Mesothelin promotes brain metastasis of non-small cell lung cancer by activating MET.

BACKGROUND: Brain metastasis (BM) is common among cases of advanced non-small cell lung cancer (NSCLC) and is the leading cause of death for these patients. Mesothelin (MSLN), a tumor-associated antigen expressed in many solid tumors, has been reported to be involved in the progression of multiple tumors. However, its potential involvement in BM of NSCLC and the underlying mechanism remain unknown. METHODS: The expression of MSLN was validated in clinical tissue and serum samples using immunohistochemistry and enzyme-linked immunosorbent assay. The ability of NSCLC cells to penetrate the blood-brain barrier (BBB) was examined using an in vitro Transwell model and an ex vivo multi-organ microfluidic bionic chip. Immunofluorescence staining and western blotting were used to detect the disruption of tight junctions. In vivo BBB leakiness assay was performed to assess the barrier integrity. MET expression and activation was detected by western blotting. The therapeutic efficacy of drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) on BM was evaluated in animal studies. RESULTS: MSLN expression was significantly elevated in both serum and tumor tissue samples from NSCLC patients with BM and correlated with a poor clinical prognosis. MSLN significantly enhanced the brain metastatic abilities of NSCLC cells, especially BBB extravasation. Mechanistically, MSLN facilitated the expression and activation of MET through the c-Jun N-terminal kinase (JNK) signaling pathway, which allowed tumor cells to disrupt tight junctions and the integrity of the BBB and thereby penetrate the barrier. Drugs targeting MSLN (anetumab) and MET (crizotinib/capmatinib) effectively blocked the development of BM and prolonged the survival of mice. CONCLUSIONS: Our results demonstrate that MSLN plays a critical role in BM of NSCLC by modulating the JNK/MET signaling network and thus, provides a potential novel therapeutic target for preventing BM in NSCLC patients.

Nomogram based on multimodal magnetic resonance combined with B7-H3mRNA for preoperative lymph node prediction in esophagus cancer.

BACKGROUND: Accurate preoperative prediction of lymph node metastasis (LNM) in esophageal cancer (EC) patients is of crucial clinical significance for treatment planning and prognosis. AIM: To develop a clinical radiomics nomogram that can predict the preoperative lymph node (LN) status in EC patients. METHODS: A total of 32 EC patients confirmed by clinical pathology (who underwent surgical treatment) were included. Real-time fluorescent quantitative reverse transcription-polymerase chain reaction was used to detect the expression of B7-H3 mRNA in EC tissue obtained during preoperative gastroscopy, and its correlation with LNM was analyzed. Radiomics features were extracted from multi-modal magnetic resonance imaging of EC using Pyradiomics in Python. Feature extraction, data dimensionality reduction, and feature selection were performed using XGBoost model and leave-one-out cross-validation. Multivariable logistic regression analysis was used to establish the prediction model, which included radiomics features, LN status from computed tomography (CT) reports, and B7-H3 mRNA expression, represented by a radiomics nomogram. Receiver operating characteristic area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the predictive performance and clinical application value of the model. RESULTS: The relative expression of B7-H3 mRNA in EC patients with LNM was higher than in those without metastasis, and the difference was statistically significant (P < 0.05). The AUC value in the receiver operating characteristic (ROC) curve was 0.718 (95%CI: 0.528-0.907), with a sensitivity of 0.733 and specificity of 0.706, indicating good diagnostic performance. The individualized clinical prediction nomogram included radiomics features, LN status from CT reports, and B7-H3 mRNA expression. The ROC curve demonstrated good diagnostic value, with an AUC value of 0.765 (95%CI: 0.598-0.931), sensitivity of 0.800, and specificity of 0.706. DCA indicated the practical value of the radiomics nomogram in clinical practice. CONCLUSION: This study developed a radiomics nomogram that includes radiomics features, LN status from CT reports, and B7-H3 mRNA expression, enabling convenient preoperative individualized prediction of LNM in EC patients.

[Chaihu Sanshen Capsules protect rats from myocardial ischemia reperfusion injury via PKCßâ ¡/NOX2/ROS signaling pathway].

