Visualizing Noncovalent Interactions and Property Prediction of Submicron-Sized Charge-Transfer Crystals from ab-initio Determined Structures.

The charge-transfer (CT) interactions between organic compounds are reflected in the (opto)electronic properties. Determining and visualizing crystal structures of CT complexes are essential for the design of functional materials with desirable properties. Complexes of pyranine (PYR), methyl viologen (MV), and their derivatives are the most studied water-based CT complexes. Nevertheless, very few crystal structures of CT complexes have been reported so far. In this study, the structures of two PYRs-MVs CT crystals and a map of the noncovalent interactions using 3D electron diffraction (3DED) are reported. Physical properties, e.g., band structure, conductivity, and electronic spectra of the CT complexes and their crystals are investigated and compared with a range of methods, including solid and liquid state spectroscopies and highly accurate quantum chemical calculations based on density functional theory (DFT). The combination of 3DED, spectroscopy, and DFT calculation can provide important insight into the structure-property relationship of crystalline CT materials, especially for submicrometer-sized crystals.

Phase Identification and Discovery of an Elusive Polymorph of Drug-Polymer Inclusion Complex Using Automated 3D Electron Diffraction.

3D electron diffraction (3D ED) has shown great potential in crystal structure determination in materials, small organic molecules, and macromolecules. In this work, an automated, low-dose and low-bias 3D ED protocol has been implemented to identify six phases from a multiple-phase melt-crystallisation product of an active pharmaceutical ingredient, griseofulvin (GSF). Batch data collection under low-dose conditions using a widely available commercial software was combined with automated data analysis to collect and process over 230 datasets in three days. Accurate unit cell parameters obtained from 3D ED data allowed direct phase identification of GSF Forms III, I and the known GSF inclusion complex (IC) with polyethylene glycol (PEG) (GSF-PEG IC-I), as well as three minor phases, namely GSF Forms II, V and an elusive new phase, GSF-PEG IC-II. Their structures were then directly determined by 3D ED. Furthermore, we reveal how the stabilities of the two GSF-PEG IC polymorphs are closely related to their crystal structures. These results demonstrate the power of automated 3D ED for accurate phase identification and direct structure determination of complex, beam-sensitive crystallisation products, which is significant for drug development where solid form screening is crucial for the overall efficacy of the drug product.

A Novel SiC Trench MOSFET with Self-Aligned N-Type Ion Implantation Technique.

We propose a novel silicon carbide (SiC) self-aligned N-type ion implanted trench MOSFET (NITMOS) device. The maximum electric field in the gate oxide could be effectively reduced to below 3 MV/cm with the introduction of the P-epi layer below the trench. The P-epi layer is partially counter-doped by a self-aligned N-type ion implantation process, resulting in a relatively low specific on-resistance (Ron,sp). The lateral spacing between the trench sidewall and N-implanted region (Wsp) plays a crucial role in determining the performance of the SiC NITMOS device, which is comprehensively studied through the numerical simulation. With the Wsp increasing, the SiC NITMOS device demonstrates a better short-circuit capability owing to the reduced saturation current. The gate-to-drain capacitance (Cgd) and gate-to-drain charge (Qgd) are also investigated. It is observed that both Cgd and Qgd decrease as the Wsp increases, owing to the enhanced screen effect. Compared to the SiC double-trench MOSFET device, the optimal SiC NITMOS device exhibits a 79% reduction in Cgd, a 38% decrease in Qgd, and a 41% reduction in Qgd × Ron,sp. A higher switching speed and a lower switching loss can be achieved using the proposed structure.

Polymer Chainmail: Steric Hindrance and Charge Compensation of Anion-Doped PEDOT to Boost Stress Deformation of Compressible Supercapacitor.

