Improvement of antibacterial activity of polysaccharides via chemical modification: A review.

Antibiotic residue and bacterial resistance induced by antibiotic abuse have seriously threatened food safety and human healthiness. Thus, the development and application of safe, high-efficiency, and environmentally friendly antibiotic alternatives are urgently necessary. Apart from antitumor, antivirus, anti-inflammatory, gut microbiota regulation, immunity improvement, and growth promotion activities, polysaccharides also have antibacterial activity, but such activity is relatively low, which cannot satisfy the requirements of food preservation, clinical sterilization, livestock feeding, and agricultural cultivation. Chemical modification not only provides polysaccharides with better antibacterial activity, but also promotes easy operation and large-scale production. Herein, the enhancement of the antibacterial activity of polysaccharides via acetylation, sulfation, phosphorylation, carboxymethylation, selenation, amination, acid graft, and other chemical modifications is reviewed. Meanwhile, a new trend on the application of loading chemically modified polysaccharides into nanostructures is discussed. Furthermore, possible limitations and future recommendations for the development and application of chemically modified polysaccharides with better antibacterial activity are suggested.

Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis.

Hepatocellular carcinoma (HCC) is a significant contributor to cancer-related deaths in the world. The development and progression of HCC are closely correlated with the abnormal regulation of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Important biological pathways in cancer biology, such as cell proliferation, death, and metastasis, are impacted by these ncRNAs, which modulate gene expression. The abnormal expression of non-coding RNAs in HCC raises the possibility that they could be applied as new biomarkers for diagnosis, prognosis, and treatment targets. Furthermore, by controlling the expression of cancer-related genes, miRNAs can function as either tumor suppressors or oncogenes. On the other hand, lncRNAs play a role in the advancement of cancer by interacting with other molecules within the cell, which, in turn, affects processes such as chromatin remodeling, transcription, and post-transcriptional processes. The importance of ncRNA-driven regulatory systems in HCC is being highlighted by current research, which sheds light on tumor behavior and therapy response. This research highlights the great potential of ncRNAs to improve patient outcomes in this difficult disease landscape by augmenting the present methods of HCC care through the use of precision medicine approaches.

Integration of single-cell RNA-seq and bulk RNA-seq to construct liver hepatocellular carcinoma stem cell signatures to explore their impact on patient prognosis and treatment.

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a prevalent form of primary liver cancer. Research has demonstrated the contribution of tumor stem cells in facilitating tumor recurrence, metastasis, and treatment resistance. Despite this, there remains a lack of established cancer stem cells (CSCs)-associated genes signatures for effectively predicting the prognosis and guiding the treatment strategies for patients diagnosed with LIHC. METHODS: The single-cell RNA sequencing (scRNA-seq) and bulk RNA transcriptome data were obtained based on public datasets and computerized firstly using CytoTRACE package and One Class Linear Regression (OCLR) algorithm to evaluate stemness level, respectively. Then, we explored the association of stemness indicators (CytoTRACE score and stemness index, mRNAsi) with survival outcomes and clinical characteristics by combining clinical information and survival analyses. Subsequently, weighted co-expression network analysis (WGCNA) and Cox were applied to assess mRNAsi-related genes in bulk LIHC data and construct a prognostic model for LIHC patients. Single-sample gene-set enrichment analysis (ssGSEA), Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Tumor Immune Estimation Resource (TIMER) analysis were employed for immune infiltration assessment. Finally, the potential immunotherapeutic response was predicted by the Tumor Immune Dysfunction and Exclusion (TIDE), and the tumor mutation burden (TMB). Additionally, pRRophetic package was applied to evaluate the sensitivity of high and low-risk groups to common chemotherapeutic drugs. RESULTS: A total of four genes (including STIP1, H2AFZ, BRIX1, and TUBB) associated with stemness score (CytoTRACE score and mRNAsi) were identified and constructed a risk model that could predict prognosis in LIHC patients. It was observed that high stemness cells occurred predominantly in the late stages of LIHC and that poor overall survival in LIHC patients was also associated with high mRNAsi scores. In addition, pathway analysis confirmed the biological uniqueness of the two risk groups. Personalized treatment predictions suggest that patients with a low risk benefited more from immunotherapy, while those with a high risk group may be conducive to chemotherapeutic drugs. CONCLUSION: The current study developed a novel prognostic risk signature with genes related to CSCs, which provides novel ideas for the diagnosis, prognosis and treatment of LIHC.

