The Incidence and Risk Factors of Frailty in Patients with Chronic Obstructive Pulmonary Disease: A Meta-Analysis.

Objective: COPD patients have a high incidence of frailty and numerous complications, which seriously affect their quality of life. This study systematically evaluated and analyzed the current state of frailty incidence and risk factors in COPD patients to reduce the prevalence of frailty and enhance their quality of life. Method: The Cochrane Library, PubMed, Embase, Web of Science, CBM, CNKI, VIP, and Wanfang databases were searched for relevant studies from the inception of each database until November 2022. A thorough literature screening, quality evaluation, and data extraction was conducted. Meta-analysis was performed using RevMan5.3Meta. Twelve articles were selected as most relevant to this review; 10 were in Chinese, and 2 were in English. Results: The results showed that the incidence of asthenia in COPD patients was 26% (OR 0.26, 95% CI 0.17~0.34). Discussion: The main risk factors for frailty in COPD patients were age (OR 1.32, 95% CI 1.30~1.34), GOLD pulmonary function class (OR 3.18, 95% CI 2.14~4.71), mMRC score (OR 3.90, 95% CI 1.53~9.92), comorbidity (OR 2.17, 95% CI 1.48~3.18), polypharmacy (OR 6.74, 95% CI 3.23~14.08), malnutrition (OR 3.32, 95% CI 1.77~6.24), depression (OR 1.37, 95% CI 1.07~1.76) and ≥2 admissions within 1 year (OR 4.84, 95% CI 2.45~9.57). Conclusion: The study presented comprehensive evidence through meta-analysis and proposed that the prevalence of frailty in COPD patients is 26%. Risk factors were identified, including age, pulmonary function class according to GOLD criteria, mMRC score, comorbidity polypharmacy malnutrition, depression, or 2 or more hospital admissions within a year. It is recommended that clinical medical staff identify these risk factors at an early stage.

Degradation-Based Protein Profiling: A Case Study of Celastrol.

Natural products, while valuable for drug discovery, encounter limitations like uncertainty in targets and toxicity. As an important active ingredient in traditional Chinese medicine, celastrol exhibits a wide range of biological activities, yet its mechanism remains unclear. In this study, they introduced an innovative "Degradation-based protein profiling (DBPP)" strategy, which combined PROteolysis TArgeting Chimeras (PROTAC) technology with quantitative proteomics and Immunoprecipitation-Mass Spectrometry (IP-MS) techniques, to identify multiple targets of natural products using a toolbox of degraders. Taking celastrol as an example, they successfully identified its known targets, including inhibitor of nuclear factor kappa B kinase subunit beta (IKKß), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3Kα), and cellular inhibitor of PP2A (CIP2A), as well as potential new targets such as checkpoint kinase 1 (CHK1), O-GlcNAcase (OGA), and DNA excision repair protein ERCC-6-like (ERCC6L). Furthermore, the first glycosidase degrader is developed in this work. Finally, by employing a mixed PROTAC toolbox in quantitative proteomics, they also achieved multi-target identification of celastrol, significantly reducing costs while improving efficiency. Taken together, they believe that the DBPP strategy can complement existing target identification strategies, thereby facilitating the rapid advancement of the pharmaceutical field.

Discovery of 4-Aminoquinoline-3-carboxamide Derivatives as Potent Reversible Bruton's Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis.

A structure-hopping strategy was applied to discover a series of novel 4-aminoquinoline-3-carboxamide derivatives as potent, reversible BTK inhibitors. Compared to the previously described cinnoline scaffold compounds, the 4-aminoquinoline analogues showed significantly improved drug-like properties, especially in their aqueous solubility. The most potent compound, 25, displayed a stronger inhibitory effect on both BTKWT (IC50 = 5.3 nM) and BTKC481S (IC50 = 39 nM). In a rodent collagen-induced arthritis model, compound 25 efficiently reduced paw swelling without a loss in body weight. On the basis of potency, drug-like properties, stability, and noncovalent mode of inhibition, our representative inhibitors could have a promising profile to be treatments for a wide range of autoimmune diseases.

Inhibition of Yeast-to-Hypha Transition and Virulence of Candida albicans by 2-Alkylaminoquinoline Derivatives.

