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Insect pest recognition has always been a significant branch of agriculture and ecology. The slight variance among different kinds of insects in appearance makes it hard for human experts to recognize. It is increasingly imperative to finely recognize specific insects by employing machine learning methods. In this study, we proposed a feature fusion network to synthesize feature presentations in different backbone models. Firstly, we employed one CNN-based backbone ResNet, and two attention-based backbones Vision Transformer and Swin Transformer to localize the important regions of insect images with Grad-CAM. During this process, we designed new architectures for these two Transformers to enable Grad-CAM to be applicable in such attention-based models. Then we further proposed an attention-selection mechanism to reconstruct the attention area by delicately integrating the important regions, enabling these partial but key expressions to complement each other. We only need part of the image scope that represents the most crucial decision-making information for insect recognition. We randomly selected 20 species of insects from the IP102 dataset and then adopted all 102 kinds of insects to test the classification performance. Experimental results show that the proposed approach outperforms other advanced CNN-based models. More importantly, our attention-selection mechanism demonstrates good robustness to augmented images. [ABSTRACT FROM AUTHOR]

Gas explosion (GE)-induced traumatic brain injury (TBI) can affect thyroid hormone (TH) homeostasis in miners. This study evaluated the effects of hepatic transthyretin and hypothalamic-pituitary-thyroid (HPT) axis on thyroids and explored the protective effect and mechanism of curcumin on GE-induced TBI. Thirty rats were randomly divided into three groups (10 per group): first group (control group)—rats received GE treatment once; second group (GE group)—rats received GE treatment (200 m from the source of the explosion once); third group (GE + Cur group)—rats received curcumin (Cur) by lavage at a dose of 100 mg/kg/day once every other day for 7 days after receiving GE. After GE, the pathological changes were analyzed by hemotoxylin and eosin staining, and the levels of serum reactive oxygen species (ROS), urine iodine (UI), THs, nuclear factor-kappa B (NF-κB), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and malondialdehyde (MDA) were analyzed using ELISA. Expression of proteins in the HPT axis of rats was examined by immunohistochemistry and Western blotting. We found that GE could induce pathologic changes in rat thyroid and liver. Serum levels of THs, NF-κB and serum redox state became unbalanced in rats after GE. GE could inhibit the biosynthesis and biotransformation of THs by affecting key HPT axis proteins. Additionally, GE reduced the level of hepatic transthyretin. Serum THs levels and thyroid sections were almost recovered to normal after curcumin treatment. The aforementioned key HPT axis proteins in the curcumin group showed opposite expression trends. In summary, GE affected THs balance while curcumin can protect against these injury effects by affecting TH biosynthesis, biotransformation, and transport, and inducing oxidative stress and inflammatory responses. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is among the most prevalent primary liver diseases worldwide and can develop into various conditions, ranging from simple steatosis, through non-alcoholic steatohepatitis (NASH), to fibrosis, and eventually cirrhosis and hepatocellular carcinoma. Nevertheless, there is no effective treatment for NAFLD due to the complicated etiology. Recently, activation of the NLPR3 inflammasome has been demonstrated to be a contributing factor in the development of NAFLD, particularly as a modulator of progression from initial hepatic steatosis to NASH. NLRP3 inflammasome, as a caspase-1 activation platform, is critical for processing key pro-inflammatory cytokines and pyroptosis. Various stimuli involved in NAFLD can activate the NLRP3 inflammasome, depending on the diverse cellular stresses that they cause. NLRP3 inflammasome-related inhibitors and agents for NAFLD treatment have been tested and demonstrated positive effects in experimental models. Meanwhile, some drugs have been applied in clinical studies, supporting this therapeutic approach. In this review, we discuss the activation, biological functions, and treatment targeting the NLRP3 inflammasome in the context of NAFLD progression. Specifically, we focus on the different types of therapeutic agents that can inhibit the NLRP3 inflammasome and summarize their pharmacological effectiveness for NAFLD treatment. [ABSTRACT FROM AUTHOR]

