Metabolic Engineering of High L-Lysine-Producing Escherichia coli for de Novo Production of L-Lysine-Derived Compounds.

5-Aminovalerate (5-AVA), 5-hydroxyvalerate (5-HV), and 1,5-pentanediol (1,5-PDO) are l-lysine derivatives with extensive applications in the production of materials such as polyesters, polyurethane, plasticizers, inks, and coatings. However, their large-scale production is limited by the lack of efficient synthetic pathways. Here, we aimed to construct multiple synthetic pathways by screening the key enzymes involved in the synthesis of these compounds in Escherichia coli. The engineered pathway utilizing RaiP demonstrated a superior catalytic efficiency. The LER strain that overexpressed only raiP successfully synthesized 9.70 g/L 5-HV and 8.31 g/L 5-AVA, whereas the strain LERGY that overexpressed raiP, gabT, and yahK accumulated 9.72 g/L 5-HV and 7.95 g/L 5-AVA from 20 g/L glucose. The introduction of exogenous transaminases and dehydrogenases enhanced cell growth and fermentation efficiency with respect to 5-HV synthesis, albeit without significantly impacting the yield. Strain LE05, incorporating only two exogenous enzymes, RaiP and CaR, produced 1.87 g/L 1,5-PDO, 3.85 g/L 5-HV, and 4.78 g/L 5-hydroxyglutaraldehyde from 20 g/L glucose after 6 days. The strain LE02G, fortified with transaminase, dehydrogenase, and NADPH regeneration system, accumulated 7.82 g/L 1,5-PDO, whereas the aldp-knock out LE02G2 synthesized 10.98 g/L 1,5-PDO from 50 g/L glucose in fed-batch fermentation after 6 days, yielding 0.22 g/g glucose (0.37 mol/mol). Introducing the NADPH regeneration pathway and deleting the NADPH-consuming pathways increased the 1,5-PDO yield and decreased the precursor concentration. The proposed pathways and engineering strategies presented in this study can prove instrumental in developing biological routes for the practical production of 5-AVA, 5-HV, and 1,5-PDO.

6-Methyl-5-hepten-2-one promotes programmed cell death during superficial scald development in pear.

Plants possess the ability to induce programmed cell death (PCD) in response to abiotic and biotic stresses; nevertheless, the evidence on PCD initiation during pear scald development and the involvement of the scald trigger 6-methyl-5-hepten-2-one (MHO) in this process is rudimentary. Pyrus bretschneideri Rehd. cv. 'Dangshansuli' pear was used to validate such hypothesis. The results showed that superficial scald occurred after 120-d chilling exposure, which accompanied by typical PCD-associated morphological alterations, such as plasmolysis, cell shrinkage, cytosolic and nuclear condensation, vacuolar collapse, tonoplast disruption, subcellular organelle swelling, and DNA fragmentation. These symptoms were aggravated after MHO fumigation but alleviated by diphenylamine (DPA) dipping. Through transcriptome assay, 24 out of 146 PCD-related genes, which were transcribed during cold storage, were identified as the key candidate members responsible for these cellular biological alternations upon scald development. Among these, PbrCNGC1, PbrGnai1, PbrACD6, and PbrSOBIR1 were implicated in the MHO signaling pathway. Additionally, PbrWRKY2, 34 and 39 could bind to the W-box element in the promoter of PbrGnai1 or PbrSOBIR1 and activate their transcription, as confirmed by dual-luciferase, yeast one-hybrid, and transient overexpression assays. Hence, our study confirms the PCD initiation during scald development and explores the critical role of MHO in this process.

Prognosticating accelerated deterioration in skeletally mature adolescent idiopathic scoliosis curves of 40-50° using uniplanar radiographic measures of axial rotation.

