Atractylodes macrocephala polysaccharides shield a D-galactose-induced aging model via gut microbiota modulation.

This study explored the effect of a heteropolysaccharide (RAMP) on aging model mice and the importance of changes in the gut microbiota mediated by RAMP for the first time. The findings revealed that RAMP exerted protective effects on cognitive decline and oxidative stress in mice subjected to D-gal-induced aging, potentially by regulating the intestinal flora, according to the results of the Morris water maze test; brain and immune organ indices; hematoxylin and eosin-stained cerebral cortex images; transmission electron microscopy analysis of cortical neurons; and biochemical index measurements. In addition, 16S rRNA sequencing revealed notable changes in the abundance of Acidobacteriota, Anaerovoracaceae, and GCA-900066575 in the mouse model, all of which were abrogated by RAMP. These findings confirm that RAMP regulates the composition of mouse intestinal microorganisms. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional analyses linked these changes to 27 metabolic pathways, including those of the nervous system. Furthermore, metabolomics analysis revealed four RAMP-regulated metabolites related to lipid metabolism (2-dodecylbenzenesulfonic acid, N-undecylbenzenesulfonic acid, aspartyl-isoleucine, and 1-palmitoyl-2-(5-oxo-valeroyl)-sn-glycero-3-phosphate), suggesting that the mechanism potentially associated with lipid metabolism regulation. This study provides novel insights into the antiaging mechanisms of RAMP, suggesting its potential use in antiaging treatments.

UPLC-MS/MS and HS-SPME-GC-MS reveal the flavor profiles of two geographical indications woody vegetables: Staphylea bumalda and Staphylea holocarpa.

Staphylea bumalda (SHC) and Staphylea holocarpa (PGG) were recognized as geographical indication agricultural products due to unique flavor. 1218 differential non-volatile compounds and 536 differential volatile compounds were detected and identified through UPLC-MS/MS and HS-SPME-GC-MS methods. In SHC samples, catechins, epicatechins, proanthocyanidins, quinic acid derivatives, and kaempferol glycoside derivatives were the main flavor compounds, with bitter and harsh taste. L-tartaric acid, citraconic acid and citric acid were contributed to increase acidity. 4-Hexen-1-ol acetate, butanoic acid butyl ester, 3-Hexen-1-ol acetate, (E)-, and 3-Hexen-1-ol acetate, (Z)- were identified as characteristic odor compounds with strong floral, fruity and sweet odor. In PGG samples, epicatechin gallate, quercetin glycoside derivatives, L-histidine, and L-tyrosine were the leading contributors to bitter and harsh taste. The spicy, herbal, and bad smell odor were mainly brought by 2-octanol, and 3-Octen-1-ol, (Z)-. Our results offered comprehensive insights into the flavor and quality characteristics differences between PGG and SHC.

Superhydrophobic Cellulose Nanofiber Aerogels for Efficient Hemostasis with Minimal Blood Loss.

Reducing unnecessary blood loss in hemostasis is a major challenge for traditional hemostatic materials due to uncontrolled blood absorption. Tuning the hydrophilic and hydrophobic properties of hemostatic materials provides a road to reduce blood loss. Here, we developed a superhydrophobic aerogel that enabled remarkably reduced blood loss. The aerogel was fabricated with polydopamine-coated and fluoroalkyl chain-modified bacterial cellulose via a directional freeze-drying method. Primarily, the hydrophobic feature prevented blood from uncontrolled absorption by the material and overflowing laterally. Additionally, the aerogel had a dense network of channels that allowed it to absorb water from blood due to the capillary effect, and fluoroalkyl chains trapped the blood cells entering the channels to form a compact barrier via hydrophobic interaction at the bottom of the aerogel, causing quick fibrin generation and blood coagulation. The animal experiments reveal that the aerogel reduced the hemostatic time by 68% and blood loss by 87 wt % compared with QuikClot combat gauze. The study demonstrates the superiority of superhydrophobic aerogels for hemostasis and provides new insights into the development of hemostatic materials.

Special contoured pelvic brim reconstruction titanium plate combined with trans-plate buttress screws (quadrilateral screws) for acetabular fractures with quadrilateral plate involvement through the anterior ilioinguinal approach.

