Ursolic acid loaded tri-block copolymer nanoparticles based on triphenylphosphine for mitochondria-targeted cancer therapy.

A novel biodegradable amphiphilic triblock copolymer, polyphosphate, polyethylene glycol, and polylactic acid (PAEEP-PEG-PLLA), was synthesized by twice ring-opening polymerization and triphenylphosphine (TPP) was grafted onto the block copolymer to synthesize a carrier material TPP-PAEEP-PEG-PLLA, which was identified by1H-nuclear magnetic resonance (1H-NMR) spectroscopy. The TPP-PAEEP-PEG-PLLA nanoparticles encapsulated with ursolic acid (UA) were prepared by the emulsion-solvent evaporation method and characterized by dynamic light scattering. The mitochondrial targeting ability of fluorescently labeled nanoparticles was evaluated by laser confocal microscopy. The average particle size and surface charge of the UA -loaded nanoparticle solution were 180.07 ± 1.67 nm and +15.57 ± 1.33 mV, respectively. The biocompatibility of nanoparticles was briefly evaluated by erythrocyte hemolysis assay.In vitrocell proliferation assay and scratch migration assay were performed to compare the difference in anti-tumor effect between UA and UA nanoparticles. The results showed that TPP-modified triblock copolymers had good mitochondrial targeting and improved the low bioavailability of UA, and UA nanoparticles exhibited more pronounced anti-tumor capabilities. In summary, the results suggested that our UA nanoparticles were a promising drug-targeted delivery system for the treatment of tumors.

SHC4 orchestrates ß-catenin pathway-mediated metastasis in triple-negative breast cancer by promoting Src kinase autophosphorylation.

Triple-negative breast cancer (TNBC) is highly aggressive and metastatic, and has the poorest prognosis among all breast cancer subtypes. Activated ß-catenin is enriched in TNBC and involved in Wnt signaling-independent metastasis. However, the underlying mechanisms of ß-catenin activation in TNBC remain unknown. Here, we found that SHC4 was upregulated in TNBC and high SHC4 expression was significantly correlated with poor outcomes. Overexpression of SHC4 promoted TNBC aggressiveness in vitro and facilitated TNBC metastasis in vivo. Mechanistically, SHC4 interacted with Src and maintained its autophosphorylated activation, which activated ß-catenin independent of Wnt signaling, and finally upregulated the transcription and expression of its downstream genes CD44 and MMP7. Furthermore, we determined that the PxPPxPxxxPxxP sequence on CH2 domain of SHC4 was critical for SHC4-Src binding and Src kinase activation. Overall, our results revealed the mechanism of ß-catenin activation independent of Wnt signaling in TNBC, which was driven by SHC4-induced Src autophosphorylation, suggesting that SHC4 might be a potential prognostic marker and therapeutic target in TNBC.

Development of a nomogram for predicting survival of breast cancer patients with neoadjuvant chemotherapy: a dynamic analysis for systemic inflammation response index.

Background: The systemic inflammation response index (SIRI) has been reported to associate with survival outcomes in breast cancer patients. However, the effects of baseline SIRI and SIRI change after neoadjuvant chemotherapy (NACT) have not been thoroughly investigated. This study aimed to evaluate the role of baseline SIRI and SIRI change after NACT in predicting survival outcomes, and establish a nomogram based on SIRI. Methods: A total of 260 patients diagnosed with breast cancer who received NACT between January 2014 and December 2018 at our hospital were included. The clinical data were retrospectively collected from the medical records management system. The associations between clinicopathological factors and baseline SIRI, pathological complete response (pCR) were analyzed by Student's t-test, Chi-squared test, or Fisher's exact test. The association between clinicopathological factors and disease-free survival (DFS) was evaluated by univariate and multivariate Cox regression analyses. Results: Patients with a tumor-node-metastasis (TNM) stage of I, II, and III were 1.9%, 20.0%, and 78.1% respectively. The median follow-up time was 40 months, and 74 (28.5%) patients had cancer recurrence during the follow-up. Both in the univariate and multivariate analysis, Ki-67, pCR, and baseline SIRI were independent factors associated with DFS. Patients with low baseline SIRI had prolonged DFS compared with those with high baseline SIRI [≤1.6×109 vs. >1.6×109, hazard ratio (HR) =0.545, P=0.028]. In addition, SIRI change after NACT was also an independent factor associated with DFS, and patients with minor SIRI change had longer DFS than patients with major SIRI change (>50% or <-30% vs. ≤50% and ≥-30%, HR =1.721, P=0.037). Nomograms were established based on Ki-67, pCR, and baseline SIRI or SIRI change after NACT with a concordance index of 0.665 and 0.663 respectively, and the nomogram provided a convenient tool for predicting the probability of DFS. Conclusions: The baseline SIRI and SIRI change after NACT could act as potential biomarkers for predicting survival outcomes in breast cancer. Besides, the nomogram with SIRI is an economic and convenient tool for predicting DFS. Larger prospective studies are needed to verify the results.