Conducting polymers with high theoretical capacitance and deformability are among the optimal candidates for compressible supercapacitor electrode materials. However, achieving both mechanical and electrochemical stabilities in a single electrode remains a great challenge. To address this issue, the "Polymer Chainmail" is proposed with reversible deformation capability and enhances stability because of the steric hindrance and charge compensation effect of doped anions. As a proof of concept, four common anions are selected as dopants for Poly(3,4-ethylenedioxythiophene) (PEDOT), and their effects on the adsorption and diffusion of H+ on PEDOT are verified using density functional theory calculations. Owing to the film formation effect, the PF 6 - ${{\rm{PF}}_6^- }$ doped PEDOT/nitrogen-doped carbon foam exhibits good mechanical properties. Furthermore, the composite demonstrates excellent rate performance and stability due to suitable anion doping. This finding provides new insights into the preparation of electrochemically stable conductive polymer-based compressible electrode materials.

HVTR++: Image and Pose Driven Human Avatars using Hybrid Volumetric-Textural Rendering.

Recent neural rendering methods have made great progress in generating photorealistic human avatars. However, these methods are generally conditioned only on low-dimensional driving signals (e.g., body poses), which are insufficient to encode the complete appearance of a clothed human. Hence they fail to generate faithful details. To address this problem, we exploit driving view images (e.g., in telepresence systems) as additional inputs. We propose a novel neural rendering pipeline, Hybrid Volumetric-Textural Rendering (HVTR++), which synthesizes 3D human avatars from arbitrary driving poses and views while staying faithful to appearance details efficiently and at high quality. First, we learn to encode the driving signals of pose and view image on a dense UV manifold of the human body surface and extract UV-aligned features, preserving the structure of a skeleton-based parametric model. To handle complicated motions (e.g., self-occlusions), we then leverage the UV-aligned features to construct a 3D volumetric representation based on a dynamic neural radiance field. While this allows us to represent 3D geometry with changing topology, volumetric rendering is computationally heavy. Hence we employ only a rough volumetric representation using a pose- and image-conditioned downsampled neural radiance field (PID-NeRF), which we can render efficiently at low resolutions. In addition, we learn 2D textural features that are fused with rendered volumetric features in image space. The key advantage of our approach is that we can then convert the fused features into a high-resolution, high-quality avatar by a fast GAN-based textural renderer. We demonstrate that hybrid rendering enables HVTR++ to handle complicated motions, render high-quality avatars under user-controlled poses/shapes, and most importantly, be efficient at inference time. Our experimental results also demonstrate state-of-the-art quantitative results.

Abnormal alanine aminotransferase levels in patients with moderate or severe ovarian hyperstimulation result in an increased risk of obstetric complications.

OBJECTIVES: To explore the effect of abnormally elevated serum alanine aminotransferase (ALT) on pregnancy outcomes in patients with moderate and severe ovarian hyperstimulation syndrome (OHSS) at disease onset. METHODS: This was a single-center retrospective cohort study conducted between January 1, 2014 and October 31, 2021. A total of 3550 fresh in vitro fertilization/intracytoplasmic sperm injection embryo transfer cycles were included, using Golan's three-degree, five-level classification to diagnose patients with OHSS. According to the patient's ALT level after diagnosis of OHSS, 123 (3.46%) patients with moderate-to-severe OHSS were divided into two groups. A control group included 3427 (96.54%) non-OHSS patients, and 91 (2.56%) abnormal ALT patients were matched with the control group for propensity scores. RESULTS: There was no difference in baseline data between the abnormal ALT and matched control groups. The incidence of obstetric complications was significantly higher in the abnormal ALT group than in the matched control group (P < 0.05). After adjusting for confounding factors, the incidence of obstetric complications in the abnormal ALT group was still higher than that in the normal ALT group (P < 0.05). CONCLUSION: In patients with moderate and severe OHSS, higher ALT levels resulted in an increased risk of obstetric and neonatal complications.

Accurate structure models and absolute configuration determination using dynamical effects in continuous-rotation 3D electron diffraction data.

Continuous-rotation 3D electron diffraction methods are increasingly popular for the structure analysis of very small organic molecular crystals and crystalline inorganic materials. Dynamical diffraction effects cause non-linear deviations from kinematical intensities that present issues in structure analysis. Here, a method for structure analysis of continuous-rotation 3D electron diffraction data is presented that takes multiple scattering effects into account. Dynamical and kinematical refinements of 12 compounds-ranging from small organic compounds to metal-organic frameworks to inorganic materials-are compared, for which the new approach yields significantly improved models in terms of accuracy and reliability with up to fourfold reduction of the noise level in difference Fourier maps. The intrinsic sensitivity of dynamical diffraction to the absolute structure is also used to assign the handedness of 58 crystals of 9 different chiral compounds, showing that 3D electron diffraction is a reliable tool for the routine determination of absolute structures.

