Losses of low-germinating, slow-growing species prevent grassland composition recovery from nutrient amendment.

Nutrient enrichment often alters the biomass and species composition of plant communities, but the extent to which these changes are reversible after the cessation of nutrient addition is not well-understood. Our 22-year experiment (15 years for nutrient addition and 7 years for recovery), conducted in an alpine meadow, showed that soil nitrogen concentration and pH recovered rapidly after cessation of nutrient addition. However, this was not accompanied by a full recovery of plant community composition. An incomplete recovery in plant diversity and a directional shift in species composition from grass dominance to forb dominance were observed 7 years after the nutrient addition ended. Strikingy, the historically dominant sedges with low germination rate and slow growth rate and nitrogen-fixing legumes with low germination rate were unable to re-establish after nutrient addition ceased. By contrast, rapid recovery of aboveground biomass was observed after nutrient cessation as the increase in forb biomass only partially compensated for the decline in grass biomass. These results indicate that anthropogenic nutrient input can have long-lasting effects on the structure, but not the soil chemistry and plant biomass, of grassland communities, and that the recovery of soil chemical properties and plant biomass does not necessarily guarantee the restoration of plant community structure. These findings have important implications for the management and recovery of grassland communities, many of which are experiencing alterations in resource input.

CBX7C⋠PHC2 interaction facilitates PRC1 assembly and modulates its phase separation properties.

CBX7 is a key component of PRC1 complex. Cbx7C is an uncharacterized Cbx7 splicing isoform specifically expressed in mouse embryonic stem cells (mESCs). We demonstrate that CBX7C functions as an epigenetic repressor at the classic PRC1 targets in mESCs, and its preferential interaction to PHC2 facilitates PRC1 assembly. Both Cbx7C and Phc2 are significantly upregulated during cell differentiation, and knockdown of Cbx7C abolishes the differentiation of mESCs to embryoid bodies. Interestingly, CBX7C⋅PHC2 interaction at low levels efficiently undergoes the formation of functional Polycomb bodies with high mobility, whereas the coordination of the two factors at high doses results in the formation of large, low-mobility, chromatin-free aggregates. Overall, these findings uncover the unique roles and molecular basis of the CBX7C⋅PHC2 interaction in PRC1 assembly on chromatin and Pc body formation and open a new avenue of controlling PRC1 activities via modulation of its phase separation properties.

Enhanced survival with lymphadenectomy in early-stage metachronous second primary lung cancer: A retrospective analysis.

INTRODUCTION: Lymphadenectomy is a cornerstone in the surgical management of resectable primary lung cancer. However, its prognostic significance in early-stage metachronous second primary lung cancer(MSPLC) remains poorly understood. This retrospective study aims to evaluate the prognostic impact of lymphadenectomy in these patients using data from the Surveillance, Epidemiology, and End Results (SEER) Database. METHODS: A retrospective cohort study was conducted using data from the SEER Database for patients surgically treated for stage I MSPLC between 2004 and 2015. Propensity score matching was employed to create comparable cohorts, and the Cox proportional hazards model was utilized to estimate the hazard ratio (HR) for overall survival after lymphadenectomy compared to non-lymphadenectomy. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. RESULTS: Among 920 identified patients with MSPLC, 574 (62.4%) underwent lymphadenectomy. Propensity score matching yielded 255 patients in both the lymphadenectomy and non-lymphadenectomy groups. Over a median follow-up of 38 months, the 5-year overall survival probability after a diagnosis of MSPLC was 58.7% in the lymphadenectomy group and 43.9% among in the non-lymphadenectomy group (HR 0.76; 95% confidence interval 0.64-0.90; P=0.002). CONCLUSION: In this population-based study, lymphadenectomy is associated with prolonged overall survival in patients with stage I MSPLC. These findings suggests the potential benefit of incorporating lymphadenectomy into the surgical management of MSPLC, providing valuable guidance for thoracic surgeons in clinical decision-making.

