Tubulin participates in establishing protoxylem vessel reinforcement patterns and hydraulic conductivity in maize.

Water transportation to developing tissues relies on the structure and function of plant xylem cells. Plant microtubules govern the direction of cellulose microfibrils and guide secondary cell wall formation and morphogenesis. However, the relevance of microtubule-determined xylem wall thickening patterns in plant hydraulic conductivity remains unclear. In the present study, we identified a maize (Zea mays) semi-dominant mutant, designated drought-overly-sensitive1 (ZmDos1), the upper leaves of which wilted even when exposed to well-watered conditions during growth; the wilting phenotype was aggravated by increased temperatures and decreased humidity. Protoxylem vessels in the stem and leaves of the mutant showed altered thickening patterns of the secondary cell wall (from annular to spiral), decreased inner diameters, and limited water transport efficiency. The causal mutation for this phenotype was found to be a G-to-A mutation in the maize gene α-tubulin4, resulting in a single amino acid substitution at position 196 (E196K). Ectopic expression of the mutant α-tubulin4 in Arabidopsis (Arabidopsis thaliana) changed the orientation of microtubule arrays, suggesting a determinant role of this gene in microtubule assembly and secondary cell wall thickening. Our findings suggest that the spiral wall thickenings triggered by the α-tubulin mutation are stretched during organ elongation, causing a smaller inner diameter of the protoxylem vessels and affecting water transport in maize. This study underscores the importance of tubulin-mediated protoxylem wall thickening in regulating plant hydraulics, improves our understanding of the relationships between protoxylem structural features and functions, and offers candidate genes for the genetic enhancement of maize.

Pediatric oncology provider perspectives and patient/family perceptions of chemotherapy-induced nausea and vomiting management: Experiences at an academic medical center.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is common in children undergoing cancer treatment, and significantly impacts quality of life. Clinical practice guidelines (CPGs) have been developed to guide CINV management, though many patients do not receive guideline-concordant care. Few studies have examined provider perspectives on CINV management or preferred improvement approaches, or pediatric patient perception of CINV control. METHODS: A cross-sectional study of pediatric oncology providers was conducted at a large freestanding children's hospital. Providers completed an anonymous online survey about CINV control in patients admitted for scheduled chemotherapy, and their knowledge and utilization of CINV CPGs. A survey of English and Spanish-speaking pediatric oncology patients admitted for scheduled chemotherapy was conducted to assess CINV management, with key demographics used to understand association with perceptions and adherence to antiemetic guidelines. RESULTS: For providers, 75% of respondents felt CINV management could be moderately or extremely improved, significantly more so by chemotherapy prescribers and pediatric medical residents than nurses. Over half of respondents did not have awareness of CINV CPGs, particularly pediatric medical residents. For patients, nausea was reported to be extremely well controlled in 44% of cases, and vomiting extremely well controlled in 50% of cases. There were no significant differences in patient-reported CINV across demographics, when considering emetogenicity of chemotherapy received, or concordance to guidelines. CONCLUSIONS: Implementing education in this area may help to improve provider comfort, and ultimately, the patient experience. Future studies will expand upon this novel patient perception, and develop and evaluate CINV management interventions.

Biomass Separators as a "Lifesaver" for Safe and Long-Life Lithium Metal Batteries.

The growth of lithium dendrites and the shuttle of polysulfides in lithium metal batteries (LMBs) have hindered their development. In LMBs, the cathode and anode are separated by a separator, although this does not solve the battery's issues. The use of biomass materials is widespread for modifying the separator due to their porous structure and abundant functional groups. LMBs perform more electrochemically when lithium ions are deposited uniformly and polysulfide shuttling is reduced using biomass separators. In this review, we analyze the growth of lithium dendrite and the shuttle of polysulfide in LMBs, summarize the types of biomass separator materials and the mechanisms of action (providing mechanical barriers, promoting uniform deposition of metal ions, capturing polysulfides, shielding polysulfide). The prospect of developing new separator materials from the perspective of regulating ion transport and physical sieving efficiency as well as the application of advanced technologies such as synchrotron radiation to characterize the mechanism of action of biomass separators is also proposed.

Advances in Structure Pharmaceutics from Discovery to Evaluation and Design.

