Transcriptome Analysis Reveals Antioxidant Defense Mechanisms in the Silkworm Bombyx mori after Exposure to Lead.

Lead (Pb) is a major source of heavy metal contamination, and poses a threat to biodiversity and human health. Elevated levels of Pb can hinder insect growth and development, leading to apoptosis via mechanisms like oxidative damage. The midgut of silkworms is the main organ exposed to heavy metals. As an economically important lepidopteran model insect in China, heavy metal-induced stress on silkworms causes considerable losses in sericulture, thereby causing substantial economic damage. This study aimed to investigate Pb-induced detoxification-related genes in the midgut of silkworms using high-throughput sequencing methods to achieve a deeper comprehension of the genes' reactions to lead exposure. This study identified 11,567 unigenes and 14,978 transcripts. A total of 1265 differentially expressed genes (DEGs) were screened, comprising 907 upregulated and 358 downregulated genes. Subsequently, Gene Ontology (GO) classification analysis revealed that the 1265 DEGs were distributed across biological processes, cellular components, and molecular functions. This suggests that the silkworm midgut may affect various organelle functions and biological processes, providing crucial clues for further exploration of DEG function. Additionally, the expression levels of 12 selected detoxification-related DEGs were validated using qRT-PCR, which confirmed the reliability of the RNA-seq results. This study not only provides new insights into the detoxification defense mechanisms of silkworms after Pb exposure, but also establishes a valuable foundation for further investigation into the molecular detoxification mechanisms in silkworms.

Design, synthesis and bactericidal activity of novel coumarin derivatives containing pyridinium salts.

Coumarin is a natural product known for its diverse biological activities. While its antifungal properties in agricultural chemistry have been extensively studied, there is limited research on its antibacterial potential. In this study, we developed several novel coumarin derivatives by combining coumarin with pyridinium salt through molecular hybridization and chemical synthesis. Our findings reveal that most of these derivatives exhibit promising antibacterial activity. Among them, derivative A25 has been identified as the most effective compound based on three-dimensional quantitative structure-activity relationships. It demonstrates significant in vitro and in vivo activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicola (Xoc), and Xanthomonas campestris pv. citri (Xac), outperforming the commercially available thiediazole copper. Initial investigations into its mechanism of action suggest that A25 disrupts the cell membranes of Xoc and Xoo, thereby inhibiting bacterial growth. Additionally, A25 enhances the activity of defense enzymes in rice and modulates the expression of proteins related to the pyruvate metabolism pathway. This dual action contributes to rice's resistance against bacterial infestation. We anticipate that this study will serve as a foundation for the development of coumarin-based bactericides.

Factors Associated with and Impact of Open Conversion in Laparoscopic and Robotic Minor Liver Resections: An International Multicenter Study of 10,541 Patients.

INTRODUCTION: Despite the increasing widespread adoption and experience in minimally invasive liver resections (MILR), open conversion occurs not uncommonly even with minor resections and as been reported to be associated with inferior outcomes. We aimed to identify risk factors for and outcomes of open conversion in patients undergoing minor hepatectomies. We also studied the impact of approach (laparoscopic or robotic) on outcomes. METHODS: This is a post-hoc analysis of 20,019 patients who underwent RLR and LLR across 50 international centers between 2004-2020. Risk factors for and perioperative outcomes of open conversion were analysed. Multivariate and propensity score-matched analysis were performed to control for confounding factors. RESULTS: Finally, 10,541 patients undergoing either laparoscopic (LLR; 89.1%) or robotic (RLR; 10.9%) minor liver resections (wedge resections, segmentectomies) were included. Multivariate analysis identified LLR, earlier period of MILR, malignant pathology, cirrhosis, portal hypertension, previous abdominal surgery, larger tumor size, and posterosuperior location as significant independent predictors of open conversion. The most common reason for conversion was technical issues (44.7%), followed by bleeding (27.2%), and oncological reasons (22.3%). After propensity score matching (PSM) of baseline characteristics, patients requiring open conversion had poorer outcomes compared with successful MILR cases as evidenced by longer operative times, more blood loss, higher requirement for perioperative transfusion, longer duration of hospitalization and higher morbidity, reoperation, and 90-day mortality rates. CONCLUSIONS: Multiple risk factors were associated with conversion of MILR even for minor hepatectomies, and open conversion was associated with significantly poorer perioperative outcomes.