Mendelian randomization suggests a causal relationship between gut microbiota and nonalcoholic fatty liver disease in humans.

Targeting the gut microbiota is an emerging strategy to treat nonalcoholic fatty liver disease (NAFLD). Nonetheless, the causal relationship between specific gut microbiota and NAFLD remains unclear. We first obtained genome-wide association study statistics on gut microbiota and NAFLD from publicly available databases. We then performed the Mendelian randomization (MR) analysis to determine the potential causal relationship between the gut microbiota and NAFLD by 5 different methods, and conducted a series of sensitivity analyses to validate the robustness of the MR analysis results. Furthermore, we investigated the direction of causality by bidirectional MR analysis. For 211 gut microbiota, 2 MR methods confirmed that phylum Tenericutes, class Deltaproteobacteria and class Mollicutes were significantly associated with the risk of NAFLD. Heterogeneity (P > .05) and pleiotropy (P > .05) analyses validated the robustness of the MR results. There was no causal effect of NAFLD on these bacterial taxa in the reverse MR analysis. We identified specific gut microbiota with causal effects on NAFLD through gene prediction, which may provide useful guidance for targeting the gut microbiota to intervene and treat NAFLD.

Flexible Composite Electrolyte Membranes with Fast Ion Transport Channels for Solid-State Lithium Batteries.

Numerous endeavors have been dedicated to the development of composite polymer electrolyte (CPE) membranes for all-solid-state batteries (SSBs). However, insufficient ionic conductivity and mechanical properties still pose great challenges in practical applications. In this study, a flexible composite electrolyte membrane (FCPE) with fast ion transport channels was prepared using a phase conversion process combined with in situ polymerization. The polyvinylidene fluoride-hexafluoro propylene (PVDF-HFP) polymer matrix incorporated with lithium lanthanum zirconate (LLZTO) formed a 3D net-like structure, and the in situ polymerized polyvinyl ethylene carbonate (PVEC) enhanced the interface connection. This 3D network, with multiple rapid pathways for Li+ that effectively control Li+ flux, led to uniform lithium deposition. Moreover, the symmetrical lithium cells that used FCPE exhibited high stability after 1200 h of cycling at 0.1 mA cm-2. Specifically, all-solid-state lithium batteries coupled with LiFePO4 cathodes can stably cycle for over 100 cycles at room temperature with high Coulombic efficiencies. Furthermore, after 100 cycles, the infrared spectrum shows that the structure of FCPE remains stable. This work demonstrates a novel insight for designing a flexible composite electrolyte for highly safe SSBs.

Impact of obesity on outcomes of rotator cuff repair: A systematic review and meta-analysis.

BACKGROUND: To synthesize the existing evidence on the association between obesity and rotator cuff repair outcomes such as pain, shoulder function, range of motion, and complications. METHODS: We searched PubMed, EMBASE, and Scopus databases for relevant observational studies (cohort and case-control) and randomized controlled trials (RCTs). The target population in the included studies comprised adults who had undergone rotator cuff repair procedures. The outcomes of interest were functional outcomes (such as range of motion), pain scores, patient-reported outcome measures, and complication rates (such as re-repair and readmission rates). We applied random-effects models and calculated pooled effect sizes reported as standardized mean differences (SMDs) or relative risks (RRs) with 95% confidence intervals. RESULTS: We analysed data from 11 studies. In most, the follow-up periods ranged from 12 to 60 months. Obese individuals experienced greater pain (SMD 0.30; 95% CI, 0.10, 0.50) and lower shoulder function (SMD -0.33; 95% CI, -0.54, -0.12) than other individuals in the long-term post-operative follow-up. Obese individuals also had higher risks of complications (RR 1.48; 95% CI, 1.11, 1.98) and readmission (RR 1.35; 95% CI, 1.27, 1.43), but a similar likelihood of re-repair (RR, 1.27; 95% CI, 0.82, 1.95) than non-obese/normal BMI individuals. While the forward flexion and external rotation functions were comparable, obese individuals displayed less internal rotation function than other individuals (SMD -0.59; 95% CI, -0.87, -0.30). CONCLUSION: Obesity was associated with unfavourable outcomes after rotator cuff surgery, including increased pain, reduced shoulder function, high risks of complications, and readmission. These findings emphasize the importance of addressing obesity-related factors to improve post-operative outcomes.

