Immobilization of rough morphotype Mycolicibacterium neoaurum R for androstadienedione production.

OBJECTIVES: Enhance the androstadienedione (Androst-1,4-diene-3,17-dione, ADD) production of rough morphotype Mycolicibacterium neoaurum R by repeated-batch fermentation of immobilized cells. RESULTS: M. neoaurum R was a rough colony morphotype variant, obtained from the routine plating of smooth M. neoaurum strain CICC 21097. M. neoaurum R showed rougher cell surface and aggregated in broth. The ADD production of M. neoaurum R was notably lower than that of M. neoaurum CICC 21097 during the free cell fermentation, but the yield gap could be erased after proper cell immobilization. Subsequently, repeated-batch fermentation of immobilized M. neoaurum R was performed to shorten the production cycle and enhance the bio-production efficiency of ADD. Through the optimization of the immobilization carriers and the co-solvents for phytosterols, the ADD productivity of M. neoaurum R immobilized by semi-expanded perlite reached 0.075 g/L/h during the repeated-batch fermentation for 40 days. CONCLUSIONS: The ADD production of the rough-type M. neoaurum R was notably enhanced by the immobilization onto semi-expanded perlite. Moreover, the ADD batch yields of M. neoaurum R immobilized by semi-expanded perlite were maintained at high levels during the repeated-batch fermentation.

The Effect of Hemoglobin Concentration on Hyperbaric Oxygen and Non-hyperbaric Oxygen in the Treatment of Hypertensive Intracerebral Hemorrhage After Operation at the High Altitude.

Background: The prognosis of hypertensive intracerebral hemorrhage (HICH) is poor at high altitudes. The objective of this study was to explore whether hyperbaric oxygen (HBO) can improve the results of computed tomography perfusion (CTP) imaging and the neurological function of patients with HICH, and influence the hemoglobin concentration. Method: The patients with HICH were treated with puncture and drainage. Twenty-one patients (51.22% of 41 patients in total) were treated with HBO after the operation, and the other patients received conventional treatment. CTP was performed twice, and all indices were measured. Scatter plots were used to determine the effect of hemoglobin concentration on CTP imaging. Receiver operating characteristic (ROC) curves were plotted to analyze the effects of hemoglobin concentration and hematoma volume on recovery results. The patients were followed up for 6 months. Results: Forty-one patients with HICH were treated with puncture and drainage. In total, 21 were treated with HBO after the operation, and 20 received conventional treatment as the control group. No significant differences in the CBV and CBF values of the two groups were noted before treatment. After 10 days, the values of CBV and CBF in the HBO group were significantly higher than those in the control group. A scatter diagram showed there was no significant in the HBO group, but significant correlation for the CBV and CBF values in the control group's hematoma center and margin. The ROC curves showed that hematoma volume had an influence on prognosis of the control group. The Glasgow Coma Scale (GOS) scores of the HBO group were significantly higher than those of the control group (p < 0.05). Conclusions: HBO therapy can improve the postoperative CBV and CBF values of patients with HICH and ameliorate their prognoses. There was no significant correlation between HBO group and hemoglobin concentration on admission.

N-Acylamino Saccharin as an Emerging Cysteine-Directed Covalent Warhead and Its Application in the Identification of Novel FBPase Inhibitors toward Glucose Reduction.

With a resurgence of covalent drugs, there is an urgent need for the identification of new moieties capable of cysteine bond formation. Herein, we report on the N-acylamino saccharin moieties capable of novel covalent reactions with cysteine. Their utility as alternative electrophilic warheads was demonstrated through the covalent modification of fructose-1,6-bisphosphatase (FBPase), a promising target associated with cancer and type 2 diabetes. The cocrystal structure of title compound W8 bound with FBPase unexpectedly revealed that the N-acylamino saccharin moiety worked as an electrophile warhead that covalently modified the noncatalytic C128 site in FBPase while releasing saccharin, suggesting a previously undiscovered covalent reaction mechanism of saccharin derivatives with cysteine. Treatment of title compound W8 displayed potent inhibition of glucose production in vitro and in vivo. This newly discovered reactive warhead supplements the current repertoire of cysteine covalent modifiers while avoiding some of the limitations generally associated with established moieties.

