Image_2_A PD-L1 Negative Advanced Gastric Cancer Patient With a Long Response to PD-1 Blockade After Failure of Systematic Treatment: A Case Report.pdf

BackgroundIt was widely accepted that programmed death-ligand 1 (PD-L1) positive, tumor mutational burden-high (TMB-H) or microsatellite instability-high (MSI-H) tumor are prone to have better treatment response to immune checkpoint blockade. The value of immune checkpoint blockade in PD-L1 negative gastric cancer patients has been questioned due to lower objective response rate (ORR).Case PresentationWe report an unusual case of a PD-L1 negative, proficient mismatch repair (pMMR)/microsatellite stability (MSS), tumor mutational burden-low (TMB-L) gastric cancer patient who achieved good response to immune checkpoint blockade after failure of systematic treatment. Multiple lymph nodes and bone metastases are the main characteristics of this patient. The patient survived for more than 30 months after diagnosis.ConclusionsThis case suggested that PD-L1 negative gastric cancer patient may also benefit from immune checkpoint blockade. In gastric cancer, patients with lymph node metastasis may be potential beneficiaries.</p

Long-Life Zn Anode Enabled with Complexing Ability of a Benign Electrolyte Additive

The development of aqueous zinc ion batteries (AZIBs) is hindered by several problems, including Zn dendrite/corrosion, side reactions, and hydrogen evolution reaction (HER). Herein, trisodium citrate (NaCit) additive is introduced into the ZnSO4 electrolyte to guide the preferred Zn(002) crystal plane growth, while the Cit– is preferentially adsorbed on the active sites to suppress the HER and Zn corrosion, thus achieving uniform Zn deposition without dendrites. The stable cycle life can reach 2000 h at 0.25 mA cm–2/0.05 mAh cm–2. The density functional theory simulations further indicate that the parallely placed Cit– has the lowest adsorption energy (−6.617 eV); it can form a weak interaction with Zn metal to promote the growth of (002) crystal planes. Furthermore, the assembled Zn//polyaniline full cell and pouch cell both exhibit good rate performance and long cycling stability. The complexation and dissolubilization effects of the NaCit additive provide a means for designing high-performance AZIBs

Image_1_A PD-L1 Negative Advanced Gastric Cancer Patient With a Long Response to PD-1 Blockade After Failure of Systematic Treatment: A Case Report.pdf

BackgroundIt was widely accepted that programmed death-ligand 1 (PD-L1) positive, tumor mutational burden-high (TMB-H) or microsatellite instability-high (MSI-H) tumor are prone to have better treatment response to immune checkpoint blockade. The value of immune checkpoint blockade in PD-L1 negative gastric cancer patients has been questioned due to lower objective response rate (ORR).Case PresentationWe report an unusual case of a PD-L1 negative, proficient mismatch repair (pMMR)/microsatellite stability (MSS), tumor mutational burden-low (TMB-L) gastric cancer patient who achieved good response to immune checkpoint blockade after failure of systematic treatment. Multiple lymph nodes and bone metastases are the main characteristics of this patient. The patient survived for more than 30 months after diagnosis.ConclusionsThis case suggested that PD-L1 negative gastric cancer patient may also benefit from immune checkpoint blockade. In gastric cancer, patients with lymph node metastasis may be potential beneficiaries.</p

Diverse Interleukin-7 mRNA Transcripts in Chinese Tree Shrew (<i>Tupaia belangeri chinensis</i>)

<div><p>Interleukin-7 (IL7) is a pleiotropic cytokine that is actively involved in the immune system. The Chinese tree shrew (<i>Tupaia belangeri chinensis</i>) has been proposed as an alternative experimental animal to primates in biomedical research. However, there is a lack of biological knowledge about the immune system of the tree shrew. In this study, we cloned the <i>IL7</i> gene (<i>tIL7</i>) in the Chinese tree shrew and quantified the expression of mRNA transcripts in eight tissues (heart, liver, spleen, lung, kidney, intestine, skeletal muscle and brain) from 20 individuals. Eleven <i>tIL7</i> mRNA transcripts were identified in different tissues. The canonical form (<i>tIL7c</i>) had a length of 1817 bp and encoded a predicted gene product with 177 amino acids. Phylogenetic analyses based on the amino acid sequences revealed a considerably large genetic difference between tree shrew and human. Quantification of mRNA expression of transcripts <i>tIL7c</i>, <i>tIL7-sv1</i>, <i>tIL7-sv2</i> and <i>tIL7-sv3</i> showed that these transcripts were expressed in all tissues, albeit the expression levels varied in different tissues. Transcripts <i>tIL7c</i>, <i>tIL7-sv1</i>, and <i>tIL7-sv2</i> had the lowest expression in brain, and <i>tIL7-sv3</i> had a dramatically high mRNA expression in skeletal muscle and heart. The mRNA expression levels of <i>tIL7c</i> and <i>tIL7-sv1</i> were significantly increased upon ploy(I:C) stimulation in tree shrew primary renal cells. As with human full-length IL7, tIL7c, tIL7-sv1, tIL7-sv2 and tIL7-sv3 showed similar a subcellular localization pattern. Our results identified diverse <i>tIL7</i> transcripts in the Chinese tree shrew, which may play a potential role in modulating IL7-regulated biological effects.</p></div