The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, emerging as a significant health issue on a global scale. Berberine exhibits potential for treating NAFLD, but clinical evidence remains inconclusive. This meta-analysis was conducted to assess the efficacy and safety of berberine for treating NAFLD. METHODS: This study was registered with PROSPERO (No. CRD42023462338). Identification of randomized controlled trials (RCTs) involved searching 6 databases covering the period from their initiation to 9 September 2023. The primary outcomes comprised liver function markers such as glutamyl transpeptidase (GGT), alanine transaminase (ALT), aspartate transaminase (AST), lipid indices including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment for insulin resistance (HOMA-IR) and body mass index (BMI). Review Manager 5.4 and STATA 17.0 were applied for analysis. RESULTS: Among 10 RCTs involving 811 patients, berberine demonstrated significant reductions in various parameters: ALT (standardized mean difference (SMD) = - 0.72), 95% confidence interval (Cl) [- 1.01, - 0.44], P < 0.00001), AST (SMD = - 0.79, 95% CI [- 1.17, - 0.40], P < 0.0001), GGT (SMD = - 0.62, 95% CI [- 0.95, - 0.29], P = 0.0002), TG (SMD = - 0.59, 95% CI [- 0.86, - 0.31], P < 0.0001), TC(SMD = - 0.74, 95% CI [- 1.00, - 0.49], P < 0.00001), LDL-C (SMD = - 0.53, 95% CI [- 0.88, - 0.18], P = 0.003), HDL-C (SMD = - 0.51, 95% CI [- 0.12, 1.15], P = 0.11), HOMA-IR (SMD = - 1.56, 95% CI [- 2.54, - 0.58], P = 0.002), and BMI (SMD = - 0.58, 95% CI [- 0.77, - 0.38], P < 0.00001). Importantly, Berberine exhibited a favorable safety profile, with only mild gastrointestinal adverse events reported. CONCLUSION: This meta-analysis demonstrates berberine's efficacy in improving liver enzymes, lipid profile, and insulin sensitivity in NAFLD patients. These results indicate that berberine shows promise as an adjunct therapy for NAFLD. Trial registration The protocol was registered with PROSPERO (No. CRD42023462338). Registered on September 27, 2023.

Cross-Platform Comparison of Highly Sensitive Immunoassays for Inflammatory Markers in a COVID-19 Cohort.

A variety of commercial platforms are available for the simultaneous detection of multiple cytokines and associated proteins, often employing Ab pairs to capture and detect target proteins. In this study, we comprehensively evaluated the performance of three distinct platforms: the fluorescent bead-based Luminex assay, the proximity extension-based Olink assay, and a novel proximity ligation assay platform known as Alamar NULISAseq. These assessments were conducted on human serum samples from the National Institutes of Health IMPACC study, with a focus on three essential performance metrics: detectability, correlation, and differential expression. Our results reveal several key findings. First, the Alamar platform demonstrated the highest overall detectability, followed by Olink and then Luminex. Second, the correlation of protein measurements between the Alamar and Olink platforms tended to be stronger than the correlation of either of these platforms with Luminex. Third, we observed that detectability differences across the platforms often translated to differences in differential expression findings, although high detectability did not guarantee the ability to identify meaningful biological differences. Our study provides valuable insights into the comparative performance of these assays, enhancing our understanding of their strengths and limitations when assessing complex biological samples, as exemplified by the sera from this COVID-19 cohort.

Effects of Benzo (a) Pyrene and 2,2',4,4'-Tetrabromodiphenyl Ether Exposure on the Thyroid Gland in Rats by Attenuated Total Reflection Fourier-Transform Infrared Spectroscopy.

