Table_1_Disease progression in patients with usual interstitial pneumonia and probable UIP patterns on computed tomography with various underlying etiologies: a retrospective cohort study.DOCX

BackgroundUsual interstitial pneumonia (UIP) is a pattern of interstitial pneumonia that is caused by different etiologies. This study aimed to investigate the transplant-free survival (TFS) and the decline in forced vital capacity (FVC) of the patients with UIP and probable UIP patterns on CT caused by various underlying conditions.MethodsA retrospective cohort study was conducted, enrolling patients with interstitial lung disease exhibiting a CT pattern consistent with UIP or probable UIP. Clinical and prognostic data of patients categorized by the etiology were compared.ResultsA total of 591 patients were included and classified into the following groups: idiopathic pulmonary fibrosis (IPF) (n = 320), connective tissue disease (CTD)-UIP (n = 229), asbestosis-UIP (n = 28), and hypersensitivity pneumonitis (HP)-UIP (n = 14). Advanced age, elevated levels of serum cytokeratin fraction 21-1 and percentage of neutrophils in bronchoalveolar lavage were observed in all groups. IPF patients showed a more rapid decline in FVC (133.9 mL/year) compared to CTD-UIP (24.5 mL/year, p = 0.001) and asbestosis-UIP (61.0 mL/year, p = 0.008) respectively. Sub-analysis of CTD-UIP revealed that patients with rheumatoid arthritis (RA)-UIP (88.1 mL/year) or antineutrophil cytoplasmic antibody-associated vasculitis (AAV)-UIP (72.9 mL/year) experienced a faster deterioration in FVC compared to those with primary Sjögren’s syndrome (pSS)-UIP (25.9 mL/year, p ConclusionPatients with UIP caused by different underlying conditions share certain common features, but the trajectories of disease progression and survival outcomes differ.</p

Ube2V2 Is a Rosetta Stone Bridging Redox and Ubiquitin Codes, Coordinating DNA Damage Responses

Posttranslational modifications (PTMs) are the lingua franca of cellular communication. Most PTMs are enzyme-orchestrated. However, the reemergence of electrophilic drugs has ushered mining of unconventional/non-enzyme-catalyzed electrophile-signaling pathways. Despite the latest impetus toward harnessing kinetically and functionally privileged cysteines for electrophilic drug design, identifying these sensors remains challenging. Herein, we designed “G-REX”a technique that allows controlled release of reactive electrophiles in vivo. Mitigating toxicity/off-target effects associated with uncontrolled bolus exposure, G-REX tagged <i>first-responding</i> innate cysteines that bind electrophiles under true <i>k</i>_cat/<i>K</i>_m conditions. G-REX identified two allosteric ubiquitin-conjugating proteinsUbe2V1/Ube2V2sharing a novel privileged-sensor-cysteine. This non-enzyme-catalyzed-PTM triggered responses <i>specific to each</i> protein. Thus, G-REX is an unbiased method to identify novel functional cysteines. Contrasting conventional active-site/off-active-site cysteine-modifications that regulate <i>target</i> activity, modification of Ube2V2 allosterically hyperactivated its enzymatically active binding-partner Ube2N, promoting K63-linked client ubiquitination and stimulating H2AX-dependent DNA damage response. This work establishes Ube2V2 as a Rosetta-stone bridging redox and ubiquitin codes to guard genome integrity

Loading Mode-Induced Enhancement in Friction for Microscale Graphite/Hexagonal Boron Nitride Heterojunction

Classical friction laws traditionally assume that the friction between solid pairs remains constant with a given normal load. However, our study has unveiled a remarkable deviation from conventional wisdom. In this paper, we discovered that altering the loading mode of micro graphite flakes led to significant changes in the lateral friction under identical normal loads. By adding a cap onto a single graphite flake to disperse the normal load applied by an atomic force microscope (AFM) tip, we were able to distribute the concentrated force. Astonishingly, our results demonstrated a notable 4–7 times increase in friction as a consequence of load dispersion. Finite element analysis (FEA) further confirmed that the increase in compressive stress at the edges of the graphite flake, resulting from load dispersion, led to a significant increase in friction. This study underscores the critical role of the loading mode in microscale friction dynamics, challenging the prevailing notion that friction remains static with a given normal force. Importantly, our research sheds light on the potential for achieving macroscale structural superlubricity (SSL) by assembling microscale SSL graphite flakes by using a larger cap

Genetic risk and gastric cancer: polygenic risk scores in population-based case-control study