Direct structure determination of vemurafenib polymorphism from compact spherulites using 3D electron diffraction.

The spherulitic morphology is considered to be the most common morphology of crystalline materials and is particularly apparent in melt-crystallized products. Yet, historically, the polycrystalline nature of spherulites has hindered successful crystal structure determination. Here, we report the direct structure determination of a clinical drug, vemurafenib (VMN), in compact spherulite form using 3D electron diffraction (3D ED). VMN has four known polymorphs. We first solved the crystal structures of α-, ß-, and γ-VMN from compact spherulites using 3D ED, and the resulting structures were highly consistent with those obtained by single-crystal X-ray diffraction. We then determined the crystal structure of δ-VMN-the least stable polymorph which cannot be cultivated as a single crystal-directly from the compact spherulite sample. We unexpectedly discovered a new polymorph during our studies, denoted as ε-VMN. Single crystals of ε-VMN are extremely thin and not suitable for study by X-ray diffraction. Again, we determined the structure of ε-VMN in a compact spherulite form. This successful structure elucidation of all five VMN polymorphs demonstrates the possibility of directly determining structures from melt-grown compact spherulite samples. Thereby, this discovery will improve the efficiency and broaden the scope of polymorphism research, especially within the field of melt crystallization.

Understanding integrated service delivery: a scoping review of models for noncommunicable disease and mental health interventions in low-and-middle income countries.

BACKGROUND: Noncommunicable diseases (NCDs) and mental health conditions represent a growing proportion of disease burden in low- and middle-income countries (LMICs). While past efforts have identified interventions to be delivered across health system levels to address this burden, the challenge remains of how to deliver heterogenous interventions in resource-constrained settings. One possible solution is the Integration of interventions within existing care delivery models. This study reviews and summarizes published literature on models of integrated NCD and mental health care in LMICs. METHODS: We searched Pubmed, African Index Medicus and reference lists to conduct a scoping review of studies describing an integrated model of NCD or neuropsychiatric conditions (NPs) implemented in a LMIC. Conditions of interest were grouped into common and severe NCDs and NPs. We identified domains of interest and types of service integration, conducting a narrative synthesis of study types. Studies were screened and characteristics were extracted for all relevant studies. Results are reported using PRISMA-ScR. RESULTS: Our search yielded 5004 studies, we included 219 models of integration from 188 studies. Most studies were conducted in middle-income countries, with the majority in sub-Saharan Africa. Health services were offered across all health system levels, with most models implemented at health centers. Common NCDs (including type 2 diabetes and hypertension) were most frequently addressed by these models, followed by common NPs (including depression and anxiety). Conditions and/or services were often integrated into existing primary healthcare, HIV, maternal and child health programs. Services provided for conditions of interest varied and frequency of these services differed across health system levels. Many models demonstrated decentralization of services to lower health system levels, and task shifting to lower cadre providers. CONCLUSIONS: While integrated service design is a promising method to achieve ambitious global goals, little is known about what works, when, and why. This review characterizing care integration programs is an initial step toward developing a structured study of care integration.

Fructose-6-phosphate-2-kinase/fructose-2,6-bisphosphatase regulates energy metabolism and synthesis of storage products in developing rice endosperm.

