Solvent-Switchable Remote C-H Activation via 1,4-Palladium Migration Enables Site-Selective C-P Bond Formation: A Tool for the Synthesis of P-Chiral Phosphinyl Imidazoles.

Solvent-switchable and site-selective phosphorylation of imidazoles at the C2 or C5 position of the imidazole ring was achieved via 1,4-palladium migration. P-Chiral tert-butyl(aryl)phosphine oxides were cross-coupled to 1-(2-bromophenyl)-1H-imidazoles with high enantiospecificity, thereby leading to a novel class of chiral imidazole-based phosphine oxides. As proof of concept, reduction of an analogue yielded the corresponding P-chiral 2-phosphinyl imidazole ligand, which was shown to induce high enantioselectivity in the formation of axially chiral molecules synthesized via Pd-catalyzed Suzuki-Miyaura cross-coupling.

The role of tumor parenchyma and brain cortex signal intensity ratio in differentiating solitary fibrous tumors and meningiomas.

BACKGROUND: Solitary fibrous tumors (SFT) and meningiomas (MA) have similar clinical and radiographic presentations but require different treatment approaches and have different prognoses. This emphasizes the importance of a correct preoperative diagnosis of SFT versus MA. OBJECTIVE: In this study, investigated the differences in imaging characteristics between SFT and MA to improve the accuracy of preoperative imaging diagnosis of SFT. METHODS: The clinical and imaging data of 26 patients with SFT and 104 patients with MA who were pathologically diagnosed between August 2017 and December 2022, were retrospectively analyzed. The clinical and imaging differences between SFT and MA, as well as between the various pathological grades of SFT, were analyzed. RESULTS: Age, gender, cystic change, flow void phenomenon, yin-yang sign, lobulation, narrow base, tumor/cortex signal ratio (TCSR) > 1.0 in T1-weighted imaging (T1WI), TCSR ≥ 1.1 in T2-weighted imaging (T2WI), peritumoral edema, and absence of dural tail sign varied between SFT and MA. As per the receiver operating characteristic (ROC) curve analysis, TCSR > 1 in T1WI has the maximum diagnostic accuracy for SFT. Cranial or venous sinus invasion had a positive effect on SFT (Grade III, World Health Organization (WHO) grading). CONCLUSION: Among the many radiological and clinical distinctions between SFT and MA, TCSR ≥ 1 exhibits the highest predictive efficacy for SFT; while cranial or venous sinus invasion may be a predictor of WHO grade III SFT.

Unclassified glutathione-S-transferase AiGSTu1 confers chlorantraniliprole tolerance in Agrotis ipsilon.

BACKGROUND: Chlorantraniliprole (CAP) is a diamide insecticide with high efficacy against many pest insects, including the black cutworm, Agrotis ipsilon. Agrotis ipsilon is a serious pest causing significant yield losses in crops. Glutathione-S-transferases (GSTs) belong to a family of metabolic enzymes that can detoxify a wide range of pesticides. However, little is known about the functions of GSTs in CAP tolerance in A. ipsilon. RESULTS: A cDNA sequence (designated AiGSTu1) encoding an unclassified GST was identified from A. ipsilon. AiGSTu1 is highly expressed during the 3rd -instar larval and the pupal stages. Most of the mRNA transcripts were found in larval Malpighian tubules. Exposure to CAP strongly enhanced AiGSTu1 expression, GST activity, hydrogen peroxide (H2 O2 ) and malondialdehyde levels in larvae. H2 O2 treatment upregulated the transcription level of AiGSTu1, suggesting that CAP-induced oxidative stress may activate AiGSTu1 expression. The activity of recombinant AiGSTu1 was inhibited by CAP in a dose-dependent manner. Metabolism assay results demonstrated that AiGSTu1 is capable of depleting CAP. Overexpression of AiGSTu1 enhanced the tolerance of Escherichia coli cells to H2 O2 and the oxidative stress inducer, cumene hydroperoxide. Silencing of AiGSTu1 by RNA interference increased the susceptibility of A. ipsilon larvae to CAP. CONCLUSION: The findings of this study provide valuable insights into the potential role of AiGSTu1 in CAP detoxification and will improve our understanding of CAP tolerance in A. ipsilon. © 2023 Society of Chemical Industry.

Epsilon Class Glutathione S-Transferase Confers Phoxim Tolerance in the Black Cutworm Agrotis ipsilon (Lepidoptera: Noctuidae).