Pulsed electromagnetic field-assisted reduced graphene oxide composite 3D printed nerve scaffold promotes sciatic nerve regeneration in rats.

Peripheral nerve injuries can lead to sensory or motor deficits that have a serious impact on a patient's mental health and quality of life. Nevertheless, it remains a major clinical challenge to develop functional nerve conduits as an alternative to autologous grafts. We applied reduced graphene oxide (rGO) as a bioactive conductive material to impart electrophysiological properties to a 3D printed scaffold and the application of a pulsed magnetic field to excite the formation of microcurrents and induce nerve regeneration.In vitrostudies showed that the nerve scaffold and the pulsed magnetic field made no effect on cell survival, increased S-100ßprotein expression, enhanced cell adhesion, and increased the expression level of nerve regeneration-related mRNAs.In vivoexperiments suggested that the protocol was effective in promoting nerve regeneration, resulting in functional recovery of sciatic nerves in rats, when they were damaged close to that of the autologous nerve graft, and increased expression of S-100ß, NF200, and GAP43. These results indicate that rGO composite nerve scaffolds combined with pulsed magnetic field stimulation have great potential for peripheral nerve rehabilitation.

Relationship between four insulin resistance surrogates and left ventricular hypertrophy among hypertensive adults: a case-control study.

Background: Hypertension-induced left ventricular hypertrophy (LVH) is intricately linked to insulin resistance (IR). This research aimed to elucidate the relationship of advanced indices, namely the triglyceride-glucose (TyG) index, the TyG adjusted for body mass index (TyG-BMI), the triglycerides-to-high-density lipoprotein cholesterol ratio (TG/HDL-c), and the metabolic score for IR (METS-IR), with LVH in hypertensive cohorts. Methods: This analytical case-control investigation encompassed 800 individuals aged 18 or above from the Cardiology Department of the Second Affiliated Hospital of Baotou Medical College over a span from January 2021 to April 2022. Data extraction was conducted from inpatient records. The nexus between the four metrics and LVH susceptibility was ascertained via logistic regression models. Furthermore, the receiver operating characteristic (ROC) curve's area (AUC) shed light on the discriminative capacities of the distinct IR indicators for LVH, considering other concomitant risk variables. Results: Post multifaceted covariate adjustments, the fourth quartile figures for TyG-BMI emerged as the most starkly significant (OR: 5.211, 95% CI: 2.861-9.492), succeeded by METS-IR (OR: 4.877, 95% CI: 2.693-8.835). In juxtaposition with other IR-derived indices (TyG and TG/HDL-c), TyG-BMI manifested the paramount AUC (AUC: 0.657; 95% CI: 0.606-0.708). Concurrently, METS-IR exhibited commendable predictive efficacy for LVH (AUC: 0.646; 95% CI: 0.595-0.697). Conclusion: TyG-BMI and METS-IR displayed superior discriminative capabilities for LVH, underscoring their potential as supplementary indicators in gauging LVH peril in clinical settings and prospective epidemiological research.

Chicoric acid ameliorates sepsis-induced cardiomyopathy via regulating macrophage metabolism reprogramming.

