiratory syncytial virus infection, a key host-RSV interaction in assembly. Understanding the mechanism by which the RSV M protein and actin interact will ultimately provide a basis for the development of therapeutics targeted at RSV infections.

CoNglyPred: Accurate Prediction of N-Linked Glycosylation Sites Using ESM-2 and Structural Features With Graph Network and Co-Attention.

N-Linked glycosylation is crucial for various biological processes such as protein folding, immune response, and cellular transport. Traditional experimental methods for determining N-linked glycosylation sites entail substantial time and labor investment, which has led to the development of computational approaches as a more efficient alternative. However, due to the limited availability of 3D structural data, existing prediction methods often struggle to fully utilize structural information and fall short in integrating sequence and structural information effectively. Motivated by the progress of protein pretrained language models (pLMs) and the breakthrough in protein structure prediction, we introduced a high-accuracy model called CoNglyPred. Having compared various pLMs, we opt for the large-scale pLM ESM-2 to extract sequence embeddings, thus mitigating certain limitations associated with manual feature extraction. Meanwhile, our approach employs a graph transformer network to process the 3D protein structures predicted by AlphaFold2. The final graph output and ESM-2 embedding are intricately integrated through a co-attention mechanism. Among a series of comprehensive experiments on the independent test dataset, CoNglyPred outperforms state-of-the-art models and demonstrates exceptional performance in case study. In addition, we are the first to report the uncertainty of N-linked glycosylation predictors using expected calibration error and expected uncertainty calibration error.

Deciphering the role of LGALS2: insights into tertiary lymphoid structure-associated dendritic cell activation and immunotherapeutic potential in breast cancer patients.

Recent advances in cancer research have highlighted the pivotal role of tertiary lymphoid structures (TLSs) in modulating immune responses, particularly in breast cancer (BRCA). Here, we performed an integrated analysis of bulk transcriptome data from over 6000 BRCA samples using biological network-based computational strategies and machine learning (ML) methods, and identified LGALS2 as a key marker within TLSs. Single-cell sequencing and spatial transcriptomics uncover the role of LGALS2 in TLS-associated dendritic cells (DCs) stimulation and reveal the complexity of the tumor microenvironment (TME) at both the macro and micro levels. Elevated LGALS2 expression correlates with prolonged survival, which is associated with a robust immune response marked by diverse immune cell infiltration and active anti-tumor pathways leading to a 'hot' tumor microenvironment. The colocalization of LGALS2 with TLS-associated DCs and its role in immune activation in BRCA were confirmed by hematoxylin-eosin (HE), immunohistochemistry (IHC), and in vivo validation analyses. The identification of LGALS2 as a key factor in BRCA not only highlights its therapeutic potential in novel TLS-directed immunotherapy but also opens new avenues in patient stratification and treatment selection, ultimately improving clinical management.

Exploring the optimal mechanical properties of triply periodic minimal surface structures for biomedical applications: A Numerical analysis.

Currently, cutting-edge Additive Manufacturing techniques, such as Selective Laser Melting (SLM) and Electron Beam Melting (EBM), offer manufacturers a valuable avenue, especially in biomedical devices. These techniques produce intricate porous structures that draw inspiration from nature, boast biocompatibility, and effectively counter the adverse issues tied to solid implants, including stress shielding, cortical hypertrophy, and micromotions. Within the domain of such porous structures, Triply Periodic Minimal Surface (TPMS) configurations, specifically the Gyroid, Diamond, and Primitive designs, exhibit exceptional performance due to their bioinspired forms and remarkable mechanical and fatigue properties, outshining other porous counterparts. Consequently, they emerge as strong contenders for biomedical implants. However, assessing the mechanical properties and manufacturability of TPMS structures within the appropriate ranges of pore size, unit cell size, and porosity tailored for biomedical applications remains paramount. This study aims to scrutinize the mechanical behavior of Gyroid, Diamond, and Primitive structures in solid and sheet network iterations within the morphological parameter ranges suitable for tasks like cell seeding, vascularization, and osseointegration. A comparison with the mechanical characteristics of host bones is also undertaken. The methodology revolves around Finite Element Method (FEM) analysis. The six structures are originally modeled with unit cell sizes of 1, 1.5, 2, and 2.5 mm, and porosity levels ranging from 50% to 85%. Subsequently, mechanical properties, such as elasticity modulus and yield strength, are quantified through numerical analysis. The results underscore that implementing TPMS designs enables unit cell sizes between 1 and 2.5 mm, facilitating pore sizes within the suitable range of approximately 300-1500 µm for biomedical implants. Elasticity modulus spans from 1.5 to 33.8 GPa, while yield strength ranges around 20-304.5 MPa across the 50%-85% porosity spectrum. Generally, altering the unit cell size exhibits minimal impact on mechanical properties within the range above; however, it's noteworthy that smaller porosities correspond to heightened defects in additively manufactured structures. Thus, for an acceptable pore size range of 500-1000 µm and a minimum wall thickness of 150 µm, a prudent choice would involve adopting a 2.5 mm unit cell size.