PURPOSE: The management of adolescent idiopathic scoliosis (AIS) curves between 40 and 50° is controversial. Here, we investigated the prognostic significance of simple radiographic rotational parameters to identify curves of this magnitude with accelerated deterioration following skeletal maturity. METHODS: Seventy-three patients were identified with AIS and Cobb angles of the major curve between 40 and 50° at skeletal maturity. We defined fast progressive curves as those increasing by ≥ 2° per year after skeletal maturity. From the apical vertebra of the major curve upon presentation and skeletal maturity, we determined the modified Nash-Moe index (×100), and from thoracic major curves, the Rib Index. T tests were performed to compare fast-progressive curves with those that deteriorated by < 2° per year. Receiver operator characteristic (ROC) curves were plotted to establish optimal cutoffs, sensitivity, and specificity measures for rotational parameters. RESULTS: The average duration of follow-up post was 11.8 ± 7.3 years. Thirteen out of seventy-three patients were fast progressors. The modified Nash-Moe index was similar between groups at presentation (p = 0.477) but significantly higher in fast progressors than non-fast progressors at maturity for major thoracic curves (25.40 ± 6.60 vs. 19.20 ± 4.40, p < 0.001). Rib Index values were also higher among fast progressors at skeletal maturity (2.50 ± 0.90 vs. 1.80 ± 0.60, p = 0.026). An ROC curve for a modified Nash-Moe index of 0.235 for thoracic curves achieved an area under the curve (AUC) of 0.76 for discriminating fast progressors. A threshold of 1.915 for Rib Index at maturity achieved an AUC of 0.72 for discriminating fast progressors. In combining both rotational parameters, an AUC of 0.81 was achieved. CONCLUSION: These simple rotational parameters may be useful to predict fast progression in 40-50° AIS curves following skeletal maturity indicated for early fusion, but further validation upon larger cohorts and non-thoracic major curves is required.

Association between BMI and success of transaxillary venous port implantation: A retrospective cohort study.

PURPOSE: Totally implanted venous access device are widely used for long-term chemotherapy in cancer patients. Previous studies have only focused on the analysis of complications associated with infusion port implantation, ignoring the causes of unsuccessful infusion port implantation. The purpose of this study was to investigate the association between body mass index (BMI) and the success rate of transaxillary intravenous port implantation in breast cancer patients. MATERIALS AND METHODS: To review 361 breast cancer patients who underwent intravenous port implantation from January 2021 to September 2021. Baseline data, and surgical data were collected from the patients, and the success rate of puncture of the axillary vein was recorded. The logistic regression analysis and smoothed curve fitting were used to assess the relationship between BMI and the success rate of axillary venipuncture. In addition, subgroup analyses were performed to explore potential interactions. RESULTS: Under ultrasound guidance, 67.3% of patients (243/361) had an infusion port implanted by axillary vein puncture. There was a roughly linear relationship between BMI and the success rate of axillary venipuncture. In the multiple regression equation, BMI was significantly and negatively associated with the success rate of axillary venipuncture (OR = 0.83; 95% CI = 0.77-0.89; p < 0.001). Stratified analysis showed that the relationship between BMI and the success rate of axillary venipuncture was stable and unaffected by other variables. CONCLUSIONS: The higher the patient's BMI, the higher the chance of difficult axillary venipuncture or failed cannulation.

EXPRESS: Exploring the association between hemoglobin, albumin, lymphocyte, and platelet score and all-cause mortality among middle-aged and older patients with osteoarthritis.

Integrating hemoglobin, albumin, lymphocyte, and platelets (HALP) score can simultaneously reflect systemic inflammation and nutritional status. Some evidence suggests its prognostic value in certain malignancies, however, the impact of HALP on individuals with osteoarthritis (OA) who were middle-aged and older remains unknown.This retrospective cohort study included 3,566 individuals from National Health and Nutrition Examination Survey (NHANES) 2003-2018. The study endpoint was the all-cause mortality of OA patients. Weighted Cox models were used to assess the relationship between HALP score and all-cause mortality. Subgroup analyses stratified by age, gender, diabetes, dyslipidemia, cardiovascular disease (CVD) was conducted. After the follow-up is terminated, 920 participants experienced all-cause mortality, and 2,646 participants survived. After adjusting for covariates, the continuous analysis revealed an inverse association between HALP score and all-cause mortality [hazard ratio (HR)=0.89, 95% confidence interval (CI): 0.83-0.95]. The categorical analysis indicated that the lowest quartile of HALP score was related to higher all-cause mortality by using the highest quartile of HALP score as a reference (HR=1.46, 95%CI: 1.18-1.81). The association between HALP score with lowest quartile and all-cause mortality remained significant across different subgroups.This study suggested that HALP score was linked with all-cause mortality among middle-aged and older individuals diagnosed with OA, thereby indicating its potential as a reliable prognostic indicator for this patient population.