BACKGROUND: Sepsis-related cardiac dysfunction is believed to be a primary cause of high morbidity and mortality. Metabolic reprogramming is closely linked to NLRP3 inflammasome activation and dysregulated glycolysis in activated macrophages, leading to inflammatory responses in septic cardiomyopathy. Succinate dehydrogenase (SDH) and succinate play critical roles in the progression of metabolic reprogramming in macrophages. Inhibition of SDH may be postulated as an effective strategy to attenuate macrophage activation and sepsis-induced cardiac injury. PURPOSE: This investigation was designed to examine the role of potential compounds that target SDH in septic cardiomyopathy and the underlying mechanisms involved. METHODS/RESULTS: From a small molecule pool containing about 179 phenolic compounds, we found that chicoric acid (CA) had the strongest ability to inhibit SDH activity in macrophages. Lipopolysaccharide (LPS) exposure stimulated SDH activity, succinate accumulation and superoxide anion production, promoted mitochondrial dysfunction, and induced the expression of hypoxia-inducible factor-1α (HIF-1α) in macrophages, while CA ameliorated these changes. CA pretreatment reduced glycolysis by elevating the NAD+/NADH ratio in activated macrophages. In addition, CA promoted the dissociation of K(lysine) acetyltransferase 2A (KAT2A) from α-tubulin, and thus reducing α-tubulin acetylation, a critical event in the assembly and activation of NLRP3 inflammasome. Overexpression of KAT2A neutralized the effects of CA, indicating that CA inactivated NLRP3 inflammasome in a specific manner that depended on KAT2A inhibition. Importantly, CA protected the heart against endotoxin insult and improved sepsis-induced cardiac mitochondrial structure and function disruption. Collectively, CA downregulated HIF-1α expression via SDH inactivation and glycolysis downregulation in macrophages, leading to NLRP3 inflammasome inactivation and the improvement of sepsis-induced myocardial injury. CONCLUSION: These results highlight the therapeutic role of CA in the resolution of sepsis-induced cardiac inflammation.

Effect of monosaccharide composition and proportion on the bioactivity of polysaccharides: A review.

Polysaccharides have been widely used in pharmaceutical and food industries due to their diverse bioactivity, high safety, and few or no side effects. However, inability to quickly produce, screen, and synthesize bioactive polysaccharides is the limiting factor for their development and application. Structural features determine and influence the bioactivity of polysaccharides. Among them, monosaccharide is the basic unit of polysaccharide, which not only affects electrification, functional group, and bioactivity of polysaccharide but also is one of the simplest polysaccharide indexes to be detected. At present, effects of monosaccharide composition and proportion on anti-inflammatory, antioxidant, antitumor, immunomodulatory, antibacterial, and prebiotic activities of polysaccharides are reviewed. Further problems need to be considered during regulation and analysis of monosaccharide composition and proportion of polysaccharides. Overall, present work will provide help and reference for production, development, and structure-function investigation of polysaccharides based on their monosaccharide.

Characterization of the physicochemical properties of Lipu Colocasia esculenta (L.) Schott starch: A potential new food ingredient.

The physicochemical properties of Lipu taro starch (LTS), cassava starch (CS) and wheat starch (WS) were analyzed. These starches exhibited a comparable starch content (86 %). However, LTS had a significantly lower amylose content (15.93 %) compared to CS (26.62 %) and WS (33.53 %). Moreover, LTS demonstrated an irregular polygonal cubic morphology with a smaller particle size of 2.55 µm while possessed an A-type crystal structure with high crystallinity at 25.07 %. In contrast, CS and WS had larger particle sizes of 13.33 µm and 16.68 µm, respectively, with lower crystallinities of 22.52 % and 20.33 %. Due to these physicochemical properties, LTS exhibited superior emulsification properties with a higher emulsifying activity index of 8.63 m2/g and an emulsion stability index of 69.18 min, whereas CS and WS had values of 2.35 m2/g and 25.15 min, and 0.37 m2/g and 11.48 min, respectively. LTS also demonstrated enhanced thermal stability, characterized by higher gelatinization temperature (indicated by To, Tp, Tc, and ΔT) and reduced paste viscosity (indicated by PV, TV, FV, SBV, and BDV) compared to CS. However, the mechanical strength of the gel made from LTS (indicated by hardness, adhesiveness, springiness, gumminess, and chewiness) was comparatively inferior to those from CS and WS.

