Interaction domains of Sos1/Grb2 are finely tuned for cooperative control of embryonic stem cell fate.

Metazoan evolution involves increasing protein domain complexity, but how this relates to control of biological decisions remains uncertain. The Ras guanine nucleotide exchange factor (RasGEF) Sos1 and its adaptor Grb2 are multidomain proteins that couple fibroblast growth factor (FGF) signaling to activation of the Ras-Erk pathway during mammalian development and drive embryonic stem cells toward the primitive endoderm (PrE) lineage. We show that the ability of Sos1/Grb2 to appropriately regulate pluripotency and differentiation factors and to initiate PrE development requires collective binding of multiple Sos1/Grb2 domains to their protein and phospholipid ligands. This provides a cooperative system that only allows lineage commitment when all ligand-binding domains are occupied. Furthermore, our results indicate that the interaction domains of Sos1 and Grb2 have evolved so as to bind ligands not with maximal strength but with specificities and affinities that maintain cooperativity. This optimized system ensures that PrE lineage commitment occurs in a timely and selective manner during embryogenesis.

Binder-Free MOF-Based and MOF-Derived Nanoarrays for Flexible Electrochemical Energy Storage: Progress and Perspectives.

The fast development of Internet of Things and the rapid advent of next-generation versatile wearable electronics require cost-effective and highly-efficient electroactive materials for flexible electrochemical energy storage devices. Among various electroactive materials, binder-free nanostructured arrays have attracted widespread attention. Featured with growing on a conductive and flexible substrate without using inactive and insulating binders, binder-free 3D nanoarray electrodes facilitate fast electron/ion transportation and rapid reaction kinetics with more exposed active sites, maintain structure integrity of electrodes even under bending or twisted conditions, readily release generated joule heat during charge/discharge cycles and achieve enhanced gravimetric capacity of the whole device. Binder-free metal-organic framework (MOF) nanoarrays and/or MOF-derived nanoarrays with high surface area and unique porous structure have emerged with great potential in energy storage field and been extensively exploited in recent years. In this review, common substrates used for binder-free nanoarrays are compared and discussed. Various MOF-based and MOF-derived nanoarrays, including metal oxides, sulfides, selenides, nitrides, phosphides and nitrogen-doped carbons, are surveyed and their electrochemical performance along with their applications in flexible energy storage are analyzed and overviewed. In addition, key technical issues and outlooks on future development of MOF-based and MOF-derived nanoarrays toward flexible energy storage are also offered.

KLHDC7B as a novel diagnostic biomarker in urine exosomal mRNA promotes bladder urothelial carcinoma cell proliferation and migration, inhibits apoptosis.

Bladder cancer is a common kind of urinary system cancer, in which bladder urothelial carcinoma (BLCA) comprises approximately 90% of all bladder cancer types. In our previous study, we discovered KLHDC7B in urine exosomal messenger RNA (mRNA) as a prospective molecular marker for bladder cancer detection. To systematically study the role and mechanism of KLHDC7B in BLCA, we focused on the most common type of BLCA in this study. First, we used RNA sequencing to discover that KLHDC7B was considerably increased in BLCA patients' urine exosomes compared to healthy controls. Then, we validated this result in an independent cohort and identified it as an effective tool for diagnosing and distinguishing high-grade and low-grade BLCA. Finally, we studied the role and mechanism of KLHDC7B in BLCA at the cellular level, providing a functional basis for its expression as a novel laboratory diagnostic biomarker for BLCA exosomal mRNA, which has important theoretical and clinical significance.

