Targeting KRASG12D mutation in non-small cell lung cancer: molecular mechanisms and therapeutic potential.

Lung malignant tumors are a type of cancer with high incidence and mortality rates worldwide. Non-small cell lung cancer (NSCLC) accounts for over 80% of all lung malignant tumors, and most patients are diagnosed at advanced stages, leading to poor prognosis. Over the past decades, various oncogenic driver alterations associated with lung cancer have been identified, each of which can potentially serve as a therapeutic target. Rat sarcoma (RAS) genes are the most commonly mutated oncogenes in human cancers, with Kirsten rat sarcoma (KRAS) being the most common subtype. The role of KRAS oncogene in NSCLC is still not fully understood, and its impact on prognosis remains controversial. Despite the significant advancements in targeted therapy and immune checkpoint inhibitors (ICI) that have transformed the treatment landscape of advanced NSCLC in recent years, targeting KRAS (both directly and indirectly) remains challenging and is still under intensive research. In recent years, significant progress has been made in the development of targeted drugs targeting the NSCLC KRASG12C mutant subtype. However, research progress on target drugs for the more common KRASG12D subtype has been slow, and currently, no specific drugs have been approved for clinical use, and many questions remain to be answered, such as the mechanisms of resistance in this subtype of NSCLC, how to better utilize combination strategies with multiple treatment modalities, and whether KRASG12D inhibitors offer substantial efficacy in the treatment of advanced NSCLC patients.

Reprogramming of lipid metabolism in the tumor microenvironment: a strategy for tumor immunotherapy.

Lipid metabolism in cancer cells has garnered increasing attention in recent decades. Cancer cells thrive in hypoxic conditions, nutrient deficiency, and oxidative stress and cannot be separated from alterations in lipid metabolism. Therefore, cancer cells exhibit increased lipid metabolism, lipid uptake, lipogenesis and storage to adapt to a progressively challenging environment, which contribute to their rapid growth. Lipids aid cancer cell activation. Cancer cells absorb lipids with the help of transporter and translocase proteins to obtain energy. Abnormal levels of a series of lipid synthases contribute to the over-accumulation of lipids in the tumor microenvironment (TME). Lipid reprogramming plays an essential role in the TME. Lipids are closely linked to several immune cells and their phenotypic transformation. The reprogramming of tumor lipid metabolism further promotes immunosuppression, which leads to immune escape. This event significantly affects the progression, treatment, recurrence, and metastasis of cancer. Therefore, the present review describes alterations in the lipid metabolism of immune cells in the TME and examines the connection between lipid metabolism and immunotherapy.

Targeting Neutrophil Extracellular Traps: A Novel Antitumor Strategy.

The clinical efficacy of surgery, radiotherapy, and chemotherapy for cancer is usually limited by the deterioration of tumor microenvironment (TME). Neutrophil extracellular traps (NETs) are decondensed chromatin extruded by neutrophils and are widely distributed among various cancers, such as pancreatic cancer, breast cancer, and hepatocellular carcinoma. In the TME, NETs interact with stromal components, immune cells and cancer cells, which allows for the reshaping of the matrix and the extracellular environment that favors the initiation, progression, and metastasis of cancer. In addition, NETs impair the proliferation and activation of T cells and NK cells, thus producing a suppressive TME that restricts the effect of immunotherapy. A better understanding of the function of NETs in the TME will provide new opportunities for the prevention of cancer metastasis and the discovery of novel therapy strategies.

PCIF1, the only methyltransferase of N6,2-O-dimethyladenosine.

N6-methyladenosine(m6A), is the most abundant post-transcriptional modification of mRNA in biology. When the first nucleotide after the m7G cap is adenosine, it is methylated at the N6 position to form N6,2-O-dimethyladenosine (m6Am). m6Am is a reversible modification located at the first transcribed nucleotide, which is present in about 30% of cellular mRNAs, thus m6Am can have a significant impact on gene expression in the transcriptome. Phosphorylated CTD interaction factor 1(PCIF1), the unique and specific methyltransferase of m6Am, has been shown to affect mRNA stability, transcription, and translation. Several studies have shown that PCIF1 is clearly associated with tumor, viral, and endocrine diseases. Moreover, PCIF1 may be related to the tumor microenvironment, immune cell typing, and programmed cell death protein 1(PD-1) drug resistance. Here, we summarize the mechanism of PCIF1 involvement in mRNA modifications, and outline m6Am modifications and diseases in which PCIF1 is involved. We also summarized the role of PCIF1 in immune and immune checkpoint blockade(ICB) treatment, and predicted the possibility of PCIF1 as a biomarker and therapeutic target.