Drug delivery systems (DDSs) play an important role in delivering active pharmaceutical ingredients (APIs) to targeted sites with a predesigned release pattern. The chemical and biological properties of APIs and excipients have been extensively studied for their contribution to DDS quality and effectiveness; however, the structural characteristics of DDSs have not been adequately explored. Structure pharmaceutics involves the study of the structure of DDSs, especially the three-dimensional (3D) structures, and its interaction with the physiological and pathological structure of organisms, possibly influencing their release kinetics and targeting abilities. A systematic overview of the structures of a variety of dosage forms, such as tablets, granules, pellets, microspheres, powders, and nanoparticles, is presented. Moreover, the influence of structures on the release and targeting capability of DDSs has also been discussed, especially the in vitro and in vivo release correlation and the structure-based organ- and tumor-targeting capabilities of particles with different structures. Additionally, an in-depth discussion is provided regarding the application of structural strategies in the DDSs design and evaluation. Furthermore, some of the most frequently used characterization techniques in structure pharmaceutics are briefly described along with their potential future applications.

Carbon nitride/positive carbon black anchoring PtNPs assembled byγ-rays as ORR catalyst with excellent stability.

Electrocatalytic performance of low-cost graphitic carbon nitride (CN) is greatly limited by its limited conductivity and small specific surface area. Herein, a simple and cost-effective idea to produce novel nanocomposite is constructed by the CN and cetyl trimethyl ammonium bromide functionalized carbon black (CB) anchored platinum nanoparticles as highly efficient oxygen reduction catalysts based on gamma irradiation. The assembled carbon nitride/positive carbon black anchoring PtNPs (Pt/CN2-CB+1) catalyst exhibits significantly improved specific surface area, high graphitization, and uniformly dispersed ultra-small platinum nanoparticles. For the oxygen reduction reaction (ORR) performance, the catalyst shows more positive onset-potential (0.93 V versus RHE) and larger diffusion limiting current density (5.65 mA cm-2) compared with benchmark Pt/C catalysts in alkaline medium. Moreover, the Pt/CN2-CB+1catalyst exhibits a small Tafel slope (92 mV dec-1). Besides, the catalyst was demonstrated the remarkable methanol tolerance and good long-term stability under working conditions. This work provides a new and effectiveγ-rays irradiation for synthesizing the carbon nitride catalysts for energy conversion and storage applications.

Comprehensive characterization of TSV etching performance with phase-contrast X-ray microtomography.

Comprehensive evaluation of through-silicon via (TSV) reliability often requires deterministic and 3D descriptions of local morphological and statistical features of via formation with the Bosch process. Here, a highly sensitive phase-contrast X-ray microtomography approach is presented based on recorrection of abnormal projections, which provides comprehensive and quantitative characterization of TSV etching performance. The key idea is to replace the abnormal projections at specific angles in principles of linear interpolation of neighboring projections, and to distinguish the interface between silicon and air by using phase-retrieval algorithms. It is demonstrated that such a scheme achieves high accuracy in obtaining the etch profile based on the 3D microstructure of the vias, including diameter, bottom curvature radius, depth and sidewall angle. More importantly, the 3D profile error of the via sidewall and the consistency of parameters among all the vias are achieved and analyzed statistically. The datasets in the results and the 3D microstructure can be applied directly to a reference and model for further finite element analysis. This method is general and has potentially broad applications in 3D integrated circuits.

Quantitative toxicological study of dose-dependent arsenic-induced cells via synchrotron-based STXM and FTIR measurement.