A machine learning model for identifying systemic lupus erythematosus through laboratory information system and electronic medical record.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Its diagnosis poses significant challenges especially at early stages and in atypical cases. The aim of this study was to develop a machine learning model based on common laboratory tests that can aid SLE diagnosis. METHODS: A standard protocol was developed to collect data of SLE and control immune diseases. A 10-fold cross-validation was performed in the modeling dataset (n=862), and an external dataset (n=198) was used for model validation. Machine learning algorithms were applied to construct a diagnostic model. Performance was evaluated based on area under the curve (AUC) values, F1-score, negative predictive value, positive predictive value, accuracy, sensitivity, and specificity. RESULTS: The optimal model was based on a random forest algorithm with 10 clinical features. Thrombin time, prothrombin activity, and uric acid contributed most to the diagnostic model. The SLE diagnostic model showed sufficient predictive accuracy, with AUC values of 0.8286 in the validation dataset. CONCLUSIONS: Our diagnostic model based on 10 common laboratory tests identified the patients with SLE with high accuracy. An online version of the model can potentially be applied in clinical settings for the differential diagnosis of SLE.

Ca-Mg modified attapulgite for phosphate removal and its potential as phosphate-based fertilizer.

The urgent concerns of controlling water body eutrophication and the alleviating phosphorus shortage have led to an urgent need for action. The removal of phosphate from polluted waters and its reuse are essential for the prevention of eutrophication and for the sustainable utilization of phosphate resources. In this study, modified attapulgite with different Ca:Mg molar ratios was synthesized to facilitate the recovery of phosphate, with subsequent use of soil fertilizer. Ca-Mg modified attapulgite with the optimal ratio (ACM-5:3) exhibited an exceptional adsorption quality, achieving a maximum adsorption capacity of 63.2 mg/g. The pseudo-second-order model and Langmuir model could well describe the adsorption kinetics and isotherms, respectively. The adsorption mechanism analyses suggested that the interaction between ACM-5:3 and phosphate depended mainly on ion exchange and electrostatic attraction. Moreover, phosphate-laden-ACM-5:3 demonstrated a significant potential as a phosphorus-releasing fertilizer. It could promote corn growth by ensuring a continuous supply of phosphorus and minimizing phosphorus runoff losses. The above results suggested that ACM-5:3 was a potential adsorbent for efficient phosphate removal and recovery.

Polarization-resolved and helicity-resolved Raman spectra of monolayer XP3 (X = Ge and In).

Monolayer XP3 (X = Ge, In) is a theoretically predicted two-dimensional (2D) material with fascinating adsorption efficiency, foreshadowing its potential applications in the photovoltaic and optoelectronic communities. To achieve a comprehensive understanding of its optical properties and to further boost quickly identifying its specific applications, in this paper we systematically investigated the polarization-resolved and helicity-resolved Raman spectra excited by two commonly used laser lines (532 nm and 633 nm) through density functional theory. The dynamical stability of monolayer XP3 is demonstrated by phonon dispersion. Monolayer GeP3 and InP3 are found to exhibit significantly different point group symmetries and thereby Raman properties due to the big difference in atomic size and electronic configurations between the Ge atom and In atom. Raman anisotropy of monolayer XP3 has been found when the wave vector of linear polarized incident light is parallel to the monolayer, and all the anisotropic Raman active phonons are categorized in terms of the locations of two (four) maxima in polarization angle dependent Raman intensities of the parallel (perpendicular) configuration. The polarization direction averaged Raman spectra have been further discussed according to the characteristics of light absorbance. The calculations of helicity-resolved Raman spectra indicate a stronger helicity selection rule under helical excitation with the wave vector normal to the monolayer. The present work paves the way for the suitable design, characterization and exploitation of the proposed 2D material with controllable surface properties for applications in electronics and optoelectronics.

Designing novel monolayer and multilayer h-CSe crystals with tunable photoelectric properties.