Quality evaluation of Hawk tea from different months and regions based on quantitative analysis of multiple components with a single marker (QAMS) combined with HPLC fingerprint.

BACKGROUND: Hawk tea, a medicinal and edible plant, has been consumed for thousands of years in Southwest China. To date, no unified food safety standard for Hawk tea has been established, and systematic research on the quality of Hawk tea is lacking. OBJECTIVE: The aim of this study was to develop a comprehensive evaluation method for the quality of Hawk tea based on inclusions content, high-performance liquid chromatography (HPLC) fingerprinting combined with the quantitative analysis of multiple components with a single marker (QAMS) method. METHODS: The contents of total flavonoids, total phenols, total polysaccharides, and total protein were determined using the colorimetric method. An effective comprehensive evaluation method was established to classify the 16 batches of samples based on HPLC fingerprint analysis combined with similarity analysis (SA), hierarchical cluster analysis (HCA), principal component analysis (PCA), partial least-squares discrimination analysis (PLS-DA), and the QAMS method. RESULTS: Flavonoids were the main chemical components of Hawk tea. The accuracy of the QAMS method was verified by comparing the calculated results with those of the external standard method (ESM). No significant differences were found between the two methods. Additionally, the fingerprint of Hawk tea was also established. CONCLUSION: The method established in this study can be used for the comprehensive quality evaluation of Hawk tea and can also provide a reference for the quality evaluation of other herbal medicines.

Mechanisms of N6­methyladenosine modification in tumor development and potential therapeutic strategies (Review).

N6­methyladenosine (m6A) modification, as the most common and abundant type of RNA modification in mammalian cells, participates in the processes of mRNA transcription, translation, splicing and degradation, serving to regulate RNA stability. In recent years, a large number of studies have indicated that m6A modification is able to affect tumor progression, participate in tumor metabolism, regulate tumor cell ferroptosis and change the tumor immune microenvironment, thereby affecting tumor immunotherapy. In the current review, the main features of m6A­associated proteins are presented with a focus on the mechanisms underpinning their roles in tumor progression, metabolism, ferroptosis and immunotherapy, also emphasizing the potential of targeting m6A­associated proteins as a promising strategy for the treatment of cancer.

RNA N6-methyladenosine (m6A) modification in HNSCC: molecular mechanism and therapeutic potential.

Head and neck squamous cell carcinoma ranks seventh in incidence of malignant tumours in the world. Although there are treatments including surgery, radiotherapy and chemotherapy, targeted therapy and immunotherapy, drug resistance to treatment is caused by various reasons, and the survival rate of patients remains frustrating. To overcome the bottleneck of treatment at this stage, it is urgent to identify possible diagnostic and prognostic markers. N6-methyladenosine is a methylation modification on the sixth N atom of adenine which is the most abundant epitope transcriptome modification in mammalian genes. N6-methyladenosine modification is reversible and results from the interaction among writers, erasers and readers. A large number of studies have proven that N6-methyladenosine modification has important significance in promoting the progression and treatment of tumours and have made great progress in research. In this review, we introduce how N6-methyladenosine modification promotes the occurrence and development of tumours, the mechanism of drug resistance, and new findings of N6-methyladenosine modification in radiotherapy and chemotherapy, immunotherapy, and targeted therapy. N6-methyladenosine modification provides more possibilities for improving the overall survival rate and prognosis of patients.

PYGL-mediated glucose metabolism reprogramming promotes EMT phenotype and metastasis of pancreatic cancer.