A rapid increase in Candida albicans infection and drug resistance has caused an emergent need for new clinical strategies against this fungal pathogen. In this study, we evaluated the inhibitory activity of a series of 2-alkylaminoquinoline derivatives against C. albicans isolates. A total of 28 compounds were assessed for their efficacy in inhibiting the yeast-to-hypha transition, which is considered one of the key virulence factors in C. albicans Several compounds showed strong activity to decrease the morphological transition and virulence of C. albicans cells. The two leading compounds, compound 1 (2-[piperidin-1-yl]quinolone) and compound 12 (6-methyl-2-[piperidin-1-yl]quinoline), remarkably attenuated C. albicans hyphal formation and cytotoxicity in a dose-dependent manner, but they showed no toxicity to either C. albicans cells or human cells. Intriguingly, compound 12 showed an excellent ability to inhibit C. albicans infection in the mouse oral mucosal infection model. This leading compound also interfered with the expression levels of hypha-specific genes in the cyclic AMP-protein kinase A and mitogen-activated protein kinase signaling pathways. Our findings suggest that 2-alkylaminoquinoline derivatives could potentially be developed as novel therapeutic agents against C. albicans infection due to their interference with the yeast-to-hypha transition.

The effect of Mg2+ on digestion performance and microbial community structures in sludge digestion systems.

The important criteria in anaerobic digestion is the rate-limiting step which decides the fate of value-added products especially from waste-activated sludge (WAS). Hence, the present study investigated the effect of magnesium (Mg2+) addition on anaerobic digestion of WAS. The lab-scale experiments were conducted at 25 °C with Mg2+ doses ranging from 0.01 to 0.2 mol/L. Maximum total volatile fatty acids (VFAs) production (372.78 mg COD/L) occurred at a Mg2+ dose of 0.2 mol/L, which was about eight times higher than the control tests. Further, Mg2+ addition facilitated sludge dewaterability and phosphorus removal. The mechanism of improved VFAs generation was analyzed from the view of both chemical and biological effects. Chemical effect significantly enhanced the release of calcium and iron in WAS, resulting in the disintegration of WAS, which benefited hydrolysis and acidification processes. Illumina MiSeq sequencing analysis revealed that enrichment of functional bacteria and the increase of bacterial diversity were obtained in the 0.2 mol Mg2+/L experiment, while the influence was negative on the reactor with 0.025 mol/L Mg2+. Meanwhile, methanogens were accordantly inhibited in the experiments with Mg2+ addition.

The key role of biogenic manganese oxides in enhanced removal of highly recalcitrant 1,2,4-triazole from bio-treated chemical industrial wastewater.

The secondary effluent from biological treatment process in chemical industrial plant often contains refractory organic matter, which deserves to be further treated in order to meet the increasingly stringent environmental regulations. In this study, the key role of biogenic manganese oxides (BioMnOx) in enhanced removal of highly recalcitrant 1,2,4-triazole from bio-treated chemical industrial wastewater was investigated. BioMnOx production by acclimated manganese-oxidizing bacterium (MOB) consortium was confirmed through scanning electronic microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) analysis. Pseudomonas and Bacillus were found to be the most predominant species in acclimated MOB consortium. Mn2+ could be oxidized optimally at neutral pH and initial Mn2+ concentration below 33 mg L-1. However, 1,2,4-triazole removal by BioMnOx produced occurred optimally at slightly acidic pH. High dosage of both Mn2+ and 1,2,4-triazole resulted in decreased 1,2,4-triazole removal. In a biological aerated filter (BAF) coupled with manganese oxidation, 1,2,4-triazole and total organic carbon removal could be significantly enhanced compared to the control system without the participation of manganese oxidation, confirming the key role of BioMnOx in the removal of highly recalcitrant 1,2,4-triazole. This study demonstrated that the biosystem coupled with manganese oxidation had a potential for the removal of various recalcitrant contaminants from bio-treated chemical industrial wastewater.

Enhancing anaerobic digestion of waste activated sludge by the combined use of NaOH and Mg(OH)2: Performance evaluation and mechanism study.