New-Style Logic Operation and Neuromorphic Computing Enabled by Optoelectronic Artificial Synapses in an MXene/Y:HfO2 Ferroelectric Memristor.

Today's computing systems, to meet the enormous demands of information processing, have driven the development of brain-inspired neuromorphic systems. However, there are relatively few optoelectronic devices in most brain-inspired neuromorphic systems that can simultaneously regulate the conductivity through both optical and electrical signals. In this work, the Au/MXene/Y:HfO2/FTO ferroelectric memristor as an optoelectronic artificial synaptic device exhibited both digital and analog resistance switching (RS) behaviors under different voltages with a good switching ratio (>103). Under optoelectronic conditions, optimal weight update parameters and an enhanced algorithm achieved 97.1% recognition accuracy in convolutional neural networks. A new logic gate circuit specifically designed for optoelectronic inputs was established. Furthermore, the device integrates the impact of relative humidity to develop an innovative three-person voting mechanism with a veto power. These results provide a feasible approach for integrating optoelectronic artificial synapses with logic-based computing devices.

Partial Alleviation of Homologous Superinfection Exclusion of SeMNPV Latently Infected Cells by G1 Phase Infection and G2/M Phase Arrest.

Viral infection can regulate the cell cycle, thereby promoting viral replication. Hijacking and altering the cell cycle are important for the virus to establish and maintain a latent infection. Previously, Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV)-latently infected P8-Se301-C1 cells, which grew more slowly than Se301 cells and interfered with homologous SeMNNPV superinfection, were established. However, the effects of latent and superinfection with baculoviruses on cell cycle progression remain unknown. In this study, the cell cycle profiles of P8-Se301-C1 cells and SeMNPV or Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-infected P8-Se301-C1 cells were characterized by flow cytometry. The results showed that replication-related genes MCM4, PCNA, and BAF were down-regulated (p < 0.05) in P8-Se301-C1 cells, and the S phase of P8-Se301-C1 cells was longer than that of Se301 cells. P8-Se301-C1 cells infected with SeMNPV did not arrest in the G2/M phase or affect the expression of Cyclin B and cyclin-dependent kinase 1 (CDK1). Furthermore, when P8-Se301-C1 cells were infected with SeMNPV after synchronized treatment with hydroxyurea and nocodazole, light microscopy and qRT-PCR analysis showed that, compared with unsynchronized cells and S and G2/M phase cells, SeMNPV-infected P8-Se301-C1 cells in G1 phase induced G2/M phase arrest, and the amount of virus adsorption and intracellular viral DNA replication were significantly increased (p < 0.05). In addition, budded virus (BV) production and occlusion body (OB)-containing cells were both increased at 120 h post-infection (p < 0.05). The expression of Cyclin B and CDK1 was significantly down-regulated at 48 h post-infection (p < 0.05). Finally, the arrest of SeMNPV-infected G1 phase cells in the G2/M phase increased BV production (p < 0.05) and the number of OB-containing cells. In conclusion, G1 phase infection and G2/M arrest are favorable to SeMNPV proliferation in P8-Se301-C1 cells, thereby alleviating the homologous superinfection exclusion. The results contribute to a better understanding of the relationship between baculoviruses and insect cell cycle progression and regulation.

A novel fluorescence platform for specific detection of tetracycline antibiotics based on [MQDA-Eu3+] system.