Epithelial-mesenchymal transition (EMT) is closely associated with tumor invasion and metastasis. However, key regulators of EMT in pancreatic ductal adenocarcinoma (PDAC) need to be further studied. Bioinformatics analyses of pancreatic cancer public datasets showed that glycogen phosphorylase L (PYGL) expression is elevated in quasimesenchymal PDAC (QM-PDAC) and positively associated with EMT. In vitro cellular experiments further confirm PYGL as a crucial EMT regulator in PDAC cells. Functionally, PYGL overexpression promotes cell migration and invasion in vitro and facilitates liver metastasis in vivo, while PYGL knockdown has opposite effects. Mechanically, hypoxia induces PYGL expression in a hypoxia inducible factor 1α (HIF1α)-dependent manner and promotes glycogen accumulation. Elevated PYGL mobilizes accumulated glycogen to fuel glycolysis via its activity as a glycogen phosphorylase, thus inducing the EMT process, which could be suppressed by the glycolysis inhibitor 2-deoxy-D-glucose (2-DG). Clinically, PYGL expression is upregulated in PDAC and correlates with its malignant features and poor prognosis. Collectively, the data from our study reveal that the hypoxia/PYGL/glycolysis-induced EMT promotes PDAC metastasis, which establishes the rational for targeting hypoxia/PYGL/glycolysis/EMT signaling pathway against PDAC.

m6A methylation modification and immune cell infiltration: implications for targeting the catalytic subunit m6A-METTL complex in gastrointestinal cancer immunotherapy.

N6-methyladenosine (m6A) methylation modification is a ubiquitous RNA modification involved in the regulation of various cellular processes, including regulation of RNA stability, metabolism, splicing and translation. Gastrointestinal (GI) cancers are some of the world's most common and fatal cancers. Emerging evidence has shown that m6A modification is dynamically regulated by a complex network of enzymes and that the catalytic subunit m6A-METTL complex (MAC)-METTL3/14, a core component of m6A methyltransferases, participates in the development and progression of GI cancers. Furthermore, it has been shown that METTL3/14 modulates immune cell infiltration in an m6A-dependent manner in TIME (Tumor immune microenvironment), thereby altering the response of cancer cells to ICIs (Immune checkpoint inhibitors). Immunotherapy has emerged as a promising approach for treating GI cancers. Moreover, targeting the expression of METTL3/14 and its downstream genes may improve patient response to immunotherapy. Therefore, understanding the role of MAC in the pathogenesis of GI cancers and its impact on immune cell infiltration may provide new insights into the development of effective therapeutic strategies for GI cancers.

Risk Factors for Contralateral Occult Papillary Thyroid Carcinoma in Patients with Clinical Unilateral Papillary Thyroid Carcinoma: A Case-Control Study.

Introduction: Papillary thyroid cancer (PTC) is one of the most prevalent endocrine malignancies that has increased in recent decades around the world. Although the indicator for navigating the surgical extent in PTC patients is still in debate, a key issue is how to predict that there are undetected preoperative tumors in the contralateral thyroid lobe. This study aims to find risk factors for contralateral occult papillary thyroid cancer (COPTC) to facilitate more accurate surgical decisions made for patients with PTC. Materials and Methods: In our study, we included 229 patients who underwent total thyroidectomy plus central and ipsilateral lateral lymph nodes dissection from January 1, 2019, to September 1, 2021. Univariate and multivariate logistic regression analyses were conducted to assess the association between COPTC and clinical-pathological characteristics, as well as the relation between the diameter of the occult lesions and predictors. The forest plot was plotted to visualize the prediction factors from the output of the multivariate regression analysis. A ROC curve was used to evaluate the combining potency of all the risk factors. Results: Of the 229 patients included in our study, 46 with COPTC were assigned to the case group, representing 20.1% in this study. Multifocality in one lobe (OR = 2.21, P=0.03), intact capsule (OR = 2.54, P=0.01), central lymph node metastasis (OR = 3.00, P=0.02), and Hashimoto's thyroiditis (OR = 2.08, P = 0.04) are more prone to present contralateral occult papillary thyroid carcinoma. The ROC curve of the aggregate potency of the risk factors presents AUC = 0.701 (P < 0.001), and the best cutoff value was 2.02, with a sensitivity of 78.3% and specificity of 55.2%. Furthermore, there was no statistical correlation between the diameter of the occult tumor and the four obtained variables. Conclusion: Patients with multifocality in one lobe, intact capsule, central lymph node metastasis, and HT may harbor contralateral papillary thyroid carcinoma. It is essential to be prudent to make a surgical or follow-up decision on these patients. In addition, more clinical rather than postoperative pathological indicators need to be revealed in the future.

ACSL4 is essential for radiation-induced intestinal injury by initiating ferroptosis.