Using the first-principles method, a new structure of monolayer h-CSe was predicted, exhibiting good dynamical and thermal stability. The geometrical, electronic and optical properties of monolayer h-CSe are examined at the HSE level. Furthermore, the influences of the in-plane strain and layer number on the electric properties of the two dimensional h-CSe material are studied. The results indicate that it possesses an indirect band gap, which exhibits a rich variety of behaviors depending on the small in-plane biaxial strain. The band gap of monolayer h-CSe could be easily tuned in the energy range from 0.82 eV to 2.61 eV under small in-plane biaxial strain (from -3% to 3%). Also, a band gap transition between direct and indirect types is not found. The band gap of the h-CSe materials decreases with the increase of their layer number. In addition, it was found that these h-CSe materials show excellent optical properties, including strong light harvesting ability for the ultra-violet light range of the solar spectrum. The results obtained here indicate that monolayer h-CSe may have significant potential applications in future nanoelectronic fields.

Porous Carbon with Alumina Coating Nanolayer Derived from Biomass and the Enhanced Electrochemical Performance as Stable Anode Materials.

With the ever-increasing world population, the energy produced from green, environmentally friendly approaches is in high demand. In this work, we proposed a green and cost-effective strategy for synthesizing a porous carbon electrode decorated with alumina oxide (Al2O3) from cherry blossom leaves using the pyrolysis method followed by a sol-gel method. An Al2O3-coating nano-layer (4-6 nm) is formed on the porous carbon during the composition fabrication, which further adversely affects battery performance. The development of a simple rich-shell-structured C@Al2O3 nanocomposite anode is expected to achieve stable electrochemical performances as lithium storage. A significant contributing factor to enhanced performance is the structure of the rich-shell material, which greatly enhances conductivity and stabilizes the solid-electrolyte interface (SEI) film. In the battery test assembled with composite C@Al2O3 electrode, the specific capacity is 516.1 mAh g-1 at a current density of 0.1 A g-1 after 200 cycles. The average discharge capacity of carbon is 290 mAh g-1 at a current density of 1.0 A g-1. The present study proposes bioinspired porous carbon electrode materials for improving the performance of next-generation lithium-ion batteries.

Semantic Representation of Robot Manipulation with Knowledge Graph.

Autonomous indoor service robots are affected by multiple factors when they are directly involved in manipulation tasks in daily life, such as scenes, objects, and actions. It is of self-evident importance to properly parse these factors and interpret intentions according to human cognition and semantics. In this study, the design of a semantic representation framework based on a knowledge graph is presented, including (1) a multi-layer knowledge-representation model, (2) a multi-module knowledge-representation system, and (3) a method to extract manipulation knowledge from multiple sources of information. Moreover, with the aim of generating semantic representations of entities and relations in the knowledge base, a knowledge-graph-embedding method based on graph convolutional neural networks is proposed in order to provide high-precision predictions of factors in manipulation tasks. Through the prediction of action sequences via this embedding method, robots in real-world environments can be effectively guided by the knowledge framework to complete task planning and object-oriented transfer.

A potent synthetic nanobody with broad-spectrum activity neutralizes SARS-CoV-2 virus and the Omicron variant BA.1 through a unique binding mode.

The major challenge to controlling the COVID pandemic is the rapid mutation rate of the SARS-CoV-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-CoV-2 variants. Here, we report a synthetic nanobody (named C5G2) obtained by phage display and subsequent antibody engineering. C5G2 has a single-digit nanomolar binding affinity to the RBD domain and inhibits its binding to ACE2 with an IC50 of 3.7 nM. Pseudovirus assays indicated that monovalent C5G2 could protect the cells from infection with SARS-CoV-2 wild-type virus and most of the viruses of concern, i.e., Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against Omicron BA.1 among all the variants, with an IC50 of 4.9 ng/mL. The cryo-EM structure of C5G2 in complex with the spike trimer showed that C5G2 binds to RBD mainly through its CDR3 at a conserved region that does not overlap with the ACE2 binding surface. Additionally, C5G2 binds simultaneously to the neighboring NTD domain of the spike trimer through the same CDR3 loop, which may further increase its potency against viral infection. Third, the steric hindrance caused by FR2 of C5G2 could inhibit the binding of ACE2 to RBD as well. Thus, this triple-function nanobody may serve as an effective drug for prophylaxis and therapy against Omicron as well as future variants.

