Inhibition of CTR1 expression improves hypoxia/reoxygenation-induced myoblast injury by blocking cuproptosis.

Skeletal muscle ischemia-reperfusion injury (IRI) is a common severe disease with a complex pathological process. This study found that copper chloride (CuCl2) inhibited cell viability in a concentration dependent manner, increased intracellular copper levels and downregulated copper transporter 1 (CTR1) expression. CTR1 upregulation promoted copper uptake by myoblasts and then enhanced cuproptosis, leading to a significant increase in the levels of dihydrolipoamide S-acetyltransferase (DLAT) oligomers, while a significant decrease in the levels of lipoylated (Lip)-dihydrolipoamide S-succinyltransferase (DLST) and Lip-DLAT, ultimately inhibiting cell viability and inducing cell injury. Inducing cuproptosis with elesclomol plus CuCl2 (ES + Cu) further confirmed that "ES + Cu" treatment significantly reduced the contents of adenosine triphosphate (ATP) and glutathione (GSH), decreased the activities of mitochondrial complex I and III, and increased the contents of lactate (LA), malondialdehyde (MDA), creatine kinase (CK) and lactate dehydrogenase (LDH); when tetrathiomolybdate (TTM) was added to inhibit cuproptosis, myoblast injury was recovered significantly. Meanwhile, hypoxia/reoxygenation (H/R) induced CTR1 expression, increased the levels of intracellular copper, DLAT oligomers, LA, MDA, CK and LDH, reduced the levels of Lip-DLST, Lip-DLAT, ATP and GSH, and weakened the activities of mitochondrial complex I and III; after knocking down CTR1 expression, the levels of intracellular copper and the activation of cuproptosis pathway were decreased, and cell viability, injury and inflammation levels were significantly improved. Therefore, cuproptosis can promote myoblast injury, while H/R enhances copper uptake by inducing CTR1 expression, thereby enhancing cuproptosis and inducing cell injury, indicating that cuproptosis is a new mechanism of H/R-induced myoblast injury.

A bulge uridine in the HIF2a IRE allows IRP1 but not IRP2 to selectively regulate HIF2a expression and ensuing EPO levels.

Iron regulatory proteins (IRP1 and IRP2) play a pivotal role in maintaining cellular iron homeostasis by binding to iron-responsive elements (IREs) of target mRNAs and regulating the expression of these iron-related genes. Mice and humans that lack functional IRP1 develop erythrocytosis due to erythropoietin overproduction, whereas those that lack IRP2 develop microcytic anemia believed to result from iron deficiency of erythroblasts. Here, we discovered that IRP2 deficiency reduced the expression of hypoxia inducible factor 2 alpha (HIF2a) and its transcriptional target, erythropoietin (EPO), thereby compromising the stress erythropoiesis response to generate RBCs upon anemia. The distinct consequences of IRP2 and IRP1 on EPO result from the higher binding affinity of the HIF2a IRE for IRP1 compared to IRP2. This difference in binding affinity arises from a bulge uridine in the upper stem of HIF2a IRE that impairs the ability of IRP2 to bind the IRE. These results reveal that IRP1 and IRP2 play distinct roles in erythropoiesis and unveil an unsuspected IRE binding preference that contributes to the divergent phenotypes observed in IRP1 and IRP2 deficient mammals.

Frontier role of extracellular vesicles in kidney disease.

Kidney diseases represent a diverse range of conditions that compromise renal function and structure which characterized by a progressive deterioration of kidney function, may ultimately necessitate dialysis or kidney transplantation as end-stage treatment options. This review explores the complex landscape of kidney diseases, highlighting the limitations of existing treatments and the pressing need for innovative strategies. The paper delves into the role of extracellular vesicles (EVs) as emerging biomarkers and therapeutic agents in the context of kidney pathophysiology. Urinary extracellular vesicles (uEVs), in particular, offer a non-invasive means of assessing renal injury and monitoring disease progression. Additionally, mesenchymal stem cell-derived EVs (MSC-EVs) are examined for their immunomodulatory and tissue repair capabilities, presenting a promising avenue for novel therapeutic interventions. And discusses the potential of engineering EVs to enhance their targeting and therapeutic efficacy. This paper systematically integrates the latest research findings and aims to provide a comprehensive overview of the role of EVs in kidney disease, providing cutting-edge insights into their potential as a diagnostic and therapeutic tool.