Metastasis is a multistep process that depends on the interactions between tumor cells and their microenvironment. Macrophages in the tumor microenvironment show high polarization plasticity and have a paradoxical role in cancer progression. Hijacked by tumor-promoting signals, the polarization status of macrophages was pathologically disturbed and believed to be the decisive mechanism forcing the progression of metastasis. In this study, we explored the immunological activity of Chamaejasmin B (ICJ), a previously proved inhibitor for metastasis, in macrophages from metastatic microenvironment. When intravenously injected of 4T1 cells in mice, ICJ significantly inhibited its metastatic outgrowth. Taking tumor cell and macrophage as a functional integrity, an adoptive transfer model was established in vitro to exclude the direct effect of ICJ on tumor. The findings suggest a dual influence of ICJ on both tumors and macrophages, as indicated by the rebalance of macrophage polarization and suppression of clonogenic potential in tumor cells. Mechanistically, ICJ redirected M2-dominant polarization of tumor-associated macrophage in an IL-4-mTOR-dependent manner. Collectively, our study revealed that ICJ rebalanced macrophage polarization in malignant microenvironment and showed promising effect in suppressing metastatic outgrowth in breast cancer model. [ABSTRACT FROM AUTHOR]

Background/Aim: Macrophage polarization and phenotypic switching of smooth muscle cells (SMCs) are multi-faceted events dominating atherosclerosis (AS) progression. TGF-β was proved to been one of the bridge on the crosstalk between macrophage and SMC. ShenLian (SL) was extracted from a potent anti-atherosclerotic formula. However, its exact mechanism rebalancing inflammatory microenvironment of AS remain largely unknown. Within the entirety of macrophage and SMC, this study investigated the pharmacological effects of SL on stabilizing atherosclerotic plaques. Methods: The main components of SL were examined by high performance liquid chromatography. Co-culture and conditioned medium models of macrophage/SMC interactions were designed to identify the relationship between macrophage polarization and switching of SMC phenotypes. Flow cytometry, immunofluorescent staining, RT-PCR, western blotting, and ELISA were used to determine the expression of molecules relating to AS progression. An atherosclerosis animal model, established by placing a perivascular collar on the right common carotid artery in ApoE−/− mice, was used to investigate whether TGF-β is the key molecular mediator of SL in crosstalk between macrophage and SMC. Plaque size was defined by nuclear magnetic resonance imaging. Key markers related to phenotypic transformation of macrophage and SMC were determined by immunohistochemical staining. Results: Results revealed that, accompanied by rebalanced M2 macrophage polarization, SL supported SMC phenotypic transformation and functionally reconstruct the ECM of plaques specifically in macrophage-SMC co-cultural model. Molecularly, such activity of SL closely related to the activation of STAT3/SOCS3 pathway. Furthermore, in co-culture system, up-regulation of α-SMA induced by SL could neutralized by 1D11, a TGF-β neutralizing antibody, indicating that SL mediated Macrophage-SMC communication by enhancing TGF-β. In the AS model constructed by ApoE−/− mice, effects of SL on phenotypic transformation of macrophage and SMC has been well verified. Specific blocking of TGF-β largely attenuated the aforementioned effects of SL. Conclusion: Our findings highlighted that TGF-β might be the responsive factor of SL within macrophage and SMC communication. This study revealed that crosstalk between macrophage and SMC forms a holistic entirety promoting atherosclerotic plaque stability. [ABSTRACT FROM AUTHOR]