Effect of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The present systematic review and meta-analysis of randomized clinical trials (RCTs) aimed to investigate the effects of pulmonary rehabilitation in individuals with chronic obstructive pulmonary disease (COPD). METHODS: The RCTs of pulmonary rehabilitation programs published between 1999 and 2021 were retrieved from electronic databases (PubMed, Cochrane Library, and Embase). Two reviewers independently assessed the topical relevance and trial quality and extracted data for meta-analysis using the Stata software version 14.0. RESULTS: A total of 39 trials involving 2,397 participants with COPD were evaluated. We found that patients who received pulmonary rehabilitation program had significant improvement in the 6-min walk test (6MWT), St. George Respiratory Questionnaire score, and the modified British Medical Research Council score as compared to those who received usual care. Yoga and Tai Chi showed significant improvement in the forced expiratory volume (FEV1)% in 1 s predicted value. However, no significant difference was detected in the modified Borg score, forced vital capacity (FVC), and FEV1/FVC predicted value between the pulmonary rehabilitation and usual care groups. CONCLUSION: Yoga and Tai Chi showed a significant improvement in the FEV1% predicted value. Also, pulmonary rehabilitation program improved the exercise capacity, the quality of life, and dyspnoea in patients with COPD.Key messagesA total of 39 trials involving 2,397 participants with COPD were evaluated.We found that patients who received pulmonary rehabilitation program had significant improvement in the 6MWT, St. George Respiratory Questionnaire score, and the modified British Medical Research Council score as compared to those who received usual care.Yoga and Tai Chi showed significant improvement in the FEV1% predicted value.No significant difference was detected in the modified Borg score, FVC, and FEV1/FVC predicted value between the pulmonary rehabilitation and usual care groups.

Physicochemical characteristics and in vitro biological activities of polysaccharides derived from raw garlic (Allium sativum L.) bulbs via three-phase partitioning combined with gradient ethanol precipitation method.

In the present study, three-phase partitioning (TPP) coupled with gradient ethanol precipitation (GEP) was developed for the first time to extract and isolate polysaccharides (GPSs) from raw garlic (Allium sativum L.) bulbs. Four kinds of fructose polymers, namely, GPS35, GPS50, GPS65, and GPS80, were obtained at the final ethanol precipitation concentrations of 35%, 50%, 65%, and 80% (v/v), respectively, and their physicochemical characteristics and in vitro biological activities were investigated. Results indicated that GPS80 had higher carbohydrate (86.68% ± 0.90%) and uronic acid (12.89% ± 0.09%) contents, lower weight-average molecular weight (8.93 × 103 Da), and looser surface morphology than the other three GPSs. Furthermore, among the four GPSs, GPS80 exhibited the strongest antioxidant capacities, inhibitory effects on α-amylase and α-glycosidase, and nitric oxide stimulatory activity on RAW264.7 macrophage cells in vitro. Therefore, this study provides a simple and feasible technological strategy for producing bioactive polysaccharides from raw Allium vegetables.

Conjugation of ferulic acid onto pectin affected the physicochemical, functional and antioxidant properties.