(-)-Guaiol inhibit epithelial-mesenchymal transition in lung cancer via suppressing M2 macrophages mediated STAT3 signaling pathway.

In the context of cancer expansion, epithelial-mesenchymal transition (EMT) plays an essential role in driving invasion and metastasis potential of cancer cells. Tumor-associated macrophages (TAMs)-derived factors involved in the initiation and progression of EMT. We assess the role of M2 macrophage in suppressing lung tumors of a natural compound (-)-Guaiol by using macrophage depleted model. Bone marrow-derived monocytes (BMDMs) were extracted and induced to M2-like phenotype in vitro. The co-culture of M2 macrophage and lung cancer cells was established to observe that inhibition of lung tumor growth by (-)-Guaiol requires presence of macrophages. This suppressed effect of (-)-Guaiol was alleviated when mice macrophage was depleted. The expression of M2-like macrophages was strongly reduced by (-)-Guaiol treated mice, but not the changes of M1-like macrophages. In vitro studies, we demonstrated that (-)-Guaiol suppressed M2 polarization of BMDMs, as well as migration, invasion, and EMT of lung cancer cells in co-culture. M2 macrophage-derived interleukin 10 (IL-10) was investigated as a critical signaling molecule between M2 macrophage and lung cancer cells. We have also verified that the mechanism of (-)-Guaiol inhibiting the EMT process of lung cancer is related to the activation of IL-10-mediated signal transducer and activator of transcription 3 (STAT3). These results suggested that the suppressive effect role of (-)-Guaiol in M2 macrophage promoting EMT of lung cancer, which was associated with inhibition of IL-10 mediated STAT3 signaling pathway.

Curcumin protects against the age-related hearing loss by attenuating apoptosis and senescence via activating Nrf2 signaling in cochlear hair cells.

Age-related hearing loss (ARHL) is a most widespread neurodegenerative disease affecting the elderly population, but effective pharmacological treatments remain limited. Curcumin is a bioactive compound of Curcuma longa with antioxidant properties. Herein, we looked into the effects of curcumin on the H2O2-induced oxidative stress in cochlear hair cells and hearing function in an ARHL animal model (C57BL/6J mice). We found that pretreatment of curcumin could attenuate H2O2-induced apoptosis and cell senescence in auditory hair cells and prevent mitochondrial function dysfunction. More specifically, Western blot and luciferase activity assay showed that curcumin activated the nuclear translocation of Nrf2, which in turn triggered the activation of its downstream target gene Heme Oxygenase1 (HO-1). The enhanced Nrf2 and HO-1 activity by curcumin was blocked by the AKT inhibitor LY294002, indicating the protective effect of curcumin was mainly achieved by activating Nrf2/HO-1 through the AKT pathway. Furthermore, the knockdown of Nrf2 with siRNA diminished the protective effects of Nrf2 against apoptosis and senescence, consolidating the pivotal role of Nrf2 in the protective effect of curcumin on auditory hair cells. More importantly, curcumin (10 mg/kg/d) could attenuate progressive hearing loss in C57BL/6J mice, as evident from the reduced threshold of auditory nerve brainstem response. Administration of curcumin also elevated the expression of Nrf2 and reduced the expression of cleaved-caspase-3, p21, and γ-H2AX in cochlear. This study is the first to demonstrate that curcumin can prevent oxidative stress-induced auditory hair cell degeneration through Nrf2 activation, highlighting its potential therapeutic value in preventing ARHL.