Structures, simulated photoelectron spectroscopy, and electronic properties of CuASix(A = Sc, Cu, x ≤ 13) clusters: Relatively stable neutral pentagonal bipyramid structures of CuASi5.

Structural design and optimization, simulated photoelectron spectroscopy, electronic properties and chemical bond analysis of CuASix(A = Sc, Cu, x ≤ 13) clusters were systematically studied using the PBE scheme to integrate with global search program of ABCluster. Firstly, neutral MS (the most stable structures) of CuASi5 of the basic 1 + 5 + 1 structures (1 metal + 5 silicons + 1 metal atoms) can be found as the basic units for assembling more lager clusters under the condition of neglecting distortions and minor changes. If the Cu atoms in Cu2Six(x ≤ 13) systems was replaced by one Sc atom, the geometries of MS will be reconstructed. Compared with the wheel geometries of Cu2Si12 and Cu2Si13, CuScSi12 and CuScSi13 clusters belong to near-wheel geometries with peripheral metal atoms. The neutral CuScSi5 and Cu2Si5 clusters possess relatively higher stability in all of cluster sizes. A combination of NPA analysis of CuASi5, sp of the Cu atom and spd of the Sc atom hybridizations were crucial to the chemical bonds of A-Si in the neutral CuASi5 clusters. In view of the higher SED value of the Cu2Si5 molecule, chemical bond analysis was carried out using MO, HLg and AdNDP analysis. 18 localized bonds and four delocalized bonds can play a positive role for the relative stabilities of neutral pentagonal bipyramid structures of Cu2Si5. Thus, the Cu2Si5 cluster with a lager HLg(1.80 eV) may be a good candidate for the basic unit of silicon-based semiconductor material assembly.

3D Printed Leaf-Vein-Like Al2O3/EP Biohybrid Structures with Enhanced Thermal Conductivity.

The high computility of electronic components put urgent requirements on the dissipation efficiency of a high thermal conductive substrate. Herein, inspired by the nature structure, leaf-vein-like Al2O3 skeleton was first designed though topology optimization algorithm and manufactured via vat photopolymerization (VPP) 3D printing, then compounded with epoxy (EP) to prepare leaf-vein-like biohybrid structures. The biohybrid structure had a high λ (14.65 Wm-1 K-1 with the solid fraction of 40 vol %), which was 5585% higher than neat EP and 269% higher than the random dispersed Al2O3/EP composite at the same solid amount. Moreover, it further showed a high enhancement in the cooling ecoefficiency of the lighting-emitting diode (LED) cooling system. Compared with 40 vol % random dispersed Al2O3/EP composite as a cooling substrate, the leaf-vein-like biohybrid structure with the same solid fraction reduced the working temperature of LED by 8.9 °C. Our strategy has a significant potential as a viable type and mass-producible bionic cooling substrate.

Automated model discovery for textile structures: The unique mechanical signature of warp knitted fabrics.

