Explore the vast range of titles available.

Old yellow enzymes (OYEs) have been proven as powerful biocatalysts for the asymmetric reduction of activated alkenes. Fungi appear to be valuable sources of OYEs, but most of the fungal OYEs are unexplored. To expand the OYEs toolbox, a new thermophilic-like OYE ( Af OYE1) was identified from Aspergillus flavus strain NRRL3357. The thermal stability analysis showed that the T 1/2 of Af OYE1 was 60 °C, and it had the optimal temperature at 45 °C. Moreover, Af OYE1 exhibited high reduction activity in a wide pH range (pH 5.5–8.0). Af OYE1 could accept cyclic enones, acrylamide, nitroalkenes, and α, β-unsaturated aldehydes as substrates and had excellent enantioselectivity toward prochiral alkenes (> 99% ee). Interestingly, an unexpected ( S )-stereoselectivity bioreduction toward 2-methylcyclohexenone was observed. The further crystal structure of Af OYE1 revealed that the “cap” region from Ala132 to Thr182, the loop of Ser316 to Gly325, α short helix of Arg371 to Gln375, and the C-terminal “finger” structure endow the catalytic cavity of Af OYE1 quite deep and narrow, and flavin mononucleotide (FMN) heavily buried at the bottom of the active site tunnel. Furthermore, the catalytic mechanism of Af OYE1 was also investigated, and the results confirmed that the residues His211, His214, and Tyr216 compose its catalytic triad. This newly identified thermophilic-like OYE would thus be valuable for asymmetric alkene hydrogenation in industrial processes. Key points A new thermophilic-like OYE AfOYE1 was identified from Aspergillus flavus, and the T 1/2 of AfOYE1 was 60 °C AfOYE1 catalyzed the reduction of 2-methylcyclohexenone with (S)-stereoselectivity The crystal structure of AfOYE1 was revealedv

Styrene monooxygenases (SMOs) are powerful enzymes for the synthesis of enantiopure epoxides, but these SMOs have narrow substrate spectra, and the residues in controlling enantioselectivity of SMOs remains unclear. A monooxygenase from Herbaspirillum huttiense ( Hh MO) was found to have excellent enantioselectivities and diastereoselectivities in the epoxidation of unconjugated terminal alkenes. Here we found that Hh MO could also transfer styrene into styrene epoxide with 75% ee, and it could also catalyze the epoxidation of styrene derivatives into the corresponding epoxides with enantioselectivities up to 99% ee. Meanwhile, site 199 in the substrate access channel of Hh MO was found to play an important role in the controlling enantioselectivity of the epoxidation. The E199L variant catalyzed the epoxidation of styrene with > 99% ee. The identification of critical residue that affects the enantioselectivity of SMOs would thus be valuable for creating efficient monooxygenases for the preparation of essential enantiopure epoxides. Key points • Bioexpoxidation of both conjugated and unconjugated alkenes by HhMO with excellent enantioselectivities. • Gating residue 199 played an essential role in controlling the enantioselectivity of SMO. • HhMO E199L catalyzed the epoxidation of styrenes with up to > 99% ee.

Developing strategies that emulate the killing mechanism of neutrophils, which involves the enzymatic cascade of superoxide dismutase (SOD) and myeloperoxidase (MPO), shows potential as a viable approach for cancer therapy. Nonetheless, utilizing natural enzymes as therapeutics is hindered by various challenges. While nanozymes have emerged for cancer treatment, developing SOD-MPO cascade in one nanozyme remains a challenge. Here, we develop nanozymes possessing both SOD- and MPO-like activities through alloying Au and Pd, which exhibits the highest cascade activity when the ratio of Au and Pd is 1:3, attributing to the high d-band center and adsorption energy for superoxide anions, as determined through theoretical calculations. The Au 1 Pd 3 alloy nanozymes exhibit excellent tumor therapeutic performance and safety in female tumor-bearing mice, with safety attributed to their tumor-specific killing ability and renal clearance ability caused by ultrasmall size. Together, this work develops ultrasmall AuPd alloy nanozymes that mimic neutrophil enzymatic cascades for catalytic treatment of tumors. Emulating the killing function of neutrophils, which involves the enzymatic cascade of superoxide dismutase (SOD) and myeloperoxidase (MPO), is promising for cancer therapy, but developing SOD-MPO cascade in one nanozyme is challenging. Here the authors report ultrasmall AuPd alloy nanozymes that mimic neutrophil enzymatic cascades for catalytic treatment of tumors.