Starch accounts for about 80-85 % of the dry weight of grains and determines yield by impact on grain weight. And, the content and composition of starch also determine appearance, eating, cooking and nutritional quality of rice. By coordinating crucial reactions of the primary carbohydrate metabolism in all eukaryotes, fructose-2,6-bisphosphate (Fru-2,6-P2) is a traffic signal in metabolism. However, the metabolic regulation of starch in plant sink tissues by Fru-2,6-P2 remains unclear. Here we isolated rice mutant floury endosperm23 (flo23) which has opaque endosperm and anomalous compound starch grains (SGs). flo23 mutant grains had reduced contents of starch, lipids and proteins. Map-based cloning and genetic complementation experiments showed that FLO23 encodes a cytoplasmic Fructose-6-phosphate-2-kinase/Fructose-2,6-bisphosphatase (F2KP). Mutation of OsF2KP2 decreased Fru-2,6-P2 content in endosperm cells, leading to drastically reduced phosphoenolpyruvate (PEP) and pyruvate contents and disordered glycolysis and energy metabolism. The results imply that OsF2KP2 participates in the glycolytic pathway by providing precursors and energy for synthesis of grain storage compounds.

Supercrystal engineering of atomically precise gold nanoparticles promoted by surface dynamics.

The controllable packing of functional nanoparticles (NPs) into crystalline lattices is of interest in the development of NP-based materials. Here we demonstrate that the size, morphology and symmetry of such supercrystals can be tailored by adjusting the surface dynamics of their constituent NPs. In the presence of excess tetraethylammonium cations, atomically precise [Au25(SR)18]- NPs (where SR is a thiolate ligand) can be crystallized into micrometre-sized hexagonal rod-like supercrystals, rather than as face-centred-cubic superlattices otherwise. Experimental characterization supported by theoretical modelling shows that the rod-like crystals consist of polymeric chains in which Au25 NPs are held together by a linear SR-[Au(I)-SR]4 interparticle linker. This linker is formed by conjugation of two dynamically detached SR-[Au(I)-SR]2 protecting motifs from adjacent Au25 particles, and is stabilized by a combination of CH⋯π and ion-pairing interactions between tetraethylammonium cations and SR ligands. The symmetry, morphology and size of the resulting supercrystals can be systematically tuned by changing the concentration and type of the tetraalkylammonium cations.

Improving data quality for three-dimensional electron diffraction by a post-column energy filter and a new crystal tracking method.

Three-dimensional electron diffraction (3D ED) has become an effective technique to determine the structures of submicrometre- (nanometre-)sized crystals. In this work, energy-filtered 3D ED was implemented using a post-column energy filter in both STEM mode and TEM mode [(S)TEM denoting (scanning) transmission electron microscope]. The setups for performing energy-filtered 3D ED on a Gatan imaging filter are described. The technique and protocol improve the accessibility of energy-filtered 3D ED post-column energy filters, which are available in many TEM laboratories. In addition, a crystal tracking method in STEM mode using high-angle annular dark-field imaging is proposed. This method enables the user to monitor the crystal position while collecting 3D ED data at the same time, allowing a larger tilt range without foregoing any diffraction frames or imposing extra electron dose. In order to compare the differences between energy-filtered and unfiltered 3D ED data sets, three well known crystallized inorganic samples have been studied in detail. For these samples, the final R 1 values improved by 10-30% for the energy-filtered data sets compared with the unfiltered data sets, and the structures became more chemically reasonable. Possible reasons for improvement are also discussed.

A metamaterial-free fluid-flow cloak.

The model of ideal fluid flow around a cylindrical obstacle exhibits a long-established physical picture, where originally straight streamlines are deflected over the whole space by the obstacle. Inspired by transformation optics and metamaterials, recent theories have proposed the concept of fluid cloaking, which is able to recover the straight streamlines, as if the obstacle did not exist. However, such a cloak, similar to all previous transformation-optics-based devices, relies on complex metamaterials with inhomogeneous parameters and is difficult to implement. Here we deploy the theory of scattering cancellation and report on the experimental realization of a fluid-flow cloak without metamaterials. This cloak is realized by engineering the geometry of the fluid channel, which effectively cancels the dipole-like scattering of the obstacle. The cloaking effect is demonstrated through the direct observation of recovered straight streamlines in the fluid flow. Our work sheds new light on conventional fluid control and may find application in microfluidic devices.

Higher baseline alanine aminotransferase level is associated with lower live birth rate after freeze-thawed embryo transfer.