Besides pathogen evading, Acute Lung Injury (ALI), featuring the systematic inflammation and severe epithelial damages, is widely believed to be the central non-infectious factor controlling the progression of infectious diseases. ALI is partly caused by host immune responses. Under the inspiration of unsuccessful treatment in COVID-19, recent insights into pathogen–host interactions are leading to identification and development of a wide range of host-directed therapies with different mechanisms of action. The interaction unit consisting of macrophages and the alveolar epithelial cells has recently revealed as the therapeutic basis targeting ALI. Lian Hua Qing Wen capsule is the most effective and commonly-used clinical formula in treating respiratory infection for thousands of years in China. However, little is known about its relevance with ALI, especially its protective role against ALI-induced alveolar tissue damages. Aiming to evaluate its contribution in antibiotics-integrating therapies, this study pharmacologically verified whether LHQW could alleviate lipopolysaccharide (LPS)-induced ALI and explore its potential mechanisms in maintaining the physiology of macrophage-epithelial unit. In ALI mouse model, the pathological parameters, including the anal temperature, inflammation condition, lung edema, histopathological structures, have all been systematically analyzed. Results consistently supported the effectiveness of the combined strategy for LHQW and low-dose antibiotics. Furthermore, we established the macrophages-alveolar epithelial cells co-culture model and firstly proved that LHQW inhibited LPS-induced ER stress and TRAIL secretion in macrophages, thereby efficiently protected epithelial cells against TRAIL-induced apoptosis. Mechanistically, results showed that LHQW significantly deactivated NF-κB and reversed the SOCS3 expression in inflammatory macrophages. Furthermore, we proved that the therapeutic effects of LHQW were highly dependent on JNK-AP1 regulation. In conclusion, our data proved that LHQW is an epithelial protector in ALI, implying its promising potential in antibiotic alternative therapy. [ABSTRACT FROM AUTHOR]

Posttranscriptional modification of mRNA sequences through RNA editing can increase transcriptome and proteome diversity in eukaryotes. Studies of fetal and adult tissues showed that adenosine‐to‐inosine RNA editing plays a crucial role in early human development, but there is a lack of global understanding of dynamic RNA editing during mammalian early embryonic development. Therefore, here we used RNA sequencing data from human, pig and mouse during early embryonic development to detect edited genes that may regulate stem cell pluripotency. We observed that although most of the RNA editing sites are located in intergenic, intron and UTR, a few editing sites are in coding regions and may result in nonsynonymous amino acid changes. Some editing sites are predicted to change the structure of a protein. We also report that HNF1A, TBX3, ACLY, ECI1 and ERDR1 are related to embryonic development and cell division. [ABSTRACT FROM AUTHOR]

The neovascularization functions essentially for malignant upgrading and predicts poor prognosis in multiple cancers, which make it the highly effective strategy for clinical treatment. Unfortunately, the known anti-angiogenic therapies show low effectiveness against breast cancer. Recently, rebalancing the pro-angiogenic property in microenvironment shows great advantages and attracts increasing attention for breast cancer treatment. Herein, we for the first time reported that Chamaejasmine B (ICJ), extracted from Stellera chamaejasme L., possessed potent anti-angiogenic effect in breast cancer. By Transwell, tube formation and aortic-ring assays, ICJ efficiently suppressed the neovascularization potential in tumor-HUVEC co-culture model. In Matrigel plug assay, the efficacy of ICJ was further identified in vivo. Mechanistically, with little influence on HUVEC apoptosis, ICJ obviously induced autophagy as proved by the elevated LC3I/II ratio, dotted distribution of LC3 and upregulated Beclin-1. Moreover, by associating with LC3 and in turn, inhibiting the level of VEGFR2, the anti-angiogenesis efficacy was closely dependent on the initiation of autophagy. Above results proved that, by attenuating the pro-angiogenic communication through VEGFR2, ICJ is a novel angiogenic inhibitor and will be a promising supplement for anti-angiogenic chemotherapy for breast cancer. [ABSTRACT FROM AUTHOR]