Deciphering microbial community dynamics along the fermentation course of soy sauce under different temperatures using metagenomic analysis.

Fermented soy sauce consists of microorganisms that exert beneficial effects. However, the microbial community dynamics during the fermentation course is poorly characterized. Soy sauce production is classified into the stages of mash fermentation with koji (S0), brine addition (S1), microbial transformation (S2), flavor creation (S3), and fermentation completion (S4). In this study, microbial succession was investigated across stages at different temperatures using metagenomics analyses. During mash fermentation, Aspergillus dominated the fungal microbiota in all stages, while the bacterial composition was dominated by Bacillus at room temperature and by a diverse composition of enriched lactic acid bacteria (LAB) at a controlled temperature. Compared with a stable fungal composition, bacterial dynamics were mostly attributable to fluctuations of LAB, which break down carbohydrates into lactic acid. After adding brine, increased levels of Enterococcus and decreased levels of Lactococcus from S1 to S4 may reflect differences in salinity tolerance. Staphylococcus, as a fermentation starter at S0, stayed predominant throughout fermentation and hydrolyzed soybean proteins. Meanwhile, Rhizopus and Penicillium may improve the flavor. The acidification of soy sauce was likely attributable to production of organic acids by Bacillus and LAB under room temperature and controlled temperature conditions, respectively. Metagenomic analysis revealed that microbial succession was associated with the fermentation efficiency and flavor enhancement. Controlled temperature nurture more LAB than uncontrolled temperatures and may ensure the production of lactic acid for the development of soy sauce flavor.

Model for predicting immunotherapy based on M2 macrophage infiltration in TNBC.

Introduction: Compared to other types of breast cancer, triple-negative breast cancer (TNBC) does not effectively respond to hormone therapy and HER2 targeted therapy, showing a poor prognosis. There are currently a limited number of immunotherapeutic drugs available for TNBC, a field that requires additional development. Methods: Co-expressing genes with M2 macrophages were analyzed based on the infiltration of M2 macrophages in TNBC and the sequencing data in The Cancer Genome Atlas (TCGA) database. Consequently, the influence of these genes on the prognoses of TNBC patients was analyzed. GO analysis and KEGG analysis were performed for exploring potential signal pathways. Lasso regression analysis was conducted for model construction. The TNBC patients were scored by the model, and patients were divided into high- and low-risk groups. Subsequently, the accuracy of model was further verified using GEO database and patients information from the Cancer Center of Sun Yat-sen University. On this basis, we analyzed the accuracy of prognosis prediction, correlation with immune checkpoint, and immunotherapy drug sensitivity in different groups. Results: Our findings revealed that OLFML2B, MS4A7, SPARC, POSTN, THY1, and CD300C genes significantly influenced the prognosis of TNBC. Moreover, MS4A7, SPARC, and CD300C were finally determined for model construction, and the model showed good accuracy in prognosis prediction. And 50 immunotherapy drugs with therapeutic significance in different groups were screened, which were assessed possible immunotherapeutics that have potential application and demonstrated the high precision of our prognostic model for predictive analysis. Conclusion: MS4A7, SPARC, and CD300C, the three main genes used in our prognostic model, offer good precision and clinical application potential. Fifty immune medications were assessed for their ability to predict immunotherapy drugs, providing a novel approach to immunotherapy for TNBC patients and a more reliable foundation for applying drugs in subsequent treatments.

Hormesis effects of sulfoxaflor on Aphis gossypii feeding, growth, reproduction behaviour and the related mechanisms.