In this study, the combination treatment of NaOH and Mg(OH)2 was applied to anaerobic digestion of waste activated sludge (WAS) for simultaneously enhancement of volatile fatty acids (VFAs) production, nutrients removal and sludge dewaterability. The maximum VFAs production (461mg COD/g VSS) was obtained at the NaOH/Mg(OH)2 ratio of 75:25, which was much higher than that of the blank or sole NaOH. Moreover, nutrients removal and sludge dewaterability were improved by the combined using of NaOH and Mg(OH)2. Mechanism investigations revealed that the presence of Mg(OH)2 could maintain alkaline environment, which contributed to inhibit the activity of methanogens. Also, the bridging between Mg(2+) and extracellular polymeric substances (EPS) plays an important role in the solubilization and dewatering of sludge. High-throughput sequencing analysis demonstrated that the abundance of bacteria involved in sludge hydrolysis and VFAs accumulation was greatly enriched with the mixtures of NaOH and Mg(OH)2.

Utilization of phosphorus loaded alkaline residue to immobilize lead in a shooting range soil.

The alkaline residue generated from the production of soda ash using the ammonia-soda method has been successfully used in removing phosphorus (P) from aqueous solution. But the accumulation of P-containing solid after P removal is an undesirable menace to the environment. To achieve the goal of recycling, this study explored the feasibility of reusing the P loaded alkaline residue as an amendment for immobilization of lead (Pb) in a shooting range soil. The main crystalline phase and micromorphology of amendments were determined using X-ray diffraction (XRD) and scanning electron microscopy-electron dispersion spectroscopy (SEM-EDS) methods. The toxicity characteristic leaching procedure (TCLP), sequential extraction procedure, and physiologically based extraction test (PBET) were employed to evaluate the effectiveness of Pb immobilization in soil after 45 d incubation. Treatment with P loaded alkaline residue was significantly effective in reducing the TCLP and PBET extractable Pb concentrations in contrast to the untreated soil. Moreover, a positive change in the distribution of Pb fractions was observed in the treated soil, i.e., more than 60% of soil-Pb was transformed to the residual fraction compared to the original soil. On the other hand, P loaded amendments also resulted in a drastic reduction in phytoavailable Pb to the winter wheat and a mild release of P as a nutrient in treated soil, which also confirmed the improvement of soil quality.

Biodegradation of 2,4,6-trinitrophenol by Rhodococcus sp. isolated from a picric acid-contaminated soil.

A picric acid-degrading bacterium, strain NJUST16, was isolated from a soil contaminated by picric acid and identified as a member of Rhodococcus sp. based on 16S rRNA sequence. The degradation assays suggested that the strain NJUST16 could utilize picric acid as the sole source of carbon, nitrogen and energy. The isolate grew optimally at 30 degrees C and initial pH 7.0-7.5 in the mineral salts medium supplemented with picric acid. It was basically consistent with degradation of picric acid by the isolate. Addition of nitrogen sources such as yeast extract and peptone accelerated the degradation of picric acid. However, the stimulation was concentration dependent. The degradation was accompanied by release of stoichiometric amount of nitrite and acidification. The degradation of picric acid at relatively high concentrations (>3.93 mM) demonstrated that the degradation was both pH and nitrite dependent. Neutral and slightly basic pH was crucial to achieve high concentrations of picric acid degradation by the NJUST16 strain.

[Effects of nanoscale oxide particles on structure and property of PVDF hollow fiber membrane].

The preparation of nanoscale oxide/polyvinylidene fluoride (PVDF) composite hollow fiber membrane by phase transition process was introduced. The effects of nanoscale titania and alumina particles on structure and property of composite hollow fiber membrane were investigated. The separation property, microstructure and crystalline phase of composite membranes were characterized by bovine serum albumin (BSA) rejection experiment, scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FT-IR), respectively. The results show that the properties of composite membrane are improved greatly compared to the pure PVDF membranes. The BSA rejection ratios of pure PVDF, Al2O3/PVDF and TiO2/PVDF membranes were 3.27%, 67.20% and 86.67%, respectively. The pure water fluxes of Al2O3/PVDF and TiO2/PVDF membranes were 2.3 and 2.6 times higher than that of pure PVDF membranes. Moreover, the pore size and its distribution of composite membrane characterized by nitrogen isothermal absorption measurement are smaller and narrower than pure PVDF membranes.