Lipid peroxidation-induced ferroptosis is a newly recognized type of programmed cell death. With the method of RNA sequencing, we found that irradiation (IR) markedly increased the expression of ferroptosis promotive genes, whereas reduced the expression of ferroptosis suppressive genes in murine intestine tissues, when compared with those of liver and lung tissues. By using ferroptosis inducer RSL-3 and inhibitor liproxstatin-1, we found that ferroptosis is essential for IR-induced intestinal injury. Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) is an important component for ferroptosis execution, and we found that ACSL4 expression was significantly upregulated in irradiated intestine tissues, but not in liver or lung tissues. Antibacterial and antifungal regents reduced the expression of ASCL4 and protected against tissue injury in irradiated intestine tissues. Further studies showed that troglitazone, a ACSL4 inhibitor, succeeded to suppresses intestine lipid peroxidation and tissue damage after IR.

Genetic and transcriptomic dissection of an artificially induced paired spikelets mutant of wheat (Triticum aestivum L.).

KEY MESSAGE: Morphological, genetic and transcriptomic characterizations of an EMS-induced wheat paired spikelets (PS) mutant were performed. A novel qualitative locus WPS1 on chromosome 1D was identified. Grain yield of wheat is significantly associated with inflorescence or spike architecture. However, few genes related to wheat spike development have been identified and their underlying mechanisms are largely unknown. In this study, we characterized an ethyl methanesulfonate (EMS)-induced wheat mutant, wheat paired spikelets 1 (wps1). Unlike a single spikelet that usually develops at each node of rachis, a secondary spikelet appeared below the primary spikelet at most of the rachis nodes of wps1. The microscope observation showed that the secondary spikelet initiated later than the primary spikelet. Genetic analysis suggested that the PS of wps1 is controlled by a single dominant nuclear gene, designated WHEAT PAIRED SPIKELETS 1 (WPS1). Further RNA-seq based bulked segregant analysis and molecular marker mapping localized WPS1 in an interval of 208.18-220.92 Mb on the chromosome arm 1DL, which is different to known genes related to spike development in wheat. By using wheat omics data, TraesCS1D02G155200 encoding a HD-ZIP III transcription factor was considered as a strong candidate gene for WPS1. Transcriptomic analysis indicated that PS formation in wps1 is associated with auxin-related pathways and may be regulated by networks involving TB1, Ppd1, FT1, VRN1, etc. This study laid the solid foundation for further validation of the causal gene of WPS1 and explored its regulatory mechanism in PS formation and inflorescence development, which may benefit to kernel yield improvement of wheat based on optimization or design of spike architecture in the future.

[Source Apportionment of PM2.5 Based on Hybrid Chemical Transport and Receptor Model in Chongqing].

In order to further improve the accuracy of fine particulate matter (PM2.5) source apportionment results, a hybrid source apportionment approach (CTM-RM) combining the capabilities of a receptor model (RM) and chemical transport model (CTM) was developed. The CTM-RM method was evaluated and applied according to a typical PM2.5 pollution process from January 21 to 27, 2019 in Chongqing. The average value of square prediction error based on CTM-RM was 84.58% lower than that of CAMx/PSAT during the campaign. Compared with that of CAMx/PSAT, the fractional error of PM2.5 and its chemical component concentrations decreased by 15.69%-92.86%. Furthermore, the temporal and spatial variations in PM2.5 source impacts could be obtained using the CTM-RM method in Chongqing. The average adjustment factor (R) values were 1.39±0.38 (agriculture sources), 1.54±0.48 (industrial sources), 1.01±0.13 (power sources), 1.02±0.58 (residential sources), 0.86±0.59 (transportation sources), and 0.58±0.67 (other sources) in the main urban areas of Chongqing. Additionally, the cumulative distribution functions of R were found to be distinct among the six sources. The residential and industrial sources were the main sources of PM2.5, with contributions of 46.23% and 28.23%, respectively. In contrast to that of the other sources, the transportation source impacts of PM2.5 (8.62%) increased significantly from the clear period to pollution period (P<0.001), indicating that the increase in PM2.5 concentrations was mainly driven by vehicular emissions during the pollution period in the main urban areas of Chongqing. The fitting functions between the initial simulated concentrations and R values of each source in the main urban areas of Chongqing could be used to evaluate PM2.5 concentrations at 47 air quality monitoring stations in Chongqing, and the correlation between the refined simulated concentrations and measured concentration of PM2.5 was significant (r=0.82, P<0.001). Compared with that during the clear period, the increases in the percentages of industrial source impacts of PM2.5 in Northeast Chongqing and residential source impacts of PM2.5 in Southeast Chongqing were 17.20% and 9.15% higher, respectively, than that in other areas during the pollution period. By contrast, the increasing percentage of transportation source impacts of PM2.5 in the main urban areas of Chongqing (66.39%) and Western Chongqing (84.16%) from the clear period to the pollution period were higher than that in other areas. The results of CTM-RM on January 26 indicated that the residential source impacts in Northeast Chongqing (64.56%) were higher than those in other areas, and the industry source impacts of PM2.5 were primarily observed in the main urban areas of Chongqing and Western Chongqing, with contributions of 25.26% and 21.20%, respectively.