Statin use and development and progression of non-alcohol fatty liver disease based on ultrasonography: a cohort study.

INTRODUCTION: Non-alcohol fatty liver disease (NAFLD) has emerged as a public health issue, while no drugs have been specifically approved for treatment. This study aimed to examine the association between statin use and NAFLD occurrence, progression, and regression. METHODS: A cohort study was designed based on the Kailuan Study and electronic medical records (EMRs) from the Kailuan General Hospital. Participants aged 18 years with statin indication, including statin and non-statin users, were enrolled in 2010-2017. Propensity score-matched cohorts were also used. RESULTS: In the entire cohort, 21 229 non-NAFLD and 22 419 NAFLD patients (including 12 818 mild NAFLD) were included in the final analysis. After a median follow-up of about four years, the incidence of NAFLD occurrence and progression for statin users were lower than those for non-statin users (occurrence: 84.7 vs. 106.5/1000 person-years; progression: 60.7 vs. 75.5/1000 person-years). Compared with non-statin users, the risk of NAFLD occurrence (hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.70-0.87) and regression (HR [95%CI], 0.71[0.60-0.84]) was decreased in statin users. The significantly negative association was only observed in those with cumulative statin duration ≥ 2 years (HR [95%CI] for occurrence 0.56 [0.46-0.69] vs. 0.52 [0.30-0.90] for progression) and those with low or moderate ASCVD-risk (HR [95%CI] for occurrence 0.74 [0.66-0.82] vs. 0.68 [0.57-0.80] for progression). No significant correlation was observed between statin use, statin use duration, and NAFLD regression. The PS-matched cohort had similar results. CONCLUSION: Taking statin may decrease the risk of NAFLD occurrence and progression in the population with statin indication, suggesting the potential role of statin in both primary and secondary prevention strategies for NAFLD, especially among those with low or moderate ASCVD risk.

Integrating myocardial metabolic imaging and stress myocardial contrast echocardiography to improve the diagnosis of coronary microvascular diseases in rabbits.