Inorganic arsenic (iAs) is a well-known naturally occurring metalloid with abundant hazards to our environment, especially being a human carcinogen through arsenic-contaminated drinking water. The iAs-related contamination is usually examined by a chemical assay system or fluorescence staining technique to investigate iAs accumulation and its deleterious effects. In this work, we present a dual-modality measurement and quantitative analysis methods for the overall evaluation of various dose-dependent iAs-related cytotoxicological manifestations by the combination of the synchrotron-radiation-based scanning transmission soft X-ray microscopy (SR-STXM) and Fourier transform infrared micro-spectroscopy (SR-FTIR) techniques. The gray level co-occurrence matrix (GLCM) based machine learning was employed on SR-STXM data to quantify the cytomorphological feature changes and the dose-dependent iAs-induced feature classifications with increasing doses. The infrared spectral absorption peaks and changes of dose-dependent iAs-induced cells were obtained by the SR-FTIR technique and classified by the multi-spectral-variate principle component analysis (PCA-LDA) method, showing the separated spatial distribution of dose-dependent groups. In addition, the quantitative comparisons of trivalent and pentavalent iAs under high dose conditions (iAsIII_H & iAsV_H) demonstrated that iAsIII_H and its compounds were more toxic than iAsV_H. This method has a potential in providing the morphological and spectral characteristics evolution of the iAs-related cells or particles, revealing the actual risk of arsenic contamination and metabolism.

A robust method for high-precision quantification of the complex three-dimensional vasculatures acquired by X-ray microtomography.

The quantification of micro-vasculatures is important for the analysis of angiogenesis on which the detection of tumor growth or hepatic fibrosis depends. Synchrotron-based X-ray computed micro-tomography (SR-µCT) allows rapid acquisition of micro-vasculature images at micrometer-scale spatial resolution. Through skeletonization, the statistical features of the micro-vasculature can be extracted from the skeleton of the micro-vasculatures. Thinning is a widely used algorithm to produce the vascular skeleton in medical research. Existing three-dimensional thinning methods normally emphasize the preservation of topological structure rather than geometrical features in generating the skeleton of a volumetric object. This results in three problems and limits the accuracy of the quantitative results related to the geometrical structure of the vasculature. The problems include the excessively shortened length of elongated objects, eliminated branches of blood vessel tree structure, and numerous noisy spurious branches. The inaccuracy of the skeleton directly introduces errors in the quantitative analysis, especially on the parameters concerning the vascular length and the counts of vessel segments and branching points. In this paper, a robust method using a consolidated end-point constraint for thinning, which generates geometry-preserving skeletons in addition to maintaining the topology of the vasculature, is presented. The improved skeleton can be used to produce more accurate quantitative results. Experimental results from high-resolution SR-µCT images show that the end-point constraint produced by the proposed method can significantly improve the accuracy of the skeleton obtained using the existing ITK three-dimensional thinning filter. The produced skeleton has laid the groundwork for accurate quantification of the angiogenesis. This is critical for the early detection of tumors and assessing anti-angiogenesis treatments.

[In situ investigation to three dimensional structures of Chinese medicines seeds].

This paper is aimed to microscopic identification of traditional Chinese medicines (TCMs) using an in situ imaging method. In this study, two kinds of Zingiberaceae seeds, Amomi Rotundus Fructus and Alpiniae Katsumadai Semen, were investigated by synchrotron radiation in-line X-ray phase-contrast computed tomography (IXPCT) imaging method. The results showed that the microstructures of these Zingiberaceae seeds could be clearly obtained from the virtual slices information in different observing angles. It proves that IXPCT is an effective imaging method, which can provide the imaging information for the microscopic identification of the intact TCMs in situ and non-destructively.

Measurement of mass force field driving water refilling of cuttage.

Cuttage is a common plant cultivation method, and the key to its survival is the restoration of water refilling, which remains unclear up to now. We report 3D dynamic imaging of water refilling of cuttage without resorting to any contrast agent. Hydrodynamics of the refilled water flow over time reveals the existence of a unit mass force field with a gradient along the refilling direction, which means that cutting plants also have a gradient force field to drive the recovery of water refilling, as predicted by Cohesion-Tension theory in normal plants. We found that force fields of different functional regions are isolated and independently distributed, which is conducive to ensure the safety of water transmission. At the same time, we also found that there is a so-called "inchworm effect" in the mass force field, which contributes to the force transfer inside the cutting through local force accumulation. Results of this paper demonstrate that the developed method for the measurement of mass force field in-vivo is applicable to help decipher the mechanism of plant water refilling.

The role of internal defects on anisotropic tensile failure of L-PBF AlSi10Mg alloys.