The black cutworm Agrotis ipsilon is a serious crop pest. Phoxim, an organophosphorus insecticide, has been widely used to control A. ipsilon. When phoxim is extensively applied, the susceptibility of A. ipsilon to insecticide is reduced. However, the mechanisms of tolerance of A. ipsilon to phoxim remain unclear. Herein, we report that an epsilon class glutathione S-transferase, AiGSTE1, confers phoxim tolerance in A. ipsilon. Exposure to a sublethal concentration (LC50) of phoxim caused oxidative stress and activated the transcription of AiGSTe1 genes in A. ipsilon larvae. Recombinant AiGSTE1 expressed in Escherichia coli could metabolize phoxim. Furthermore, E. coli cells overexpressing AiGSTE1 displayed significant tolerance to oxidative stress. Knockdown of AiGSTe1 by RNA interference significantly increased the mortality of A. ipsilon larvae to phoxim. These results demonstrate that AiGSTE1 confers phoxim tolerance in A. ipsilon by metabolizing the insecticide and preventing phoxim-induced oxidative stress.

Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase.

OBJECTIVE: To provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction (JP) and to explore its mechanism of anti-cancer cachexia. METHODS: A mouse model of colon cancer (CT26)-induced cancer cachexia (CC) was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate (MPA). Thirty-six mice were equally divided into 6 groups: normal control, CC, MPA (100 mg•kg-1•d-1), MPA + low-dose (20 mg•kg-1•d-1) JP (L-JP), MPA + medium-dose (30 mg•kg-1•d-1) JP (M-JP), and MPA + high-dose (40 mg•kg-1•d-1) JP (H-JP) groups. After successful modeling, the mice were administered by gavage for 11 d. The body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after implantation. The liver, heart, spleen, lung, kidney, tumor and gastrocnemius muscle of mice were collected and weighed. The pathological changes of the tumor was observed, and the cross-sectional area of the gastrocnemius muscle was calculated. The protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western blot. In addition, an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle atrophy. In vitro experiments were divided into control, model, and JP serum groups. After 2-d administration, microscopic photographs were taken and myotube diameters were calculated. Western blot was performed to measure the protein expressions of STAT3 and E3 ubiquitinase. RESULTS: JP combined with MPA restored tumor-induced weight loss (P<0.05, vs. CC) and muscle fiber size (P<0.01, vs. CC). Mechanistically, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo (P<0.05, vs. CC). In addition, JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation (P<0.05 or P<0.01 vs. model group) in C2C12 myotubes treated with dexamethasone in vitro. CONCLUSIONS: Administration of JP combined with MPA restores tumor-induced cachexia conditions. In addition, the profound effect of JP combined with MPA on tumor-induced cachexia may be due to its inhibition of muscle proteolysis (E3 ubiquitinase system).

Death in children with influenza A (H3N2) virus infection-associated encephalopathy: two case reports.

We herein report two cases involving children who died of influenza A (H3N2) virus infection-associated encephalopathy/encephalitis (IAE). Both children developed convulsions and impaired consciousness within a relatively short period and eventually died of brainstem failure. Patient 1 presented with high fever, vomiting, and diarrhea. Laboratory tests indicated persistently high lactate, alanine aminotransferase, and urea nitrogen concentrations in the blood as well as a high protein concentration in the cerebrospinal fluid. Patient 2 presented with persistent hyperthermia and progressive disturbance of consciousness, but the cerebrospinal fluid remained normal during the disease course. Both patients were actively given oseltamivir antiviral treatment after diagnosis of influenza virus infection. However, the disease progressed and invasive mechanical ventilation was performed. Both children's condition quickly progressed to IAE, and they eventually died. IAE is a rare complication of influenza virus infection with high mortality, and its pathogenesis remains unclear. The purpose of this report is to draw attention to the serious central nervous system complications of influenza infection and raise awareness of the fatal consequences of this disease among pediatricians.

A thioredoxin peroxidase protects Pieris rapae from oxidative stress induced by chlorantraniliprole exposure.

Chlorantraniliprole (CAP) is an insecticide widely used to control the small white butterfly (SWB), Pieris rapae. Exposure to CAP can cause oxidative injury in SWB; however, it is unclear if antioxidant enzymes are involved in the defense process. In this study, a thioredoxin peroxidase (PrTPX1) gene was identified from SWB by using a homology search method. The gene encoded a 195 amino-acid PrTPX1 protein. Sequence characteristics and phylogenetic analysis indicated that PrTPX1 was a typical "2-Cys" TPX, and the PrTPX1 gene consisted of four exons and three introns. Reverse transcription-quantitative polymerase chain reaction analysis indicated that the messenger RNA levels of PrTPX1 were highest in third-, fourth- and fifth-instar larval stages and in the larval midgut. Treatment with sublethal doses (LD20 and LD50 ) of CAP for 6, 12, 18, and 24 h resulted in increased H2 O2 concentration in SWB larvae, indicating insecticide-induced oxidative stress. The transcriptional levels of PrTPX1 were significantly enhanced in larvae exposed to CAP. Recombinant PrTPX1 protein was expressed in Escherichia coli. Enzymatic assay revealed that the protein displayed antioxidant activity and was able to protect against oxidative challenge. These results indicated that PrTPX1 plays an important role in oxidative stress responses and may contribute to the CAP tolerance in SWB.

