AKT Degradation Selectively Inhibits the Growth of PI3K/PTEN Pathway-Mutant Cancers with Wild-Type KRAS and BRAF by Destabilizing Aurora Kinase B.

Unlabelled: Using a panel of cancer cell lines, we characterized a novel degrader of AKT, MS21. In mutant PI3K-PTEN pathway cell lines, AKT degradation was superior to AKT kinase inhibition for reducing cell growth and sustaining lower signaling over many days. AKT degradation, but not kinase inhibition, profoundly lowered Aurora kinase B (AURKB) protein, which is known to be essential for cell division, and induced G2-M arrest and hyperploidy.

Post-infection cognitive impairments in a cohort of elderly patients with COVID-19.

Background: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19.

Methods: This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020.

Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk.

Background: Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult.

A T-shaped gate tunneling field effect transistor with negative capacitance, super-steep subthreshold swing.

With the development of semiconductor technology, the size of traditional metal oxide semiconductor field effect transistor devices continues to decrease, but it cannot meet the requirements of high performance and low power consumption. Low power tunneling field effect transistor (TFET) has gradually become the focus of researchers. This paper proposes a novel T-shaped gate TFET based on the silicon with the negative capacitance (NC-TGTFET).

Silica-confined Ru highly dispersed on ZrO with enhanced activity and thermal stability in dichloroethane combustion.

An efficient strategy (spontaneous deposition to enhance noble metal dispersity and core-shell confinement to inhibit noble metal sintering) is presented to synthesize highly active and thermally stable Ru/ZrO2@SiO2 catalysts for dichloroethane combustion.

Combination of Anti-EGFR and Anti-VEGF Drugs for the Treatment of Previously Treated Metastatic Colorectal Cancer: A Case Report and Literature Review.

The standard third-line treatment of metastatic colorectal cancer (mCRC) includes the small-molecule anti-vascular drugs (Regofenib and Fruquintinib) and the chemotherapy drug trifluridine and tipiracil hydrochloride (TAS-102). There is no standard treatment for mCRC if the third-line treatment failed. Therefore, it is a pressing need to develop new therapeutic approaches to improve the survival of patients who developed drug resistance to the third-line treatment.

Mixing during Trapping Enabled a Continuous-Flow Microfluidic Smartphone Immunoassay Using Acoustic Streaming.

Smartphone-enabled microfluidic chemiluminescence immunoassay is a promising portable system for point-of-care (POC) biosensing applications. However, due to the rather faint emitted light in such a limited sample volume, it is still difficult to reach the clinically accepted range when the smartphone serves as a standalone detector. Besides, the multiple separation and washing steps during sample preparation hinder the immunoassay's applications for POC usage.

TF-PROTACs Enable Targeted Degradation of Transcription Factors.

Transcription factors (TFs) represent a major class of therapeutic targets for the treatment of human diseases including cancer. Although the biological functions and even crystal structures of many TFs have been clearly elucidated, there is still no viable approach to target the majority of TFs, thus rendering them undruggable for decades. PROTACs (proteolysis targeting chimeras) emerge as a powerful class of therapeutic modalities, which rely on induced protein-protein interactions between the proteins of interest (POIs) and E3 ubiquitin ligases to aid the degradation of POIs by the ubiquitin-proteasome system (UPS).

Mode of action and efficacy of quinolinic acid for the control of Ceratocystis fimbriata on sweet potato.

Background: Ceratocystis fimbriata is a hazardous fungal pathogen able to cause black rot disease on sweet potato. The management of C. fimbriata strongly relies on the use of toxic fungicides, and there is a lack of efficient alternative strategies.

The role of decidual natural killer cell-derived soluble factors in early pregnancy.

Decidual natural killer cells (dNK), the predominant decidual lymphocytes in early pregnancy, are primarily identified based on their CD56 CD16 phenotype and play an important role in maintaining immune tolerance at the maternal-fetal interface. dNK dysfunction reportedly leads to pathological pregnancy. Indeed, various dNK-derived soluble factors are involved in a series of key processes related to pregnancy outcomes.

Activated low-grade phosphate rocks for simultaneously reducing the phosphorus loss and cadmium uptake by rice in paddy soil.

Cadmium (Cd) pollution and phosphorus (P) leaching in paddy soils has raised the global concern. In this study, two kinds of the low grade phosphate rocks activated by the sodium lignosulfonate (SL) and humic acid (HA) were fabricated for soil Cd passivation and reduction of the soil P leaching simultaneously. The mechanisms of the Cd adsorption and passivation by the activated phosphate rocks (APRs) were investigated through the batch experiment and the indoor culture test (i.

Topics in the mathematical design of materials.

We present a perspective on several current research directions relevant to the mathematical design of new materials. We discuss: (i) design problems for phase-transforming and shape-morphing materials, (ii) epitaxy as an approach of central importance in the design of advanced semiconductor materials, (iii) selected design problems in soft matter, (iv) mathematical problems in magnetic materials, (v) some open problems in liquid crystals and soft materials and (vi) mathematical problems on liquid crystal colloids. The presentation combines topics from soft and hard condensed matter, with specific focus on those design themes where mathematical approaches could possibly lead to exciting progress.

Quantitative analysis of compatible microstructure by electron backscatter diffraction.