Theoretical assessment of Raman spectra on MXene Ti2C: from monolayer to bilayer.

The structural, vibrational and Raman spectra properties of monolayer and bilayer Ti2C excited by two commonly used laser lines (532 nm and 633 nm) are investigated by first principles calculations to establish a correlation among layer stacks and optical features for two-dimensional MXenes. The stability of the monolayer and the energetically preferable stacking configuration are demonstrated by phonon dispersion. The monolayer and bilayer Ti2C systems are found to exhibit different point group symmetries and thereby the Raman properties due to the symmetry breaking of the bilayer structure caused by interlayer van der Waals interactions. We listed all Raman-active modes for monolayer (bilayer) Ti2C, i.e., one (five) out-of-plane A1g (A1) and one (five) pair (pairs) of degenerate in-plane Eg (E) vibration modes. Polarization angle dependent Raman intensity has been discussed in terms of the locations of two (four) maxima in the parallel (perpendicular) configuration, which might be applied in experimentally identifying monolayer and bilayer Ti2C. The difference in the polarization direction averaged Raman spectra between monolayer and bilayer Ti2C can be explained by the characteristics of light absorbance.

Crk1/2 and CrkL play critical roles in maintaining podocyte morphology and function.

Podocytes are actin-rich epithelial cells whose effacement and detachment are the main cause of glomerular disease. Crk family proteins: Crk1/2 and CrkL are reported to be important intracellular signaling proteins that are involved in many biological processes. However, the roles of them in maintaining podocyte morphology and function remain poorly understood. In this study, specific knocking down of Crk1/2 and CrkL in podocytes caused abnormal cell morphology, actin cytoskeleton rearrangement and dysfunction in cell adhesion, spreading, migration, and viability. The p130Cas, focal adhesion kinase, phosphatidylinositol 3-kinase/Akt, p38 and JNK signaling pathways involved in these alterations. Furthermore, knocking down CrkL alone conferred a more modest phenotype than did the Crk1/2 knockdown and the double knockdown. Kidney biopsy specimens from patients with focal segmental glomerulosclerosis and minimal change nephropathy showed downregulation of Crk1/2 and CrkL in glomeruli. In zebrafish embryos, Crk1/2 and CrkL knockdown compromised the morphology and caused abnormal glomerular development. Thus, our results suggest that Crk1/2 and CrkL expression are important in podocytes; loss of either will cause podocyte dysfunction, leading to foot process effacement and podocyte detachment.

Surface Loops in a Single SH2 Domain Are Capable of Encoding the Spectrum of Specificity of the SH2 Family.

Src homology 2 (SH2) domains play an essential role in cellular signal transduction by binding to proteins phosphorylated on Tyr residue. Although Tyr phosphorylation (pY) is a prerequisite for binding for essentially all SH2 domains characterized to date, different SH2 domains prefer specific sequence motifs C-terminal to the pY residue. Because all SH2 domains adopt the same structural fold, it is not well understood how different SH2 domains have acquired the ability to recognize distinct sequence motifs. We have shown previously that the EF and BG loops that connect the secondary structure elements on an SH2 domain dictate its specificity. In this study, we investigated if these surface loops could be engineered to encode diverse specificities. By characterizing a group of SH2 variants selected by different pY peptides from phage-displayed libraries, we show that the EF and BG loops of the Fyn SH2 domain can encode a wide spectrum of specificities, including all three major specificity classes (p + 2, p + 3 and p + 4) of the SH2 domain family. Furthermore, we found that the specificity of a given variant correlates with the sequence feature of the bait peptide used for its isolation, suggesting that an SH2 domain may acquire specificity by co-evolving with its ligand. Intriguingly, we found that the SH2 variants can employ a variety of different mechanisms to confer the same specificity, suggesting the EF and BG loops are highly flexible and adaptable. Our work provides a plausible mechanism for the SH2 domain to acquire the wide spectrum of specificity observed in nature through loop variation with minimal disturbance to the SH2 fold. It is likely that similar mechanisms may have been employed by other modular interaction domains to generate diversity in specificity.