This study aims to explore the pathogenesis of myocardial ischaemia reperfusion injury(MIRI) based on oxidative stress-mediated programmed cell death and the mechanism and targets of Chaihu Sanshen Capsules in treating MIRI via the protein kinase Cß(PKCßⅡ)/NADPH oxidase 2(NOX2)/reactive oxygen species(ROS) signaling pathway. The rat model of MIRI was established by the ligation of the left anterior descending branch. Rats were randomized into 6 groups: sham group, model group, clinically equivalent-, high-dose Chaihu Sanshen Capsules groups, N-acetylcysteine group, and CGP53353 group. After drug administration for 7 consecutive days, the area of myocardial infarction in each group was measured. The pathological morphology of the myocardial tissue was observed by hematoxylin-eosin(HE) staining. The apoptosis in the myocardial tissue was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL). Enzyme-linked immunosorbent assay(ELISA) was employed to measure the le-vels of indicators of myocardial injury and oxidative stress. The level of ROS was detected by flow cytometry. The protein and mRNA levels of the related proteins in the myocardial tissue were determined by Western blot and real-time quantitative PCR(RT-qPCR), respectively. Compared with the sham group, the model group showed obvious myocardial infarction, myocardial structural disorders, interstitial edema and hemorrhage, presence of a large number of vacuoles, elevated levels of myocardial injury markers, myocardial apoptosis, ROS, and malondialdehyde(MDA), lowered superoxide dismutase(SOD) level, and up-regulated protein and mRNA le-vels of PKCßⅡ, NOX2, cysteinyl aspartate specific proteinase-3(caspase-3), and acyl-CoA synthetase long-chain family member 4(ACSL4) in the myocardial tissue. Compared with the model group, Chaihu Sanshen Capsules reduced the area of myocardial infarction, alleviated the pathological changes in the myocardial tissue, lowered the levels of myocardial injury and oxidative stress indicators and apoptosis, and down-regulated the mRNA and protein levels of PKCßⅡ, NOX2, caspase-3, and ACSL4 in the myocardial tissue. Chaihu Sanshen Capsules can inhibit oxidative stress and programmed cell death(apoptosis, ferroptosis) by regulating the PKCßⅡ/NOX2/ROS signaling pathway, thus mitigating myocardial ischemia reperfusion injury.

Distinct fibroblast subpopulations associated with bone, brain or intrapulmonary metastasis in advanced non-small-cell lung cancer.

BACKGROUND: Bone or brain metastases may develop in 20-40% of individuals with late-stage non-small-cell lung cancer (NSCLC), resulting in a median overall survival of only 4-6 months. However, the primary lung cancer tissue's distinctions between bone, brain and intrapulmonary metastases of NSCLC at the single-cell level have not been underexplored. METHODS: We conducted a comprehensive analysis of 14 tissue biopsy samples obtained from treatment-naïve advanced NSCLC patients with bone (n = 4), brain (n = 6) or intrapulmonary (n = 4) metastasis using single-cell sequencing originating from the lungs. Following quality control and the removal of doublets, a total of 80 084 cells were successfully captured. RESULTS: The most significant inter-group differences were observed in the fraction and function of fibroblasts. We identified three distinct cancer-associated fibroblast (CAF) subpopulations: myofibroblastic CAF (myCAF), inflammatory CAF (iCAF) and antigen-presenting CAF (apCAF). Notably, apCAF was prevalent in NSCLC with bone metastasis, while iCAF dominated in NSCLC with brain metastasis. Intercellular signalling network analysis revealed that apCAF may play a role in bone metastasis by activating signalling pathways associated with cancer stemness, such as SPP1-CD44 and SPP1-PTGER4. Conversely, iCAF was found to promote brain metastasis by activating invasion and metastasis-related molecules, such as MET hepatocyte growth factor. Furthermore, the interaction between CAFs and tumour cells influenced T-cell exhaustion and signalling pathways within the tumour microenvironment. CONCLUSIONS: This study unveils the direct interplay between tumour cells and CAFs in NSCLC with bone or brain metastasis and identifies potential therapeutic targets for inhibiting metastasis by disrupting these critical cell-cell interactions.

An Eco-Friendly Manner to Prepare Superwetting Melamine Sponges with Switchable Wettability for the Separation of Oil/Water Mixtures and Emulsions.