We propose a scheme for assigning the martensite variant using electron backscatter diffraction in a martensite material that undergoes a solid-solid phase transformation. Based on the solutions of the crystallographic equations of martensite, we provide an algorithm to assign martensite variants to a particular microscopic region, and to check the elastic compatibility of the microstructure corresponding to low hysteresis and high reversibility in shape memory alloys. This article is part of the theme issue 'Topics in mathematical design of complex materials'.

A novel shift in the glass transition temperature of polymer nanocomposites: a molecular dynamics simulation study.

The effect of the loading of nanoparticles on the glass transition temperature, Tg, of polymer nanocomposites is studied by using molecular dynamics simulations. Tg is estimated from the variation of system volume with temperature and the temperature-dependent diffusion of the polymer described by the Vogel-Fulcher-Tammann law. The estimated values of Tg from the two methods are consistent with each other.

A randomized controlled study on an integrated approach to prevent and treat re-adhesion after transcervical resection of moderate-to-severe intrauterine adhesions.

Objectives: This study aims to compare the clinical efficacy of an integrated approach to prevent and treat the recurrence of moderate-to-severe intrauterine adhesions (IUA) after hysteroscopic transcervical resection of adhesion (TCRA).

Methods: The study included a total of 70 patients with moderate-to-severe IUAs who underwent TCRA. Patients were randomly divided into two groups: treatment group (n=35) and control group n=35).

Large-scale growth of few-layer two-dimensional black phosphorus.

Two-dimensional materials provide opportunities for developing semiconductor applications at atomistic thickness to break the limits of silicon technology. Black phosphorus (BP), as a layered semiconductor with controllable bandgap and high carrier mobility, is one of the most promising candidates for transistor devices at atomistic thickness. However, the lack of large-scale growth greatly hinders its development in devices.

OsPHR2 modulates phosphate starvation-induced OsMYC2 signalling and resistance to Xanthomonas oryzae pv. oryzae.

Phosphate (Pi) and MYC2-mediated jasmonate (JA) pathway play critical roles in plant growth and development. In particular, crosstalk between JA and Pi starvation signalling has been reported to mediate insect herbivory resistance in dicot plants. However, its roles and mechanism in monocot-bacterial defense systems remain obscure.

Activation of Blood Vessel Development in Endometrial Stromal Cells In Vitro Cocultured with Human Peri-Implantation Embryos Revealed by Single-Cell RNA-Seq.

In humans, the maternal endometrium participates in the physical and physiological interaction with the blastocyst to begin implantation. A bidirectional crosstalk is critical for normal implantation and then a successful pregnancy. While several studies have used animal models or cell lines to study this step, little knowledge was acquired to address the role of endometrial cells in humans.

Identification of QTLs and a Candidate Gene for Reducing Pre-Harvest Sprouting in - Chromosome Segment Substitution Lines.

Wheat pre-harvest sprouting (PHS) causes serious losses in wheat yield. In this study, precise mapping was carried out in the chromosome segment substitution lines (CSSL) F population generated by a direct cross of Zhoumai 18 (PHS-sensitive) and accession T093 (highly PHS-resistant). Three -derived quantitative trait loci (QTLs), , , and , were detected on chromosome 3DL using four simple sequence repeats (SSR) markers and 10 developed Kompetitive allele-specific PCR (KASP) markers.

Targeting Replicative Stress and DNA Repair by Combining PARP and Wee1 Kinase Inhibitors Is Synergistic in Triple Negative Breast Cancers with Cyclin E or Alteration.

The identification of biomarker-driven targeted therapies for patients with triple negative breast cancer (TNBC) remains a major clinical challenge, due to a lack of specific targets. Here, we show that cyclin E, a major regulator of G1 to S transition, is deregulated in TNBC and is associated with mutations in DNA repair genes (e.g.

Sulfonic-Group-Grafted TiCT MXene: A Silver Bullet to Settle the Instability of Polyaniline toward High-Performance Zn-Ion Batteries.

Polyaniline (PANI) is a promising cathode material for Zn-ion batteries (ZIBs) due to its intrinsic conductivity and redox activity; however, the achievements of PANI in high-performance ZIBs are largely hindered by its instability during the repeated charge/discharge. Taking advantage of the high conductivity, flexibility, and grafting ability together, a surface-engineered TiCT MXene is designed as a silver bullet to fight against the deprotonation and swelling/shrinking issues occurring in the redox process of PANI, which are the origins of its instability. Specifically, the sulfonic-group-grafted TiCT(S-TiCT) continuously provides protons to improve the protonation degree of PANI and maintains the polymer backbone at a locally low pH, which effectively inhibits deprotonation and brings high redox activity along with good reversibility.

Translocation of a looped polymer threading through a nanopore.

Recent experiments reported that the complicated translocation dynamics of a looped DNA chain through a nanopore can be detected by ionic current blockade profiles. Inspired by the experimental results, we systematically study the translocation dynamics of a looped polymer, formed by three building blocks of a loop in the middle and two tails of the same length connected with the loop, by using Langevin dynamics simulations. Based on two entering modes (tail-leading and loop-leading) and three translocation orders (loop-tail-tail, tail-loop-tail, and tail-tail-loop), the translocation of the looped polymer is classified into six translocation pathways, corresponding to different current blockade profiles.

Tensile mechanical analysis of anisotropy and velocity dependence of the spinal cord white matter: a biomechanical study.

In spinal cord injuries, external forces from various directions occur at various velocities. Therefore, it is important to physically evaluate whether the spinal cord is susceptible to damage and an increase in internal stress for external forces. We hypothesized that the spinal cord has mechanical features that vary under stress depending on the direction and velocity of injury.