Textile fabrics have unique mechanical properties, which make them ideal candidates for many engineering and medical applications: They are initially flexible, nonlinearly stiffening, and ultra-anisotropic. Various studies have characterized the response of textile structures to mechanical loading; yet, our understanding of their exceptional properties and functions remains incomplete. Here we integrate biaxial testing and constitutive neural networks to automatically discover the best model and parameters to characterize warp knitted polypropylene fabrics. We use experiments from different mounting orientations, and discover interpretable anisotropic models that perform well during both training and testing. Our study shows that constitutive models for warp knitted fabrics are highly sensitive to an accurate representation of the textile microstructure, and that models with three microstructural directions outperform classical orthotropic models with only two in-plane directions. Strikingly, out of 214=16,384 possible combinations of terms, we consistently discover models with two exponential linear fourth invariant terms that inherently capture the initial flexibility of the virgin mesh and the pronounced nonlinear stiffening as the loops of the mesh tighten. We anticipate that the tools we have developed and prototyped here will generalize naturally to other textile fabrics-woven or knitted, weft knit or warp knit, polymeric or metallic-and, ultimately, will enable the robust discovery of anisotropic constitutive models for a wide variety of textile structures. Beyond discovering constitutive models, we envision to exploit automated model discovery for the generative material design of wearable devices, stretchable electronics, and smart fabrics, as programmable textile metamaterials with tunable properties and functions. Our source code, data, and examples are available at https://github.com/LivingMatterLab/CANN. STATEMENT OF SIGNIFICANCE: Textile structures are rapidly gaining popularity in many biomedical applications including tissue engineering, wound healing, and surgical repair. A precise understanding of their unique mechanical properties is critical to tailor them to their specific functions. Here we integrate mechanical testing and machine learning to automatically discover the best models for knitted polypropylene fabrics. We show that warp knitted fabrics possess a complex symmetry with three distinct microstructural directions. Along these, the behavior is dominated by an exponential linear term that characterize the initial flexibility of the virgin mesh and the nonlinear stiffening as the loops of the fabric tighten. We expect that our technology will generalize naturally to other fabrics and enable the robust discovery of complex anisotropic models for a wide variety of textile structures.

Octahedral vs Tiara-like Pd6(SR)12 Clusters.

Atomically precise Pd-thiolate clusters are well-known for their well-defined structures and diverse applications involving catalysis, sensors, and biomedicine. While many of these clusters have been studied, their molecular structures typically feature a tiara-like arrangement. In this study, we present the first example of a non-tiara-like Pd-thiolate cluster: the octahedral Pd6(SC6H11)12 (denoted as Pd6-Oct). The composition and geometric structure of the cluster were characterized using electrospray ionization mass spectrometry (ESI-MS) together with single-crystal X-ray diffraction (SXRD). Despite having a similar chemical composition to tiara-like Pd6(SC2H4Ph)12 (denoted as Pd6-Tia), Pd6-Oct exhibits a distinctly different geometric structure. Additionally, UV-vis-NIR absorption spectroscopy combined with quantum chemical calculations provided valuable insights into the electronic structures of these clusters. The excited-state dynamics, host-guest chemistry, and the catalytic properties of Pd6-Oct and Pd6-Tia were examined to compare their structure-property relationships. This research represents significant advances in the synthesis and understanding of structure-property correlations in Pd-thiolate clusters.

Composite metastructure with tunable ultra-wide low-frequency three-dimensional band gaps for vibration and noise control.

Low-frequency vibration and noise control present enduring engineering challenges that garner extensive research attention. Despite numerous active and passive control solutions, achieving multiple ultra-wide attenuation regions remains elusive. Addressing vibration and noise control across a multidirectional broad low-frequency spectrum, three-dimensional metastructures have emerged as innovative solutions. This study introduces a novel three-dimensional composite metastructure featuring multiple ultra-wide three-dimensional complete band gaps. The research emphasizes the design strategy of elastic ligaments to achieve multiple ultra-wide attenuation regions spanning from 0.7 to 40 kHz. The band structures are elucidated through modal analysis and further substantiated by an analytical model based on a spring-mass chain with an additional resonator. The underlying physical mechanism for the formation of multiple ultra-wide band gaps is revealed through novel vibration modes from finite element analyses. Furthermore, we demonstrate that the distribution and the relative width of the ultra-wide band gaps can be tuned by modifying the geometric parameters of the metastructure. Utilizing additive manufacturing, prototypes are fabricated, and low-amplitude vibration tests are conducted to evaluate real-time vibration attenuation properties. Consistency is observed among theoretical, numerical, and experimental results. The proposed structure shows significant potential for high-performance meta-devices aimed at controlling noise and vibration across an extremely wide low-frequency spectrum.

Multi-omics profiling and experimental verification of tertiary lymphoid structure-related genes: molecular subgroups, immune infiltration, and prognostic implications in lung adenocarcinoma.