Berberine is one of active alkaloids from Rhizoma coptidis in traditional Chinese medicine. The pharmacokinetics of berberine in rat plasma were compared between normal and chronic visceral hypersensitivity irritable bowel syndrome rats (CVH-IBS) established by mechanical colon irritation using angioplasty balloons for 2 weeks after oral administration of berberine hydrochloride (25 mg/kg) with the equivalent dose of 22 mg/kg for berberine according to body weight. Immunohistochemical analysis of c-fos and myosin light chain kinase (MLCK) and immunofluorescence analysis of MLCK in rat colon were conducted. Quantification of berberine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 15 different points in time and the pharmacokinetic parameters were analyzed by WinNonlin software. The great different pharmacokinetic behavior of berberine was observed between normal and CVH-IBS model rats. Compared with normal group, T and AUC of berberine in the model group were significantly increased, respectively (573.21 ± 127.53 vs 948.22 ± 388.57 min; 8,657.19 ± 1,562.54 vs 11,415.12 ± 1,670.72 min.ng/ml). Cl/F of berberine in the model group significantly decreased, respectively (13.89 ± 1.69 vs 9.19 ± 2.91 L/h/kg). Additionally, the expressions of c- fos and MLCK in model group were higher than those in normal group. The pharmacokinetic behavior of berberine was significantly altered in CVH-IBS pathological conditions, which indicated the dosage modification of berberine hydrochloride in CVH-IBS were necessary. Especially, improved exposure to berberine in rat plasma in CVH-IBS model rats was attributed to increased the expression of MLCK. [ABSTRACT FROM AUTHOR]

Wuji Wan (WJW), containing Rhizoma Coptidis (Huanglian in Chinese, HL), Frutus Evodiae Rutaecarpae (Wuzhuyu, WZY) and Radix Paeoniae Alba (Baishao, BS), is a classical traditional Chinese medical formula employed in treating intestinal disorders. Berberine (BBR) and palmatine (PMT) are the major active alkaloids in HL and have analgesic and anti-microbial effects. A sensitive, specific and validated ultra-performance liquid chromatography-tandem mass spectrometric method was developed to investigate the pharmacokinetic profiles of BBR and PMT in rat plasma and in situ intestinal perfusion solution. In comparison with the pharmacokinetic parameters of BBR and PMT, t, C, T, AUC, CL and MRT after intragastric (i.g.) administration with HL extract alone, those remarkably changed after i.g. administration with WJW formulas 1 and 2 (herb proportions are 12:2:3 and 12:1:12). Particularly, the oral bioavailability of PMT in WJW formula 1 was significantly increased. In rat intestinal perfusion experiments, the apparent permeability coefficient value of PMT was (1.45 ± 0.72) × 10 cm/s when perfusion with HL was performed, and the value was significantly increased to (3.92 ± 0.52) × 10 cm/s on perfusion with WJW formula 1. These results indicate that the pharmacokinetic parameters and absorption of BBR and PMT are affected by the other herbs or ingredients from WJW formulas. [ABSTRACT FROM AUTHOR]

Oct4 is exclusively expressed in rodent inner cell mass (ICM) but silenced in its trophectoderm (TE). However, for many non-rodent animals, including pig, cattle, rabbit, goat, and human, OCT4 has a remarkable expression in early TE. This study, applying pig as the main research model, proves that OCT4 expression in TE is supported by a unique GATA motif in the OCT4 upstream conserved regulatory region, and GATA4 is responsible for its activation. Moreover, OCT4 acts as a specific regulator of a narrow range of genes (including BCL2A1 and HNRNP2AB1) that are essential for the first wave of rapid proliferation in early TE. This study describes the regulatory mechanism to direct the OCT4 expression and its significance in TE of porcine preimplantation embryo. [Display omitted] • GATA4 binds to OCT4 upstream of CR4 to support OCT4 prolonged expression in porcine TE • Variation of TCFAP2 motif does not cause prolonged OCT4 expression in porcine TE • CDX2 fails to downregulate OCT4 in porcine early TE due to stable CDX2/OCT4 ratio • OCT4 is essential for the rapid proliferation of porcine TE OCT4 expression is maintained in early TE of many non-rodent animals, but its molecular basis and significance remain elusive. Bou et al. demonstrate that, in porcine TE, GATA4 transcriptionally activates OCT4 to guarantee TE rapid proliferation and emphasize the importance of embryonic studies in more species. [ABSTRACT FROM AUTHOR]