This paper investigates the effects of defects on tensile failure of additive manufactured AlSi10Mg alloy focusing particularly on the role of large pancake shaped loss of fusion (LOF) defects lying perpendicular to the build direction (BD). Time-lapse in situ synchrotron radiation X-ray micro-computed tomography during straining reveals how, when tested parallel to the BD, the LOF defects extend laterally with straining connecting to other defects and giving rise to low plasticity and an essentially brittle failure mode. When they are aligned edge-on to the straining direction, failure is characterised by a ductile cup-cone failure with significant elongation of the defects axially and extensive necking prior to failure. The soft fish-scale melt pool boundaries were also found to affect the fracture path. These results highlight the anisotropic effect of loss of fusion defects in controlling tensile ductility and the need to minimize their size and aspect ratio. In cases where these cannot be fully eliminated the component should be fabricated such that the BD is not aligned with the dominant in-service loading direction.

Phase retrieval for hard X-ray computed tomography of samples with hybrid compositions.

X-ray tomography of samples containing both weakly and strongly absorbing materials are necessary in material and biomedical imaging. Extending the validity of the phase-attenuation duality (PAD) method, the propagation-based phase-contrast computed tomography (PPCT) of a sample with hybrid compositions of both the light and dense components with 60 keV of synchrotron radiation is investigated. The experimental results show that the PAD-based PPCT is effective in imaging both the weakly and strongly absorbing components simultaneously. Compared with the direct PPCT technique, the PAD-based PPCT technique demonstrates its excellent capability in material discrimination and characterization. In addition, the PAD-based PPCT exhibits a striking performance on the image contrast enhancement and noise suppression. Therefore, this technique is useful for material and biomedical imaging applications, especially when the radiation dose involved imposes a serious constraint.

A Biomimetic Composite Bilayer Dressing Composed of Alginate and Fibroin for Enhancing Full-Thickness Wound Healing.

Full-thickness skin wound dressings are critically important for acute cutaneous wound healing. In this study, a bilayer sheet originating from biological macromolecules, mimicking skin hierarchy structure is developed. This sheet is composed of a steady silk fibroin (SF)/sodium alginate (SA) composite scaffold as the bottom regenerative layer and a SA film as the protective top layer. Scanning electron microscope analysis revealed the thickness of the top layer is ≈25 µm and is tightly adhered to the composite scaffold layer with interconnected pores (≈150 µm). The bilayer sheets are displayed suitable water uptake capacity and high stability in water. The mass retention percentage of the bilayer sheets is ≈50% during three weeks of PBS degradation in vitro. The tensile strength of the bilayer sheets is significantly increased from 13.41 ± 3.75 kPa (single scaffold) to 59.81 ± 5.98 kPa. The composite scaffolds are more conducive to the growth and proliferation of human dermal microvascular endothelial cells. The experiment results in vivo are demonstrated superior and faster epithelialization and dermal regeneration in the wound treated with bilayer sheets because the sheets are accelerated wound closure, reduced the inflammatory response, and promoted protein synthesis in the extracellular matrix and blood vessel ingrowth.

Tissue- and cell-expression of druggable host proteins provide insights into repurposing drugs for COVID-19.

Several human host proteins play important roles in the lifecycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many drugs targeting these host proteins have been investigated as potential therapeutics for coronavirus disease 2019 (COVID-19). The tissue-specific expressions of selected host proteins were summarized using proteomics data retrieved from the Human Protein Atlas, ProteomicsDB, Human Proteome Map databases, and a clinical COVID-19 study. Protein expression features in different cell lines were summarized based on recent proteomics studies. The half-maximal effective concentration or half-maximal inhibitory concentration values were collected from in vitro studies. The pharmacokinetic data were mainly from studies in healthy subjects or non-COVID-19 patients. Considerable tissue-specific expression patterns were observed for several host proteins. ACE2 expression in the lungs was significantly lower than in many other tissues (e.g., the kidneys and intestines); TMPRSS2 expression in the lungs was significantly lower than in other tissues (e.g., the prostate and intestines). The expression levels of endocytosis-associated proteins CTSL, CLTC, NPC1, and PIKfyve in the lungs were comparable to or higher than most other tissues. TMPRSS2 expression was markedly different between cell lines, which could be associated with the cell-dependent antiviral activities of several drugs. Drug delivery receptor ICAM1 and CTSB were expressed at a higher level in the lungs than in other tissues. In conclusion, the cell- and tissue-specific proteomics data could help interpret the in vitro antiviral activities of host-directed drugs in various cells and aid the transition of the in vitro findings to clinical research to develop safe and effective therapeutics for COVID-19.