High-resolution detection of quantitative trait loci for seven important yield-related traits in wheat (Triticum aestivum L.) using a high-density SLAF-seq genetic map.

BACKGROUND: Yield-related traits including thousand grain weight (TGW), grain number per spike (GNS), grain width (GW), grain length (GL), plant height (PH), spike length (SL), and spikelet number per spike (SNS) are greatly associated with grain yield of wheat (Triticum aestivum L.). To detect quantitative trait loci (QTL) associated with them, 193 recombinant inbred lines derived from two elite winter wheat varieties Chuanmai42 and Chuanmai39 were employed to perform QTL mapping in six/eight environments. RESULTS: A total of 30 QTLs on chromosomes 1A, 1B, 1D, 2A, 2B, 2D, 3A, 4A, 5A, 5B, 6A, 6D, 7A, 7B and 7D were identified. Among them, six major QTLs QTgw.cib-6A.1, QTgw.cib-6A.2, QGw.cib-6A, QGl.cib-3A, QGl.cib-6A, and QSl.cib-2D explaining 5.96-23.75% of the phenotypic variance were detected in multi-environments and showed strong and stable effects on corresponding traits. Three QTL clusters on chromosomes 2D and 6A containing 10 QTLs were also detected, which showed significant pleiotropic effects on multiple traits. Additionally, three Kompetitive Allele Specific PCR (KASP) markers linked with five of these major QTLs were developed. Candidate genes of QTgw.cib-6A.1/QGl.cib-6A and QGl.cib-3A were analyzed based on the spatiotemporal expression patterns, gene annotation, and orthologous search. CONCLUSIONS: Six major QTLs for TGW, GL, GW and SL were detected. Three KASP markers linked with five of these major QTLs were developed. These QTLs and KASP markers will be useful for elucidating the genetic architecture of grain yield and developing new wheat varieties with high and stable yield in wheat.

[Speciated Emission Inventory of VOCs from Industrial Sources and Their Ozone Formation Potential in Chongqing].

Based on the basic information of the Second National Pollution Source Census and the VOCs source profiles of industrial industries, we established the speciated emission inventory of major industrial sources in Chongqing in 2017, estimated their ozone formation potential (OFP), and identified the key control species of industrial VOCs and their sources. The results showed that the total VOCs emission from industrial sources and their OFPs were 144.12 kt and 477.34 kt, respectively. Automobile manufacturing, equipment manufacturing, plastic manufacturing, and chemical raw materials and chemical products were all industries that contributed significantly to VOCs emissions and OFP, with VOCs emissions of 37.18, 33.09, 19.47, and 18.14 kt and OFP of 191.43, 153.69, 27.21, and 57.51 kt, respectively. Aromatics were the components with the largest contribution to VOCs emissions and OFP, accounting for 62.55% of the total VOCs emissions and 82.15% of the total OFP, mainly from metal surface coating and petrochemical industries. The major reactive species of industrial source VOCs were m/p-xylene, toluene, ethylbenzene, o-xylene, and propylene, with OFP of 130.47, 103.37, 46.37, 42.83, and 28.26 kt, respectively, cumulatively accounting for 71.11% of the total OFP. In terms of spatial distribution, the emission intensity of VOCs and O3 pollution degree in all districts and counties of Chongqing were relatively consistent; the high value points of VOCs emissions and OFP were mainly distributed in the main urban area and the western area, and the sources of VOCs emission in the main urban area and western area were mainly in metal surface coating and the petrochemical industry, respectively.

[Atmospheric VOCs Pollution Characteristics and Health Risk Assessment of Large-scale Integrated Industrial Area and Surrounding Areas in Southwest China].