BACKGROUND: Pectin, as a functional ingredient, is best known as a gelling and thickening agent, stabilizer, and fat substitute in processed foods. The synthesis of pectin graft copolymers is considered one of the most fascinating ways to improve its physicochemical and functional properties. In this study, therefore, water-soluble pectin or ultrasound-treated pectins (UP30 and UP60) grafted with ferulic acid (FA) conjugates, pectin-g-FA, UP30-g-FA and UP60-g-FA, were synthesized via a free radical-mediated grafting procedure, and their physicochemical, structural, and functional characteristics were investigated. Moreover, 2,2-diphenyl-1-picryl-hydrazyl (DPPH)-radical scavenging activity, Trolox equivalent antioxidant capacity (TEAC) assay and ferric-reducing ability of plasma (FRAP) assay were used to evaluate their antioxidant activities in vitro. RESULTS: Results showed that FA was covalently grafted onto pectin or ultrasound-treated pectins, and the grafting ratios of pectin-g-FA, UP30-g-FA and UP60-g-FA were 65.43 ± 1.30, 82.55 ± 1.71 and 75.82 ± 0.89 mg FA/g, respectively. Although the molecular weights, apparent viscosities, and thermal stabilities of the three FA-grafted pectin conjugates decreased and their surface morphologies were different from those of native pectin and ultrasound-treated pectins, they possessed prominent DPPH-radical scavenging ability [half maximal inhibitory concentration (IC50 ) of 0.32 to 0.89 mg mL-1 ) and antioxidant capacity (TEAC of 100.02 to 153.42 µmol Trolox/g sample; FRAP: 166.41 to 270.27 µmol FeSO4 /g sample). Their antioxidant potentials were positively correlated with the grafting ratio. CONCLUSION: This study provided a promising strategy for the functionalization of pectin, and the prepared FA-grafted pectin conjugates could be explored as functional ingredients that showed potential for applications in food and agriculture systems. © 2020 Society of Chemical Industry.

Amplified Cancer Immunotherapy of a Surface-Engineered Antigenic Microparticle Vaccine by Synergistically Modulating Tumor Microenvironment.

Efficient cancer vaccines not only require the co-delivery of potent antigens and highly immunostimulatory adjuvants to initiate robust tumor-specific host immune response but also solve the spatiotemporal consistency of host immunity and tumor microenvironment (TME) immunomodulation. Here, we designed a biomaterials-based strategy for converting tumor-derived antigenic microparticles (T-MPs) into a cancer vaccine to meet this conundrum and demonstrated its therapeutic potential in multiple murine tumor models. The internal cavity of T-MPs was employed to store nano-Fe3O4 (Fe3O4/T-MPs), and then dense adjuvant CpG-loaded liposome arrays (CpG/Lipo) were tethered on the surface of Fe3O4/T-MP through mild surface engineering to get a vaccine (Fe3O4/T-MPs-CpG/Lipo), demonstrating that co-delivery of Fe3O4/T-MPs and CpG/Lipo to antigen presenting cells (APCs) could elicit strong tumor antigen-specific host immune response. Meanwhile, vaccines distributed in the TME could reverse infiltrated tumor-associated macrophages into a tumor-suppressive M1 phenotype by nano-Fe3O4, amazingly induce abundant infiltration of cytotoxic T lymphocytes, and transform a "cold" tumor into a "hot" tumor. Furthermore, amplified antitumor immunity was realized by the combination of an Fe3O4/T-MPs-CpG/Lipo vaccine and immune checkpoint PD-L1 blockade, specifically inhibiting ∼83% of the progression of B16F10-bearing mice and extending the median survival time to 3 months. Overall, this study synergistically modulates the tumor immunosuppressive network and host antitumor immunity in a spatiotemporal manner, which suggests a general cell-engineering strategy tailored to a personalized vaccine from autologous cancer cell materials of each individual patient.

Quaternized curdlan/pectin polyelectrolyte complexes as biocompatible nanovehicles for curcumin.

In this study, a positively charged quaternized curdlan (Qcurd) was used to fabricate polyelectrolyte complex nanoparticles (PEC NPs) with a negatively charged pectin via electrostatic complexation. Results showed that the Qcurd/pectin PEC NPs prepared with 0.5 mg/mL Qcurd and pectin solutions, 1:2 pectin/Qcurd mass ratio, and pH 4.0 in the absence of NaCl were characterized by a spherical morphology in nanoscale, an average particle size of 68 nm, and good dispersibility in aqueous solutions. Curcumin was encapsulated in the Qcurd/pectin PEC NPs through hydrogen bonding with an encapsulation efficiency of ∼82%, a loading content of 13%, and a pH-dependent controlled release. Curcumin-loaded PEC NPs exhibited a significantly enhanced water solubility, excellent free radical scavenging ability and antioxidant capacity in vitro as compared with those of free curcumin.