Explore the vast range of titles available.

In addition to the lung, the liver is considered another major target for paraquat (PQ) poisoning. Hydrogen sulfide (H2S) has been demonstrated to be effective in the inhibition of oxidative stress and inflammation. The aim of this study was to investigate the protective effect of exogenous H2S against PQ-induced acute liver injury. The acute liver injury model was established by a single intraperitoneal injection of PQ, evidenced by histological alteration and elevated serum aminotransferase levels. Different doses of NaHS were administered intraperitoneally one hour before exposure to PQ. Analysis of the data shows that exogenous H2S attenuated the PQ-induced liver injury and oxidative stress in a dose-dependent manner. H2S significantly suppressed reactive oxygen species (ROS) generation and the elevation of malondialdehyde content while it increased the ratio of GSH/GSSG and levels of antioxidant enzymes including SOD, GSH-Px, HO-1, and NQO-1. When hepatocytes were subjected to PQ-induced oxidative stress, H2S markedly enhanced nuclear translocation of Nrf2 via S-sulfhydration of Keap1 and resulted in the increase in IDH2 activity by regulating S-sulfhydration of SIRT3. In addition, H2S significantly suppressed NLRP3 inflammasome activation and subsequent IL-1β excretion in PQ-induced acute liver injury. Moreover, H2S cannot reverse the decrease in SIRT3 and activation of the NLRP3 inflammasome caused by PQ in Nrf2-knockdown hepatocytes. In summary, H2S attenuated the PQ-induced acute liver injury by enhancing antioxidative capability, regulating mitochondrial function, and suppressing ROS-induced NLRP3 inflammasome activation. The antioxidative effect of H2S in PQ-induced liver injury can at least partly be attributed to the promotion of Nrf2-driven antioxidant enzymes via Keap1 S-sulfhydration and regulation of SIRT3/IDH2 signaling via Nrf2-dependent SIRT3 gene transcription as well as SIRT3 S-sulfhydration. Thus, H2S supplementation can form the basis for a promising novel therapeutic strategy for PQ-induced acute liver injury.

Two-component systems (TCS) in plants have evolved into a more complicated multi-step phosphorelay (MSP) pathway, which employs histidine kinases (HKs), histidine-containing phosphotransfer proteins (HPts), and response regulators (RRs) to regulate various aspects of plant growth and development. How plants perceive the external signals, then integrate and transduce the secondary signals specifically to the desired destination, is a fundamental characteristic of the MSP signaling network. The TCS elements involved in the MSP pathway and molecular mechanisms of signal transduction have been best understood in the model plant Arabidopsis thaliana. In this review, we focus on updated knowledge on TCS signal transduction in Arabidopsis. We first present a brief description of the TCS elements; then, the protein–protein interaction network is established. Finally, we discuss the possible molecular mechanisms involved in the specificity of the MSP signaling at the mRNA and protein levels.

Background Hip replacement is a standard treatment for femoral neck fractures, but the optimal surgical approach remains uncertain. This study aimed to compare the clinical outcomes of the lateral-position direct anterior approach (DAA) and the posterolateral approach (PLA) in patients undergoing hemiarthroplasty. Materials and methods This retrospective cohort study analyzed clinical data from 56 patients with femoral neck fractures who underwent hemiarthroplasty between February 2019 and September 2022. Patients were classified into a PLA group ( n  = 28) and a DAA group (lateral-position DAA, n  = 28). Perioperative indices, postoperative pain assessed by the visual analogue scale (VAS), Harris Hip Score, Barthel Index, quality-of-life measures, and early postoperative complications were evaluated. Results The DAA group had a shorter operation time (100.54 ± 11.64 min vs. 110.48 ± 22.32 min, p  = 0.041), smaller incision length (9.31 ± 0.31 cm vs. 12.31 ± 1.21 cm, p  < 0.001), less intraoperative blood loss (214.95 ± 32.22 mL vs. 268.49 ± 23.53 mL, p  < 0.001), and shorter hospital stay (10.68 ± 3.31 days vs. 17.49 ± 2.21 days, p  < 0.001) compared with the PLA group. VAS scores were lower in the DAA group on postoperative days 1, 3, and 7 (all p  < 0.001). Harris Hip Scores and Barthel Index scores were higher at discharge and at 1 and 3 months postoperatively (all p  < 0.001). The incidence of early postoperative complications was lower in the DAA group than in the PLA group (7.14% vs. 42.86%, p  = 0.002), including a reduced rate of hip dislocation (3.57% vs. 25.00%). Conclusion Lateral-position DAA using conventional instruments was associated with improved perioperative outcomes, faster early functional recovery, and fewer early complications compared with PLA in this retrospective cohort. These findings suggest that lateral-position DAA may be a feasible alternative approach; however, prospective studies are required to confirm these results.