Heart failure (HF) imposes a substantial burden on patients and healthcare systems. Hospital-to-home transitional care, involving time-limited interventions delivered predominantly by nurses, was introduced to lighten this burden. This study aimed to examine the effectiveness and dose-response of nurse-led transitional care interventions (TCIs) on healthcare utilization among patients with HF. Health-related databases were systematically searched for articles published from January 2000 to June 2020. We included randomized controlled trials (RCTs) that compared nurse-led TCIs with usual care for adults hospitalized with HF and reported the following healthcare utilization outcomes: all-cause readmissions, HF-specific readmissions, emergency department visits, or length of hospital stay. Random-effects meta-analysis, meta-regression analysis, and dose-response analysis were performed to estimate the treatment effects and explain the heterogeneity. Twenty-five RCTs including 8422 patients with HF were included. Nurse-led TCIs for patients with HF resulted in a mean 9% (RR = 0.91; 95% CI = 0.82 to 0.99; p = 0.04; I2 = 46%) and 29% (RR = 0.71; 95% CI = 0.60 to 0.84; p < 0.0001; I2 = 0%) reduction in all-cause and HF-specific readmission risks respectively compared to usual care. The interventions were also effective in shortening the length of hospital stay (MD = -2.37; 95% CI = -3.16 to -1.58; p < 0.0001; I2 = 14%). However, no significant reduction was found for emergency department visits (RR = 0.96; 95% CI = 0.84 to 1.10; p = 0.58; I2 = 0%). The effect of meta-regression coefficients on all-cause and HF-specific readmissions was not statistically significant for any prespecified trial-level characteristic. Dose-response analysis revealed that the HF-specific readmission risk decreased in a dose-dependent manner with the complexity and intensity of nurse-led TCIs. Nurse-led TCIs were effective in decreasing all-cause and HF-specific readmission risks, as well as in reducing the length of hospital stay; however, the interventions were not effective in reducing the frequency of emergency department visits.

Standardized guidelines for optimal tunnel length in tunneled peripherally inserted central catheters (PICCs) are lacking. The objective of this study was to evaluate the real-world impact of tunnel length on clinical outcomes. This retrospective cohort study included 207 cancer patients who received tunneled PICCs, categorized into a control group (tunnel length > 4 cm, n = 134) and an observation group (tunnel length ≤ 4 cm, n = 73). Propensity score matching (PSM) was used to address baseline heterogeneity. Cox regression analyses were used to assess the risk of complication during a 120-day follow-up. Compared to the control group (tunnel length > 4 cm), the observation group (tunnel length ≤ 4 cm) had a significantly higher adjusted overall complication risk (HR = 2.92, 95% CI: 1.07-7.94, P = 0.036) and unplanned catheter removal rate (4.4% vs. 0.0%, P = 0.027), confirming the safety of longer tunnels despite comparable comfort levels between groups. After PSM, Cox regression analysis showed results consistent with those from the unmatched cohort. Subgroup analyses revealed a reduced risk of complications with longer tunnels in patients with BMI ≤ 25 kg/m² (HR = 0.29, 95% CI: 0.11-0.82), without hypertension (HR = 0.36, 95% CI: 0.13-1.00), without diabetes (HR = 0.38, 95% CI: 0.15-0.97), and with solid tumors (HR = 0.31, 95% CI: 0.11-0.85). The results show that tunnel lengths > 4 cm reduce overall complications and prolong catheter retention, supporting the implementation of standardized protocols while advocating for personalized adjustments based on BMI, comorbidities, and cancer type.