A heat shock protein protects against oxidative stress induced by lambda-cyhalothrin in the green peach aphid Myzus persicae.

Lambda-cyhalothrin (LCT) is a pyrethroid insecticide widely used to control insect pests. Insect exposure to LCT may cause abnormal accumulation of reactive oxygen species (ROS) and result in oxidative damage. Heat shock proteins (HSPs) may help protect against oxidative stress. However, little is known about the role of HSPs in response to LCT in the green peach aphid, Myzus persicae. This insect is an important agricultural pest causing severe yield losses in crops. In this study, we characterized a cDNA sequence (MpHsp70) encoding a member of the HSP70 family in M. persicae. MpHsp70 encoded a 623 amino acid protein putatively localized in the cytosol. The highest expression level of MpHsp70 occurred in fourth-instar nymphs. Treatment of M. persicae with LCT resulted in oxidative stress and significantly increased H2O2 and malondialdehyde levels. This led to an elevated transcription level of MpHsp70. Injection of H2O2 into M. persicae also upregulated the MpHsp70 expression level, suggesting that MpHsp70 is responsive to ROS, particularly H2O2, induced by LCT. Recombinant MpHSP70 protein was expressed in Escherichia coli. E. coli cells overexpressing MpHSP70 exhibited significant tolerance to H2O2 and the ROS generators, cumene hydroperoxide and paraquat. This indicated that MpHSP70 protects against oxidative stress. Furthermore, knockdown of MpHsp70 by RNA interference resulted in increased susceptibility in apterous adults of M. persicae to LCT. These findings indicate that MpHsp70 plays an important role in defense against LCT-induced oxidative stress and insecticide susceptibility in M. persicae.

Identification and Functional Analysis of Differentially Expressed Genes in Myzus persicae (Hemiptera: Aphididae) in Response to Trans-anethole.

Plant essential oils, with high bioactivity and biodegradability, provide promising alternatives to synthetic pesticides for pest control. Trans-anethole is the major component of essential oil from star anise, Illicium verum Hook. The compound has a strong contact toxicity against the green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae), which is a major insect pest of many vegetables and crops. However, little information is known about how M. persicae responds to trans-anethole at the molecular level. We conducted a comparative transcriptome analysis of M. persicae in response to a LD50 dose of trans-anethole. A total of 559 differentially expressed genes were detected in the treated individuals, with 318 genes up-regulated, and 241 genes down-regulated. Gene ontology (GO) analysis revealed that these genes were classified into different biological processes and pathways. We also found that genes encoding ATP-binding cassette (ABC) transporters, DnaJ, and cuticle proteins were dramatically up-regulated in response to trans-anethole. To study the function of these genes, we performed RNA interference (RNAi) analysis. Knockdown of an ABC transporter gene (ABCG4) and a DnaJ gene (DnaJC1) resulted in a significantly increased mortality rate in M. persicae following trans-anethole exposure, indicating the involvement of these two genes in the toxicity response to trans-anethole. The findings provide new insights into the mechanisms of M. persicae in coping with plant essential oils.

Molecular characterization of a catalase gene from the green peach aphid (Myzus persicae).

The green peach aphid, Myzus persicae (Sulzer), is a serious agricultural pest with a worldwide distribution. Catalase (CAT), which is encoded by the catalase (Cat) gene, is an extremely important antioxidant enzyme that plays a pivotal role in protecting cells against the toxic effects of hydrogen peroxide. The Cat gene has not been characterized in M. persicae; therefore, this study describes the identification of the Cat (MpCat) gene from M. persicae. MpCat contains an open reading frame of 1515 bp and encodes a MpCAT protein consisting of 504 amino-acid residues. MpCAT possesses features typical of other insect catalases, including 7 conserved amino acids involved in binding heme and 15 involved in binding nicotinamide adenine dinucleotide phosphate. Phylogenetic analysis showed that MpCAT was closely related to orthologs from other aphid species. MpCat consisted of nine exons and eight introns, and the number and insertion sites of introns are consistent with those of Cat genes from Acyrthosiphon pisum (Harris) and Aphis gossypii Glover. The mRNA transcripts of MpCat were detected at all tested developmental stages, with the highest mRNA level in alate adults. The expression of MpCat was significantly upregulated when M. persicae was exposed to low and high temperatures, ultraviolet radiation, Beauveria bassiana, and permethrin. The transcription of MpCat and the activity of catalase were suppressed by RNA interference, and knockdown of MpCat significantly reduced the survival rate in M. persicae under heat stress. The results provide valuable information for further study on the physiological functions of MpCat.