OBJECTIVE: The aim of this retrospective analysis was to explore whether an elevated ALT level before pregnancy is associated with a reduction in live birth rate after IVF-FET. DESIGN: Retrospective observational study. SETTING: Shiyan People's Hospital, China between January 2019 and December 2019. PATIENTS: Women aged ≤ 40 years. INTERVENTION(S): Freeze-thawed embryo transfer (FET). MAIN OUTCOME MEASURE(S): The live birth rate, which was defined as the delivery of a live baby after 24 weeks of gestation. RESULTS: The analysis included 365 FET cycles. There was a significant difference between groups in the live birth rate (p < .05), which was highest for the low ALT tertile and lowest for the high ALT tertile. Multiple regression analysis with adjustment for multiple potential confounders revealed that the odds of live birth were decreased for each one standard deviation increase in ALT (OR = 0.56, 95%CI = 0.42-0.75, p < .0001) and lower for the high ALT tertile than for the low ALT tertile (OR = 0.38, 95%CI = 0.19-0.75, p = .0055). Smooth curve fitting showed an inverse relationship between ALT and live birth rate. CONCLUSION: Our findings indicate that relatively small elevations in baseline serum ALT level can have a clinically relevant impact on the success of FET.

Direct Location of Organic Molecules in Framework Materials by Three-Dimensional Electron Diffraction.

In the study of framework materials, probing interactions between frameworks and organic molecules is one of the most important tasks, which offers us a fundamental understanding of host-guest interactions in gas sorption, separation, catalysis, and framework structure formation. Single-crystal X-ray diffraction (SCXRD) is a conventional method to locate organic species and study such interactions. However, SCXRD demands large crystals whose quality is often vulnerable to, e.g., cracking on the crystals by introducing organic molecules, and this is a major challenge to use SCXRD for structural analysis. With the development of three-dimensional electron diffraction (3D ED), single-crystal structural analysis can be performed on very tiny crystals with sizes on the nanometer scale. Here, we analyze two framework materials, SU-8 and SU-68, with organic molecules inside their inorganic crystal structures. By applying 3D ED, with fast data collection and an ultralow electron dose (0.8-2.6 e- Å-2), we demonstrate for the first time that each nonhydrogen atom from the organic molecules can be ab initio located from structure solution, and they are shown as distinct and well-separated peaks in the difference electrostatic potential maps showing high accuracy and reliability. As a result, two different spatial configurations are identified for the same guest molecule in SU-8. We find that the organic molecules interact with the framework through strong hydrogen bonding, which is the key to immobilizing them at well-defined positions. In addition, we demonstrate that host-guest systems can be studied at room temperature. Providing high accuracy and reliability, we believe that 3D ED can be used as a powerful tool to study host-guest interactions, especially for nanocrystals.

Single-crystal structure determination of nanosized metal-organic frameworks by three-dimensional electron diffraction.

Metal-organic frameworks (MOFs) have attracted considerable interest due to their well-defined pore architecture and structural tunability on molecular dimensions. While single-crystal X-ray diffraction (SCXRD) has been widely used to elucidate the structures of MOFs at the atomic scale, the formation of large and well-ordered crystals is still a crucial bottleneck for structure determination. To alleviate this challenge, three-dimensional electron diffraction (3D ED) has been developed for structure determination of nano- (submicron-)sized crystals. Such 3D ED data are collected from each single crystal using transmission electron microscopy. In this protocol, we introduce the entire workflow for structural analysis of MOFs by 3D ED, from sample preparation, data acquisition and data processing to structure determination. We describe methods for crystal screening and handling of crystal agglomerates, which are crucial steps in sample preparation for single-crystal 3D ED data collection. We further present how to set up a transmission electron microscope for 3D ED data acquisition and, more importantly, offer suggestions for the optimization of data acquisition conditions. For data processing, including unit cell and space group determination, and intensity integration, we provide guidelines on how to use electron and X-ray crystallography software to process 3D ED data. Finally, we present structure determination from 3D ED data and discuss the important features associated with 3D ED data that need to be considered. We believe that this protocol provides critical details for implementing and utilizing 3D ED as a structure determination platform for nano- (submicron-)sized MOFs as well as other crystalline materials.

Community-based care models for arterial hypertension management in non-pregnant adults in sub-Saharan Africa: a literature scoping review and framework for designing chronic services.