Background: Persistent challenges associated with misdiagnosis and underdiagnosis of coronary microvascular disease (CMVD) necessitate the exploration of noninvasive imaging techniques to enhance diagnostic accuracy. Therefore, we aimed to integrate multimodal imaging approaches to achieve a higher diagnostic rate for CMVD using high-quality myocardial metabolism imaging (MMI) and myocardial contrast echocardiography (MCE). This combination diagnostic strategy may help address the urgent need for improved CMVD diagnosis. Methods: In this study, we established five distinct pretreatment groups, each consisting of nine male rabbit: a fasted group, a nonfasted group, a sugar load group, an acipimox group, and a combination group of nonfasted rabbits administered insulin. Moreover, positron emission tomography-computed tomography (PET/CT) scan windows were established at 30-, 60-, and 90-minute intervals. We developed 10 CMVD models and conducted a diagnosis of CMVD through an integrated analysis of MMI and MCE, including image acquisition and processing. For each heart segment, we calculated the standardized uptake value (SUV) based on body weight (SUVbw), as well as certain ratios of SUV including SUV of the heart (SUVheart) to that of the liver (SUVliver) and SUVheart to SUV of the lung (SUVlung). Additionally, we obtained three coronary SUVbw uptake values. To clarify the relationship between SUVbw uptake values and echocardiographic parameters of the myocardial contrast agent more thoroughly, we conducted a comprehensive analysis across different pretreatment protocols. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic accuracy of each parameter in the context of CMVD. Results: In the context of MMI, the nonfasted-plus-insulin group, as observed during the 60-minute examination, exhibited a noteworthy total 18F-fluorodeoxyglucose (18F-FDG) uptake of 47.44±6.53 g/mL, which was found to be statistically different from the other groups. To ascertain the reliability of the results, two double-blind investigators independently assessed the data and achieved a good level of agreement, according to the intraclass correlation coefficient (ICC) (0.957). The SUVbw of the nonfasted-plus-insulin group exhibited a moderate correlation with the microvascular blood flow reserve (MBFR) parameters derived from the MCE examination, as evidenced by a r value of 0.686. For the diagnosis of CMVD disease, the diagnostic accuracy of the combined diagnostic method [area under the curve (AUC) =0.789; 95% confidence interval (CI): 0.705-0.873] was significantly higher than that of the MBFR (AUC =0.697; 95% CI: 0.597-0.797) and SUVbw (AUC =0.715; 95% CI: 0.622-0.807) methods (P<0.05). Conclusions: Our study demonstrated the feasibility of a simple premedication approach involving free feeding and intravenous insulin in producing high-quality gated heart 18F-FDG PET/CT images in adult male New Zealand white rabbits. This technique holds considerable potential for ischemic heart disease research in rabbits and can enhance CMVD diagnosis via the comprehensive assessment of myocardial metabolism and perfusion.

Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a "3414" field trial.

Scientific fertilization is an important technical means of achieving high and stable peanut yields. Using soil testing and formula fertilization, the "3414" optimal regression design was used and included 14 nitrogen (N), phosphorus (P), and potassium (K) fertilization treatments. Ternary quadratic functions of the fertilizer effect were established according to three-season field experiments and the regression analysis of fertilizer-yield function was performed to explore the optimal fertilizer application mode and ratio for peanuts under mulched drip irrigation (MDI), and a suitable fertilizer application system was established. The ternary quadratic equation relating peanut yield (y) and the fertilizer application rates of N (N), P (P2O5), and K (K2O) was obtained after fitting, i.e., y = 2912.528 + 21.432N + 16.324P + 6.181K - 0.051N2 - 0.109P2 - 0.061K2 + 0.017NP + 0.023NK + 0.086PK, and significance analysis and typicality assessment were performed. The model R 2 was 0.9709, both values are extremely significant (p < 0.01), which indicates that the obtained ternary quadratic fertilizer effect function is typical and could be used for statistical purposes and fertilization recommendations. Three quadratic fertilizer effect functions were obtained. Among them, the equation for K is extremely significant, and the equations of N and P are significant. According to the assumption that the marginal yield is zero and the marginal profit is zero, the fertilizer application rate with the maximum yield, the fertilizer application rate with the best economic benefits, and the corresponding yields were obtained. The optimal fertilizer application rate predicted by the ternary quadratic fertilizer effect function was relatively high, so the three quadratic fertilizer effect functions were used for prediction. Under the test conditions, the recommended fertilizer application rates for peanuts under MDI are 256.6 kg N per ha, 164.2 kg P2O5 per ha, and 213.2 kg K2O per ha, the recommended fertilization ratio is 1:0.64:0.83, and the recommended ratio under formula fertilization is 23:15:19. The study has developed a data-based decision support system for Xinjiang drip-irrigated peanut, which assists farmers and agricultural managers in making more scientific and precise fertilization decisions based on the specific growth requirements of the crops and soil conditions. This evidence-based methodology enhances the precision of agricultural management, which is conducive to increasing crop yields while reducing resource wastage and environmental impact. However, multipoint and multiyear experiments are still needed to ensure that the findings are adaptable to the diverse soil conditions and fluctuating climate patterns that may be encountered in practice.

UPLC-MS/MS reveals the differences in lipids composition of Camellia oleifera from northern margin distribution area.