Oil/water separation processes have garnered significant global attention due to the quick growth in industrial development, recurring chemical leakages, and oil spills. Hence, there is a significant demand for the development of inexpensive superwetting materials in an eco-friendly manner to separate oil/water mixtures and emulsions. In this study, a superwetting melamine sponge (SMS) with switchable wettabilities was prepared by modifying melamine sponge (MS) with sodium dodecanoate. The as-prepared SMS exhibited superhydrophobicity, superoleophilicity, underwater superoleophobicity, and underoil superhydrophobicity. The SMS can be utilized in treating both light and heavy oil/water mixtures through the prewetting process. It demonstrated fast permeation fluxes (reaching 108,600 L m-2 h-1 for a light oil/water mixture and 147,700 L m-2 h-1 for a heavy oil/water mixture) and exhibited good separation efficiency (exceeding 99.56%). The compressed SMS was employed in separating surfactant-stabilized water-in-oil emulsions (SWOEs), as well as surfactant-stabilized oil-in-water emulsions (SOWEs), giving high permeation fluxes (reaching 7210 and 5054 L m-2 h-1, respectively). The oil purity for SWOEs' filtrates surpassed 99.98 wt% and the separation efficiencies of SOWEs exceeded 98.84%. Owing to their remarkable capability for separating oil/water mixtures and emulsions, eco-friendly fabrication method, and feasibility for large-scale production, our SMS has a promising potential for practical applications.

Revision of residual deformities after primary surgery for Wassel-Flatt IV-D thumb duplication using a microsurgical free lateral great toe flap.

We report the application and results of skin defect coverage using the free lateral great toe flap in revision surgery for residual postoperative deformities in Wassel-Flatt type IV-D thumb duplications. This retrospective study included five patients treated between June 2020 and September 2021 to correct angular deformity and repair the secondary skin defect. All the flaps survived. The patients were followed up for 8-12 months and all the reconstructed thumbs had a satisfactory appearance. The results of the Japanese Society for Surgery of the Hand scoring system were excellent in one patient, good in three patients and fair in one patient. The results of the Alignment, Ulnar and Radial stability, Range of motion and Aesthetical aspects (ALURRA) scoring system were good in four patients and moderate in one patient.Level of evidence: IV.

Fatty acid modification of casein bioactive peptides nano-assemblies, synthesis, characterization and anticarcinogenic effect.

In this study, the nano-assemblies of bovine casein hydrolyzed peptides (HP) modified by fatty acids with various alkyl chain lengths (C8, C10, C12 and C14) were synthesized. The physicochemical properties of HP-C8-HP-C14 nano-assemblies were characterized using spectra, laser particle size analyzer, contact angle meter, scanning electron microscope (SEM) and cryo-transmission electron microscope (Cryo-TEM). HP-C8 and HP-C10 self-assembled into a hollow cube cage with an average size of ~500 nm, and the assembly of HP-C12 showed a flower-shaped morphology with more dispersed behavior, and droplet size was observed as ~20 nm. The in vitro cytotoxicity against human breast cancer cells MCF-7 was tested using CCK-8 assay and flow cytometry analysis. HP-C12 showed the highest cytotoxicity for MCF-7 cells with an inhibition rate of 66.03 % ± 0.35 % with an IC50 value of 7.4 µM among HP-Cn. HP-C8, HP-C10 and HP-C12 significantly affected on the migration, invasion and apoptosis of MCF-7 cells. The apoptosis mechanism may depend on the upregulation of anti-apoptotic protein Bcl-2 as well as pro-apoptotic proteins Bax and caspase-8. The dead MCF-7 cells were analyzed with UHPLC-MS/MS using untargeted metabolomics, revealing key metabolic pathways.

Nucleophilic aromatization of monoterpenes from isoprene under nickel/iodine cascade catalysis.

As a large number of organic compounds possessing two isoprene units, monoterpenes and monoterpenoids play important roles in pharmaceutical, cosmetic, agricultural, and food industries. In nature, monoterpenes are constructed from geranyl pyrophosphate (C10) via various transformations. Herein, the bulk C5 chemical-isoprene, is used for the creation of various monoterpenoids via a nucleophilic aromatization of monoterpenes under cascade catalysis of nickel and iodine. Drugs and oil mixtures from conifer and lemon can be convergently transformed to the desired monoterpenoid. Preliminary mechanistic studies are conducted to get insights about reaction pathway. Two types of cyclic monoterpenes can be respectively introduced onto two similar heterocycles via orthogonal C-H functionalization. And various hybrid terpenyl indoles are programmatically assembled from abundant C5 or C10 blocks. This work not only contributes a high chemo-, regio-, and redox-selective transformation of isoprene, but also provides a complementary approach for the creation of unnatural monoterpenoids.