BACKGROUND: Arterial hypertension (aHT) is the leading cardiovascular disease (CVD) risk factor in sub-Saharan Africa; it remains, however, underdiagnosed, and undertreated. Community-based care services could potentially expand access to aHT diagnosis and treatment in underserved communities. In this scoping review, we catalogued, described, and appraised community-based care models for aHT in sub-Saharan Africa, considering their acceptability, engagement in care and clinical outcomes. Additionally, we developed a framework to design and describe service delivery models for long-term aHT care. METHODS: We searched relevant references in Embase Elsevier, MEDLINE Ovid, CINAHL EBSCOhost and Scopus. Included studies described models where substantial care occurred outside a formal health facility and reported on acceptability, blood pressure (BP) control, engagement in care, or end-organ damage. We summarized the interventions' characteristics, effectiveness, and evaluated the quality of included studies. Considering the common integrating elements of aHT care services, we conceptualized a general framework to guide the design of service models for aHT. RESULTS: We identified 18,695 records, screened 4,954 and included twelve studies. Four types of aHT care models were identified: services provided at community pharmacies, out-of-facility, household services, and aHT treatment groups. Two studies reported on acceptability, eleven on BP control, ten on engagement in care and one on end-organ damage. Most studies reported significant reductions in BP values and improved access to comprehensive CVDs services through task-sharing. Major reported shortcomings included high attrition rates and their nature as parallel, non-integrated models of care. The overall quality of the studies was low, with high risk of bias, and most of the studies did not include comparisons with routine facility-based care. CONCLUSIONS: The overall quality of available evidence on community-based aHT care is low. Published models of care are very heterogeneous and available evidence is insufficient to recommend or refute further scale up in sub-Sahara Africa. We propose that future projects and studies implementing and assessing community-based models for aHT care are designed and described according to six building blocks: providers, target groups, components, location, time of service delivery, and their use of information systems.

Scipion-ED: a graphical user interface for batch processing and analysis of 3D ED/MicroED data.

Three-dimensional electron diffraction (3D ED)/microcrystal electron diffraction (MicroED) techniques are gaining in popularity. However, the data processing often does not fit existing graphical user interface software, instead requiring the use of the terminal or scripting. Scipion-ED, described in this article, provides a graphical user interface and extendable framework for processing of 3D ED/MicroED data. An illustrative project is described, in which multiple 3D ED/MicroED data sets collected on tetragonal lysozyme were processed with DIALS through the Scipion-ED interface. The ability to resolve unmodelled features in the electrostatic potential map was compared between three strategies for merging data sets.

Protein phosphatase 1 regulatory inhibitor subunit 14C promotes triple-negative breast cancer progression via sustaining inactive glycogen synthase kinase 3 beta.

Triple-negative breast cancer (TNBC) is fast-growing and highly metastatic with the poorest prognosis among the breast cancer subtypes. Inactivation of glycogen synthase kinase 3 beta (GSK3ß) plays a vital role in the aggressiveness of TNBC; however, the underlying mechanism for sustained GSK3ß inhibition remains largely unknown. Here, we find that protein phosphatase 1 regulatory inhibitor subunit 14C (PPP1R14C) is upregulated in TNBC and relevant to poor prognosis in patients. Overexpression of PPP1R14C facilitates cell proliferation and the aggressive phenotype of TNBC cells, whereas the depletion of PPP1R14C elicits opposite effects. Moreover, PPP1R14C is phosphorylated and activated by protein kinase C iota (PRKCI) at Thr73. p-PPP1R14C then represses Ser/Thr protein phosphatase type 1 (PP1) to retain GSK3ß phosphorylation at high levels. Furthermore, p-PPP1R14C recruits E3 ligase, TRIM25, toward the ubiquitylation and degradation of non-phosphorylated GSK3ß. Importantly, the blockade of PPP1R14C phosphorylation inhibits xenograft tumorigenesis and lung metastasis of TNBC cells. These findings provide a novel mechanism for sustained GSK3ß inactivation in TNBC and suggest that PPP1R14C might be a potential therapeutic target.