The lipids accumulation characteristics in 23Camellia oleifera lines from northern margin distribution area were investigated through quantitative lipidomics. Combined lipids content-function analysis indicated that NQ1, HT1, HT2, ZA2, ZB1, ZB2, and SN2 lines had potential to develop functional foods due to abundant glycerolipids (GLs), glycerophospholipids (GPs), fatty acids (FAs), and prenol lipids (PRs). 673 lipids components were detected, and 293 differential components were identified in NQ1, ZA2, HB1, and HT1. 4 kinds free fatty acids (FFAs) were higher in NQ1, 5 triglycerides (TGs) were higher in HT1, and 2 phosphatidyl serines (PSs) and 1 phosphatidyl glycerol (PG) were higher in ZA2. GLs, GPs, and FFAs had strong relation at intra- and inter-category level. Glycerolipid metabolism, glycerophospholipid metabolism, and fatty acid biosynthesis were the significantly differential lipids pathways. Our study elucidated lipids differences of 23 C. oleifera lines, and offered valuable references for lipids biosynthesis, directional breeding, and lipids utilization.

The Mechanism of SIRT3 Regulating SRV2-Mediated Mitochondrial Fission of Fibroblasts to Inhibit Myocardial Fibrosis after Acute Myocardial Infarction.

OBJECTIVE: Cardiac dysfunction can result from excessive fibrosis in cardiac fibroblasts (CFs) following an acute myocardial infarction (AMI). SIRT3 has been shown to be associated with numerous cardiovascular diseases. This study aimed to investigate the mechanism by which SIRT3 influences myocardial fibrosis following AMI. METHODS: An AMI model was established in rats and echocardiography was used to assess cardiac systolic function. Triphenyl tetrazolium chloride (TTC) and H&E staining were employed to observe the myocardial histopathological status. Masson trichrome staining was used to detect fibrosis, and the changes in expression of fibrosis-related proteins were detected by Western Blot (WB). In this study, we utilized in vitro cell models stimulated by Ang II to investigate the underlying mechanisms. We employed Transwell and CCK-8 assays to detect the function of CFs. Additionally, we used transmission electron microscopy (TEM) to observe the structural morphology of mitochondria, whereas WB was performed to quantify fibrosis-associated proteins and to assay the changes in SIRT3, SRV2, and Drp1. RESULTS: We observed a significant decrease in the expression of SIRT3 and an increase in mitochondrial fragmentation in rats with AMI. Additionally, we observed upregulation of fibrosis-associated signature proteins and collagen proteins expression. Through the use of vitro Ang II stimulation we observed a downregulation of SIRT3 expression, an increase in mitochondrial fragmentation, and an increase in the proliferation and migration of CFs. Opposite effects were observed when SIRT3 was overexpressed. Additive mitochondrial division agonists were found to stimulate the proliferation and migration of CFs, however, SIRT3 expression was unchanged. Interference with SRV2 and SIRT3 revealed that SIRT3 effectively prevented the expression of SRV2/Drp1, resulting in the inhibition of mitochondrial division and the suppression of CFs proliferative migration. CONCLUSION: In summary, SIRT3 can suppress myocardial fibrosis after acute myocardial infarction by regulating SRV2/Drp1-mediated mitochondrial division.

Methylisothiazolinone pollution inhibited root stem cells and regeneration through auxin transport modification in Arabidopsis thaliana.

Methylisothiazolinone (MIT) is a widely used preservative and biocide to prevent product degradation, yet its potential impact on plant growth remains poorly understood. In this study, we investigated MIT's toxic effects on Arabidopsis thaliana root growth. Exposure to MIT significantly inhibited Arabidopsis root growth, associated with reduced root meristem size and root meristem cell numbers. We explored the polar auxin transport pathway and stem cell regulation as key factors in root meristem function. Our findings demonstrated that MIT suppressed the expression of the auxin efflux carrier PIN1 and major root stem cell regulators (PLT1, PLT2, SHR, and SCR). Additionally, MIT hindered root regeneration by downregulating the quiescent center (QC) marker WOX5. Transcriptome analysis revealed MIT-induced alterations in gene expression related to oxidative stress, with physiological experiments confirming elevated reactive oxygen species (ROS) levels and increased cell death in root tips at concentrations exceeding 50 µM. In summary, this study provides critical insights into MIT's toxicity on plant root development and regeneration, primarily linked to modifications in polar auxin transport and downregulation of genes associated with root stem cell regulation.