Simple Summary: In the freezing process of boar sperm, there are obvious differences in freezability between individuals. Studies suggest that specific freezability markers might be useful in good (GFE) and poor freezability ejaculate (PFE) selection prior to cryopreservation. Therefore, we performed UHPLC-qTOF-MS analysis to explore the difference in the metabolic level of seminal plasma between boars with differential freezability, and the results showed that the content of D-aspartic acid, N-acetyl-L-glutamate (NAG), and inosine were significantly different. These findings present new insights into the role of metabolism in sperm freezability and provide research directions for exploring potential biomarkers of freezability. Some potential markers of boar sperm freezability have been found in spermatozoa, but little attention has been paid to seminal plasma. The seminal plasma is composed of secretions from the testis, epididymis, and accessory sex glands. The exposure of spermatozoa to small molecules such as metabolites can affect sperm function. However, details and significance of the seminal plasma metabolome related to boar sperm freezability are unknown. Therefore, the main aim of this study was to explore the differences in the metabolic level of seminal plasma between boars with differential freezability and to explore the candidate biomarkers of semen freezability. A total of 953 metabolites were identified in boar semen plasma by UHPLC-qTOF-MS analysis, and 50 metabolites showed significant change between the GFE group and PFE group. Further, twelve metabolites were subjected to metabolic target analysis, and three metabolites (D-aspartic acid, N-acetyl-L-glutamate (NAG), and inosine) showed differences. In conclusion, there is significant difference in the metabolome of seminal plasma between GFE and PFE individuals. D-aspartic acid, NAG, and inosine in seminal plasma may be potential markers for assessing sperm cryopreservation resistance in boars. [ABSTRACT FROM AUTHOR]

Background: Despite years of research, porcine-induced pluripotent stem cells (piPSCs) with germline chimeric capacity have not been established. Furthermore, the key transcription factors (TFs) defining the naïve state in piPSCs also remain elusive, even though TFs in the inner cell mass (ICM) are believed to be key molecular determinants of naïve pluripotency. In this study, interferon regulatory factor 1 (IRF-1) was screened to express higher in ICM than trophectoderm (TE). But the impact of IRF-1 on maintenance of pluripotency in piPSCs was not determined. Methods: Transcriptome profiles of the early ICM were analyzed to determine highly interconnected TFs. Cells carrying these TFs' reporter were used to as donor cells for somatic cell nuclear transfer to detect expression patterns in blastocysts. Next, IRF1-Flag was overexpressed in DOX-hLIF-2i piPSCs and AP staining, qRT-PCR, and RNA-seq were conducted to examine the effect of IRF-1 on pluripotency. Then, the expression of IRF-1 in DOX-hLIF-2i piPSCs was labeled by GFP and qRT-PCR was conducted to determine the difference between GFP-positive and GFP-negative cells. Next, ChIP-Seq was conducted to identify genes target by IRF-1. Treatment with IL7 in wild-type piPSCs and STAT3 phosphorylation inhibitor in IRF-1 overexpressing piPSCs was conducted to confirm the roles of JAK-STAT3 signaling pathway in IRF-1's regulation of pluripotency. Moreover, during reprogramming, IRF-1 was overexpressed and knocked down to determine the change of reprogramming efficiency. Results: IRF-1 was screened to be expressed higher in porcine ICM than TE of d6~7 SCNT blastocysts. First, overexpression of IRF-1 in the piPSCs was observed to promote the morphology, AP staining, and expression profiles of pluripotency genes as would be expected when cells approach the naïve state. Genes, KEGG pathways, and GO terms related to the process of differentiation were also downregulated. Next, in the wild-type piPSCs, high-level fluorescence activated by the IRF-1 promoter was associated with higher expression of naïve related genes in piPSCs. Analysis by ChIP-Seq indicated that genes related to the JAK-STAT pathway, and expression of IL7 and STAT3 were activated by IRF-1. The inhibitor of STAT3 phosphorylation was observed could revert the expression of primed genes in IRF-1 overexpressing cells, but the addition of IL7 in culture medium had no apparent change in the cell morphology, AP staining results, or expression of pluripotency related genes. In addition, knockdown of IRF-1 during reprogramming appeared to reduce reprogramming efficiency, whereas overexpression exerted the converse effect. Conclusion: The IRF-1 expressed in the ICM of pigs' early blastocyst enhances the pluripotency of piPSCs, in part through promoting the JAK-STAT pathway. [ABSTRACT FROM AUTHOR]