Short-term influence of polytetrafluoroethylene micro/nano-plastics on the inhibition of copper and/or ciprofloxacin on the nitrifying sludge activities based on concentration addition and independent action models.

Short-term influence of polytetrafluoroethylene micro/nano-plastics (PTFE-MPs/NPs) on the inhibition of copper (Cu2+) and/or ciprofloxacin (CIP) on the nitrifying sludge activities was explored based on concentration addition (CA) and independent action (IA) models. The half maximal inhibitory concentration (IC50) of Cu2+, CIP, PTFE-MPs (3 µm), and PTFE-NPs (800 nm) on the specific ammonium oxidation rate (SAOR) of nitrifying sludge was 64.57, 51.29, 102.33 and 93.33 mg L-1, respectively, while those on the specific nitrite oxidation rate (SNOR) of nitrifying sludge were 77.62, 32.36, 104.70 and 97.72 mg L-1, respectively. Among the five binary mixtures and two ternary mixtures composed by Cu2+, CIP, and/or PTFE-MPs/NPs, it was found that the two joint inhibitory actions from ternary mixtures on the SAOR and SNOR of the sludge showed time-dependent characteristics by analyzing of CA and IA models, while the five combined inhibitory effects from different binary mixtures did not all have time-dependent features. The two joint inhibition actions from diverse ternary mixtures on the SAOR at the exposure time of 60 min and on the SNOR at 90 min showed always concentration-dependent features, while the combined inhibitions with concentration-dependent characteristics had never been observed in the binary Cu2+ and PTFE-NPs mixtures at different exposure time. The Cu2+, CIP, and PTFE-MPs mixtures (or Cu2+, CIP, and PTFE-NPs mixtures) had synergistic actions on the SAOR at 90 min and antagonistic effects on the SNOR at 60 min based on CA and IA models, and these combined inhibitions did not exhibit concentration-dependent characteristics. In contrast, the joint inhibitory effects (on the SAOR and SNOR) with concentration-dependent features were found in the binary mixtures of CIP and PTFE-MPs at different exposure time, and the join inhibition changed from synergism to antagonism as the increasing concentration of mixed CIP and PTFE-MPs. This study provides novel perspectives for understanding the combined influence of plastic particles with different sizes, antibiotics, and heavy metals on the biological wastewater treatment process.

Inhibition of Proliferation, Migration, and Invasion of Keloid Fibroblasts By miR-183-5p Through Downregulating EGR1 / Inhibición de la Proliferación, Migración e Invasión de Fibroblastos Queloides por miR-183-5p Mediante la Regulación Negativa de EGR1

SUMMARY: Keloid scar is a unique benign fibroproliferative tumor of the human skin. Previously, it was reported that early growth response 1 (EGR1), a transcription factor, promotes keloid fibrosis; however, the mechanism by which EGR1 modulates keloid formation was not elaborated. In this research, the specific function and the microRNA (miRNA) regulatory network of EGR1 in keloids was examined. Keloid fibroblasts (KFs) were transfected with EGR1-small interfering RNA (siEGR1), EGR1-overexpression plasmid (pcDNA3.1-EGR1), and microRNA (miR-183-5p)-mimics to regulate the expression of EGR1 and miR-183-5p. The study employed dual-luciferase reporter assays to explore the targeting regulation of miR-183-5p on EGR1. Additionally, Western blotting, flow cytometry, qRT-PCR, cell count kit-8 (CCK-8), transwell, and wound healing assays, and RNA sequencing were conducted. EGR1 was upregulated in KFs, and EGR1 silencing diminished proliferation, fibrosis, migration, invasion, and apoptosis of cells. In KFs, the expression of miR- 183-5p was reduced, leading to the inhibition of cell proliferation, migration, and invasion. Conversely, it enhanced apoptosis. By targeting EGR1, miR-183-5p partially counteracted the impact of EGR1 on migration, invasion, and fibrosis in KFs. The findings imply that miR-183-5p suppresses keloid formation by targeting EGR1. As a result, EGR1 holds promise as a potential therapeutic target for preventing and treating keloids.