Efficient extraction and formation mechanism of fulvic acid from lignite: Experimental and DFT studies.

Enhancing the coal-based fulvic acid (FA) yield through the effect of oxidation methods was of great importance. However, the realization of an efficient and environmentally friendly method for the preparation of FA, along with understanding of its formation mechanism, remains imperative. Herein, coal-based FA was prepared by oxidizing lignite with H2O2 and NaOH/KOH. The experimental data showed that ML lignite was pickled with HCl, metal ions such as iron, aluminum, and calcium can be removed, and this lignite is used as raw material, the reaction time was 150 min, the reaction temperature was 50 °C, and the volume ratio of H2O2 (30%) to KOH (3 mol/L) was 1:1, the effect of H2O2 and KOH on FA extraction was the best. The coal-based FA yield could reach 60.49%. The addition of silicone defoaming agent during the experiment resulted in a significant diminished the presence of bubbles and prevent the production of CO2. A decrease in N2 content was detected by GC. The FTIR, XPS, Py-GC/MS and other characterization results showed that FA has more polar functional groups (-COOH, -OH), and it contains more O-CO structure. Consequently, a greater quantity of FA molecules is generated during the reaction process. Moreover, the partial Gibbs free energies during the formation process of coal-based FA were calculated by density-functional theory (DFT). The highest energy required for free radicals was found to be between 1.3 and 1.7 eV. This study would provide theoretical support for exploring the FA formation process and the promotion of lignite humification by adding H2O2 or alkali to lignite.

Global changes of miRNA expression indicates an increased reprogramming efficiency of induced mammary epithelial cells by repression of miR-222-3p in fibroblasts.

Background: Our previous studies have successfully reported the reprogramming of fibroblasts into induced mammary epithelial cells (iMECs). However, the regulatory relationships and functional roles of MicroRNAs (miRNAs) in the progression of fibroblasts achieving the cell fate of iMECs are insufficiently understood. Methods: First, we performed pre-and post-induction miRNAs sequencing analysis by using high-throughput sequencing. Following that, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies were used to determine the primary roles of the significantly distinct miRNAs and targeted genes. Finally, the effect of miR-222-3p on iMECs fate reprogramming in vitro by transfecting. Results: As a result goat ear fibroblasts (GEFs) reprogramming into iMECs activates a regulatory program, involving 79 differentially expressed miRNAs. Besides, the programming process involved changes in multiple signaling pathways such as adherens junction, TGF-ß signaling pathway, GnRH secretion and the prolactin signaling pathway, etc. Furthermore, it was discovered that the expression of miR-222-3p downregulation by miR-222-3p inhibitor significantly increase the reprogramming efficiency and promoted lipid accumulation of iMECs.

Bioadhesive and drug-loaded cellulose nanofiber/alginate film for healing oral mucosal wounds.

Recurrent oral ulcers are common oral mucosal lesions that severely reduce patients' quality of life. Commercial mucoadhesive films are easily disrupted due to oral movement and complex wet environments, thus reducing drug utilization and even causing toxic side effects. Herein, we report a mucoadhesive film composed of Ca2+-crosslinked carboxymethylated cellulose nanofibers and alginate, in which two drugs of dexamethasone (DXM) and dyclonine hydrochloride (DYC) are loaded for the treatment of oral ulcers. The wet films have a high Young's modulus of 7.1 ± 2.6 MPa and a large strain of 53.6 ± 9.8 % and adhere to tissue strongly, which allows them to resist the deformation caused by frequent oral movement. The films also have nice durability against water and excellent biocompatibility. Moreover, the drug release was controlled at different rates. The fast release of DYC facilitates the quick relief of pain, while the slow release of DXM benefits the long-term treatment of wounds. Finally, the animal experiment demonstrates the films displayed excellent therapeutic efficacy in healing oral ulcers.

Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside.

Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with high incidence, recurrence, and metastasis rates. The emergence of immunotherapy has improved the treatment of advanced HCC, but problems such as drug resistance and immune-related adverse events still exist in clinical practice. The immunosuppressive tumor microenvironment (TME) of HCC restricts the efficacy of immunotherapy and is essential for HCC progression and metastasis. Therefore, it is necessary to elucidate the mechanisms behind immunosuppressive TME to develop and apply immunotherapy. This review systematically summarizes the pathogenesis of HCC, the formation of the highly heterogeneous TME, and the mechanisms by which the immunosuppressive TME accelerates HCC progression and metastasis. We also review the status of HCC immunotherapy and further discuss the existing challenges and potential therapeutic strategies targeting immunosuppressive TME. We hope to inspire optimizing and innovating immunotherapeutic strategies by comprehensively understanding the structure and function of immunosuppressive TME in HCC.

Systematic identification and functional analysis of root meristem growth factors (RGFs) reveals role of PgRGF1 in modulation of root development and ginsenoside production in Panax ginseng.

Panax ginseng C.A. Mey., known for its medicinal and dietary supplement properties, primarily contains pharmacologically active ginsenosides. However, the regulatory mechanisms linking ginseng root development with ginsenoside biosynthesis are still unclear. Root meristem growth factors (RGFs) are crucial for regulating plant root growth. In our study, we identified five ginseng RGF peptide sequences from the ginseng genome and transcriptome libraries. We treated Arabidopsis and ginseng adventitious roots with exogenous Panax ginseng RGFs (PgRGFs) to assess their activities. Our results demonstrate that PgRGF1 influences gravitropic responses and reduces lateral root formation in Arabidopsis. PgRGF1 has been found to restrict the number and length of ginseng adventitious root branches in ginseng. Given the medicinal properties of ginseng, We determined the ginsenoside content and performed transcriptomic analysis of PgRGF1-treated ginseng adventitious roots. Specifically, the total ginsenoside content in ginseng adventitious roots decreased by 19.98 % and 63.71 % following treatments with 1 µM and 10 µM PgRGF1, respectively, compared to the control. The results revealed that PgRGF1 affects the accumulation of ginsenosides by regulating the expression of genes associated with auxin transportation and ginsenoside biosynthesis. These findings suggest that PgRGF1, as a peptide hormone regulator in ginseng, can modulate adventitious root growth and ginsenoside accumulation.

Silver-catalyzed P-centered anion nucleophilic addition to isocyanide: access to 2-phosphinoyl indoles/indol-3-ols.

A silver-catalyzed chemoselective cascade nucleophilic addition of a P-centered anion to isocyanides and cyclization reaction was developed for the efficient and practical synthesis of a wide range of 2-phosphinoyl indole and indol-3-ol derivatives. Unlike the well-documented synthesis of phosphorus-functionalized heterocycles via a P-centered radical, an anionic reactivity profile of phosphine oxides is most likely involved in this domino transformation.

Historic dog Furs Unravel the Origin and Artificial Selection of Modern Nordic Lapphund and Elkhound dog Breeds.

The origins and extreme morphological evolution of the modern dog breeds are poorly studied because the founder populations are extinct. Here, we analyse eight 100 to 200 years old dog fur samples obtained from traditional North Swedish clothing, to explore the origin and artificial selection of the modern Nordic Lapphund and Elkhound dog breeds. Population genomic analysis confirmed the Lapphund and Elkhound breeds to originate from the local dog population, and showed a distinct decrease in genetic diversity in agreement with intense breeding. We identified eleven genes under positive selection during the breed development. In particular, the MSRB3 gene, associated with breed-related ear morphology, was selected in all Lapphund and Elkhound breeds, and functional assays showed that a SNP mutation in the 3'UTR region suppresses its expression through miRNA regulation. Our findings demonstrate analysis of near-modern dog artifacts as an effective tool for interpreting the origin and artificial selection of the modern dog breeds.

