Targeting tumor-associated macrophage: an adjuvant strategy for lung cancer therapy

The emergence of immunotherapy has revolutionized the treatment landscape for various types of cancer. Nevertheless, lung cancer remains one of the leading causes of cancer-related mortality worldwide due to the development of resistance in most patients. As one of the most abundant groups of immune cells in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) play crucial and complex roles in the development of lung cancer, including the regulation of immunosuppressive TME remodeling, metabolic reprogramming, neoangiogenesis, metastasis, and promotion of tumoral neurogenesis. Hence, relevant strategies for lung cancer therapy, such as inhibition of macrophage recruitment, TAM reprograming, depletion of TAMs, and engineering of TAMs for drug delivery, have been developed. Based on the satisfactory treatment effect of TAM-targeted therapy, recent studies also investigated its synergistic effect with current therapies for lung cancer, including immunotherapy, radiotherapy, chemotherapy, anti-epidermal growth factor receptor (anti-EGFR) treatment, or photodynamic therapy. Thus, in this article, we summarized the key mechanisms of TAMs contributing to lung cancer progression and elaborated on the novel therapeutic strategies against TAMs. We also discussed the therapeutic potential of TAM targeting as adjuvant therapy in the current treatment of lung cancer, particularly highlighting the TAM-centered strategies for improving the efficacy of anti-programmed cell death-1/programmed cell death-ligand 1 (anti-PD-1/PD-L1) treatment

Indoor solid fuel use and tuberculosis in China: a matched case-control study

<p>Abstract</p> <p>Background</p> <p>China ranks second among the 22 high burden countries for tuberculosis. A modeling exercise showed that reduction of indoor air pollution could help advance tuberculosis control in China. However, the association between indoor air pollution and tuberculosis is not yet well established. A case control study was conducted in Anhui, China to investigate whether use of solid fuel is associated with tuberculosis.</p> <p>Methods</p> <p>Cases were new sputum smear positive tuberculosis patients. Two controls were selected from the neighborhood of each case matched by age and sex using a pre-determined procedure. A questionnaire containing demographic information, smoking habits and use of solid fuel for cooking or heating was used for interview. Solid fuel (coal and biomass) included coal/lignite, charcoal, wood, straw/shrubs/grass, animal dung, and agricultural crop residue. A household that used solid fuel either for cooking and (/or) heating was classified as exposure to combustion of solid fuel (indoor air pollution). Odds ratios and their corresponding 95% confidence limits for categorical variables were determined by Mantel-Haenszel estimate and multivariate conditional logistic regression.</p> <p>Results</p> <p>There were 202 new smear positive tuberculosis cases and 404 neighborhood controls enrolled in this study. The proportion of participants who used solid fuels for cooking was high (73.8% among cases and 72.5% among controls). The majority reported using a griddle stove (85.2% among cases and 86.7% among controls), had smoke removed by a hood or chimney (92.0% among cases and 92.8% among controls), and cooked in a separate room (24.8% among cases and 28.0% among controls) or a separate building (67.8% among cases and 67.6% among controls). Neither using solid fuel for cooking (odds ratio (OR) 1.08, 95% CI 0.62-1.87) nor using solid fuel for heating (OR 1.04, 95% CI 0.54-2.02) was significantly associated with tuberculosis. Determinants significantly associated with tuberculosis were household tuberculosis contact (adjusted OR, 27.23, 95% CI 8.19-90.58) and ever smoking tobacco (adjusted OR 1.64, 96% CI 1.01-2.66).</p> <p>Conclusion</p> <p>In a population where the majority had proper ventilation in cooking places, the association between use of solid fuel for cooking or for heating and tuberculosis was not statistically significant.</p

Genome-Wide Identification, Evolutionary Analysis and Expression Profiles of LATERAL ORGAN BOUNDARIES DOMAIN Gene Family in Lotus japonicus and Medicago truncatula.

The LATERAL ORGAN BOUNDARIES DOMAIN (LBD) gene family has been well-studied in Arabidopsis and play crucial roles in the diverse growth and development processes including establishment and maintenance of boundary of developmental lateral organs. In this study we identified and characterized 38 LBD genes in Lotus japonicus (LjLBD) and 57 LBD genes in Medicago truncatula (MtLBD), both of which are model legume plants that have some specific development features absent in Arabidopsis. The phylogenetic relationships, their locations in the genome, genes structure and conserved motifs were examined. The results revealed that all LjLBD and MtLBD genes could be distinctly divided into two classes: Class I and II. The evolutionary analysis showed that Type I functional divergence with some significantly site-specific shifts may be the main force for the divergence between Class I and Class II. In addition, the expression patterns of LjLBD genes uncovered the diverse functions in plant development. Interestingly, we found that two LjLBD proteins that were highly expressed during compound leaf and pulvinus development, can interact via yeast two-hybrid assays. Taken together, our findings provide an evolutionary and genetic foundation in further understanding the molecular basis of LBD gene family in general, specifically in L. japonicus and M. truncatula

Experimental Study on the Workability and Stability of Steel Slag Self-Compacting Concrete

There is important application value and economic value in exploring the potential use of steel slag to prepare self-compacting concrete (SCC) and make full use of solid waste resources. In this paper, steel slag self-compacting concrete (SSCC) with relatively ideal workability is prepared by using steel slag instead of natural fine aggregate based on mix proportion optimization and SSCC performance research. The filling ability, passing ability and resistance segregation were tested to evaluate the workability of SSCC. The results show that when the content of steel slag sand is 20%, the workability performance of SSCC is similar to that of SCC with natural aggregates. When the content of steel slag sand is less than 60%, the performance of SSCC can also meet the workability requirements after adjusting the amount of raw materials

Distribution of conserved motifs and gene structure analysis of LBD gene family from <i>Lotus japonicus</i> and <i>Medicago truncatula</i>.

<p>(A) Conserved motifs analysis by MEME suite. The colorful boxes represent the different motifs 1–15. (B) The exons and introns splicing patterns. The green boxes and black lines represent the exon ans intron, respectively. The numbers indicate the intron phase. The motifs and gene sizes are indicated at the bottom of the figure.</p

The functional divergence analysis between classes or subclasses.

<p>The estimated mean coefficients of Type-I (θI) and type-II (θII) functional divergence based on the aligned LOB domain sequences from <i>Lotus japonicus</i> and <i>Medicago truncatula</i>.</p

The phylogenetic tree of LBD proteins form <i>Lotus japonicus</i> and <i>Medicago truncatula</i>.

<p>The amino acid sequences of the LBD proteins were aligned with Clustal X, and the phylogenetic tree was constructed using the neighbor-joining method of MEGA 5.0 software.</p

Expression profiles of LBD genes in <i>Lotus japonicus</i>.

<p>(A) Heatmap showing LBD gene expression patterns in different tissues/organs/development stages. The scale at the bottom represents log2 value. (B) Some genes highly expressed in leaf (the blue box) were confirmed by quantitative RT-PCR. The expression level of stem sample was normalized to 1.</p

Amino acid sequence alignments of LOB domain region from <i>Lotus japonicus</i> and <i>Medicago truncatula</i>.

<p>The N-terminal LOB domain includes cysteine C block, GAS block and leucine-zipper-like regions is displayed. The valine (V) and leucine (L) residues required for motor organ specification in pea were denoted by red arrow and red frame. An arginine (R) in the GAS block required for motor organ specification was denoted by red arrow.</p