Spatio-temporal evolution law of gas-temperature coupling field in "110 method" goaf and prevention of spontaneous combustion.

To investigate the distribution characteristics of spontaneous combustion disaster (SCD) zones in the goaf of "110" mining method with U + L ventilation system and formulate corresponding fire prevention measures, enclosed coal oxidation experiments were carried out to measure the oxidation characteristics of Dongrong Coal Mine bituminous coal sample. A coupled 3DEC-CFD (3 dimensional Distinct Element Code) model was established. The 3D transient distribution characteristics of SCD zones in the "110" mining goaf under U+L ventilation condition were analyzed. Nitrogen injection in the tailgate was proposed for coal spontaneous combustion prevention. The results show that air leakage changed the distribution of oxygen and temperature fields in the "110" goaf, causing the region 20~60 m parallel to the retained roadway to remain in the oxidation zone for spontaneous combustion. As the working face advanced, the area change curve of SCD zones in the "110" goaf exhibited a "double inflection point" pattern. Eliminating the "retained roadway oxidation zone" can effectively reduce the spontaneous combustion risks in the "110" goaf and ensure mining safety. This study enriches the mechanisms of coal spontaneous combustion.

A retrospective study of transarterial chemoembolization (TACE) combined with lenvatinib compared with TACE monotherapy for BCLC B2 stage hepatocellular carcinoma.

The present study aimed to compare the efficacy and safety of combination therapy with lenvatinib (Len) plus transarterial chemoembolization (TACE) and TACE alone in patients with Barcelona Clinic Liver Cancer (BCLC) B2 stage hepatocellular carcinoma (HCC). A total of 66 patients with BCLC B2 stage HCC were retrospectively reviewed in the present study, of which 34 patients received Len + TACE, while 32 patients received TACE alone between May 2018 and May 2020. Survival outcome, tumor response and adverse events (AEs) were compared between the two treatment groups. The 6-month, 1- and 2-year overall survival (OS) rates were significantly higher in the Len + TACE group (97.1, 85.3 and 76.3%, respectively) compared with those in the TACE group [(93.8, 81.1 and 45.4%, respectively); hazard ratio (HR), 0.395; 95% confidence interval (CI), 0.180-0.867; P=0.023], but no significant difference in progression-free survival rate was observed between the two groups (HR, 0.815; 95% CI, 0.437-1.520; P=0.510). Patients receiving Len + TACE demonstrated a higher objective response rate compared with those receiving TACE alone (64.7 vs. 34.4%; P=0.014). Therefore, Len + TACE combination therapy was associated with increased OS and tumor response compared with that of TACE monotherapy in patients with BCLC B2 stage HCC. However, large-scale, multicenter, prospective studies are needed to further confirm these results.

On-top plasty combined with modified Bilhaut-Cloquet procedure for reconstructing complicated radial polydactyly.

PURPOSE: To present a surgical technique of combining the on-top plasty with modified Bilhaut-Cloquet procedure for reconstructing a rare type of complicated radial polydactyly and evaluate the outcomes. METHODS: Fourteen complicated radial polydactyly in 13 patients were corrected by combining the on-top plasty with modified Bilhaut-Cloquet procedure. Osteotomies were performed as required, and the acral part of the ulnar thumb was transposed onto the proximal part of the radial thumb. The distal parts of the two thumbs were isolated as neurovascular pedicled composite tissue flaps, including part of the distal phalanx and nail bed, and were attached together in an extra-articular way. The tendons were rebalanced, and the nail bed was reconstructed. Objective and subjective outcomes were assessed. RESULTS: The average follow-up time was 32.4 months (6-60 months). All reconstructed thumbs were rated as good in appearance and function. The mean Vancouver Scar Scale score was 1.3 (range 1-2) and the mean Wang-Gao score of the reconstructed thumbnail was 9.4 (range 8-11). The Tada score for the function of the reconstructed thumb was 5.5 (range 5-6). The main active range of motion (ROM) of the interphalangeal joint (IPJ) was 2.1-38.9°. All parents were satisfied with the outcomes. CONCLUSIONS: Because of the diverse manifestations of thumb polydactyly, individualized surgical treatment is recommended, and careful preoperative planning should be made with the principle of combining the best parts of the two thumbs. By combining an on-top plasty with modified Bilhaut-Cloquet procedure, a satisfactory result can be achieved for treating complicated radial polydactyly.

Efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Atezolizumab plus bevacizumab and lenvatinib are the current first-line systematic therapy for unresectable hepatocellular carcinoma (uHCC). However, the selection of initial treatment among the two therapies are controversial. This meta-analysis aims to compare efficacy and safety between atezolizumab plus bevacizumab and lenvatinib. METHODS: We systematically searched for studies on atezolizumab plus bevacizumab and lenvatinib in the online databases PubMed, Embase, Web of Science and Cochrane Library. The outcome data including overall survival (OS), progression free survival (PFS), tumor response and adverse events (AEs), were independently extracted by two authors in a standardized way. RESULTS: Eight retrospective cohort studies with 3690 patients (atezolizumab plus bevacizumab: 1680, lenvatinib: 2010) were included in the meta-analysis. The atezolizumab plus bevacizumab group had significant longer PFS [hazard ratio (HR) 0.76, 95% confidence intervals (CI) 0.65-0.88; I squared statistic (I2) = 0.0%, p = 0.590], compared with lenvatinib group but no significant difference in OS (HR 0.87, 95% CI 0.75-1.01; I2 = 0.0%, p = 0.597), objective response rate (ORR) [risk ratio (RR) 0.89, 95% CI 0.79-1.02; I2 = 19.3%, p = 0.283] and disease control rate (DCR) (RR 1.03, 95% CI 0.98-1.09; I2 = 0.0%, p = 0.467) among them. Moreover, patients receiving atezolizumab plus bevacizumab exhibited lower incidences of grade 3/4 AEs than those receiving lenvatinib (RR 0.65, 95% CI 0.51-0.83; I2 = 69.3%, p = 0.003). However, in non-viral patients group, lenvatinib delivered favorable outcomes in OS (HR 1.32, 95% CI 1.04-1.67; I2 = 0.0%, p = 0.380) compared with atezolizumab plus bevacizumab. CONCLUSION: Atezolizumab plus bevacizumab provides potential advantage in efficacy and better safety than lenvatinib in the treatment of uHCC. Lenvatinib is an appropriate effective alternative to atezolizumab plus bevacizumab in patients without viral infecting.

Efficacy and safety of transarterial chemoembolization plus lenvatinib with or without programmed death-1 inhibitors in the treatment of unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Programmed death-1 inhibitors plus lenvatinib and transarterial chemoembolization (TACE) (P-L-T) is a novel combination strategy. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of P-L-T compared with lenvatinib and TACE (L-T) therapy in patients with unresectable hepatocellular carcinoma. METHODS: A systematic literature search of the PubMed, Embase, Web of Science and Cochrane Library databases for studies investigating P-L-T therapy was performed. Data regarding outcome data, including overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs), were independently extracted by two authors using a standardized protocol. RESULTS: Eight cohort studies comprising 847 patients (P-L-T: 416, L-T: 431) were included in the meta-analysis. The P-L-T group exhibited significantly longer OS (hazard ratio (Page et al.) 0.51 [95% confidence interval (CI) 0.42-0.62]; I2 = 9.8%; p = 0.354] and PFS (HR 0.51 [95% CI 0.43-0.61]; I2 = 0%; p = 0.824), and higher objective response rate (risk ratio [RR] 1.54 [95% CI 1.33-1.78]; I2 = 0%, p = 0.858]) and disease control rate (RR 1.27 [95% CI 1.17-1.38]; I2 = 17.3%; p = 0.467). Grade 3/4 AEs were more prevalent in the P-L-T group, including hypertension (RR 1.91 [95% CI 1.16-3.15]), vomiting or nausea (RR 2.29 [95% CI 1.01-5.19]), and hypothyroidism (RR 12.21 [95% CI 1.63-91.23]). CONCLUSION: Compared with L-T combination therapy, P-L-T demonstrated a significant advantage in terms of OS, PFS, objective response rate, disease control rate, and manageable AEs.