Acute pancreatitis (AP) is an acute abdominal inflammatory disease with episodes ranging from mild to fulminant symptoms which could include necrosis, systemic inflammation and multiple organ dysfunction. Increasing experimental evidence demonstrates that specific bioactive ingredients from natural plants have a favourable therapeutic effect on AP. The objective of this review is to summarize the protective effects and potential mechanisms of action of phytochemicals on the attenuation of AP. Experimental studies in vivo or in vitro between January 2016 and June 2021 were sought in PubMed and Web of Science using the following search terms: ('phytochemicals' OR 'medicinal plant' OR 'traditional medicine') AND ('pancreatitis' OR 'pancreatic damage' OR 'pancreatic injury'). Data concerning the basic characteristics of phytochemicals, therapeutic dose and potential molecular mechanisms related to AP were extracted in this study. A total of 30 phytochemicals with potential therapeutic effects were reviewed and summarized systematically. According to their molecular pathways in AP, the underlying mechanisms of the phytochemicals were illustrated in detail. The phytochemicals with anti-inflammatory and antioxidant abilities may be efficient candidate drugs for AP treatment. Importantly, more preclinical investigations are needed to illustrate the efficacy of future phytochemicals.

The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN‐SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non‐dynamic photo‐crosslinked bonds respectively. The single network hydrogel before photo‐crosslinking exhibits excellent injectability and thus can be printed and photo‐crosslinked in situ to form double network hydrogels. DN‐SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an “operando” comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN‐SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN‐DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds. Spermidine‐functionalized hydrogel can mitigate aseptic inflammation induced by exogenous biomaterials and direct more natural healings of acute and diabetic wounds. The aspiration is to mitigate foreign body response by the local administration of spermidine in biomaterials, which may be a game changer for medical implants and even for organ transplantation.

Breast cancer brain metastasis (BCBM) remains a major clinical problem. Approximately 10–16% of patients with breast cancer develop brain metastases (BCBM). However, no systemic therapy has gained regulatory approval for the specific treatment of BCBM and this remains an area of persistent, unmet medical need. Rapid, predictive and clinically-relevant animal models are critical to study the biology of brain metastases and to identify effective therapeutic approaches for patients with BCBM. Here, we describe a method for efficient establishment of orthotopic mouse models of patient-derived brain metastases via an improved intracarotid injection protocol that permits tumor cell growth in the unique brain microenvironment without compromising the blood-brain barrier (BBB). We demonstrate that our newly improved models of patient-derived brain metastases recapitulate the histologic, molecular, and genetic characteristics of their matched patient tumor specimens and thus represent a potentially powerful tool for pre-clinical and translational research.

Histidine phosphotransfer proteins (HPs) are key elements of the two-component signaling system, which act as a shuttle to transfer phosphorylation signals from histidine kinases (HKs) to response regulators (RRs). CYTOKININ INDEPENDENT 1 (CKI1), a key regulator of central cell specification in the Arabidopsis female gametophyte, activates the cytokinin signaling pathway through the Arabidopsis histidine phosphotransfer proteins (AHPs). There are five HP genes in Arabidopsis, AHP1–AHP5, but it remains unknown which AHP genes act downstream of CKI1 in Arabidopsis female gametophyte development. Promoter activity analysis of AHP1–AHP5 in embryo sacs revealed AHP1, AHP2, AHP3, and AHP5 expression in the central cell. Phenotypic studies of various combinations of ahp mutants showed that triple mutations in AHP2, AHP3, and AHP5 resulted in defective embryo sac development. Using cell-specific single and double markers in the female gametophyte, the ahp2-2 ahp3 ahp5-2/+ triple mutant ovules showed loss of central cell and antipodal cell fates and gain of egg cell or synergid cell attributes, resembling the cki1 mutant phenotypes. These data suggest that AHP2, AHP3, and AHP5 are the major factors acting downstream of CKI1 in the two-component cytokinin signaling pathway to promote Arabidopsis female gametophyte development.