Tetracycline antibiotics (TCs) are extensively used in clinical medicine, animal husbandry, and aquaculture because of their cost-effectiveness and high antibacterial efficacy. However, the presence of TCs residues in the environment poses risks to humans. In this study, an inner filter effect (IFE) fluorescent probe, 2,2'-(ethane-1,2-diylbis((2-((2-methylquinolin-8-yl)amino)-2-oxoethyl)azanediyl))diacetic acid (MQDA), was developed for the rapid detection of Eu3+ within 30 s. And its complex [MQDA-Eu3+] was successfully used for the detection of TCs. Upon coordination of a carboxyl of MQDA with Eu3+ to form a [MQDA-Eu3+] complex, the carboxyl served as an antenna ligand for the effective detection of Eu3+ to intensify the emission intensity of MQDA via "antenna effect", the process was the energy absorbed by TCs via UV excitation was effectively transferred to Eu3+. Fluorescence quenching of the [MQDA-Eu3+] complex was caused by the IFE in multicolor fluorescence systems. The limits of detection of [MQDA-Eu3+] for oxytetracycline, chlorotetracycline hydrochloride, and tetracycline were 0.80, 0.93, and 1.7 µM in DMSO/HEPES (7:3, v/v, pH = 7.0), respectively. [MQDA-Eu3+] demonstrated sensitive detection of TCs in environmental and food samples with satisfactory recoveries and exhibited excellent imaging capabilities for TCs in living cells and zebrafish with low cytotoxicity. The proposed approach demonstrated considerable potential for the quantitative detection of TCs.

Neuromorphic Computing of Optoelectronic Artificial BFCO/AZO Heterostructure Memristors Synapses.

Compared with purely electrical neuromorphic devices, those stimulated by optical signals have gained increasing attention due to their realistic sensory simulation. In this work, an optoelectronic neuromorphic device based on a photoelectric memristor with a Bi2FeCrO6/Al-doped ZnO (BFCO/AZO) heterostructure is fabricated that can respond to both electrical and optical signals and successfully simulate a variety of synaptic behaviors, such as STP, LTP, and PPF. In addition, the photomemory mechanism was identified by analyzing the energy band structures of AZO and BFCO. A convolutional neural network (CNN) architecture for pattern classification at the Mixed National Institute of Standards and Technology (MNIST) was used and improved the recognition accuracy of the MNIST and Fashion-MNIST datasets to 95.21% and 74.19%, respectively, by implementing an improved stochastic adaptive algorithm. These results provide a feasible approach for future implementation of optoelectronic synapses.

Design, Synthesis, Antibacterial Activity, and Mechanisms of Novel Benzofuran Derivatives Containing Disulfide Moieties.

The unsatisfactory effects of conventional bactericides and antimicrobial resistance have increased the challenges in managing plant diseases caused by bacterial pests. Here, we report the successful design and synthesis of benzofuran derivatives using benzofuran as the core skeleton and splicing the disulfide moieties commonly seen in natural substances with antibacterial properties. Most of our developed benzofurans displayed remarkable antibacterial activities to frequently encountered pathogens, including Xanthomonas oryzae pv oryzae (Xoo), Xanthomonas oryzae pv oryzicola (Xoc), and Xanthomonas axonopodis pv citri (Xac). With the assistance of the three-dimensional quantitative constitutive relationship (3D-QSAR) model, the optimal compound V40 was obtained, which has better in vitro antibacterial activity with EC50 values of 0.28, 0.56, and 10.43 µg/mL against Xoo, Xoc, and Xac, respectively, than those of positive control, TC (66.41, 78.49, and 120.36 µg/mL) and allicin (8.40, 28.22, and 88.04 µg/mL). Combining the results of proteomic analysis and enzyme activity assay allows the antibacterial mechanism of V40 to be preliminarily revealed, suggesting its potential as a versatile bactericide in combating bacterial pests in the future.

An adjustable multistage resistance switching behavior of a photoelectric artificial synaptic device with a ferroelectric diode effect for neuromorphic computing.