Construction of MoS2/Mxene heterostructure on stress-modulated kapok fiber for high-rate sodium-ion batteries.

Molybdenum disulfide (MoS2) has possession of a layered structure and high theoretical capacity, which is a candidate anode material for sodium ion batteries. However, unmodified MoS2 are inflicted with a poor cycling stability and an inferior rate capability upon charge/discharge processes. Considering that the shape and size of anode materials play a key role in the performance of anode materials, this paper proposes a multi-level composite structure formed by the micro-nano materials based on self-assembled molybdenum disulfide (MoS2) nanoflowers, Mxene and hollow carbonized kapok fiber (CKF). The micro-nano materials can be connected to form heterojunction and agglomeration can be avoided. The load bearing of heterostructure and stress release of CKF are coordinated to form a double protection mechanism, which improves the conductivity and structural stability of hybrid materials. Based on the above advantages, it has higher specific capacity than pure MoS2, and has better rate performance (639.3, 409.5, 386.2, 372, 338, 422.8 and 434.7 mAh g-1 at the current density of 0.05, 0.1, 0.2, 0.5, 1 ,0.1 and 0.05 A·g-1, respectively). The stress-modulated strategies can provide new insights for the design and construction of transition metal sulfides heterostructures to achieve high performance sodium ion batteries.

Tissue-Specific Proteomics Analysis of Anti-COVID-19 Nucleoside and Nucleotide Prodrug-Activating Enzymes Provides Insights into the Optimization of Prodrug Design and Pharmacotherapy Strategy.

Nucleoside and nucleotide analogs are an essential class of antivirals for COVID-19 treatment. Several nucleoside/nucleotide analogs have shown promising effects against SARS-CoV-2 in vitro; however, their in vivo efficacy is limited. Nucleoside/nucleotide analogs are often formed as ester prodrugs to improve pharmacokinetics (PK) performance. After entering cells, the prodrugs undergo several enzymatic metabolism steps to form the active metabolite triphosphate nucleoside (TP-Nuc); prodrug activation is therefore associated with the abundance and catalytic activity of the corresponding activating enzymes. Having the activation of nucleoside/nucleotide prodrugs occur at the target site of action, such as the lung, is critical for anti-SARS-CoV-2 efficacy. Herein, we conducted an absolute quantitative proteomics study to determine the expression of relevant activating enzymes in human organs related to the PK and antiviral efficacy of nucleoside/nucleotide prodrugs, including the lung, liver, intestine, and kidney. The protein levels of prodrug-activating enzymes differed significantly among the tissues. Using catalytic activity values reported previously for individual enzymes, we calculated prodrug activation profiles in these tissues. The prodrugs evaluated in this study include nine McGuigan phosphoramidate prodrugs, two cyclic monophosphate prodrugs, two l-valyl ester prodrugs, and one octanoate prodrug. Our analysis showed that most orally administered nucleoside/nucleotide prodrugs were primarily activated in the liver, suggesting that parenteral delivery routes such as inhalation and intravenous infusion could be better options when these antiviral prodrugs are used to treat COVID-19. The results also indicated that the l-valyl ester prodrug design can plausibly improve drug bioavailability and enhance effects against SARS-CoV-2 intestinal infections. This study further revealed that an octanoate prodrug could provide a long-acting antiviral effect targeting SARS-CoV-2 infections in the lung. Finally, our molecular docking analysis suggested several prodrug forms of favipiravir and GS-441524 that are likely to exhibit favorable PK features over existing prodrug forms. In sum, this study revealed the activation mechanisms of various nucleoside/nucleotide prodrugs relevant to COVID-19 treatment in different organs and shed light on the development of more effective anti-COVID-19 prodrugs.

The Neural Correlates of Effortful Cognitive Processing Deficits in Schizophrenia: An ERP Study.