To investigate the characteristics of atmospheric volatile organic compound (VOCs) pollution and promote VOCs pollution prevention and control in industrial areas, in December 2020, VOCs samples collected using Summa Canisters at three observation sites were used to study the characteristics of VOCs pollution and source apportionment and to conduct a health risk assessment in large integrated industrial areas and surrounding urban areas in southwest China. The results showed that the mean φ(TVOCs) at site A and site B in an industrial area and at a third urban site were 105.25×10-9, 222.92×10-9, and 82.87×10-9, respectively. Monochloromethane, dichloromethane, acetone, ethanol, and ethane were the species with higher volume fractions at the three sites. Aromatic hydrocarbons and OVOCs had a large contribution to the ozone formation potential (OFP), with a cumulative contribution of more than 50%, and the main reactive species were methyl methacrylate, toluene, p-xylene, and o-xylene; the secondary organic aerosol formation potential (SOAP) of aromatic hydrocarbons contributed more than 80%, with the main active species being toluene, p-xylene, and o-xylene. The results of PMF source analysis showed six main sources of VOCs, in the descending order of the petrochemical industry (21.83%), industrial waste incineration (18.6%), pharmaceutical manufacturing (16.99%), fossil fuel combustion (16.03%), motor vehicle exhaust (14.23%), and chemical manufacturing (12.32%). The mean values of the hazard index (HI) of site A and site B in the industrial area and in the urban site were 0.55, 0.68, and 0.41, respectively, and the mean lifetime cancer risk (LCR) values were 6.71×10-6, 6.72×10-6, and 6.58×10-6, respectively. Both HI and LCR in industrial areas were larger than those in urban areas. The quantitative assessment of risk sources showed that motor vehicle exhaust and fossil fuel combustion contributed relatively high carcinogenic risks.

Genetic dissection of quantitative trait loci for grain size and weight by high-resolution genetic mapping in bread wheat (Triticum aestivum L.).

KEY MESSAGE: Six major QTLs for wheat grain size and weight were identified on chromosomes 4A, 4B, 5A and 6A across multiple environments, and were validated in different genetic backgrounds. Grain size and weight are crucial components of wheat yield. Dissection of their genetic control is thus essential for the improvement of yield potential in wheat breeding. We used a doubled haploid (DH) population to detect quantitative trait loci (QTLs) for grain width (GW), grain length (GL), and thousand grain weight (TGW) in five environments. Six major QTLs, QGw.cib-4B.2, QGl.cib-4A, QGl.cib-5A.1, QGl.cib-6A, QTgw.cib-4B, and QTgw.cib-5A, were consistently identified in at least three individual environments and in best linear unbiased prediction (BLUP) datasets, and explained 5.65-34.06% of phenotypic variation. QGw.cib-4B.2, QTgw.cib-4B, QGl.cib-5A.1 and QGl.cib-6A had no effect on grain number per spike (GNS). In addition to QGl.cib-4A, the other major QTLs were further validated by using Kompetitive Allele Specific PCR (KASP) markers in different genetic backgrounds. Moreover, significant interactions between the three major GL QTLs and two major TGW QTLs were observed. Comparison analysis showed that QGl.cib-5A.1 and QGl.cib-6A are likely new loci. Notably, QGw.cib-4B.2 and QTgw.cib-4B were co-located on chromosome 4B and improved TGW by increasing only GW, unlike nearby or overlapped loci reported previously. Three genes associated with grain development within the QGw.cib-4B.2/QTgw.cib-4B interval were identified by searches on sequence similarity, spatial expression patterns, and orthologs. The major QTLs and KASP markers reported here will be useful for elucidating the genetic architecture of grain size and weight and for developing new wheat cultivars with high and stable yield.

Epigallocatechin gallate prevents peritoneal fibrosis by inhibiting epithelial-mesenchymal transition in human peritoneal mesothelial cells.