Neuromorphic computing, which mimics biological neural networks, is widely regarded as the optimal solution for addressing the limitations of traditional von Neumann computing architecture. In this work, an adjustable multistage resistance switching ferroelectric Bi2FeCrO6 diode artificial synaptic device was fabricated using a sol-gel method with a simple process. The device exhibits nonlinearity in its electrical characteristics, demonstrating tunable multistage resistance switching behavior and a strong ferroelectric diode effect through the manipulation of ferroelectric polarization. One of its salient advantages resides in its capacity to dynamically regulate its polarization state in response to an external electric field, thereby facilitating the fine-tuning of synaptic connection strength while maintaining synaptic stability. The device is capable of accurately simulating the fundamental properties of biological synapses, including long/short-term plasticity, paired-pulse facilitation, and spike-timing-dependent plasticity. Additionally, the device exhibits a distinctive photoelectric response and is capable of inducing synaptic plasticity by light signal activation. The utilization of a femtosecond laser for the scrutiny of carrier transport mechanisms imparts profound insights into the intricate dynamics governing the optical memory effect. Furthermore, utilizing a convolutional neural network (CNN) architecture, the recognition accuracy of the MNIST and fashion MNIST datasets was improved to 95.6% and 78%, respectively, through the implementation of improved random adaptive algorithms. These findings present a new opportunity for utilizing Bi2FeCrO6 materials in the development of artificial synapses for neuromorphic computation.

Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models: A Cross-sectional Study in Rural Guangxi.

Objective: This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods: We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength. Results: In the multimetal linear regression, Cu (ß = -2.119), As (ß = -1.318), Sr (ß = -2.480), Ba (ß = 0.781), Fe (ß = 1.130) and Mn (ß = -0.404) were significantly correlated with grip strength ( P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95% confidence interval: -1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn ( P interactions of 0.003 and 0.018, respectively). Conclusion: In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Cucurbitacin B suppresses hepatocellular carcinoma progression through inducing DNA damage-dependent cell cycle arrest.

BACKGROUND: The mortality rate of liver cancer ranks third in the world, and hepatocellular carcinoma (HCC) is a malignant tumor of the digestive tract. Cucurbitacin B (CuB), a natural compound extracted from Cucurbitaceae spp., is the main active component of Chinese patent medicine the Cucurbitacin Tablet, which has been widely used in the treatment of various malignant tumors in clinics, especially HCC. PURPOSE: This study explored the role and mechanism of CuB in the suppression of liver cancer progression. METHODS: Cell Counting Kit-8 (CCK-8) and colony formation assays were used to detect the inhibitory function of CuB in Huh7, Hep3B, and Hepa1/6 hepatoma cells. Calcein-AM/propidium iodide (PI) staining and lactate dehydrogenase (LDH) measurement assays were performed to determine cell death. Mitochondrial membrane potential (Δψm) was measured, and flow cytometry was performed to evaluate cell apoptosis and cell cycle. Several techniques, such as proteomics, Western blotting (WB), and ribonucleic acid (RNA) interference, were utilized to explore the potential mechanism. The animal experiment was performed to verify the results of in vitro experiments. RESULTS: CuB significantly inhibited the growth of Huh7, Hep3B, and Hepa1/6 cells and triggered the cell cycle arrest in G2/M phage without leading to cell death, especially apoptosis. Knockdown of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a target of CuB, did not reverse CuB elicited cell cycle arrest. CuB enhanced phosphorylated ataxia telangiectasia mutated (p-ATM) and phosphorylated H2A histone family member X (γ-H2AX) levels. Moreover, CuB increased p53 and p21 levels and decreased cyclin-dependent kinase 1 (CDK1) expression, accompanied by improving phosphorylated checkpoint kinase 1 (p-CHK1) level and suppressing cell division cycle 25C (CDC25C) protein level. Interestingly, these phenomena were partly abolished by a deoxyribonucleic acid (DNA) protector methylproamine (MPA). Animal studies showed that CuB also significantly suppressed tumor growth in BALB/c mice bearing Hepa1/6 cells. In tumor tissues, CuB reduced the expression levels of proliferating cell nuclear antigen (PCNA) and γ-H2AX but did not change the terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) level. CONCLUSION: This study demonstrated for the first time that CuB could effectively impede HCC progression by inducing DNA damage-dependent cell cycle arrest without directly triggering cell death, such as necrosis and apoptosis. The effect was achieved through ataxia telangiectasia mutated (ATM)-dependent p53-p21-CDK1 and checkpoint kinase 1 (CHK1)-CDC25C signaling pathways. These findings indicate that CuB may be used as an anti-HCC drug, when the current findings are confirmed by independent studies and after many more clinical phase 1, 2, 3, and 4 testings have been done.