Activation of Kupffer cells in NAFLD and NASH: mechanisms and therapeutic interventions.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging as the leading causes of liver disease worldwide. These conditions can lead to cirrhosis, liver cancer, liver failure, and other related ailments. At present, liver transplantation remains the sole treatment option for end-stage NASH, leading to a rapidly growing socioeconomic burden. Kupffer cells (KCs) are a dominant population of macrophages that reside in the liver, playing a crucial role in innate immunity. Their primary function includes phagocytosing exogenous substances, presenting antigens, and triggering immune responses. Moreover, they interact with other liver cells during the pathogenesis of NAFLD, and this crosstalk may either delay or exacerbate disease progression. Stimulation by endogenous signals triggers the activation of KCs, resulting in the expression of various inflammatory factors and chemokines, such as NLRP3, TNF-α, IL-1B, and IL-6, and contributing to the inflammatory cascade. In the past 5 years, significant advances have been made in understanding the biological properties and immune functions of KCs in NAFLD, including their interactions with tissue molecules, underlying molecular mechanisms, signaling pathways, and relevant therapeutic interventions. Having a comprehensive understanding of these mechanisms and characteristics can have enormous potential in guiding future strategies for the prevention and treatment of NAFLD.

Discovery and Structural Optimization of Novel Quinolone Derivatives as Potent Irreversible Pan-Fibroblast Growth Factor Receptor Inhibitors for Treating Solid Tumors.

Aberrant activation of fibroblast growth factor receptors (FGFRs) has been identified as an oncogenic driver force for multiple cancer types, making FGFRs a compelling target for anticancer therapy. Because of the renewed interest in irreversible inhibitors, considerable efforts have been made to find irreversible FGFR inhibitors. Herein, we discovered a series of novel quinolone-based covalent pan-FGFR inhibitors by further optimizing the lead compound (lenvatinib) under the guidance of molecular docking. The representative pan-FGFR inhibitor I-5 exhibited significant inhibitory potency against FGFR1-4 with nanomolar activity and effectively suppressed the proliferation of Huh-7 and Hep3B HCC cells. I-5 displayed high selectivity against a panel of 369 kinases at 1 µM. The irreversible binding to target proteins was characterized by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Moreover, I-5 exhibited favorable PK properties in vivo and induced significant TGI in the Huh-7 and NCI-H1581 xenograft mouse models.

Engineering the Staple Oil Crop Brassica napus Enriched with α-Linolenic Acid Using the Perilla FAD2-FAD3 Fusion Gene.

Modern people generally suffer from α-linolenic acid (ALA) deficiency, since most staple food oils are low in ALA content. Thus, the enhancement of ALA in staple oil crops is of importance. In this study, the FAD2 and FAD3 coding regions from the ALA-king species Perilla frutescens were fused using a newly designed double linker LP4-2A, driven by a seed-specific promoter PNAP, and engineered into a rapeseed elite cultivar ZS10 with canola quality background. The mean ALA content in the seed oil of PNAP:PfFAD2-PfFAD3 (N23) T5 lines was 3.34-fold that of the control (32.08 vs 9.59%), with the best line being up to 37.47%. There are no significant side effects of the engineered constructs on the background traits including oil content. In fatty acid biosynthesis pathways, the expression levels of structural genes as well as regulatory genes were significantly upregulated in N23 lines. On the other hand, the expression levels of genes encoding the positive regulators of flavonoid-proanthocyanidin biosynthesis but negative regulators of oil accumulation were significantly downregulated. Surprisingly, the ALA level in PfFAD2-PfFAD3 transgenic rapeseed lines driven by the constitutive promoter PD35S was not increased or even showed a slight decrease due to the lower level of foreign gene expression and downregulation of the endogenous orthologous genes BnFAD2 and BnFAD3.

Clinical Efficacy and Imaging Observation of Three Surgical Approaches in Treatment of Thoracolumbar Fractures.