Sulfoxaflor, an important alternative insecticide in integrated pest management (IPM) strategies, can effectively control sap-feeding insect pests such as Aphis gossypii. Although the side effects of sulfoxaflor have recently attracted widespread attention, its toxicological characteristics and mechanisms are still largely undefined. Therefore, the biological characteristics, life table and feeding behaviour of A. gossypii were studied to evaluate the hormesis effect of sulfoxaflor. Then, the potential mechanisms of induced fecundity associated with the vitellogenin (Ag. Vg) and vitellogenin receptor (Ag. VgR) genes were investigated. Although the LC10 and LC30 concentrations of sulfoxaflor significantly reduced the fecundity and net reproduction rate (R0) of the directly exposed sulfoxaflor-resistant and susceptible aphids, hormesis effects on fecundity and R0 were observed in the F1 generation of Sus A. gossypii when the parental generation was exposed to the LC10 of sulfoxaflor. Moreover, the hormesis effects of sulfoxaflor on phloem feeding were observed in both A. gossypii strains. Additionally, enhanced expression levels and protein content of Ag. Vg and Ag. VgR were observed in progeny generations when F0 was subjected to the trans- and multigenerational sublethal sulfoxaflor exposure. Therefore, sulfoxaflor-induced resurgence might occur in A. gossypii after exposure to sublethal concentrations. Our study could contribute to a comprehensive risk assessment and provide convincing reference to optimize sulfoxaflor in IPM strategies.

Subchronic Oral Toxicity Study of Food-Related Titanium Dioxide Nanoparticles in Rats Involved in Ti Biodistribution and Gut Microbiota.

The widespread use of titanium dioxide nanoparticles (TiO2 NPs) in the food industry has brought about human safety risks related to nanotoxicity. In this study, food-related TiO2 NPs (anatase, 40 nm) were given to rats by oral gavage for 90 days at doses of 10, 100, and 1000 mg/kg bw. An additional two satellite groups underwent the same protocol for 45 days and for 90 days followed by a 28 day recovery. TiO2 NPs tended to agglomerate together in H2O, AGJ, and AIJ. No systemic toxicity was observed after 90 day agglomerated TiO2 NP exposure with no Ti distribution in major tissues/organs. Furthermore, TiO2 NP consumption for 90 days had no impact on microbiota diversity; the community structure of the gut microbiota is shifted to some extent at the genus level. Collectively, the NOAEL of agglomerated TiO2 NPs for 90 days of oral administration was 1000 mg/kg bw, the highest dose tested in male and female rats.

Splicing factor SNRPA associated with microvascular invasion promotes hepatocellular carcinoma metastasis through activating NOTCH1/Snail pathway and is mediated by circSEC62/miR-625-5p axis.

Microvascular invasion (MVI) is a crucial risk factor related to the metastasis of hepatocellular carcinoma (HCC), but the underlying mechanisms remain to be revealed. Characterizing the inherent mechanisms of MVI may aid in the development of effective treatment strategies to improve the prognosis of HCC patients with metastasis. Through the Gene Expression Omnibus (GEO) database, we identified that small nuclear ribonucleoprotein polypeptide A (SNRPA) was related to MVI in HCC. SNRPA was overexpressed in MVI-HCC and correlated with poor patient survival. Mechanistically, SNRPA promoted the epithelial-mesenchymal transition (EMT)-like process for HCC cells to accelerate metastasis by activating the NOTCH1/Snail pathway in vitro and in vivo. Importantly, circSEC62 upregulated SNRPA expression in HCC cells via miR-625-5p sponging. Taking these results together, our study identified a novel regulatory mechanism among SNRPA, miR-625-5p, circSEC62 and the NOTCH1/Snail pathway in HCC, which promoted metastasis of HCC and may provide effective suggestions for improving the prognosis of HCC patients with metastasis.

Microbial Communities Along 2,3,7,8-tetrachlorodibenzodioxin Concentration Gradient in Soils Polluted with Agent Orange Based on Metagenomic Analyses.