Benzo[a]pyrene (B[a]P) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) are widespread environmental pollutants and can destroy thyroid function. We assessed the biochemical changes in the thyroid tissue of rats exposed to B[a]P and BDE-47 using attenuated total reflection Fourier-transform infrared spectroscopy combined with support vector machine(SVM). After B[a]P and BDE-47 treatment in rats, the structure of thyroid follicles was destroyed and epithelial cells were necrotic, indicating that B[a]P and BDE-47 may lead to changes of the thyroid morphology of the rats. These damages are mainly related to C=O stretch vibrations of lipids (1743 cm-1), as well as the secondary structure of proteins [amide I (1645 cm-1) and amide II (1550 cm-1)], and carbohydrates [C-OH (1138 cm-1), C-O (1106 cm-1, 1049 cm-1, 991 cm-1), C-C (1106 cm-1) stretching] and collagen (phosphodiester stretching at 922 cm-1) vibration modes. When SVM was used for classification, there was a substantial separation between the control and the exposure groups (accuracy = 96%; sensitivity = 98%; specificity = 87%), and there was also a major separation between the exposed groups (accuracy = 93%; sensitivity = 94%; and specificity = 92%).

Canagliflozin regulates metabolic reprogramming in diabetic kidney disease by inducing fasting-like and aestivation-like metabolic patterns.

AIMS/HYPOTHESIS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) are antihyperglycaemic drugs that protect the kidneys of individuals with type 2 diabetes mellitus. However, the underlying mechanisms mediating the renal benefits of SGLT2i are not fully understood. Considering the fuel switches that occur during therapeutic SGLT2 inhibition, we hypothesised that SGLT2i induce fasting-like and aestivation-like metabolic patterns, both of which contribute to the regulation of metabolic reprogramming in diabetic kidney disease (DKD). METHODS: Untargeted and targeted metabolomics assays were performed on plasma samples from participants with type 2 diabetes and kidney disease (n=35, 11 women) receiving canagliflozin (CANA) 100 mg/day at baseline and 12 week follow-up. Next, a systematic snapshot of the effect of CANA on key metabolites and pathways in the kidney was obtained using db/db mice. Moreover, the effects of glycine supplementation in db/db mice and human proximal tubular epithelial cells (human kidney-2 [HK-2]) cells were studied. RESULTS: Treatment of DKD patients with CANA for 12 weeks significantly reduced HbA1c from a median (interquartile range 25-75%) of 49.0 (44.0-57.0) mmol/mol (7.9%, [7.10-9.20%]) to 42.2 (39.7-47.7) mmol/mol (6.8%, [6.40-7.70%]), and reduced urinary albumin/creatinine ratio from 67.8 (45.9-159.0) mg/mmol to 47.0 (26.0-93.6) mg/mmol. The untargeted metabolomics assay showed downregulated glycolysis and upregulated fatty acid oxidation. The targeted metabolomics assay revealed significant upregulation of glycine. The kidneys of db/db mice undergo significant metabolic reprogramming, with changes in sugar, lipid and amino acid metabolism; CANA regulated the metabolic reprogramming in the kidneys of db/db mice. In particular, the pathways for glycine, serine and threonine metabolism, as well as the metabolite of glycine, were significantly upregulated in CANA-treated kidneys. Glycine supplementation ameliorated renal lesions in db/db mice by inhibiting food intake, improving insulin sensitivity and reducing blood glucose levels. Glycine supplementation improved apoptosis of human proximal tubule cells via the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. CONCLUSIONS/INTERPRETATION: In conclusion, our study shows that CANA ameliorates DKD by inducing fasting-like and aestivation-like metabolic patterns. Furthermore, DKD was ameliorated by glycine supplementation, and the beneficial effects of glycine were probably due to the activation of the AMPK/mTOR pathway.

Digital cholangioscopy-assisted, direct visualization-guided, radiation-free, endoscopic retrograde intervention for cholelithiasis: technical feasibility, efficacy, and safety.