Ammonia nitrogen removal from coking wastewater and high quality gypsum recovery by struvite recycling by using calcium hydroxide as decomposer.

This study deals with the highly significant and cost-effective pretreatment of the high concentration of the Total Ammonia Nitrogen (TAN) in coking wastewater to improve the biodegradability. Struvite crystallization is a promising process for TAN removal, but the high operating cost hinders its application. To solve this problem, a novel struvite recycling process was proposed for pre-treating TAN present in the coking wastewater, within which struvite was decomposed in the solid-liquid system using Ca(OH)2 as the decomposer. The results indicates that 91% of ammonium in struvite could be stripped out from the decomposition solution, with Ca(OH)2:NH4+ in the molar ratio of 2:1, temperature at 35 °C and a gas to liquid volume ratio of 3500. The resulting solution, post the escape of the ammonia, was dissolved by sulfuric acid. Approximately 100% of the phosphate and magnesium were observed to be released from the insoluble phosphate compounds, resulting in the formation of high-purity gypsum. A TAN removal efficiency of 89% could be achieved by reusing the supernatant after the dissolution of the decomposition product, at pH 9.5 and the Mg:TAN:PO4-P molar ratio of 1.2:1:1. The pilot-scale test demonstrated that approximately 86% TAN was removed from the coking wastewater and the purity of recovered could reach over 99%. Further economic analysis proves that the operation cost of the proposed process is 0.55$ per m3 of coking wastewater, showing a 73% cost reduction when compared to struvite crystallization without recycling.

Structural basis for arginine methylation-independent recognition of PIWIL1 by TDRD2.

The P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway plays a central role in transposon silencing and genome protection in the animal germline. A family of Tudor domain proteins regulates the piRNA pathway through direct Tudor domain-PIWI interactions. Tudor domains are known to fulfill this function by binding to methylated PIWI proteins in an arginine methylation-dependent manner. Here, we report a mechanism of methylation-independent Tudor domain-PIWI interaction. Unlike most other Tudor domains, the extended Tudor domain of mammalian Tudor domain-containing protein 2 (TDRD2) preferentially recognizes an unmethylated arginine-rich sequence from PIWI-like protein 1 (PIWIL1). Structural studies reveal an unexpected Tudor domain-binding mode for the PIWIL1 sequence in which the interface of Tudor and staphylococcal nuclease domains is primarily responsible for PIWIL1 peptide recognition. Mutations disrupting the TDRD2-PIWIL1 interaction compromise piRNA maturation via 3'-end trimming in vitro. Our work presented here reveals the molecular divergence of the interactions between different Tudor domain proteins and PIWI proteins.

Persulfate oxidation for alternative sludge treatment and nutrient recovery: An assessment of technical and economic feasibility.

The introduce of tighter waste disposal regulations and increasing resource scarcity make the re-utilization of waste activated sludge a hot and crucial research topic. Compared with traditional sludge disposal technologies (e.g. landfill and incineration), advanced oxidation processes have been proven to be an environmentally friendly method for sludge stabilization and disintegration. However, the effectiveness of persulfate oxidation for sludge degradation, and the re-utilization of its embedded nutrients have been rarely reported. Therefore, this work is to investigate the technical and economic feasibility of using persulfate oxidation and struvite precipitation for sludge degradation and nutrient recovery. The results show that with the assistance of ultraviolet radiation, released phosphate and ammonia nitrogen from sludge could reach 233.4 and 265.6 mg/L. Besides, 92.8% phosphate and 32.6% ammonia-nitrogen could be recovered by struvite precipitation at a pH of 9.5, with an Mg: P molar ratio of 1.1:1. The economic analysis shows that the operational cost of the proposed process was 25% higher than traditional sludge disposal (267.5 $/ton), but its capital investment is much lower. Investigations on chemical dosage minimization, energy reclamation and process optimization are suggested to reduce the process's operating cost in the future.