Background: Managing complicated acetabular fractures involving the quadrilateral plate (QLP) can be challenging for surgeons, especially when complicated by comminution and osteoporosis. Traditional implants do not provide sufficient fixed strength or a proper match. The new-type pre-contoured infrapectineal buttress plates may have drawbacks, such as inaccurate fitting on the medial surface of QLP and an inability to apply reversed compression force to resist medial displacement of femoral head. Therefore, the primary purpose of this study is to introduce a novel technique that utilizes a special contoured pelvic brim reconstruction titanium plate combined with quadrilateral screws to reduce and stabilize acetabular fractures involving the QLP through the ilioinguinal approach. Additionally, the secondary purpose is to evaluate both clinical effectiveness and radiological outcomes of this technique for QLP fractures. Methods: We conducted a retrospective analysis of prospectively collected data from 48 patients (31 males and 17 females) who suffered from acute displaced fractures of the QLP and were treated between January 2012 and December 2019 using a special contoured plate combined with quadrilateral screws. The patients' mean age was 47.56 ± 11.31 years (range: 19-73 years). Fracture patterns included 20 both-column fractures, 12 anterior column and posterior hemitransverse fractures, eight T-type fractures, five transverse fractures and three anterior column fractures with the QLP affected, all of which had femoral head protrusion. Immediate postoperative reduction quality was evaluated according to Matta's criteria. Final clinical functions were assessed during follow-up using the modified Merle d'Aubigné and Harris Hip scores (HHS). Results: The patients were followed up for an average of 48.36 ± 12.94 months (ranging from 24 to 84 months). The mean operative time was 246.08 ± 54.30 min (ranging from 178 to 397 min), and the average blood loss was 715.16 ± 263.84 ml (ranging from 400 to 2000ml). The radiological grading at postoperative stage showed anatomical reduction in 30 patients (62.50%), satisfactory reduction in 14 patients (29.17%), and poor reduction in four patients (8.33%). At the final follow-up, no re-protrusion of the femoral head was observed. In terms of functional outcome, the mean modified Merle d'Aubigné-Postel score was excellent in 26 patients (54.17%), good in 17 patients (35.42%), fair in four patients (8.33%), and poor in one patient (2.08%). The HHS was excellent in 23 patients (47.92%), good in 20 patients (41.67%), fair in four patients (8.33%), and poor in one patient (2.08%). The average HHS was 87.38 ± 7.86 (ranging from 52 to 98). Postoperative complications included lateral femoral cutaneous nerve injury in two patients, delayed wound healing and subsequent development of an inguinal hernia in one patient. Late complications were observed in two patients, with one case of heterotopic ossification and another case of post-traumatic osteoarthritis underwent hip arthroplasty within two years after surgery. Conclusion: Our results indicate that employing the contoured plate specifically designed for QLP injuries, in conjunction with quadrilateral screws through the ilioinguinal approach, can lead to positive outcomes in the treatment of displaced acetabular fractures involving the QLP. This straightforward and efficient technique offers a viable option for surgeons who are managing complex acetabular fractures.

Anti-inflammatory effects of 1,7-dihydroxy-3,4-dimethoxyxanthone through inhibition of M1-phenotype macrophages via arginine/mitochondrial axis.

It is known that 1,7-dihydroxy-3,4-dimethoxyxanthone (XAN), derived from Securidaca inappendiculata Hassk., exhibits anti-inflammatory and analgesic activities and inhibits M1 polarization of macrophages. However, its ability to alleviate inflammation induced by pro-inflammatory cytokines in THP-1 cells and its anti-inflammatory mechanisms remain unclear. THP-1 cells were treated with phorbol 12-myristate-13-acetate to differentiate and divided into three groups. They were stimulated with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). The toxicity of XAN was assessed using Cell Counting Kit-8, and the expression of various genes and proteins was analyzed using real-time quantitative polymerase chain reaction, flow cytometry, and western blotting. Transmission electron microscopy was used to observe changes in mitochondrial structure. XAN at concentrations ≤ 10 µg/mL did not affect THP-1 cell viability and reduced the mRNA expression of pro-inflammatory factors, including interleukin (IL)-1ß, inducible nitric oxide synthase (iNOS), NOD-like receptor thermal protein domain protein 3 (NLRP3), and tumor necrosis factor-α (TNF-α). XAN also increased the levels of anti-inflammatory factors, including chemokine ligand 22, mannose receptor (CD206), IL-10, peroxisome proliferator-activated receptor-γ, and transglutaminase 2. Additionally, XAN downregulated the expression of inflammation-related proteins iNOS, NLRP3, and IL-1ß; significantly increased the expression of arginase 1, ornithine decarboxylase, and arginine metabolism-related proteins and genes; inhibited mitochondrial damage; and reduced reactive oxygen species (ROS) generation. XAN enhanced the arginine metabolism pathway, prevented mitochondrial damage, reduced ROS levels, and provided an effective defensive response against LPS/IFN-γ-induced inflammation.

Deciphering soil environmental regulation on reassembly of the soil bacterial community during wetland restoration.

Soil bacteria are vital to regulate biogeochemical processes in wetlands, however, little is known about the patterns and mechanisms of soil bacterial re-organization during wetland restoration. Here, we used a space-for-time substitution approach and examined the ecological processes that drive soil bacterial assembly from cultivated to restored to natural wetlands. Results showed a decrease of soil bacterial α diversity and increase of bacterial community similarity and bacterial interaction (cooperation vs. competition) with years of restoration, which was dominantly influenced by deterministic processes. Identified bacterial keystone taxa (e.g. Variibacter, Acidibacter) with nutrient metabolism capacity exerted strong positive effect on bacterial interaction. Furthermore, changes of soil water condition and nutrient status showed dominantly direct positive effects on soil bacterial reassembly, while falling soil pH significantly promoted bacterial reassembly by increasing keystone taxa and bacterial interaction during wetland restoration. Overall, findings highlighted the crucial role of environmental filtering and its pathway in influencing keystone bacterial taxa that promotes the reassembly of bacterial community during wetland restoration. Our work thus provides a new crucial and timely insight for improving the management of soil bacterial community assembly within the plethora of current and future wetland restoration projects.