BACKGROUND: Nonradiation, digital cholangioscope (DCS)-assisted endoscopic intervention for cholelithiasis has not been widely performed. For this study, we aimed to report the feasibility, efficacy, and safety of an established DCS-guided lithotomy procedure. METHODS: Data relating to biliary exploration, stone clearance, adverse events, and follow-up were obtained from 289 patients. The choledocholithiasis-related outcomes via the DCS-guided procedure were subsequently compared to those via conventional endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Biliary access was achieved in 285 patients. The technical success rate for the exploration of the common bile duct, the cystic stump, the hilar ducts, and secondary radicals was 100%. Moreover, the success rates were 98.4%, 61.7%, and 20.7%, for the exploration of the cystic duct, complete cystic duct, and gallbladder, respectively. Suspicious or confirmed suppurative cholecystitis, cholesterol polyps, and hyperplastic polyps were detected in 42, 23, and 5 patients, respectively. Stone clearance was achieved in one session in 285 (100%), 11 (100%), 13 (100%), 7 (100%), 6 (100%), and 3 (14.3%) patients with choledocholithiasis and hepatolithiasis, cystic duct stump stones, nondiffuse located intrahepatic lithiasis, a single cystic duct stone, a single gallbladder stone, and diffuse located intrahepatic lithiasis, respectively. Complete stone clearance for diffuse intrahepatic lithiasis was achieved in 19 (90.5%) patients, and fractioned re-lithotomy was performed in 16 (76.2%) patients. One patient developed mild acute cholangitis, and 12 developed mild pancreatitis. Stones recurred in one patient. Compared with conventional ERCP, DCS-guided lithotomy has the advantages of clearing difficult-to-treat choledocholithiasis and revealing concomitant biliary lesions, and this technique has fewer complications and a decreased risk of stone recurrence. CONCLUSIONS: The technical profile, efficacy, and safety of nonradiation-guided and DCS-guided lithotomy are shown in this study. We provide a feasible modality for the endoscopic removal of cholelithiasis.

Biosynthesis of poly(ß-L-malic acid) from rubberwood enzymatic hydrolysates in co-fermentation by Aureobasidium pullulans.

Co-fermentation of multiple substrates has emerged as the most effective method to improve the yield of bioproducts. Herein, sustainable rubberwood enzymatic hydrolysates (RWH) were co-fermented by Aureobasidium pullulans to produce poly(ß-L-malic acid) (PMA), and RWH + glucose/xylose was also investigated as co-substrates. Owing to low inhibitor concentration and abundant natural nitrogen source content of RWH, a high PMA yield of 0.45 g/g and a productivity of 0.32 g/L/h were obtained by RWH substrate fermentation. After optimization, PMA yields following the fermentation of RWH + glucose and RWH + xylose reached 59.92 g/L and 53.71 g/L, respectively, which were 52 % and 36 % higher than that after the fermentation of RWH. RWH + glucose more significantly affected the correlation between PMA yield and substrate concentration than RWH + xylose. The results demonstrated that the co-fermentation of RWH co-substrate is a promising method for the synthesis of bioproducts.

Upregulation of UHRF1 Promotes PINK1-mediated Mitophagy to Alleviates Ferroptosis in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a common diabetic complication. Studies show that mitophagy inhibition induced-ferroptosis plays a crucial role in DN progression. UHRF1 is associated with mitophagy and is highly expression in DN patients, however, the effect of UHRF1 on DN is still unclear. Thus, in this study, we aimed to investigate whether UHRF1 involves DN development by the mitophagy/ferroptosis pathway. We overexpressed UHRF1 using an adeno-associated virus 9 (AAV9) system in high-fat diet/streptozotocin-induced diabetic mice. Renal function index, pathological changes, mitophagy factors, and ferroptosis factors were detected in vivo. High-glucose cultured human renal proximal tubular (HK-2) cells were used as in vitro models to investigate the mechanism of UHRF1 in DN. We found that diabetic mice exhibited kidney damage, which was alleviated by UHRF1 overexpression. UHRF1 overexpression promoted PINK1-mediated mitophagy and inhibited the expression of thioredoxin interacting protein (TXNIP), a factor associated with mitochondrial dysfunction. Additionally, UHRF1 overexpression alleviated lipid peroxidation and free iron accumulation, and upregulated the expression of GPX4 and Slc7a11, indicating the inhibition effect of UHRF1 overexpression on ferroptosis. We further investigated the mechanism of UHRF1 in the mitophagy/ferroptosis pathway in DN. We found that UHRF1 overexpression promoted PINK1-mediated mitophagy via inhibiting TXNIP expression, thus suppressing ferroptosis. These findings confirmed that upregulation of UHRF1 expression alleviates DN, indicating that UHRF1 has a reno-protective effect against DN.