Design, synthesis and biological evaluation of 1,2,3-triazole benzothiazole derivatives as tubulin polymerization inhibitors with potent anti-esophageal cancer activities.

In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18, exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC50 values were 0.042 and 0.038 µM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC50 = 0.446 µM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18, which possesses significant potential for treating esophageal cancers.

Annual review of PROTAC degraders as anticancer agents in 2022.

Following nearly two decades of development, significant advancements have been achieved in PROTAC technology. As of the end of 2022, more than 20 drugs have entered clinical trials, with ARV-471 targeting estrogen receptor (ER) showing remarkable progress by entering phase III clinical studies. In 2022, significant progress has been made on multiple targets. The first reversible covalent degrader designed to target the KRASG12C mutant protein, based on cyclopropionamide, has been reported. Additionally, the activity HDCA1 degrader surpassed submicromolar levels during the same year. A novel FEM1B covalent ligand called EN106 was also discovered, expanding the range of available ligands. Furthermore, the first PROTAC drug targeting SOS1 was reported. Additionally, the first-in-class degraders that specifically target BRD4 isoforms (BRD4 L and BRD4 S) have recently been reported, providing a valuable tool for further investigating the biological functions of these isoforms. Lastly, a breakthrough was also achieved with the first degrader targeting both CDK9 and Cyclin T1. In this review, we aimed to update the PROTAC degraders as potential anticancer agents covering articles published in 2022. The design strategies, degradation effects, and anticancer activities were highlighted, which might provide an updated sight to develop novel PROTAC degraders with great potential as anticancer agents as well as favorable drug-like properties.

From bench to bedside: current development and emerging trend of KRAS-targeted therapy.

Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) is the most frequently mutated oncogene in human cancers with mutations predominantly occurring in codon 12. These mutations disrupt the normal function of KRAS by interfering with GTP hydrolysis and nucleotide exchange activity, making it prone to the GTP-bound active state, thus leading to sustained activation of downstream pathways. Despite decades of research, there has been no progress in the KRAS drug discovery until the groundbreaking discovery of covalently targeting the KRASG12C mutation in 2013, which led to revolutionary changes in KRAS-targeted therapy. So far, two small molecule inhibitors sotorasib and adagrasib targeting KRASG12C have received accelerated approval for the treatment of non-small cell lung cancer (NSCLC) harboring KRASG12C mutations. In recent years, rapid progress has been achieved in the KRAS-targeted therapy field, especially the exploration of KRASG12C covalent inhibitors in other KRASG12C-positive malignancies, novel KRAS inhibitors beyond KRASG12C mutation or pan-KRAS inhibitors, and approaches to indirectly targeting KRAS. In this review, we provide a comprehensive overview of the molecular and mutational characteristics of KRAS and summarize the development and current status of covalent inhibitors targeting the KRASG12C mutation. We also discuss emerging promising KRAS-targeted therapeutic strategies, with a focus on mutation-specific and direct pan-KRAS inhibitors and indirect KRAS inhibitors through targeting the RAS activation-associated proteins Src homology-2 domain-containing phosphatase 2 (SHP2) and son of sevenless homolog 1 (SOS1), and shed light on current challenges and opportunities for drug discovery in this field.

A naked-eye visible aluminium (III)-based complex fluorescence sensor for sensitive detection of mesotrione.