This study aimed to screen and identify common variants and long noncoding RNA (lncRNA) single nucleotide polymorphisms (SNPs) associated with gastric cancer risk, and construct prediction models based on polygenic risk score (PRS). The risk factors associated with gastric cancer were screened following meta-analysis and bioinformatics, verified by population-based case-control study. We constructed PRS and weighted genetic risk scores (wGRS) derived from the validation data set. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to evaluate model. The PRS was divided into 10 quantiles, with the 40–60% quantile as a reference. A risk gradient was revealed across quantile of the PRS, the risk of gastric cancer in the highest 10 quantile of PRS was 3.24-fold higher than that in control population (OR = 3.24, 95%CI: 2.07, 5.06). For NRI and IDI, PRS combinations were significantly improved compared to wGRS model combinations (P  The model based on PRS combined with lncRNA SNPs, H. pylori infection, smoking, and drinking had the optimal predictive ability for gastric cancer risk, which was helpful to distinguish high-risk groups.</p

High-efficiency production of human serum albumin in the posterior silk glands of transgenic silkworms, <i>Bombyx mori</i> L

<div><p>Human serum albumin (HSA) is an important biological preparation with a variety of biological functions in clinical applications. In this study, the mRNA of a fusion transposase derived from the pESNT-PBase plasmid and a pBHSA plasmid containing the <i>HSA</i> gene under the control of a <i>fibroin light chain</i> (<i>FL</i>) promoter were co-injected into fertilized eggs. Fifty-six transgenic silkworm pedigrees expressing theexogenous recombinant HSA (rHSA) in the posterior silk glands (PSGs) with stable inheritance were successfully obtained. The SDS-PAGE and Western blot results confirmed that the rHSA was secreted into the transgenic silkworm cocoon, and the rHSA could be easily extracted with phosphate-buffered saline (PBS). In our research, the isolated highest amount rHSA constituted up to 29.1% of the total soluble protein of the cocoon shell, indicating that the transgenic silkworm produced an average of 17.4 μg/mg of rHSA in the cocoon shell. The production of soluble rHSA in the PSGs by means of generating transgenic silkworms is a novel approach, whereby a large amount of virus-free and functional HSA can be produced through the simple rearing of silkworms.</p></div

List of primer sequences used in this study.

<p>List of primer sequences used in this study.</p

The structure of pBHSA and pESNT-PBase plasmids.

<p><b>(A)</b>. Schematic representation of the pBHSA plasmid used in our transgenic experiment. pBL and pBR: the sequence of the left and right arms of the <i>piggy</i>Bac transposon plasmid; FL promoter, the promoter sequence of the <i>fibroin light chain</i> gene; FLSP, the signal peptide sequence of the <i>fibroin light chain</i> gene; His6 tag, the sequential 6×His-tag; DDDDK, enterokinase recognition site; HSA CDS, the HSA coding sequence; FL polyA, the polyA signal sequence of the <i>fibroin light chain</i> gene; 3×P3 promoter, the artificial promoter specifically driving the marker gene expression in the eyes and nervous system; DsRed CDS, the coding sequence of the red fluorescent protein gene; SV40 polyA, the SV40 polyA signal sequence. <b>(B)</b>. Schematic representation of the pESNT-PBase plasmid used in this transgenic experiment, which was constructed in our previous study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191507#pone.0191507.ref026" target="_blank">26</a>].</p

The fluorescence phenotypes of the DsRed-specific expressed in the eyes of the transgene-positive silkworm.

<p><b>A</b> and <b>C</b> are the wild-type silkworm larvae and moths viewed under the normal light; <b>B</b> and <b>D</b> are transgene-positive silkworm larvae and moths viewed under the normal light. <b>A</b>' and <b>C</b>' are wild-type silkworm larvae and moths viewed under the red fluorescence; <b>B</b>' and <b>D</b>' are transgene-positive silkworm larvae and moths viewed under the red fluorescence. White arrows indicate the position of the eye.</p

Locations of the insertion site of the transgenic silkworm pedigrees on the chromosome.

<p>Locations of the insertion site of the transgenic silkworm pedigrees on the chromosome.</p

Identification of <i>rHSA</i> gene expression in transgenic silkworm pedigrees using qRT-PCR, SDS-PAGE and Western blot, and purification of rHSA protein from the cocoon shells.

<p><b>(A)</b> The relative expression levels of the <i>rHSA</i> gene in the PSGs of the transgenic silkworm pedigrees on the 3^rd day of the 5^th instar were measured by qRT-PCR. WT: the wild-type silkworm <i>Lan</i> 10. HSA-1, HSA-2, HSA-3, HSA-4 and HSA-5: the transgene-positive silkworm pedigrees. (<b>B</b>) SDS-PAGE analysis of rHSA derived from the soluble protein of cocoon shells and (<b>C</b>) Western blot analysis of the cocoon layer. WT: the protein samples from the wild-type silkworm <i>Lan</i> 10. HSA-1, HSA-2, HSA-3, HSA-4 and HSA-5: the protein samples from the transgene-positive silkworm pedigrees. (<b>D</b>) The results of purification of the rHSA protein. S: the protein sample. W1, W2: recovered solutions after adding binding buffer. E1-E4: recovered solutions after adding elution buffer.</p