Background 3-Phenylpropanol with a pleasant odor is widely used in foods, beverages and cosmetics as a fragrance ingredient. It also acts as the precursor and reactant in pharmaceutical and chemical industries. Currently, petroleum-based manufacturing processes of 3-phenypropanol is environmentally unfriendly and unsustainable. In this study, we aim to engineer Escherichia coli as microbial cell factory for de novo production of 3-phenypropanol via retrobiosynthesis approach. Results Aided by in silico retrobiosynthesis analysis, we designed a novel 3-phenylpropanol biosynthetic pathway extending from l -phenylalanine and comprising the phenylalanine ammonia lyase (PAL), enoate reductase (ER), aryl carboxylic acid reductase (CAR) and phosphopantetheinyl transferase (PPTase). We screened the enzymes from plants and microorganisms and reconstructed the artificial pathway for conversion of 3-phenylpropanol from l -phenylalanine. Then we conducted chromosome engineering to increase the supply of precursor l -phenylalanine and combined the upstream l -phenylalanine pathway and downstream 3-phenylpropanol pathway. Finally, we regulated the metabolic pathway strength and optimized fermentation conditions. As a consequence, metabolically engineered E. coli strain produced 847.97 mg/L of 3-phenypropanol at 24 h using glucose-glycerol mixture as co-carbon source. Conclusions We successfully developed an artificial 3-phenylpropanol pathway based on retrobiosynthesis approach, and highest titer of 3-phenylpropanol was achieved in E. coli via systems metabolic engineering strategies including enzyme sources variety, chromosome engineering, metabolic strength balancing and fermentation optimization. This work provides an engineered strain with industrial potential for production of 3-phenylpropanol, and the strategies applied here could be practical for bioengineers to design and reconstruct the microbial cell factory for high valuable chemicals.

Due to frequent water level fluctuations and complex hydrochemical environments, rock slopes in reservoir areas progressively deteriorate and become unstable. This study investigated the coupling effect of drying−wetting cycles and acidic solutions on the physical and mechanical properties, strain field evolution, failure mode, and micro-mechanism of red sandstone using a series of laboratory experiments (wave velocity tests, uniaxial compression tests, the digital image correlation method, scanning electron microscopy, and X-ray diffraction). The results showed that with increasing drying−wetting cycles, the mass, P-wave velocity, elastic modulus, and uniaxial compressive strength decreased monotonically, while the water absorption and apparent strain in the strain localization band increased. Moreover, the failure mode transitioned gradually from tensile failure to shear failure or tensile-shear composite failure. The decrease in the solution pH values aggravated the changes in the physical and mechanical parameters and contributed to an increase in the secondary cracks and the occurrence of shear behavior. In addition, the coupling effect of drying−wetting cycles and acidic solutions accelerated the worsening of the microstructure and the dissolution of minerals, resulting in a loose structure with well-developed pores and fissures. These changes provide a favorable explanation for the mechanical property deterioration of red sandstone subjected to acidic drying−wetting cycles.

Background Peanut is the most essential oil and food crop globally due to its high oil and protein content. Root-knot nematode infects peanut roots, causing poor development and severely limiting peanut yields worldwide. The discovery of peanut genome identified a considerable number of genetic loci controlling the peanut root-knot nematode; however, the molecular mechanism of root-knot nematode remains unknown. Results The heterogeneous response to root-knot nematode stress in peanut roots was identified using whole-transcriptome RNA-seq. A total of 430 mRNAs, 111 miRNAs, 4453 lncRNAs, and 123 circRNAs were found to have differential expression between infected and non-infected peanuts. The expression profiles of the lncRNA/circRNA-miRNA-mRNA network were developed to understand the potential pathways that lead to root-knot nematodes in peanut roots. During root-knot nematodes stress, a total of 10 lncRNAs, 4 circRNAs, 5 miRNAs, and 13 mRNAs can create competing endogenous RNA and participate in the oxidation–reduction process as well as other biological metabolism processes in peanuts. The findings will highlight the role of peanut ceRNAs in response to root-knot nematodes. Conclusion The GO classification and KEGG pathway enrichment study of core regulatory networks revealed that ceRNAs are involved in oxidation–reduction, peroxidase activity, lignin synthesis in the xylem, and flavonoid synthesis. Overall, these findings may help researchers better understand the role of non-coding RNAs in response to root-knot nematodes.