The 2,3,7,8-tetrachlorodibenzodioxin (TCDD), a contaminant in Agent Orange released during the US-Vietnam War, led to a severe environmental crisis. Approximately, 50 years have passed since the end of this war, and vegetation has gradually recovered from the pollution. Soil bacterial communities were investigated by 16S metagenomics in habitats with different vegetation physiognomies in Central Vietnam, namely, forests (S0), barren land (S1), grassland (S2), and developing woods (S3). Vegetation complexity was negatively associated with TCDD concentrations, revealing the reasoning behind the utilization of vegetation physiognomy as an indicator for ecological succession along the gradient of pollutants. Stark changes in bacterial composition were detected between S0 and S1, with an increase in Firmicutes and a decrease in Acidobacteria and Bacteroidetes. Notably, dioxin digesters Arthrobacter, Rhodococcus, Comamonadaceae, and Bacialles were detected in highly contaminated soil (S1). Along the TCDD gradients, following the dioxin decay from S1 to S2, the abundance of Firmicutes and Actinobacteria decreased, while that of Acidobacteria increased; slight changes occurred at the phylum level from S2 to S3. Although metagenomics analyses disclosed a trend toward bacterial communities before contamination with vegetation recovery, non-metric multidimensional scaling analysis unveiled a new trajectory deviating from the native state. Recovery of the bacterial community may have been hindered, as indicated by lower bacterial diversity in S3 compared to S0 due to a significant loss of bacterial taxa and recruitment of fewer colonizers. The results indicate that dioxins significantly altered the soil microbiomes into a state of disorder with a deviating trajectory in restoration.

Prognostic value of comprehensive typing based on m6A and gene cluster in TNBC.

BACKGROUND: Triple-negative breast cancer (TNBC) is resistant to targeted therapy with HER2 monoclonal antibodies and endocrine therapy, because it lacks the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC is a subtype of breast cancer with the worst prognosis and the highest mortality rate compared to other subtypes. N6-methyladenosine (m6A) modification is significant in cancer and metastasis, because it can alter gene expression and function at numerous levels, such as RNA splicing, stability, translocation, and translation. There are limited investigations into the connection between TNBC and m6A. MATERIALS AND METHODS: Breast cancer-related data were retrieved from the Cancer Genome Atlas (TCGA) database, and 116 triple-negative breast cancer cases were identified from the data. The GSE31519 data set, which included 68 cases of TNBC, was obtained from the Gene Expression Omnibus (GEO) database. Survival analysis was used to determine the prognosis of distinct m6A types based on their m6A group, gene group, and m6A score. To investigate the potential mechanism, GO and KEGG analyses were performed on the differentially expressed genes. RESULTS: The expression of m6A-related genes and their impact on prognosis in TNBC patients were studied. According to the findings, m6A was crucial in determining the prognosis of TNBC patients, and the major m6A-linked genes in this process were YTHDF2, RBM15B, IGFBP3, and WTAP. YTHDF2, RBM15B and IGFBP3 are associated with poor prognosis, while WTAP is associated with good prognosis. By cluster analysis, the gene cluster and the m6A cluster were beneficial in predicting the prognosis of TNBC patients. The m6A score based on m6A and gene clusters was more effective in predicting the prognosis of TNBC patients. Furthermore, the tumor microenvironment may play an important role in the process of m6A, influencing TNBC prognosis. CONCLUSIONS: N6-adenylic acid methylation (m6A) was important in altering the prognosis of TNBC patients, and the key m6A-associated genes in this process were YTHDF2, RBM15B, IGFBP3, and WTAP. Furthermore, the comprehensive typing based on m6A and gene clusters was useful in predicting TNBC patients' prognosis, showing potential as valuable evaluating tools for TNBC.

Seed treatment with chlorantraniliprole and carbaryl mixture for managing fall armyworm on maize: systemic synergism, control efficiency and synergistic mechanism.