Relationship Between Control of Cardiovascular Risk Factors and Chronic Kidney Disease Progression, Cardiovascular Disease Events, and Mortality in Chinese Adults.

BACKGROUND: Patients with chronic kidney disease (CKD) are at an elevated risk of cardiovascular disease (CVD) and premature mortality compared to the general population. OBJECTIVES: This study aimed to investigate whether the excess risk of CVD events and death among patients with CKD could be reduced or eliminated through strict control of blood pressure (systolic blood pressure: <130 mm Hg), lipids (low-density lipoprotein cholesterol: <2.6 mmol/L), and glucose (fasting blood glucose: <6.1 mmol/L). METHODS: The authors included 20,254 patients with CKD who were free of CVD or end-stage renal disease and matched them with 35,236 control individuals based on age (±2 years) and sex from the Kailuan study. RESULTS: During a median follow-up period of 12.2 to 12.8 years, 3,875 deaths, 1,888 cases of stroke, 513 cases of myocardial infarction, and 4,825 cases of CKD progression were documented. Among patients with CKD, risk factor controls showed an association with a reduction in myocardial infarction, stroke, CKD progression, and all-cause mortality risk in a dose-dependent manner. Moreover, compared to the non-CKD control individuals, having all 3 risk factors within the target ranges could theoretically eliminate the excess risk of CVD and mortality associated with CKD. Among patients with CKD who had all 3 risk factors controlled, the HRs were 0.80 (95% CI: 0.56-1.14) for myocardial infarction, 0.93 (95% CI: 0.78-1.12) for stroke, and 1.10 (95% CI: 0.98-1.24) for all-cause mortality compared to the non-CKD control individuals. CONCLUSIONS: Patients with CKD who had controlled blood pressure, lipids, and glucose showed no excess risk of death, myocardial infarction, or stroke compared to the general population.

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.

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.

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.

Arabidopsis BTB-A2s Play a Key Role in Drought Stress.

Drought stress significantly impacts plant growth, productivity, and yield, necessitating a swift fine-tuning of pathways for adaptation to harsh environmental conditions. This study explored the effects of Arabidopsis BTB-A2.1, BTB-A2.2, and BTB-A2.3, distinguished by their exclusive possession of the Broad-complex, Tramtrack, and Bric-à-brac (BTB) domain, on the negative regulation of drought stress mediated by abscisic acid (ABA) signaling. Promoter analysis revealed the presence of numerous ABA-responsive and drought stress-related cis-acting elements within the promoters of AtBTB-A2.1, AtBTB-A2.2, and AtBTB-A2.3. The AtBTB-A2.1, AtBTB-A2.2, and AtBTB-A2.3 transcript abundances increased under drought and ABA induction according to qRT-PCR and GUS staining. Furthermore, the Arabidopsis btb-a2.1/2/3 triple mutant exhibited enhanced drought tolerance, supporting the findings from the overexpression studies. Additionally, we detected a decrease in the stomatal aperture and water loss rate of the Arabidopsis btb-a2.1/2/3 mutant, suggesting the involvement of these genes in repressing stomatal closure. Importantly, the ABA signaling-responsive gene levels within Arabidopsis btb-a2.1/2/3 significantly increased compared with those in the wild type (WT) under drought stress. Based on such findings, Arabidopsis BTB-A2s negatively regulate drought stress via the ABA signaling pathway.

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.

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.

Metabolic engineering of Escherichia coli for de novo production of 5-hydroxyvalerate via L-lysine α-oxidase pathway.

5-hydroxyvalerate (5-HV) is a crucial C5 platform chemical with versatile applications, yet its efficient production remains a challenge. The Raip, gabT, and yahK genes were integrated into the E. coli LE genome, deleted gabD, and enhanced gabP expression, resulting in the QluMG strain. Additionally, the impact of ethanol and H2O2 on 5-HV production was investigated. Further enhancement was achieved by incorporating an NADPH supplementation system, resulting in the QluMG strain. In the 5 L fermenter, the QluMGD strain produced 21.7 g/L of 5-HV from 50 g/L glucose, with a conversion rate of 43.4 %. The successful integration of the RaiP pathway into the E. coli genome significantly enhanced 5-HV production. The QluMG strain achieved the highest reported yield from glucose in engineered E. coli to date. This study provides a new strategy for the efficient production of 5-HV and other chemicals using 5-HV as a precursor, demonstrating potential for industrial application.

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.

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.

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.

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.

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.

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.