La cicatriz queloide es un tumor fibroproliferativo benigno único de la piel humana. Anteriormente, se informó que la respuesta de crecimiento temprano 1 (EGR1), un factor de transcripción, promueve la fibrosis queloide; sin embargo, no se explicó el mecanismo por el cual EGR1 modula la formación de queloides. En esta investigación, se examinó la función específica y la red reguladora de microARN (miARN) de EGR1 en queloides. Se transfectaron fibroblastos queloides (KF) con ARN de interferencia pequeño de EGR1 (siEGR1), plásmido de sobreexpresión de EGR1 (pcDNA3.1-EGR1) y miméticos de microARN (miR-183-5p) para regular la expresión de EGR1 y miR-183. -5p. El estudio empleó ensayos de indicador de luciferasa dual para explorar la regulación dirigida de miR-183-5p en EGR1. Además, se realizaron pruebas de transferencia Western, citometría de flujo, qRT-PCR, kit de recuento celular-8 (CCK-8), transwell y curación de heridas, y secuenciación de ARN. EGR1 estaba regulado positivamente en KF, y el silenciamiento de EGR1 disminuyó la proliferación, fibrosis, migración, invasión y apoptosis de las células. En KF, la expresión de miR- 183-5p se redujo, lo que llevó a la inhibición de la proliferación, migración e invasión celular. Por el contrario, mejoró la apoptosis. Al apuntar a EGR1, miR-183-5p contrarrestó parcialmente el impacto de EGR1 en la migración, invasión y fibrosis en KF. Los hallazgos implican que miR-183-5p suprime la formación de queloides al apuntar a EGR1. Como resultado, EGR1 es prometedor como objetivo terapéutico potencial para prevenir y tratar los queloides.

Metal-organic framework-modulated Fe3O4 composite au nanoparticles for antibacterial wound healing via synergistic peroxidase-like nanozymatic catalysis.

Bacterial wound infections are a serious threat due to the emergence of antibiotic resistance. Herein, we report an innovative hybrid nanozyme independent of antibiotics for antimicrobial wound healing. The hybrid nanozymes are fabricated from ultra-small Au NPs via in-situ growth on metal-organic framework (MOF)-stabilised Fe3O4 NPs (Fe3O4@MOF@Au NPs, FMA NPs). The fabricated hybrid nanozymes displayed synergistic peroxidase (POD)-like activities. It showed a remarkable level of hydroxyl radicals (·OH) in the presence of a low dose of H2O2 (0.97 mM). Further, the hybrid FMA nanozymes exhibited excellent biocompatibility and favourable antibacterial effects against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The animal experiments indicated that the hybrid nanozymes promoted wound repair with adequate biosafety. Thus, the well-designed hybrid nanozymes represent a potential strategy for healing bacterial wound infections, without any toxic side effects, suggesting possible applications in antimicrobial therapy.

Disrupted cardiac fibroblast BCAA catabolism contributes to diabetic cardiomyopathy via a periostin/NAP1L2/SIRT3 axis.