BACKGROUND: Fall armyworm (Spodoptera frugiperda) is one of the major invasive pests in China, and has been widely controlled by labor-intensive foliar sprays of agrochemicals in maize (Zea mays L.). RESULTS: Systemic bioassay showed that mixtures of chlorantraniliprole (Chlor) and carbaryl (Carb) had dramatically synergistic effect on toxicity to S. frugiperda. Particularly, a mixture of Chlor with Carb at a mass ratio of 2:1 (MCC) exhibited the highest toxicity to S. frugiperda. Therefore, seed treatment of Chlor mixed with Carb was studied as a simple, accurate, efficient and low-cost control technology. Our results showed that MCC treatment shortened the median lethal time and 90% lethal time to S. frugiperda compared to Chlor- and Carb-alone treatments. Meanwhile, smaller leaf consumption by S. frugiperda was recorded under MCC treatment compared to Chlor- and Carb-alone treatments. In field trial, maize-seed treatment with MCC showed efficacy up to 39 days post-emergence in preventing S. frugiperda foliar damage at a low infestation pressure. Moreover, chemical quantification by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) showed that Chlor residues were more absorbed and concentrated in maize leaves of MCC treatment, compared to that of Chlor-alone treatment. CONCLUSION: These results suggested that seed treatment with MCC can be applied to increase the control efficacy and reduce the cost of Chlor-alone treatment for controlling S. frugiperda. The present study provided evidence of an enhanced translocation and accumulation of Chlor residues in maize leaves under MCC treatment, which likely contributed to a synergistic effect against S. frugiperda. © 2022 Society of Chemical Industry.

bFGF stimulated plasminogen activation factors, but inhibited alkaline phosphatase and SPARC in stem cells from apical Papilla: Involvement of MEK/ERK, TAK1 and p38 signaling.

INTRODUCTION: Basic fibroblast growth factor (bFGF) plays a critical role in odontoblast differentiation and dentin matrix deposition, thereby aiding pulpo-dentin repair and regeneration. OBJECTIVES: The purpose of this study was to clarify the effects of bFGF on plasminogen activation factors, TIMP-1), ALP; and SPARC (osteonectin) expression/production of stem cells from apical papilla (SCAP) in vitro; and the involvement of MEK/ERK, p38, Akt, and TAK1 signaling. METHODS: SCAP were exposed to bFGF with/without pretreatment and co-incubation with various signal transduction inhibitors (U0126, SB203580, LY294002, and 5Z-7-oxozeaenol). The expression of FGF receptors (FGFRs), PAI-1, uPA, p-ERK, p-TAK1, and p-p38 was analyzed via immunofluorescent staining. The gene expression and protein secretion of SCAP were determined via real-time PCR and ELISA. ALP activity was evaluated via ALP staining. RESULTS: SCAP expressed FGFR1, 2, 3, and 4. bFGF stimulated the PAI-1, uPA, uPAR, and TIMP-1 mRNA expression (p < 0.05). bFGF induced PAI-1, uPA, and soluble uPAR production (p < 0.05) but suppressed the ALP activity and SPARC production (p < 0.05) of SCAP. bFGF stimulated ERK, TAK1, and p38 phosphorylation of SCAP. U0126 (a MEK/ERK inhibitor) and 5Z-7-oxozeaenol (a TAK1 inhibitor) attenuated the bFGF-induced PAI-1, uPA, uPAR, and TIMP-1 expression and production of SCAP, but SB203580 (a p38 inhibitor) did not. LY294002, SB203580, and 5Z-7oxozeaenol could not reverse the inhibition of ALP activity caused by bFGF. Interestingly, U0126 and 5Z-7-oxozeaenol prevented the bFGF-induced decline of SPARC production (p < 0.05). CONCLUSION: bFGF may regulate fibrinolysis and matrix turnover via modulation of PAI-1, uPA, uPAR, and TIMP-1, but bFGF inhibited the differentiation (ALP, SPARC) of SCAP. These events are mainly regulated by MEK/ERK, p38, and TAK1. Combined use of bFGF and SCAP may facilitate pulpal/root repair and regeneration via regulation of the plasminogen activation system, migration, matrix turnover, and differentiation of SCAP.

An insecticide phenotypic resistance diagnostic kit for cotton aphid Aphis gossypii Glover (Hemiptera Aphididae).