Supplementary Table S1 from Aspirin Use and Risk of Breast Cancer: Systematic Review and Meta-analysis of Observational Studies

Methodological quality of the cohort studies, based on the NOS for assessing the quality of epidemiological studies.</p

Macrophage-derived exosomes regulate gastric cancer cell oxaliplatin resistance by wrapping circ 0008253

Oxaliplatin (OXA) is a first-line chemotherapy drug for gastric cancer. We aimed to investigate the effect of circ 0008253, contained in M2 polarized macrophage-derived exosomes, on OXA resistance of gastric carcinoma cells. Flow cytometry was performed to detect the differentiation of macrophages and cell apoptosis. Cell Counting Kit-8 assay was conducted to examine the cell viability. Transmission electron microscopy, Nanoparticle Tracking Analysis, Western bolt, and Immunofluorescence were carried out. Cell proliferation was detected with a colony formation experiment. Levels of CD206, Arg1, IL-10, and TGF-β were increased in M2 polarized macrophages. Cell viability was decreased gradually with the increase of time and OXA concentration. Apoptosis of gastric carcinoma cells was decreased after co-culture with M2-polarized macrophages. Exosomes isolated from M2-polarized macrophages (M2-Exos) could be co-located with gastric carcinoma cells. M2-Exos enhanced drug resistance, reduced apoptosis and OXA resistance. Bioinformatics analysis showed that circ 0008253 could be transferred from M2-Exos to gastric carcinoma cells. Overexpressing circ 0008253 increased cell viability, tumor size, and ABCG2 levels, decreased OXA sensitivity. Circ 0008253, contained in M2-Exos, was directly transferred from tumor-associated macrophage to gastric carcinoma cells, finally enhancing OXA resistance.</p

Supplementary Figure S1 from Aspirin Use and Risk of Breast Cancer: Systematic Review and Meta-analysis of Observational Studies

Funnel plot of studies on aspirin use and breast cancer risk. The solid line in the center is the natural logarithm of pooled relative risk, and two oblique dotted lines are pseudo 95% CIs. Closed circles indicate the estimates of each individual study. Open circles indicate the estimates of the potential missing studies according to the trim-and-fill method.</p

Supplementary Figure Legend from Aspirin Use and Risk of Breast Cancer: Systematic Review and Meta-analysis of Observational Studies

Supplementary Figure Legend</p

Nucleotide and deduced amino acid sequence of the <i>IL7</i> gene in Chinese tree shrew.

<p>The six exons were marked by arrows and alternative splicing fragment of transcript <i>tIL7-sv6</i> in the 5′-UTR was shaded. Potential polyadenylation signal AATAAA was marked with a box. Three predicted N-glycosylation sites were marked with dots below the respective amino acid. Three single nucleotide polymorphisms were underlined in this gene and were marked by “ = ”.</p

Schematic structure of <i>IL7</i> mRNA and its transcripts in Chinese tree shrew.

<p>(A) Eleven mRNA transcripts of <i>tIL7</i> gene. All transcripts were amplified by using primer pair tIL7F and tIL7R. Exons were indicated as boxes. Broken lines indicated alternative splicing of exons in <i>tIL7</i> transcripts. (B) A 21-bp insertion between exons 3 and 4 in transcripts <i>tIL7-sv9</i> and <i>tIL7-sv10</i> would result in a truncated peptide in the C-terminal of predicted protein. Transcripts <i>tIL7-sv6</i>, <i>tIL7-sv9</i> and <i>tIL7-sv10</i> complied with the splicing rule and were GT-AG introns.</p