Background: Individuals' information processing includes automatic and effortful processes and the latter require sustained concentration or attention and larger amounts of cognitive "capacity." Event-related potentials (ERPs) reflect all neural activities that are related to a certain stimulus. Investigating ERP characteristics of effortful cognitive processing in people with schizophrenia would be helpful in further understanding the neural mechanism of schizophrenia. Methods: Both schizophrenia patients (SCZ, n = 33) and health controls (HC, n = 33) completed ERP measurements during the performance of the basic facial emotion identification test (BFEIT) and the face-vignette task (FVT). Data of ERP components (N100, P200, and N250), BFEIT and FVT performances were analyzed. Results: Schizophrenia patients' accuracies of face emotion detection in the BFEIT and vignette emotion detection in the FVT were both significantly worse than the performance of the HC group. Repeated-measures ANOVAs performed on mean amplitudes and latencies revealed that the interaction effect for group × experiment × site (prefrontal, frontal, central, parietal, and occipital site) was significant for N250 amplitude. In FVT experiment, N250 amplitudes at prefrontal and frontal sites in schizophrenia group were larger than those of HC group; the maximum N250 amplitude was present at the prefrontal site in both the groups. For N250 latency, the interaction effect for group × experiment was significant; N250 latencies in the schizophrenia group were longer than those of the HC group. Conclusion: Schizophrenia patients present effortful cognitive processing dysfunctions which reflect in abnormal ERP components, especially N250 at prefrontal cortex and frontal cortex sites. These findings have important implications for further clarifying the neural mechanism of effortful cognitive processing deficits in schizophrenia.

"Self-doping" defect engineering in SnP3@gamma-irradiated hard carbon anode for rechargeable sodium storage.

Reasonable design of defect engineering in the electrode materials for sodium-ion batteries (SIBs) can significantly optimize battery performance. Here, compared with the traditional "foreign-doping" defects method, we report an innovative gamma-irradiation technique to introduce the "self-doping" defects in the popcorn hard carbon (HC). Considering the advantages of adsorption-intercalation-alloying sodium storage mechanism, the defect-rich HC-coated alloy structure (SnP3@HC-γ) was integrated. Due to the high energy and strong penetrability of γ-rays, the constructed "self-doping" defect engineering effectively expands the interlayer structure of HC and forms the irregular ring structure. Simultaneously, the exposed large number of coordination unsaturated sites can accelerate the reaction kinetics on the surface. Based on the synergistic effect of the SnP3@HC-γ, the composites exhibit an excellent reversible capacity of 668 mAh g-1 at 0.1 A g-1 in SIBs. Even, after 400 cycles at 1.0 A g-1, an exceptional cyclability with 88% capacity retention (430 mAh g-1) can be maintained. We envision that the γ-irradiation technology used in this research not only overturns the general perception that "self-doping" defects will reduce performance, but also provides reliable technical support for large-scale construction of high-defect, high-capacity and stable sodium-ion anode materials.

Micro-morphological feature visualization, auto-classification, and evolution quantitative analysis of tumors by using SR-PCT.

Tissue micro-morphological abnormalities and interrelated quantitative data can provide immediate evidences for tumorigenesis and metastasis in microenvironment. However, the multiscale three-dimensional nondestructive pathological visualization, measurement, and quantitative analysis are still a challenging for the medical imaging and diagnosis. In this work, we employed the synchrotron-based X-ray phase-contrast tomography (SR-PCT) combined with phase-and-attenuation duality phase retrieval to reconstruct and extract the volumetric inner-structural characteristics of tumors in digesting system, helpful for tumor typing and statistic calculation of different tumor specimens. On the basis of the feature set including eight types of tumor micro-lesions presented by our SR-PCT reconstruction with high density resolution, the AlexNet-based deep convolutional neural network model was trained and obtained the 94.21% of average accuracy of auto-classification for the eight types of tumors in digesting system. The micro-pathomophological relationship of liver tumor angiogenesis and progression were revealed by quantitatively analyzing the microscopic changes of texture and grayscale features screened by a machine learning method of area under curve and principal component analysis. The results showed the specific path and clinical manifestations of tumor evolution and indicated that these progressions of tumor lesions rely on its inflammation microenvironment. Hence, this high phase-contrast 3D pathological characteristics and automatic analysis methods exhibited excellent recognizable and classifiable for micro tumor lesions.