BACKGROUND: Aphis gossypii is a notorious pest worldwide, and evidence of resistance of A. gossypii to various insecticides has been documented. Diagnostic tools for the rapid and accurate assessment of insecticide resistance are urgently needed to implement effective pest control and insecticide resistance management strategies. RESULTS: Using this diagnostic kit based on the glass vial bioassay, detection results can be obtained in 3 h and the values of 897.86, 133.57, 12 037.45, 2849.26, 19 457.33 and 215.60 ng/cm2 were finally identified as the actual diagnostic doses of imidacloprid, acetamiprid, thiamethoxam, nitenpyram, dinotefuran and sulfoxaflor, respectively. The regression equation between mortalities under diagnostic doses and actual resistance ratios tested by the leaf-dipping method were conducted in different strains of A. gossypii, and the diagnostic mortality of A. gossypii was negatively correlated with the resistance ratio to imidacloprid (r = -0.986, P = 0.002), acetamiprid (r = -0.964, P = 0.008), thiamethoxam (r = -0.930, P = 0.022), nitenpyram (r = -0.950, P = 0.013), dinotefuran (r = -0.976, P = 0.004) and sulfoxaflor (r = -0.937, P = 0.019). Moreover, four A. gossypii field populations were selected to apply the diagnostic kit in the field. CONCLUSIONS: A diagnostic kit based on the glass vial bioassay for the rapid detection of resistance to imidacloprid, acetamiprid, thiamethoxam, nitenpyram, dinotefuran and sulfoxaflor in A. gossypii was developed. The insecticide diagnostic kit for A. gossypii can be a useful screening tool to determine effective insecticides quickly and accurately. © 2022 Society of Chemical Industry.

A missense mutation in ISPD contributes to maintain muscle fiber stability.

BACKGROUND: Livestock and poultry skeletal muscle development was regulated by a variety of genetic factors playing an essential role in this process. In our de novo sequencing, a missense mutation in ISPD exon 2 showed a selected signature for well-developed muscles. However, the relationship between this mutation and muscle phenotypes remains unclear. RESULTS: Based on the genotype bias of this missense mutation in gamecock chickens, we compared the cross-section of muscle fibers among the individuals with different genotypes with the results showing a genotype preference of this missense mutation in the chickens with hypertrophic muscle fibers. Comparing TT- and CC-genotype ISPD showed that TT- genotype was associated with heavier skeletal muscle and a better effect on myogenesis and myofiber stability. At cellular level, ISPD was identified to inhibit myoblast proliferation, differentiation and antagonize of muscular atrophy. CONCLUSION: It can be concluded that the missense mutation of Arg84Lys in ISPD was associated with well-developed muscles and demonstrated to improve chicken muscles' development.

Chicken Protein S Gene Regulates Adipogenesis and Affects Abdominal Fat Deposition.

(1) Background: Excessive abdominal fat deposition in broilers not only causes feed waste but also leads to a series of metabolic diseases. It has gradually become a new breeding goal of the broiler industry to improve growth rates and to reduce abdominal fat rates. In a previous study, PROS1 was highly expressed in low-abdominal fat broilers, suggesting a potential role in broilers adipogenesis. However, the function of PROS1 in preadipocytes and its association with abdominal fat traits need to be characterized. (2) Methods: qRT-PCR and Western Blot were used to quantify gene expression at the RNA and protein levels; flow cytometry and EdU were carried out to detect cell proliferation; and a GLM analysis was used to determine the association between PROS1 SNPs and carcass traits. (3) Results: PROS1 was downregulated in high-abdominal fat chicken; PROS1 contributed preadipocyte proliferation but suppressed preadipocyte differentiation; and the SNPs in the PROS1 5' flank were significantly associated with the abdominal fat weight rate. (4) Conclusions: Chicken PROS1 is able to suppress adipogenesis, and its polymorphisms are associated with the abdominal fat weight rate, which can be considered the molecular markers for chicken breeding, indicating that PROS1 is an effective potential gene in regulating abdominal fat deposition.

A nomogram based on clinical factors for preoperative prediction of nipple involvement in breast cancer.