Objective: To observe the efficacy and imaging of surgical treatment of thoracolumbar fractures via the paravertebral muscle space approach. Methods: A retrospective analysis was conducted on patients with thoracolumbar fractures receiving surgery in Baoding First Central Hospital from January 2019 to December 2020. According to different surgical approaches, they were divided into paravertebral approach group, posterior median approach group and minimally invasive percutaneous approach group. They received surgery via the paravertebral muscle space approach, posterior median approach and minimally invasive percutaneous approach, respectively. Results: Statistically significant differences were found in surgical duration, intraoperative bleeding volume, intraoperative fluoroscopy frequency, postoperative drainage volume and hospital stay among the three groups. One year after surgery, the VAS, ADL and JOA scores of the paravertebral approach group and the minimally invasive percutaneous approach group had statistically significant differences from the posterior median approach group (P < 0.05). Conclusion: For the surgical treatment of thoracolumbar fractures, the clinical efficacy of the paravertebral muscle space approach is superior to that of the traditional posterior median approach, and the clinical efficacy of the minimally invasive percutaneous approach is similar to that of the posterior median approach. All the three approaches can effectively improve the postoperative function and pain symptoms of patients without increasing the incidence of complications. Compared with the posterior median approach, the surgery via the paravertebral muscle space and minimally invasive percutaneous approaches presents shorter surgical duration, less bleeding and shorter hospital stay, which is more conducive to postoperative recovery of patients.

Gallic acid ameliorates dextran sulfate sodium-induced ulcerative colitis in mice via inhibiting NLRP3 inflammasome.

Background: Ulcerative colitis (UC) is a chronic recurrent inflammatory bowel disease (IBD). The conventional drugs for UC may induce severe side effects. Herbal medicine is considered as a complementary and alternative choice for UC. Purpose: This study aims to estimate the effect of natural polyphenol gallic acid (GA) on the NLRP3 inflammasome with dextran sulfate sodium (DSS)-induced colitis in mice. Study design: The body weights and symptoms of BALB/c mice were recorded. Histological evaluation, ELISA, q-PCR, immunohistochemistry, and western blotting were carried out to observe the morphology, cytokine contents, mRNA expressions, and protein expressions, respectively. Lipopolysaccharide (LPS)-induced RAW264.7 macrophage was used to probe GA's effect on relative protein expression. Results: GA attenuated weight loss (p < 0.05), relieved symptoms, and ameliorated colonic morphological injury (p < 0.05) in mice with colitis induced by DSS. GA also lowered the contents of TNF-α, IL-1ß, IL-18, IL-33, and IFN-γ in the serum and colon of mice, which were elevated by DSS, downregulated protein, and mRNA expressions of the NLRP3 pathway in the colon tissue. Furthermore, GA downregulated the expressions of NLRP3 (p < 0.05), iNOS (p < 0.01), COX2 (p < 0.01), and P-p65 (p < 0.05), and suppressed NO release (p < 0.001) in LPS-induced RAW264.7 cells. Conclusion: GA ameliorated DSS-induced UC in mice via inhibiting the NLRP3 inflammasome. These findings furnish evidence for the anti-inflammatory effect of herbal medicines containing GA on UC.

Nickel-Catalyzed Unsymmetrical Bis-Allylation of Alkynes.

The catalytic bis-allylation of alkynes is an important but challenging protocol to construct all-carbon tetra-substituted alkenes. Particularly, the catalytic unsymmetrical bis-allylation of alkynes remains as an underexplored task to date. We herein report an unprecedented unsymmetrical bis-allylation by simultaneously utilizing electrophilic trifluoromethyl alkene and nucleophilic allylboronate as the allylic reagents. With the aid of robust Ni0 /NHC catalysis, valuable skipped trienes can be obtained in high regio- and stereo-selectivities under mild conditions. Mechanistic studies indicate that the reaction may proceed through a ß-fluorine elimination of a nickelacycle followed by a transmetalation step with allylboronate. The present method exhibits a good tolerance of various functional groups. Besides, the skipped triene products can undergo an array of elaborate transformations, which highlights the potential applications of this strategy.

Nickel-catalyzed divergent Mizoroki-Heck reaction of 1,3-dienes.

Developing efficient strategies to realize divergent arylation of dienes has been a long-standing synthetic challenge. Herein, a nickel catalyzed divergent Mizoroki-Heck reaction of 1,3-dienes has been demonstrated through the regulation of ligands and additives. In the presence of Mn/NEt3, the Mizoroki-Heck reaction of dienes delivers linear products under Ni(dppe)Cl2 catalysis in high regio- and stereoselectivities. With the help of catalytic amount of organoboron and NaF, the use of bulky ligand IPr diverts the selectivity from linear products to branched products. Highly aryl-substituted compounds can be transformed from dispersive Mizoroki-Heck products programmatically. Preliminary experimental studies are carried out to elucidate the role of additives.