The prevention and treatment of gastrointestinal mucosal injury caused by a plateau hypoxic environment is a clinical conundrum due to the unclear mechanism of this syndrome; however, oxidative stress and microbiota dysbiosis may be involved. The Robinia pseudoacacia L. flower, homologous to a functional food, exhibits various pharmacological effects, such as antioxidant, antibacterial, and hemostatic activities. An increasing number of studies have revealed that plant exosome-like nanoparticles (PELNs) can improve the intestinal microbiota and exert antioxidant effects. In this study, the oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles (RFELNs) significantly ameliorated hypoxia-induced gastric and small intestinal mucosal injury in mice by downregulating hypoxia-inducible factor-1α (HIF-1α) and HIF-2α expression and inhibiting hypoxia-mediated ferroptosis. In addition, oral RFELNs partially improved hypoxia-induced microbial and metabolic disorders of the stomach and small intestine. Notably, RFELNs displayed specific targeting to the gastrointestinal tract. In vitro experiments using gastric and small intestinal epithelial cell lines showed that cell death caused by elevated HIF-1α and HIF-2α under 1% O 2 mainly occurred via ferroptosis. RFELNs obviously inhibited HIF-1α and HIF-2α expression and downregulated the expression of NOX4 and ALOX5, which drive reactive oxygen species production and lipid peroxidation, respectively, suppressing ferroptosis under hypoxia. In conclusion, our findings underscore the potential of oral RFELNs as novel, naturally derived agents targeting the gastrointestinal tract, providing a promising therapeutic approach for hypoxia-induced gastric and small intestinal mucosal ferroptosis. Graphical Abstract

Polysaccharides are important bioactive components of dried tangerine peel, exhibiting antioxidant, anti-inflammatory, and hypoglycemic activities. However, the ability of dried tangerine peel polysaccharides to alleviate gastric injury remains insufficiently understood. Therefore, the structure and alleviation of gastric injury induced by dried tangerine peel polysaccharides were explored in this study. Firstly, DTPP-4 was purified from dried tangerine peel. As shown in the HPLC chromatogram, DTPP-4 is a homogeneous polysaccharide with a mean molecular weight of 1.35 × 103 kDa. DTPP-4 was mainly composed of L-Rha, L-Ara, D-Gal, and D-GalpA with percentages of 10.56%, 9.15%, 4.83%, and 75.45%, respectively. Methylation and NMR results suggested that DTPP-4 was a pectic polysaccharide with →4)-α-D-GalpA-6-OMe-(1→ and →4)-α-D-GalpA-(1→ as the backbone. The alleviation of gastric injury of dried tangerine peel polysaccharide was evaluated in ethanol-induced acute gastric injury mice. Based on the macroscopic images of gastric tissues and the area of gastric tissue injury in mice, the dried tangerine peel polysaccharide can reduce the mouse gastric lesion area and alleviate gastric tissue pathological damage. Histopathological analysis of H&E and PAS staining revealed that the dried tangerine peel polysaccharide could ameliorate the disordered arrangement and necrosis of epithelial cells, reduce inflammatory cell infiltration, and thus alleviate gastric injury. Dried tangerine peel polysaccharide confers gastroprotection by modulating MPO and PGE2 levels, reducing MDA accumulation, enhancing SOD and CAT antioxidant activities, suppressing IL-1β and TNF-α secretion, and upregulating IL-10 expression. These findings provide a theoretical foundation for subsequent structure–activity relationship investigations and provide empirical support for the subsequent development and practical application of this polysaccharide.