The current study set out to elucidate the function of epigallocatechin gallate (EGCG) against peritoneal fibrosis in peritoneal dialysis (PD) patients. Firstly, human peritoneal mesothelial cells (HPMCs) were pretreated with 0, 12.5, 25, 50 or 100µmol/L EGCG. Epithelial-mesenchymal transition (EMT) models were induced by advanced glycation end products (AGEs). Untreated-cells were regarded as the blank control group. Changes in proliferation and migration were analyzed by MTT assay and scratch test and levels of HPMC epithelial and interstitial molecular marker proteins were measured by Western blot assay and immunofluorescence, while trans-endothelial resistance was assessed using an epithelial trans membrane cell resistance meter. Inhibition rates of HPMCs, migration numbers and the levels of Snail, E-cadherin, CK and ZO-1 were all decreased, while the levels of α-SMA and FSP1 and trans cellular resistance values were increased in treatment groups (P<0.05). With the increase of EGCG concentrations, HPMCs growth inhibition rates and migration numbers, the levels of α-SMA and FSP1 and TER values were decreased and the levels of Snail, E-cadherin, CK and ZO-1 were enhanced (P<0.05). Overall, the current study highlights that EGCG effectively inhibits the proliferation and migration of HPMCs, increases permeability, suppresses EMT and ultimately delays peritoneal fibrosis.

Targeting Adipokines in Obesity-Related Tumors.

Obesity, a global epidemic, is an independent risk factor for the occurrence and development of a variety of tumors, such as breast cancer, pancreatic cancer, ovarian cancer and colorectal cancer. Adipocytes are important endocrine cells in the tumor microenvironment of obesity-related tumors, which can secrete a variety of adipokines (such as leptin, adiponectin, estrogen, resistin, MIF and MCP-1, etc.), among which leptin, adiponectin and estrogen are the most in-depth and valuable ones. These adipokines are closely related to tumorigenesis and the progression of tumors. In recent years, more and more studies have shown that under chronic inflammatory conditions such as obesity, adipocytes secrete more adipokines to promote the tumorigenesis and development of tumors. However, it is worth noting that although adiponectin is also secreted by adipocytes, it has an anti-tumor effect, and can cross-talk with other adipokines (such as leptin and estrogen) and insulin to play an anti-tumor effect together. In addition, obesity is the main cause of insulin resistance, which can lead to the increase of the expression levels of insulin and insulin-like growth factor (IGF). As important regulators of blood glucose and lipid metabolism, insulin and IGF also play an important role in the progress of obesity related tumors. In view of the important role of adipokines secreted by adipocytes and insulin/IGF in tumors, this article not only elaborates leptin, adiponectin and estrogen secreted by adipocytes and their mechanism of action in the development of obesity- related tumors, but also introduces the relationship between insulin/IGF, a regulator of lipid metabolism, and obesity related tumors. At the same time, it briefly describes the cancer-promoting mechanism of resistin, MIF and MCP-1 in obesity-related tumors, and finally summarizes the specific treatment opinions and measures for various adipokines and insulin/insulin-like growth factors in recent years.

Identification and validation of two major QTLs for spike compactness and length in bread wheat (Triticum aestivum L.) showing pleiotropic effects on yield-related traits.

KEY MESSAGE: Two major and stable QTLs for spike compactness and length were detected and validated in multiple genetic backgrounds and environments, and their pleiotropic effects on yield-related traits were analyzed. Spike compactness (SC) and length (SL) are greatly associated with wheat (Triticum aestivum L.) grain yield. To detect quantitative trait loci (QTL) associated with SC and SL, two biparental populations derived from crosses of Chuanmai42/Kechengmai1 and Chuanmai42/Chuannong16 were employed to perform QTL mapping in five environments. A total of 34 QTLs were identified, in which six major QTLs were repeatedly detected in more than four environments and the best linear unbiased prediction datasets, explaining 7.13-33.6% of phenotypic variation. These major QTLs were co-located in two genomic regions on chromosome 5A and 6A, namely QSc/Sl.cib-5A and QSc/Sl.cib-6A, respectively. By developing kompetitive allele-specific PCR (KASP) markers that linked to them, the two loci were validated in different genetic backgrounds, and their interactions were also analyzed. Comparison analysis showed that QSc/Sl.cib-5A was not Vrn-A1 and Q, and QSc/Sl.cib-6A was likely a new locus for SC and SL. Both QSc/Sl.cib-5A and QSc/Sl.cib-6A had pleiotropic effects on other yield-related traits including plant height, thousand grain weight and grain length. Therefore, the two loci combined with the developed KASP markers might be potentially applicable in wheat breeding. Furthermore, based on the spatiotemporal expression patterns, gene annotation, orthologous search and sequence differences, TraesCS5A01G301400 and TraesCS6A01G090300 were considered as potential candidates for QSc/Sl.cib-5A and QSc/Sl.cib-6A, respectively. These results provided valuable information for fine mapping and cloning of the two loci in the future.