Decomposition and decoupling analysis of carbon emissions in the Yellow River Basin: evidence from urban agglomerations.

A comprehensive understanding of carbon emission reduction and decoupling in urban agglomerations of the Yellow River Basin (YRB) has significant theoretical and practical value for formulating precise carbon reduction policies and achieving ecological conservation and high-quality development in the region. This study utilized a generalized Divisia index decomposition model to identify the primary driving factors behind carbon emission changes in urban agglomerations of the YRB. Based on this, a model measuring decoupling efforts was constructed to systematically investigate the decoupling relationship between carbon emissions. The research findings indicate that technological progress and output scale are two primary drivers of carbon emission increases in the YRB and its urban agglomerations, whereas technological carbon intensity, output carbon intensity, and energy carbon intensity play key roles in reducing carbon emissions. Except for a few years, the YRB and Jiziwan metropolitan area (JWMA) did not exhibit decoupling effects on carbon emissions. The Shandong Peninsula Urban Agglomeration (SPUA) and Central Plains Urban Agglomeration (CPUA) showed strong decoupling effects from 2016 to 2019. The Guanzhong Plain Urban Agglomeration (GPUA) demonstrated a strong decoupling effect from 2013 to 2019 (except from 2016 to 2017). The Lanxi Urban Agglomeration (LXUA) exhibited a strong decoupling effect from 2014 to 2019. Technological carbon intensity plays a decisive role in the transition from non-decoupling to decoupling. Therefore, the government must increase investments in green and low-carbon technologies and strictly implement carbon reduction measures. Thus, the YRB and its urban agglomerations have considerable potential for carbon emission reduction and strong decoupling effects.

Cross-platform comparison of highly-sensitive immunoassays for inflammatory markers in a COVID-19 cohort 1.

A variety of commercial platforms are available for the simultaneous detection of multiple cytokines and associated proteins, often employing antibody pairs to capture and detect target proteins. In this study, we comprehensively evaluated the performance of three distinct platforms: the fluorescent bead-based Luminex assay, the proximity extension-based Olink assay, and a novel proximity ligation assay platform known as Alamar NULISAseq. These assessments were conducted on serum samples from the NIH IMPACC study, with a focus on three essential performance metrics: detectability, correlation, and differential expression. Our results reveal several key findings. Firstly, the Alamar platform demonstrated the highest overall detectability, followed by Olink and then Luminex. Secondly, the correlation of protein measurements between the Alamar and Olink platforms tended to be stronger than the correlation of either of these platforms with Luminex. Thirdly, we observed that detectability differences across the platforms often translated to differences in differential expression findings, although high detectability did not guarantee the ability to identify meaningful biological differences. Our study provides valuable insights into the comparative performance of these assays, enhancing our understanding of their strengths and limitations when assessing complex biological samples, as exemplified by the sera from this COVID-19 cohort.

NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing.

The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications.

Residue of Chlormequat and Regulatory Effects on the Specialized Metabolites of Astragali Radix.