Clinical and radiological outcomes of selective fusion for rotatory olisthesis in degenerative lumbar scoliosis: a retrospective cohort study.

STUDY DESIGN: Retrospective cohort study. PURPOSE: To investigate the long-term clinical and radiological outcomes of selective fusion for rotatory olisthesis (RO) in degenerative lumbar scoliosis (DLS). OVERVIEW OF LITERATURE: DLS is often associated with RO, and selective fusion of RO is a common surgical treatment option. However, the clinical and radiological outcomes remain controversial. METHODS: A cohort of 54 consecutive patients with DLS and RO was included in the study. All the included patients underwent selective RO fusion and at least 2 years of follow-up. They were divided into two groups: group 1 with a curve <30° and group 2 with a curve ≥30°. The clinical outcomes were evaluated by the Oswestry Disability Index (ODI) and Numerical Rating Scale. The radiological assessment included RO location, offset and subluxated-disc orientation, Cobb angle, and coronal as well as sagittal alignments. RESULTS: The offset value was greater in group 2 than in group 1 (13.4±4.7 mm vs. 9.3±3.5 mm, p<0.001). The subluxated disc was mainly oriented to the concave side in group 2 (15/21) but to the convex side in group 1 (20/33) (p =0.022). Group 2 had a higher rate of postoperative adjacent RO than group 1 (14/21 vs. 1/33, p<0.001). The ODI was comparable between both groups preoperatively but higher at the final follow-up in group 2 (34.9±9.5) than in group 1 (24.4±6.2). In the multiple logistic regression analysis, the thoracolumbar/lumbar curve was identified as the risk factor for postoperative adjacent RO (odds ratio, 1.400; p=0.007). The receiver operating characteristic analysis verified it with an area under the curve of 0.960 (p<0.001). CONCLUSIONS: The clinical and radiological outcomes were maintained well in group 1 but not in group 2. Selective RO fusion in DLS with a lumbar curve <30° is a rational option. However, it should be avoided in those with a lumbar curve >30° because of a higher complication rate and a worse clinical outcome at the final follow-up.

Identification of a fatty acid metabolism-related gene signature to predict prognosis in stomach adenocarcinoma.

BACKGROUND: Fatty acid metabolism (FAM) contributes to tumorigenesis and tumor development, but the role of FAM in the progression of stomach adenocarcinoma (STAD) has not been comprehensively clarified. METHODS: The expression data and clinical follow-up information were obtained from The Cancer Genome Atlas (TCGA). FAM pathway was analyzed by gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) methods. Univariate Cox regression analysis was conducted to select prognosis genes. Molecular subtypes were classified by consensus clustering analysis. Furthermore, least absolute shrinkage and selection operator (Lasso) analysis was employed to develop a risk model. ESTIMATE and tumour immune dysfunction and exclusion (TIDE) algorithm were used to assess immunity. pRRophetic package was conducted to predict drug sensitivity. RESULTS: Based on 14 FAM related prognosis genes (FAMRG), 2 clusters were determined. Patients in C2 showed a worse overall survival (OS). Furthermore, a 7-FAMRG risk model was established as an independent predictor for STAD, with a higher riskscore indicating an unfavorable OS. High riskscore patients had higher TIDE score and these patients were more sensitive to anticancer drugs such as Bortezomib, Dasatinib and Pazopanib. A nomogram based on riskscore was an effective prediction tool applicable to clinical settings. The results from pan-cancer analysis supported a prominent application value of riskscore model in other cancer types. CONCLUSION: The FAMRGs model established in this study could help predict STAD prognosis and offer new directions for future studies on dysfunctional FAM-induced damage and anti-tumor drugs in STAD disease.