Mesotrione, which is a kind of herbicide to control broad-leaved weeds, has been increasingly used due to its excellent selectivity, rapid process and low toxicity. However, the excessive application of mesotrione have led to widespread contamination. Herein, a turn-on competitive coordination-based fluorescent probe, 2-hydroxy-1-(9-purin)-methylidenehydrazinenaphthalene (HPM), has been successfully synthesized. HPM could effectively detect Al3+ in CH3OH/HEPES (1/9, v/v) with low limit of detection (LOD) being 0.2 µM via coordination. HPM also exhibited excellent imaging capabilities for Al3+ in living cells with low cytotoxicity. On the basis of the competitive coordination of HPM with Al3+, the [HPM-Al3+] complex could also serve as a potential fluorescence sensor for detecting mesotrione with the LOD of 0.2 µM. Furthermore, [HPM-Al3+] complex was applied for the detection of mesotrione in real samples and test paper. Finally, the mechanism of [HPM-Al3+] for sensing mesotrione was investigated deeply as well. This work designed a new convenient method for on-site detection of mesotrione without the large-scale equipment or complicated pre-treatment.

Compound-composed Chinese medicine of Huachansu triggers apoptosis of gastric cancer cells through increase of reactive oxygen species levels and suppression of proteasome activities.

BACKGROUND: Huachansu (HCS), a known Chinese patent drug extracted from the Chinese toad skin, is frequently used for the treatment of various advanced cancers, especially gastric cancer, due to the good therapeutic effect. However, it is rather difficult to clarify the active substances and molecular mechanisms involved owing to the lack of appropriate research strategies. We recently proposed the concept and research ideas of compound-composed Chinese medicine formula. PURPOSE: To discover compound-composed Chinese medicine from Huachansu and to explore its mechanism of action in inducing apoptosis of gastric cancer cells. METHOD: Network pharmacology combined with serum pharmacochemistry was utilized to screen the predominant active constituents from HCS against gastric cancer. Then, the compound-composed Chinese medicine of HCS (CCMH) was prepared according to their relative contents in serum. The pharmacological effects and potential mechanisms for CCMH were investigated by assays for cell viability, cell cycle, apoptosis, mitochondrial membrane potential (MMP), proteomics, reactive oxygen species (ROS), N-Acetylcysteine (NAC) antagonism, proteasome activity, and western blot. RESULTS: CCMH was comprised of arenobufagin (11.14%), bufalin (18.67%), bufotalin (7.33%), cinobufagin (16.67%), cinobufotalin (16.74%), gamabufotalin (8.45%), resibufogenin (12.03%), and telocinobufagin (8.97%). CCMH evidently induced proliferation inhibition, cell cycle arrest, apoptosis, and MMP collapse in gastric cancer cells, possessing the better activities than HCS. Proteomic analysis showed that CCMH influenced ROS pathway, ubiquitin proteasome system, and PI3K/Akt and MAPK signaling pathways. CCMH markedly enhanced intracellular ROS levels in gastric cancer cells, which was reversed by NAC. Accordingly, NAC antagonized the apoptosis-inducing effect of CCMH. Significantly decreased proteasome 20S activity by CCMH was observed in gastric cancer cells. CCMH also regulated the expression of key proteins in PI3K/Akt and MAPK signaling pathways. CONCLUSION: CCMH possesses more significant apoptotic induction effects on gastric cancer cells than HCS, which is achieved primarily through suppression of proteasome activities and increase of ROS levels, followed by regulating PI3K/Akt and MAPK signaling pathways. Network pharmacology combined with serum pharmacochemistry is an effective strategy for discovering compound-composed Chinese medicine from traditional Chinese medicine, which can help clarify the pharmacological substances and mechanisms of action for traditional Chinese medicine.

The CXCL10/CXCR3 axis regulates Th1 cell differentiation and migration in experimental autoimmune prostatitis through the PI3K/AKT pathway.