Previously, research adopted an ultrasound-assisted extraction method to isolate crude polysaccharide from blackened jujube, followed by preliminary structural identification of the purified polysaccharide (BJP). This manuscript analyzed the accurate structure and immunomodulatory activity of BJP. Further structural identification indicated that BJP was mainly composed of →3)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →3)-β-D-GalpA-(1→, →2,4)-β-D-Galp-(1→, →4)-β-D-GalpA-(1→, →3)-α-L-Rhap-(1→ and →3,4)-α-L-Rhap-(1→. The immunomodulatory effects of BJP were examined using a mouse model with immunosuppression induced by cyclophosphamide. The findings suggested that BJP could relieve the condition of immunosuppressed mice. BJP could inhibit decreases in the body weight and organ index of mice, and HE staining showed that BJP could alleviate the harm to spleen and thymus tissues. BJP enhanced the secretion of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), immunoglobulin A (IgA), and immunoglobulin G (IgG) in serum. It also reduced liver oxidative stress by increasing superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities, while lowering malondialdehyde (MDA) levels. Moreover, BJP contributed to the maintenance of gut homeostasis by stimulating the generation of short-chain fatty acids in the cecal contents. The study aims to establish a solid basis for the comprehensive development of blackened jujube and furnish a theoretical framework for its polysaccharides’ role in immune modulation.

Background Intestinal ischemia–reperfusion (I/R) injury is a severe vascular emergency. Previous research indicated the protective effects of Emodin on I/R injury. Our study aims to explore the effect of Emodin on intestinal I/R (II/R) injury and elucidate the underlying mechanisms. Methods C57BL/6 mice and Caco-2 cells were used for in vivo and in vitro studies. We established an animal model of II/R injury by temporarily occluding superior mesenteric artery. We constructed an oxygen–glucose deprivation/reoxygenation (OGD/R) cell model using a hypoxia-reoxygenation incubator. Different doses of Emodin were explored to determine the optimal therapeutic dose. Additionally, inhibitors targeting the protein kinase B (Akt) or Heme oxygenase-1 (HO-1) were administered to investigate their potential protective mechanisms. Results Our results demonstrated that in animal experiments, Emodin mitigated barrier disruption, minimized inflammation, reduced oxidative stress, and inhibited apoptosis. When Akt or HO-1 was inhibited, the protective effect of Emodin was eliminated. Inhibiting Akt also reduced the level of HO-1. In cell experiments, Emodin reduced inflammation and apoptosis in the OGD/R cell model. Additionally, when Akt or HO-1 was inhibited, the protective effect of Emodin was weakened. Conclusions Our findings suggest that Emodin may protect the intestine against II/R injury through the Akt/HO-1 signaling pathway.

Objective The goal of epilepsy treatment is not only to control convulsive seizures but also to improve the quality of life of patients. This study aimed to investigate personality changes and the risk factors for their development in adult epilepsy patients. Methods A case-control study in a Class III, Class A hospital. The study comprised 206 adult epilepsy patients admitted to the Neurology Department at the First Hospital of Jilin University between October 2019 and December 2021, while the control group consisted of 154 community volunteers matched with the epilepsy group based on age, sex, and education. No additional treatment interventions were determined to be relevant in the context of this study. Results There is a significantly higher incidence of personality changes in epilepsy than in the general population, and patients with epilepsy were more likely to become psychoticism, neuroticism, and lie. Epilepsy patient’s employment rate and average quality of life score were significantly lower than that of the general population and had strong family intimacy but poor adaptability in this study. There are many factors affecting personality change: sleep disorders, economic status, quality of life, use of anti-seizure drugs, family cohesion and adaptability. The independent risk factors were quality of life and family cohesion. Significance The study is the first to assess the impact of financial status, family cohesion and adaptability on personality changes in people with epilepsy. It provides a new idea and relevant basis for the prevention and treatment of epilepsy comorbidity. Key bullet points There is a significantly higher incidence of personality changes in epilepsy than the general population. Epilepsy patients were more likely to develop psychosis, exhibit neuroticism, and seek social acceptance by concealing. Epilepsy patient’s employment rate and average quality of life score were significantly lower than that of the general population. Epilepsy patients enrolled in this study had strong family intimacy but poor adaptability. Quality of life and family cohesion were two independent risk factors in epilepsy patients which also were the key to improving personality disorders.