Lung adenocarcinoma (LUAD), characterized by a low 5-year survival rate, is the most common and aggressive type of lung cancer. Recent studies have shown that tertiary lymphoid structures (TLS), which resemble lymphoid structures, are closely linked to the immune response and tumor prognosis. The functions of the tertiary lymphoid structure-related genes (TLS-RGs) in the tumor microenvironment (TME) are poorly understood. Based on publicly available data, we conducted a comprehensive study of the function of TLS-RGs in LUAD. Initially, we categorized LUAD patients into two TLS and two gene subtypes. Subsequently, risk scores were calculated, and prognostic models were constructed using seven genes (CIITA, FCRL2, GBP1, BIRC3, SCGB1A1, CLDN18, and S100P). To enhance the clinical application of TLS scores, we have developed a precise nomogram. Furthermore, drug sensitivity, tumor mutational burden (TMB), and the cancer stem cell (CSC) index were found to be substantially correlated with the TLS scores. Single-cell sequencing results reflected the distribution of TLS-RGs in cells. Finally, we took the intersection of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) prognosis-related genes and then further validated the expression of these genes by qRT-PCR. Our in-depth investigation of TLS-RGs in LUAD revealed their possible contributions to the clinicopathological features, prognosis, and characteristics of TME. These findings underscore the potential of TLS-RGs as prognostic biomarkers and therapeutic targets for LUAD, thereby paving the way for personalized treatment strategies.

CCL4 as a potential serum factor in differential diagnosis of central nervous system inflammatory diseases and gliomas.

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are commonly utilized to detect brain gliomas and central nervous system inflammation diseases. However, there are instances where depending solely on medical imaging for a precise diagnosis may result in unsuitable medications or treatments. Pathological analysis is regarded as the definitive method for diagnosing brain gliomas or central nervous system inflammation diseases. To achieve this, a craniotomy or stereotaxic biopsy is necessary to collect brain tissue, which can lead to complications such as cerebral hemorrhage, neurological deficits, cerebrospinal fluid leaks, and cerebral edema. Consequently, the advancement of non-invasive or minimally invasive diagnostic techniques is currently a high priority. This study included samples from four glioma patients and five patients with central nervous system inflammatory diseases, comprising both serum and paired cerebrospinal fluid (CSF). A total of 40 human cytokines were identified in these samples. We utilized a receiver operating characteristic (ROC) analysis to assess the sensitivity and specificity for distinguishing central nervous system inflammation diseases and gliomas. Additionally, we examined the correlation of these factors between serum and CSF in the patients. Ultimately, the identified factors were validated using serum from patients with clinically confirmed gliomas and central nervous system inflammation diseases followed by detection and statistical analysis through ELISA. The levels of serum factors IL-4, IFN-α, IFN-γ, IL-6, TNF-α, CCL4, CCL11, and VEGF were found to be significantly higher in gliomas compared with inflammatory diseases of the central nervous system (p < 0.05). Furthermore, a strong correlation was observed between the levels of CCL4 in serum and CSF, with a correlation coefficient of r = 0.92 (95% CI = 0.20-0.99, p = 0.027). We gathered more clinical samples to provide further validation of the abundance of CCL4 expression. A clinical study analyzing serum samples from 19 glioma patients and 22 patients with central nervous system inflammation diseases revealed that CCL4 levels were notably elevated in the inflammatory group compared with the glioma group (p < 0.001). These results suggest that assessing serum CCL4 levels may be useful in distinguishing those patients for clinical diagnostic purposes.

Beyond the biting - limited impact of explicit mosquito dynamics in dengue models.

Mathematical models play a crucial role in assisting public health authorities in timely disease control decision-making. For vector-borne diseases, integrating host and vector dynamics into models can be highly complex, particularly due to limited data availability, making system validation challenging. In this study, two compartmental models akin to the SIR type were developed to characterize vector-borne infectious disease dynamics. Motivated by dengue fever epidemiology, the models varied in their treatment of vector dynamics, one with implicit vector dynamics and the other explicitly modeling mosquito-host contact. Both considered temporary immunity after primary infection and disease enhancement in secondary infection, analogous to the temporary cross-immunity and the Antibody-dependent enhancement biological processes observed in dengue epidemiology. Qualitative analysis using bifurcation theory and numerical experiments revealed that the immunity period and disease enhancement outweighed the impact of explicit vector dynamics. Both models demonstrated similar bifurcation structures, indicating that explicit vector dynamics are only justified when assessing the effects of vector control methods. Otherwise, the extra equations are irrelevant, as both systems display similar dynamics scenarios. The study underscores the importance of using simple models for mathematical analysis, initiating crucial discussions among the modeling community in vector-borne diseases.