BACKGROUND: Periostin is an extracellular matrix protein that plays a critical role in cell fate determination and tissue remodeling, but the underlying role and mechanism of periostin in diabetic cardiomyopathy (DCM) are far from clear. Thus, we aimed to clarify the mechanistic participation of periostin in DCM. METHODS: The expression of periostin was examined in DCM patients, diabetic mice and high glucose (HG)-exposed cardiac fibroblasts (CF). Gain- and loss-of-function experiments assessed the potential role of periostin in DCM pathogenesis. RNA sequencing was used to investigate the underlying mechanisms of periostin in DCM. RESULTS: A mouse cytokine antibody array showed that the protein expression of periostin was most significantly upregulated in diabetic mouse heart, and this increase was also observed in patients with DCM or HG-incubated CF. Periostin-deficient mice were protected from diabetes-induced cardiac dysfunction and myocardial damage, while overexpression of periostin held the opposite effects. Hyperglycemia stimulated the expression of periostin in a TGF-ß/Smad-dependent manner. RNA sequencing results showed that periostin upregulated the expression of nucleosome assembly protein 1-like 2 (NAP1L2) which recruited SIRT3 to deacetylate H3K27ac on the promoters of the branched-chain amino acid (BCAA) catabolism-related enzymes BCAT2 and PP2Cm, resulting in BCAA catabolism impairment. Additionally, CF-derived periostin induced hypertrophy, oxidative injury and inflammation in primary cardiomyocytes. Finally, we identified that glucosyringic acid (GA) specifically targeted and inhibited periostin to ameliorate DCM. CONCLUSION: Overall, manipulating periostin expression may function as a promising strategy in the treatment of DCM.

Divergent and Selective Light Alkene Cross-Coupling.

Light olefins are abundantly manufactured in the petroleum industry and thus represent ideal starting materials for modern chemical synthesis. Selective and divergent transformations of feedstock light olefins to value-added chemicals are highly sought-after but remain challenging. Herein we report an exceptionally regioselective carbonickelation of light alkenes followed by in situ trapping with three types of nucleophiles, namely a reductant, base, or Grignard reagent. This protocol enables efficient 1,2-hydrofunctionalization, dicarbofunctionalization, and branched-selective Heck-type cross-coupling of light alkenes with aryl and alkenyl reagents to streamline access to diverse alkyl arenes and complex alkenes. Harnessing bulky N-heterocyclic carbene ligands with acenaphthyl backbones for nickel catalysts is crucial to attain high reactivity and selectivity. This strategy provides a rare, modular, and divergent platform for upgrading feedstock alkenes and is expected to find broad applications in medicinal chemistry and industrial processes.

Continuous Spinning of High-Tough Hydrogel Fibers for Flexible Electronics by Using Regional Heterogeneous Polymerization.

Hydrogel fibers have attracted substantial interest for application in flexible electronics due to their ionic conductivity, high specific surface area, and ease of constructing multidimensional structures. However, universal continuous spinning methods for hydrogel fibers are yet lacking. Based on the hydrophobic mold induced regional heterogeneous polymerization, a universal self-lubricating spinning (SLS) strategy for the continuous fabrication of hydrogel fibers from monomers is developed. The universality of the SLS strategy is demonstrated by the successful spinning of 10 vinyl monomer-based hydrogel fibers. Benefiting from the universality of the SLS strategy, the SLS strategy can be combined with pre-gel design and post-treatment toughening to prepare highly entangled polyacrylamide (PAM) and ionic crosslinked poly(acrylamide-co-acrylic acid)/Fe3+ (W-PAMAA/Fe3+ ) hydrogel fibers, respectively. In particular, the W-PAMAA/Fe3+ hydrogel fiber exhibited excellent mechanical properties (tensile stress > 4 MPa, tensile strain > 400%) even after 120 days of swelling in the pH of 3-9. Furthermore, owing to the excellent multi-faceted performance and one-dimensionality of W-PAMAA/Fe3+ hydrogel fibers, flexible sensors with different dimensions and functions can be constructed bottom-up, including the one-dimensional (1D) strain sensor, two-dimensional (2D) direction sensor, three-dimensional (3D) pressure sensor, and underwater communication sensor to present the great potential of hydrogel fibers in flexible electronics.

Antibacterial activity of a polysaccharide isolated from Artemisia argyi leaf against Staphylococcus aureus and mechanism investigation.