OBJECTIVE: To investigate the mechanism of the CXCL10/CXCR3 axis regulating Th1 cell differentiation and migration through the PI3K/AKT pathway in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Experimental autoimmune prostatitis (EAP) model, a well-described and validated animal model of CP/CPPS, was used in our study. After treatment with CXCL10, the severity of EAP and Th1 cell proportion were respectively measured by HE stains, immunohistochemistry, and flow cytometry. Then, the protein expression of the PI3K/AKT pathway in CXCL10/CXCR3-regulated Th1 cell differentiation and migration was evaluated by western blotting. Additionally, by the CXCR3 antagonist AMG487 and the PI3K inhibitor LY294002 applications, the effects of CXCL10/CXCR3 through PI3K/AKT pathway on the Th1 cell differentiation and migration were further assessed. RESULTS: The EAP model was successfully built. CXCL10 increased the proportion of Th1 cells in EAP mice, accompanied by upregulation of the PI3K/AKT pathway. Additionally, the PI3K/AKT pathway was found to be involved in CXCL10/CXCR3 axis-mediated Th1 cell differentiation and migration. CONCLUSIONS: Our investigations indicate that the CXCL10/CXCR3 axis regulates Th1 cell differentiation and migration in EAP through the PI3K/AKT pathway, which provides a new perspective on the immunological mechanisms of CP/CPPS.

Complete mitochondrial genome of Parasa sinica: New insights into the phylogeny of Limacodidae.

In this study, the whole mitochondrial genome (mitogenome) of Parasa sinica was sequenced. It contains 15,306 base pairs (bp), 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and one non-coding regulatory area (CR), all of which are shared by other lepidopterans. It follows the same gene order as ordinary lepidopterans. Further, out of these 37 genes, 23 are present on the heavy strand whereas the remaining 14 are located on the light strand. The A + T composition of the mitogenome is relatively high. Although P. sinica has a negative AT-skew and GC-skew, the GC-skew value is significantly lower than the AT-skew value. All PCGs, with the exception of CO1, carry the same start codon (ATN). All tRNAs exhibit the usual cloverleaf secondary structure. We identified the conserved motif "ATAGA + poly-T″ found in other lepidopteran insects at the beginning of the CR. We collected the concatenated PCGs sequences in the mitochondrial genome of 15 species of Zygaenoidea, with the sequences of Geometridae as outgroups, including P. sinica, and constructed phylogenetic trees using Bayesian inference (BI) and maximum likelihood (ML) methods. The monolineage of each superfamily is usually well supported. Based on phylogenetic analysis, P. sinica is a member of family Limacodidae, strongly supporting the monophyly of the Zygaenoidea groups.

The analyses of the complete mitochondrial genomes of three crabs revealed novel gene rearrangements and phylogenetic relationships of Brachyura.

BACKGROUND: Brachyura crab is the largest branch of Decapoda crustacean. Phylogenetic relationships within Brachyura remain controversial to be investigated. The mitochondrial genome (mitogenome) is an important molecular marker for studying the phylogenetic relationships of Brachyura. METHODS AND RESULTS: To understand the phylogeny of Brachyura, the three complete mitogenomes from Charybdis annulata, Leptodius exaratus, and Spider crab were sequenced and annotated. Their full length was 15,747, 15,716, and 16,608 bp long, respectively. The first two crabs both contained 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes and a control region. However, Spider crab contained 13 PCGs, two rRNA genes, 25 tRNA genes and a control region. The mitogenomes of each of the three crabs exhibited high AT content (67.8%, 69.1%, and 70.8%), with negative AT skews (-0.014, - 0.028, and - 0.017) and GC skews (-0.269, - 0.286, and - 0.341). The gene order of C. annulata was identical to the ancestor of Brachyura. Compared with the ancestor of Brachyura, L. exaratus exhibited the gene rearrangements of Val (V)-rrnS-control region, and Spider crab had the four copies of Lys (K). Phylogenetic analyses indicated that C. annulata belonged to Portunidae family, Portunoidea superfamilies, L. exaratus belonged to Xanthidae family, Xanthoidea superfamilies, and Spider crab belonged to Mithracidae family, Majoidea superfamilies. Phylogenetic analyses showed that the two species (Somanniathelphusa boyangensis and Huananpotamon lichuanense) belonging to the Potamoidea were sister groups to the Thoracotremata, thus supporting the conclusion that Heterotremata is polyphyletic. CONCLUSION: The results of this study enriched the crab mitogenome database and enabled us to better understand the phylogenetic relationships of Brachyura.