Fluid confinement within a branched polymer structure enhances tribological performance of a poly(2-methacryloyloxyethyl phosphorylcholine)-surface-modified contact lens.

The poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-modified, silicone hydrogel, contact lens (CL) material lehfilcon A has previously been demonstrated to have a lubricious, antifouling and ultra-soft surface. This study provides confirmatory identification of the outer polymer structures on this CL surface as branched PMPC structures. It further aims to understand their role in providing enhanced tribological performance via fluid confinement. A combination of scanning transmission electron microscopy and atomic force microscopy infrared spectroscopy has been used to achieve both morphological and chemical confirmation of branched PMPC structures resembling the polysaccharide species present on the surface of the cornea. Measurements of the fluid-confinement behaviour of this layer, by means of nanoindentation experiments, show it to resist squeeze-out of the interstitial fluid, thereby boosting lubrication by virtue of a fluid-load-support mechanism. Tribological testing of CLs showed this effective lubrication to be maintained after one month of daily wearing.

Structural Requirements for the Outpatient Treatment of Benign Diseases of the Uterus.

In many cases, outpatient surgical treatment of benign diseases of the uterus has advantages over inpatient care. This has been demonstrated by the healthcare situation in other countries. However, the prerequisite for the provision of outpatient services is that this does not lead to any impairment in the quality of care or of patient safety. The ultimate goal should not be to reduce costs but rather to maintain and, ideally, improve the quality of care. This requires that services are not just defined by the surgical procedure but also by the entire treatment chain, including, for example, psychosocial support, and are remunerated accordingly. It is particularly worrying that the final decision as to whether an outpatient operation is possible is not the responsibility of the operating unit, but of the "Medizinischer Dienst," with the corresponding options and threats of sanctions. This situation is unique internationally and requires a paradigm shift. Furthermore, structural prerequisites must be maintained which currently only exist inadequately in Germany. Since a substantial proportion of planned outpatient operations require immediate or secondary inpatient treatment, there must be a barrier-free transition between the outpatient and inpatient sectors. This will require the creation of networks between outpatient service providers and one or more hospitals that are equipped and competent to manage even complex complications. It is important to create structures that, with intensive involvement of the operating unit, include adequate preoperative evaluation and patient education as well as needs-oriented postoperative care at home. The current separation of sectors is a significant hinderance. Moreover, when expanding and promoting outpatient surgery, the aspect of training and further education of specialist staff must be taken into account, as well as cross-sectoral quality assurance. Based on a review of the international literature, this article presents 13 recommendations for adequate structures when providing outpatient services which should serve as a prerequisite for the greatest possible guarantee of patient safety.

Chemistry/structural biology of psychedelic drugs and their receptor(s).

This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines and certain tryptamines, which possess psychedelic activity in humans. Where they are known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the 5-HT2A receptor subtype, a G-protein coupled receptor known to be the primary target of psychedelics, we refer to several X-ray and cryoEM structures, with a variety of ligands bound, to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions.

Renal-Clearable Organic Probes From D-A-D Type Aza-BODIPY Fluorophores for Multiphoton Deep-Brain Imaging.

Bright near-infrared (NIR) fluorescent probes play an important role in in vivo optical imaging. Here, renal-clearable nanodots prepared from Aza-BODIPY are reported fluorophores for multiphoton brain imaging. The design of donor-acceptor-donor (D-A-D) type conjugated structures endowed the fluorophores with large three-photon absorption cross-section for both 1620 and 2200 nm excitation. The side chain modification and lipid encapsulation yield ultrasmall nanodots (≈4 nm) and a high fluorescence quantum yield (≈0.35) at 720 nm emission in the aqueous phase. The measured three-photon action cross-section of a single Aza-BODIPY fluorophore in the nanodots is ≈30 times higher than the commonly used Sulforhodamine 101 dye. Three-photon deep brain imaging of subcortical structures is demonstrated, reaching a depth of 1900 µm below the brain surface in a live mouse study. The nanodots enabled blood flow measurement at a depth of 1617 µm using line scanning three-photon microscopy (3PM). This work provides superior fluorescent probes for multiphoton deep-brain imaging.