Abuse of antibiotics has led to excessive amounts of antibiotic residues in food and environment, thus enhancing pathogenic bacterium resistance and threatening human health. Therefore, searching and developing safe and green antibiotic alternatives are necessary. In this study, an Artemisia argyi leaf polysaccharide (AALP) fraction was extracted and analyzed. Chemical composition analysis showed that the carbohydrate, uronic acid, protein, and polyphenol content in AALP were 68.3 % ± 4.13 %, 9.4 % ± 0.86 %, 1.79 % ± 0.27 %, and 0.16 % ± 0.035 %, respectively. Chromatographic results suggested that AALP contained rhamnose, arabinose, glucosamine, galactose, glucose, xylose, mannose, galacturonic acid, and glucuronic acid in a molar ratio of 9.26, 1.35, 1.18, 3.04, 48.51, 2.33, 31.26, 3.93, and 9.08; the weight average molecular weight, number average molecular weight, and polydispersity of AALP were 5.41 kDa, 4.63 kDa, and 1.168, respectively. Fourier transform infrared spectroscopy indicated that AALP constituted the polysaccharide-specific groups of CH, CO, and OH. Meanwhile, AALP showed a dose-dependent inhibitory effect on Staphylococcus aureus in the inhibition zone assay, and the minimal inhibitory concentration was 1.25 mg/mL. Furthermore, AALP disrupted the cell wall, depolarized the inner membrane potential, and inhibited the activities of succinate dehydrogenase and malate dehydrogenase in S. aureus.

Regulation strategy, bioactivity, and physical property of plant and microbial polysaccharides based on molecular weight.

Structural features affect the bioactivity, physical property, and application of plant and microbial polysaccharides. However, an indistinct structure-function relationship limits the production, preparation, and utilization of plant and microbial polysaccharides. Molecular weight is an easily regulated structural feature that affects the bioactivity and physical property of plant and microbial polysaccharides, and plant and microbial polysaccharides with a specific molecular weight are important for exerting their bioactivity and physical property. Therefore, this review summarized the regulation strategies of molecular weight via metabolic regulation; physical, chemical, and enzymic degradations; and the influence of molecular weight on the bioactivity and physical property of plant and microbial polysaccharides. Moreover, further problems and suggestions must be paid attention to during regulation, and the molecular weight of plant and microbial polysaccharides must be analyzed. The present work will promote the production, preparation, utilization, and investigation of the structure-function relationship of plant and microbial polysaccharides based on their molecular weight.

Promoting substrates uptake and curdlan synthesis of Agrobacterium sp. by attenuating the exopolysaccharide encapsulation.

During curdlan production by Agrobacterium sp., the secreted exopolysaccharide (EPS) gradually encapsulated Agrobacterium sp., accompanied by cell aggregation, resulted in inhibited substrate uptake and curdlan synthesis. To relieve the EPS encapsulation effect, the shake-flask culture medium was quantitatively supplemented with 2 % to 10 % endo-ß-1,3-glucanase (BGN), while obtaining curdlan with a decreased weight-average molecular weight ranging from 18.99 × 104 Da to 3.20 × 104 Da. In a 7-L bioreactor, the 4 % BGN supplement substantially attenuated the EPS encapsulation, resulting in increased glucose consumption and curdlan yield to 66.41 g/L and 34.53 g/L after fermentation of 108 h, which improved 43 % and 67 %, respectively compared with the control. The disruption of EPS encapsulation with BGN treatment accelerated the regeneration of ATP and UTP, resulting in sufficient uridine diphosphate glucose for curdlan synthesis. The upregulation of related genes at the transcription level reveals that the respiratory metabolic intensity, the energy regeneration efficiency, and the curdlan synthetase activity were enhanced. This study presents a simple and novel strategy of relieving the effects of EPS encapsulation on the metabolism of Agrobacterium sp. for the high-yield and value-added production of curdlan, which could be potentially applied in producing other EPSs.

DR region of NKAα1 is a target to ameliorate hepatic lipid metabolism disturbance in obese mice.

