GIWAXS experimental methods at the NFPS-BL17B beamline at Shanghai Synchrotron Radiation Facility.

The BL17B beamline at the Shanghai Synchrotron Radiation Facility was first designed as a versatile high-throughput protein crystallography beamline and one of five beamlines affiliated to the National Facility for Protein Science in Shanghai. It was officially opened to users in July 2015. As a bending magnet beamline, BL17B has the advantages of high photon flux, brightness, energy resolution and continuous adjustable energy between 5 and 23 keV.

Structural and functional characterization of itaconyl-CoA hydratase and citramalyl-CoA lyase involved in itaconate metabolism of Pseudomonas aeruginosa.

Itaconate is a key anti-inflammatory/antibacterial metabolite in pathogen-macrophage interactions that induces adaptive changes in Pseudomonas aeruginosa-exposed airways. However, the impact and mechanisms underlying itaconate metabolism remain unclear. Our study reveals that itaconate significantly upregulates the expression of pyoverdine in P.

Bright and stable monomeric green fluorescent protein derived from StayGold.

The high brightness and photostability of the green fluorescent protein StayGold make it a particularly attractive probe for long-term live-cell imaging; however, its dimeric nature precludes its application as a fluorescent tag for some proteins. Here, we report the development and crystal structures of a monomeric variant of StayGold, named mBaoJin, which preserves the beneficial properties of its precursor, while serving as a tag for structural proteins and membranes. Systematic benchmarking of mBaoJin against popular green fluorescent proteins and other recently introduced monomeric and pseudomonomeric derivatives of StayGold established mBaoJin as a bright and photostable fluorescent protein, exhibiting rapid maturation and high pH/chemical stability.

Utilization of AlphaFold2 to Predict MFS Protein Conformations after Selective Mutation.

The major facilitator superfamily (MFS) is the largest secondary transporter family and is responsible for transporting a broad range of substrates across the biomembrane. These proteins are involved in a series of conformational changes during substrate transport. To decipher the transport mechanism, it is necessary to obtain structures of these different conformations.

Uncovering a conserved vulnerability site in SARS-CoV-2 by a human antibody.

An essential step for SARS-CoV-2 infection is the attachment to the host cell receptor by its Spike receptor-binding domain (RBD). Most of the existing RBD-targeting neutralizing antibodies block the receptor-binding motif (RBM), a mutable region with the potential to generate neutralization escape mutants. Here, we isolated and structurally characterized a non-RBM-targeting monoclonal antibody (FD20) from convalescent patients.

A synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection.

SARS-CoV-2, the causative agent of COVID-19, features a receptor-binding domain (RBD) for binding to the host cell ACE2 protein. Neutralizing antibodies that block RBD-ACE2 interaction are candidates for the development of targeted therapeutics. Llama-derived single-domain antibodies (nanobodies, ~15 kDa) offer advantages in bioavailability, amenability, and production and storage owing to their small sizes and high stability.

A high-affinity RBD-targeting nanobody improves fusion partner's potency against SARS-CoV-2.

A key step to the SARS-CoV-2 infection is the attachment of its Spike receptor-binding domain (S RBD) to the host receptor ACE2. Considerable research has been devoted to the development of neutralizing antibodies, including llama-derived single-chain nanobodies, to target the receptor-binding motif (RBM) and to block ACE2-RBD binding. Simple and effective strategies to increase potency are desirable for such studies when antibodies are only modestly effective.

Perioperative and Postoperative Complications of Supraclavicular, Ultrasound-Guided, Totally Implantable Venous Access Port via the Brachiocephalic Vein in Adult Patients: A Retrospective Multicentre Study.

Purpose: The totally implantable venous access port (TIVAP) provides patients with safe, effective and long-term convenient venous access for the administration of medications such as chemotherapy drugs. The implantation and long-term use of TIVAP are related to thrombosis, infection and other complications. In this study, the medical records of multicentre patients were collected, and the perioperative and postoperative complications were retrospectively analysed to objectively evaluate the safety of the implantation of supraclavicular, ultrasound-guided TIVAP via the brachiocephalic vein (BCV).

A Synthetic Human Antibody Antagonizes IL-18Rβ Signaling Through an Allosteric Mechanism.

The interleukin-18 subfamily belongs to the interleukin-1 family and plays an important role in modulating innate and adaptive immune responses. Dysregulation of IL-18 has been implicated in or correlated with numerous diseases, including inflammatory diseases, autoimmune disorders, and cancer. Thus, blockade of IL-18 signaling may offer therapeutic benefits in many pathological settings.

In Situ Formation of Hierarchical Bismuth Nanodots/Graphene Nanoarchitectures for Ultrahigh-Rate and Durable Potassium-Ion Storage.

Metallic bismuth (Bi) has been widely explored as remarkable anode material in alkali-ion batteries due to its high gravimetric/volumetric capacity. However, the huge volume expansion up to ≈406% from Bi to full potassiation phase K Bi, inducing the slow kinetics and poor cycling stability, hinders its implementation in potassium-ion batteries (PIBs). Here, facile strategy is developed to synthesize hierarchical bismuth nanodots/graphene (BiND/G) composites with ultrahigh-rate and durable potassium ion storage derived from an in situ spontaneous reduction of sodium bismuthate/graphene composites.

Ultrasound-guided totally implantable venous access ports via the right innominate vein: a new approach for patients with breast cancer.

Background: To evaluate the feasibility and safety of ultrasound-guided totally implantable venous access port (TIVAP) implantation via the right innominate vein in patients with breast cancer.