Presently, the utilization of chlormequat in Astragalus mongholicus Bunge (Leguminosae) cultivation is prevalent for augmenting rhizome (Astragali Radix) yield. However, indiscriminate and excessive chlormequat employment can detrimentally influence Astragali Radix quality and safety. This research aimed to comprehensively comprehend chlormequat risks and its influence on Astragali Radix metabolites. Diverse chlormequat concentrations were employed in Astragalus mongholicus cultivation, with subsequent analysis of residual chlormequat levels in Astragali Radix across treatment groups. Astragali Radix metabolic profiling was conducted through UPLC-QTOF-MS, and thirteen principal active components were quantified via UFLC-MS/MS. Findings revealed a direct correlation between chlormequat residue levels in Astragali Radix and application concentration, with high-dose residue surpassing 5.0 mg/kg. Metabolomics analysis identified twenty-six distinct saponin and flavonoid metabolites. Notably, the application of chlormequat led to the upregulation of seven saponins (e.g., astragaloside I and II) and downregulation of six flavonoids (e.g., methylnissolin-3-O-glucoside and astraisoflavan-7-O-ß-d-glucoside). Quantitative analysis demonstrated variable contents of active ingredients due to differing chlormequat concentrations, leading to astragaloside I increase (14.59-62.55%) and isoastragaloside II increase (4.8-55.63%), while methylnissolin-3-O-glucoside decreased (22.18-41.69%), as did astraisoflavan-7-O-ß-d-glucoside (21.09-47.78%). In conclusion, chlormequat application influenced multiple active components in Astragali Radix, causing constituent proportion variations. Elevated chlormequat concentrations led to increased active components alongside heightened chlormequat residues in Astragali Radix. Consequently, prudent chlormequat application during Astragali Radix production is imperative to avert potential detriments to its quality and safety.

A Photocurable Polysaccharide-Based Hydrogel Delivery of Polydeoxyribonucleotide-Loaded Vectors for Wound Treatment.

The wounds caused by war, accidents, and diseases require timely and effective treatment. Polysaccharides, as natural macromolecules, have good biocompatibility and unique functions, and are excellent substrates for constructing new wound dressings. Short-chain chitosan (SCS) has good water solubility and, importantly, retains a large number of active amino groups. We first introduce double bonds to SCS. This chitosan derivative can be entangled with sodium alginate (SA) through electrostatic interaction. The flowing sol can be applied to a wound with an irregular shape. Under the initiation of a photoinitiator, the internal double bonds are broken and cross-linked to form a gel. The prepared hydrogel wound dressing exhibited good antibacterial properties and can provide a microenvironment conducive to wound repair. A polydeoxyribonucleotide (PDRN) has been proven to have encouraging therapeutic effects for wound healing. PDRN can be condensed by branched polyethylenimine (PEI) to form a nucleic acid delivery system, which can be efficiently uptaken by cells. The cooperation of hydrogel and nucleic-acid-based therapy presented good results in a mouse full-thickness skin wound model.

Synthesis of Crocin I and Crocin II by Multigene Stacking in Nicotiana benthamiana.

Crocins are a group of highly valuable water-soluble carotenoids that are reported to have many pharmacological activities, such as anticancer properties, and the potential for treating neurodegenerative diseases including Alzheimer's disease. Crocins are mainly biosynthesized in the stigmas of food-medicine herbs Crocus sativus L. and Gardenia jasminoides fruits. The distribution is narrow in nature and deficient in resources, which are scarce and expensive. Recently, the synthesis of metabolites in the heterologous host has opened up the potential for large-scale and sustainable production of crocins, especially for the main active compounds crocin I and crocin II. In this study, GjCCD4a, GjALDH2C3, GjUGT74F8, and GjUGT94E13 from G. jasminoides fruits were expressed in Nicotiana benthamiana. The highest total content of crocins in T1 generation tobacco can reach 78,362 ng/g FW (fresh weight) and the dry weight is expected to reach 1,058,945 ng/g DW (dry weight). Surprisingly, the primary effective constituents crocin I and crocin II can account for 99% of the total crocins in transgenic plants. The strategy mentioned here provides an alternative platform for the scale-up production of crocin I and crocin II in tobacco.