Theoretical assessment of wettability on silane coatings: from hydrophilic to hydrophobic.

The potential distribution and work function of a graphene surface modified by various types of silanes are investigated by first principles quantum mechanical calculations to establish its surface hydrophobicity hierarchy. It is found that the work function relies on the electronegativity of atoms on silane. The localization feature of interaction between silane and the graphene surface is demonstrated by the electron density difference. The work function is demonstrated to be a critical quantity in understanding the surface polarizability and thereby the surface wetting properties. By performing contact angle measurements experimentally using water as the probe fluid, surfaces grafted with different silanes show hydrophobicity variation that is found to follow the reverse trend to that of the proposed surface polarizability obtained through the work function calculation. The work function-dependent contact angle can be fitted with a linear equation.

Exchange-dependent spin polarized transport and phase transition in a triple monomer molecule.

Molecular junctions contribute significantly to the fundamental understanding of the quantum information technologies in molecular spintronics. In this paper, with the aid of the state of the art numerical renormalization group method, we find a triple monomer molecule structure with strong electron-electron interactions could be a potential candidate for a multifunctional spin polarizer when an external magnetic field along the z axis is applied. It is demonstrated that the polarizing scenarios depend closely on the inter-orbital exchange couplings, and results in several kinds of spin polarizers, e.g., the unidirectional, the bidirectional, the dual, and the ternary spin polarizers. We show in detail the related phase diagram, and conclude the Zeeman effect and the charge switching for the bonding, anti-bonding and non-bonding orbitals are responsible for the spin polarizing transport. We stress even when the energy levels are chosen beyond the Kondo regime, the structure still shows a promising platform for molecular spintronics components.

Emergent electronically-controllable local-field-inducer based on a molecular break-junction with magnetic radical.

Molecular spintronics devices are receiving extensive research attention, due to their potential applications as the smallest memory and logic elements. A most fundamental issue in this field lies in generating spin polarized currents. In this communication, with the aid of the celebrated Wilson's numerical renormalization group (NRG) method, we propose theoretically a novel strategy to induce a local magnetic field that only affects the strongly correlated molecule under consideration, and could easily be manipulated through purely electronic technologies. It is also demonstrated that the device may lead to bidirectional spin polarization, where perfectly polarized spin-up and -down currents could be obtained by simply adjusting the energy level of the molecule to different regions along a single direction. Our suggested model is based on a molecular break-junction with a magnetic radical. It may provide a prospective example of a magnetoelectronics device at the molecular scale, which works without an external magnetic field.

High spin polarization in formamidinium transition metal iodides: first principles prediction of novel half-metals and spin gapless semiconductors.

The electronic structure and magnetic properties of ten formamidinium transition metal iodides in the ground state and under strain have been studied. These formamidinium transition metal iodides have a stable cubic perovskite structure. In the ground state, FAVI3 is a spin gapless semiconductor, and FAScI3, FATiI3, FACrI3, FAFeI3, FACoI3 and FANiI3 are ferromagnetic half-metals. They all have 100% spin polarization and integer total magnetic moment. Under the action of strain, the high spin polarization of some formamidinium transition metal iodides can still be well maintained, and several novel spin gapless semiconductors such as FATiI3, FAFeI3 and FACoI3 have been discovered. Magnetic studies show that these formamidinium transition metal iodides with half-metal, semiconductor and spin-gapless semiconductor properties have integral total magnetic moments under strain ranging from -10.0% to 10.0%. These newly discovered half-metallic ferromagnetic materials and spin gapless semiconductors have broad application prospects in the field of spintronics due to their high spin polarization.