Methods: Sixty-seven breast cancer patients underwent ultrasound-guided implantation of TIVAPs via the right innominate vein for administration of chemotherapy. Clinical data including technical success, success rate for the first attempt, periprocedural, and postoperative complications were recorded and retrospectively studied.

Anisotropic elasticity and plasticity of an organic crystal.

Organic crystals are generally considered to be brittle, inelastic materials, which pose challenges for application in flexible devices. Inspired by α helical proteins for their key structural role in flexible hair, here, we describe the construction of a spring-like hydrogen bonded network through the self-assembly of a-OH/e-OH cyclohexanol derivatives.

Structural basis of nonribosomal peptide macrocyclization in fungi.

Nonribosomal peptide synthetases (NRPSs) in fungi biosynthesize important pharmaceutical compounds, including penicillin, cyclosporine and echinocandin. To understand the fungal strategy of forging the macrocyclic peptide linkage, we determined the crystal structures of the terminal condensation-like (C) domain and the holo thiolation (T)-C complex of Penicillium aethiopicum TqaA. The first, to our knowledge, structural depiction of the terminal module in a fungal NRPS provides a molecular blueprint for generating new macrocyclic peptide natural products.

Aberrant microRNA-182 expression is associated with glucocorticoid resistance in lymphoblastic malignancies.

Glucocorticoid (GC) resistance in lymphoblastic malignancies is related to treatment failure and is a marker of poor prognosis. Previous studies have suggested that microRNA-182 (miR-182) functions as an oncogene and plays a role in tumorigenesis, through regulation of FOXO3A. FOXO3A has been implicated in tumor suppression and GC-induced apoptosis, suggesting that FOXO3A has potential as a therapeutic target.

Alleviating allergic airway diseases by means of short-term administration of IL-2 and dexamethasone.

Background: IL-2 combined with dexamethasone can upregulate regulatory T (Treg) cells, but the mechanism is still under exploration.

Objective: Although previous studies focused on upregulating Treg cells in normal mice, here we investigated whether the IL-2 and dexamethasone combination treatment can upregulate Treg cells in pathological conditions, specifically in alleviating allergic airway disease. We also examined the potential pathway involved in Treg cell upregulation by IL-2 and dexamethasone.

[Amaxa Nucleofector(TM) nuclear transfection apparatus transfers L1210 cell line].

Mouse L1210 leukemia cell line is widely used as a model in the study of tumorigenesis, as well as the efficacy of chemotherapeutic drugs; however, like other suspension cell lines, the mouse L1210 cell line has lowest transfection efficiency, that many barriers exist to study about the structure, function, as well as metabolism in leukemia cells. This study was aimed to obtain higher transfection efficiency of L1210 cell line to facilitate scientific research. The transfection efficiencies of nucleofector and liposome in L1210 leukemia cells were detected by converted fluorescence microscopy and flow cytometry using EGFP (enhance green fluorescent protein); cell viability was observed by trypan blue exclusion test.

miR-24 regulates apoptosis by targeting the open reading frame (ORF) region of FAF1 in cancer cells.

Background: microRNAs (miRNAs) are small noncoding RNAs that regulate cognate mRNAs at the post-transcriptional stage. Several studies have shown that miRNAs modulate gene expression in mammalian cells by base pairing to complementary sites in the 3'-untranslated region (3'-UTR) of the target mRNAs.

Methodology/principal Findings: In the present study, miR-24 was found to target fas associated factor 1(FAF1) by binding to its amino acid coding sequence (CDS) region, thereby regulating apoptosis in DU-145 cells.

A glucocorticoid amplifies IL-2-induced selective expansion of CD4(+)CD25(+)FOXP3(+) regulatory T cells in vivo and suppresses graft-versus-host disease after allogeneic lymphocyte transplantation.

Regulatory T (Treg) cells are a subpopulation of T cells that not only prevent autoimmunity, but also control a wide range of T cell-dependent immune responses. Glucocorticoid treatment (dexamethasone, or Dex) has been reported to amplify IL-2-mediated selective in vivo expansion of Treg cells. We simultaneously administered Dex and IL-2 to the donor in a murine allogeneic lymphocyte transplantation model to expand functional suppressive CD4(+)CD25(+)FOXP3(+) T cells in the graft and to raise the regulatory T cell/effector T cell (Treg/ Teff ) ratio to prevent graft-versus-host disease (GVHD).

BMPRII is a direct target of miR-21.

MicroRNAs (miRNAs) are a type of small non-coding RNAs that regulate cognate mRNA expressions at the post-transcriptional stage. Although several miRNAs are known to be involved in various biological processes, including developmental timing, patterning, embryogenesis, differentiation and organogenesis, growth control, and apoptosis, many target genes and the functions of most miRNAs are still unclear. Since there is only a partial complementarity between miRNAs and their targets in animal cells, it is difficult to identify the specific target genes for a given miRNA and elucidate its function.

MicroRNA expression profiling in diabetic GK rat model.

MicroRNAs (miRNAs), which are a newly identified class of small single-stranded non-coding RNAs, regulate their target genes via post-transcriptional pathway. It has been proved that miRNAs play important roles in many biological processes. To better understand miRNA function on type 2 diabetes, we used an oligonucleotide microarray to monitor miRNA expression profiles of Goto-Kakizaki (GK) and Wistar rats' skeletal muscle.

Glucocorticoid-induced apoptosis requires FOXO3A activity.

Dexamethasone (DEX) induces apoptosis in lymphocytes, while protecting some cancer cells from apoptosis, by a poorly understood mechanism. In this study, we examined the potential role of the forkhead transcription factor (FOXO3A) in DEX-induced apoptosis. Unphosphorylated FOXO3A, the active form of FOXO3A, can translocate into nucleus and induce apoptosis.