Background: At present, the indication for nipple-sparing mastectomy (NSM) remains inconclusive, and occult nipple involvement (NI) is one of the most important problems when carrying out NSM. Therefore, we aimed to identify the predictive factors of NI, to provide a tool for selecting suitable candidates for NSM. Methods: In this retrospective study, a total of 250 breast cancer patients who received mastectomy were recruited, and the association between NI and tumor clinicopathologic characteristics was investigated. Nipple signs, tumor size measured by ultrasound (US), and tumor location were developed as a nomogram to predict NI. Results: Among the 250 patients, 34 (12.6%) had NI, and 216 (86.4%) did not. In the training group, NI was associated with nipple signs, tumor size, tumor-nipple distance (TND), tumor location, lymph node metastasis, and HER2 overexpression. Both in the training and in the validation groups, NI showed a significant association with nipple signs, tumor size measured by ultrasound, and tumor location. Based on these three clinical factors, the preoperative model nomogram was proved to have high efficiency in predicting NI, possessing a sensitivity of 80.0% and a specificity of 86.7% in the validation group. Conclusions: We proposed a predictive model nomogram utilizing preoperative tumor characteristics, including nipple signs, tumor size measured by ultrasound, and tumor location. This predictive model could help in the planning of nipple-sparing mastectomy.

Breast Cancer Subtypes Based on Hypoxia-Related Gene Sets Identify Potential Therapeutic Agents.

Purpose: The hypoxic tumor microenvironment was reported to be involved in different tumorigenesis mechanisms of breast cancer (BC). We aimed to establish a hypoxia-related gene signature to identify a new BC subtype through the clustering analysis and explore potential compounds targeting the BC subtypes. Methods: Gene expression data and clinical features of BC and adjacent non-tumor tissues were downloaded from the Cancer Genome Atlas-Breast cancer (TCGA-BRCA) database. We comprehensively revealed the activity changes of Gene Ontology (GO) biological processes (BP) gene sets in BC by gene set variation analysis (GSVA) and identified three hypoxia-related BC subtypes. We then matched the differentially expressed gene profile of each subtype with the gene profile in CMap database to identify the potential agents targeting the BC subtypes. Results: 562 of Gene Ontology biological processes gene sets significantly correlated with hypoxia score in breast cancer. 969 BC patients were clustered into three subtypes based on the enrichment score of hypoxia-associated gene sets. Subtype 1 patients displayed better survival than subtype 2 and 3. KEGG pathway enrichment analysis of each subtype was performed based on the unique differential expression genes profile. In subtype 1, the upregulated genes were associated with lipid and amino acid metabolism regulation; in subtype 2, the upregulated genes were associated with metabolic energy regulation, while in subtype 3, the upregulated genes were associated with apoptosis and protein process. Using the CMap database, 55, 111 and 63 compounds were identified, targeting subtype 1, 2, and 3, respectively. Conclusion: In this study, novel hypoxia-related subtypes were developed for patients with BC. In addition, biological processes associated with differential expression genes profile and potential therapeutic target compounds were identified in each subtype. The new classification might provide a better understanding of the role of hypoxia in breast cancer and more individualized treatment for patients.

Comparative Toxicity and Joint Effects of Chlorantraniliprole and Carbaryl Against the Invasive Spodioptera frugiperda (Lepidoptera: Noctuidae).

Fall armyworm, Spodoptera frugiperda, is one of the most devastating invasive pests in China. Chlorantraniliprole (CH) is currently the main agent for controlling S. frugiperda. Carbaryl (CA) has been widely used as a foliar treatment to control S. frugiperda, although the pest has become highly resistant to it. This study investigates the comparative toxicity and joint effects of CH and CA on S. frugiperda. Time-toxicity results showed that CH had high toxicity to 1st and 3rd instar larvae, whereas CA had very low toxicity to 1st and 3rd instar larvae. The mixtures of CH and CA at different mass ratios showed strong synergistic effects on toxicity, and the mass ratio of 2:1 exhibited the highest toxicity to S. frugiperda. Furthermore, the synergistic toxicity of CH and CA at the 2:1 mass ratio (CH+CA) was also verified in field populations of S. frugiperda. The life-history parameters showed that CH+CA dramatically decreased the survival rate and fecundity of the parent population (F0) compared with CH treatment at the same concentration. Besides, CH and CH+CA mixture showed induction effect on cytochrome P450s and glutathione-S-transferases (GSTs) activities in S. frugiperda, with cytochrome P450s enzyme responding the fastest. In conclusion, this research found CH+CA provided synergistic effects on the toxicity and the sublethal effect on larvae. The joint effects on the life-history parameters and the detoxifying enzymes in S. frugiperda, may be useful for implementing IPM programs against this Lepidoptera pest.