BACKGROUND: Na+/K+-ATPase (NKA), an ion pumping enzyme ubiquitously expressed in various cells, is critically involved in cellular ion homeostasis and signal transduction. However, the role of NKA in hepatic lipid homeostasis has yet to be fully characterized. METHODS: The activity of NKA and NKAα1 expression were determined in steatotic cells, mice and patients. The roles of NKAα1 in hepatosteatosis were detected using hepatocyte knockout or specific overexpression of NKAα1 in mice. RESULTS: Herein, we demonstrated that the expression and activity of α1 subunit of NKA (NKAα1) were lowered in the livers of nonalcoholic fatty liver disease (NAFLD) patients, high-fat diet (HFD)-induced obese mice, and genetically obese (ob/ob, db/db) mice, as well as oleic acid-induced hepatocytes. Hepatic deficiency of NKAα1 exacerbated, while adeno-associated virus-mediated liver specific overexpression of NKAα1 alleviated hepatic steatosis through regulation of fatty acid oxidation (FAO) and lipogenesis. Mechanistically, we revealed that NKAα1 upregulated sirtuin 1 (SIRT1) via interacting with ubiquitin specific peptidase 22 (USP22), a deubiquitinating enzyme for the stabilization and deubiquitination of SIRT1, thus activating the downstream autophagy signaling. Blockade of the SIRT1/autophagy signaling pathway eliminated the protective effects of NKAα1 against lipid deposition in hepatocytes. Importantly, we found that an antibody against the DR region (897DVEDSYGQQWTYEQR911) of NKAα1 subunit (DR-Ab) ameliorated hepatic steatosis through maintaining the membrane density of NKAα1 and inducing its activation. CONCLUSIONS: Collectively, this study renews the functions of NKAα1 in liver lipid metabolism and provides a new clue for gene therapy or antibody treatment of hepatic lipid metabolism disturbance by targeting NKAα1.

Unsymmetric N-heterocyclic carbene ligand enabled nickel-catalysed arylation of bulky primary and secondary amines.

The arylation of sterically hindered amines represents one of the long-standing challenges in synthetic chemistry. Herein, we report a highly efficient Ni-catalysed arylation of sterically hindered primary and secondary amines with aryl chlorides or phenol derivatives enabled by an unsymmetric N-heterocyclic carbene (NHC) ligand. The protocol provides general, efficient, and scalable access to various sterically demanding anilines in excellent yields under mild conditions. A wide range of functional groups and heterocycles are compatible (>50 examples), including those present in biologically relevant molecules. Computational studies suggest that the unsymmetric bulky and flexible NHC ligand was critical to balance the oxidative addition and reductive elimination elementary steps, thus promoting this challenging transformation.

Comparative analysis of postoperative curative effect of liver wedge resection and liver IVb + V segment resection in patients with T2b gallbladder cancer.

Objective: To compare the therapeutic effects of wedge resection and liver segment IVb + V resection on patients with T2b gallbladder cancer. Methods: The clinical and pathological data of 40 patients with gallbladder cancer admitted to the Second Affiliated Hospital of Nanchang University from January 2017 to November 2019 were retrospectively analyzed, and they were divided into two groups according to different surgical methods. The control group underwent liver wedge resection, while the experimental group underwent liver segment IVb + V resection. Preoperative age, bilirubin index, tumor markers, postoperative complications and survival were compared between the two groups. Log-rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. Kaplan-Meier survival curves were drawn. Results: Univariate analysis showed that tumor markers and degree of differentiation were the risk factors for the prognosis of patients with gallbladder carcinoma after radical cholecystectomy (P < 0.05). Multivariate analysis showed that the elevation of CA125 and CA199, poor differentiation, and Lymph node metastasis were independent risk factors for the prognosis of gallbladder carcinoma after radical resection (P < 0.05). According to the 3-year survival rate, the survival rate of patients with liver 4B + 5 segment resection + cholecystectomy was higher than that of patients with 2 cm liver wedge resection + cholecystectomy (41.6% vs. 72.7%). Conclusion: Patients with T2b gallbladder cancer should be treated with liver segment IVb + V resection, which is helpful to improve the prognosis of patients and should be widely promoted.