Global marine microbial diversity and its potential in bioprospecting.

The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems1,2. However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications3,4. Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR-Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR-Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine.

RS-Dseg: semantic segmentation of high-resolution remote sensing images based on a diffusion model component with unsupervised pretraining.

Semantic segmentation plays a crucial role in interpreting remote sensing images, especially in high-resolution scenarios where finer object details, complex spatial information and texture structures exist. To address the challenge of better extracting semantic information and ad-dressing class imbalance in multiclass segmentation, we propose utilizing diffusion models for remote sensing image semantic segmentation, along with a lightweight classification module based on a spatial-channel attention mechanism. Our approach incorporates unsupervised pretrained components with a classification module to accelerate model convergence. The diffusion model component, built on the UNet architecture, effectively captures multiscale features with rich contextual and edge information from images. The lightweight classification module, which leverages spatial-channel attention, focuses more efficiently on spatial-channel regions with significant feature information. We evaluated our approach using three publicly available datasets: Postdam, GID, and Five Billion Pixels. In the test of three datasets, our method achieved the best results. On the GID dataset, the overall accuracy was 96.99%, the mean IoU was 92.17%, and the mean F1 score was 95.83%. In the training phase, our model achieved good performance after only 30 training cycles. Compared with other models, our method reduces the number of parameters, improves the training speed, and has obvious performance advantages.

A diagnostic model for differentiating tuberculous spondylodiscitis from pyogenic spondylodiscitis based on pathogen-confirmed patients.

OBJECTIVE: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed. METHODS: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed. RESULTS: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability. CONCLUSIONS: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS.

Isolated Calf Muscle Venous Thrombosis: A Review of Anticoagulation Strategies.

Deep vein thrombosis (DVT) of the lower extremities is divided into 2 categories according to the extent of thrombosis involvement. Thrombosis involving the popliteal vein, femoral vein, and iliac vein is classified as proximal DVT, while thrombosis involving the anterior tibial vein, posterior tibial vein, peroneal vein, and calf muscles vein is regarded as distal DVT. There are updated guidelines for the anticoagulant treatment for proximal DVT, but the best anticoagulant treatment for distal DVT is still controversial, especially for isolated calf muscular vein thrombosis (CMVT). The risk of isolated CMVT extending to the proximal deep veins and developing into pulmonary embolism is lower than with distal DVT. Some scholars believe that isolated CMVT has the risk of evolving into proximal deep vein thrombosis and pulmonary embolism, and active early anticoagulation therapy can reduce the risk and benefit patients. In addition, based on the characteristics of CMVT and the bleeding risk of anticoagulation therapy, some studies have recommended use of non-anticoagulation methods such as compression therapy. There is still a lack of multicenter, big-data, randomized, controlled trials on the benefits or risks of anticoagulation therapy. Among scholars who support anticoagulation therapy, there is still a lack of consensus on the optimal duration. This article reviews the current evidence on anticoagulant therapy for patients with isolated CMVT and how long the anticoagulation course should be if anticoagulation is required. Our research will provide a theoretical basis for subsequent research. More prospective studies with larger sample sizes are needed to provide more clinical evidence.

Dry eye disease in systemic lupus erythematosus: a cross sectional study.

AIM: To explore ocular surface manifestations of dry eye disease (DED) and its influencing factors in systemic lupus erythematosus (SLE) patients. METHODS: Ophthalmological examinations were conducted in SLE patients (n=43) and controls (n=41), including Ocular Surface Disease Index (OSDI), objective scatter index (OSI), tear meniscus height (TMH), lipid layer thickness (LLT), non-invasive Keratograph tear breakup time (NIKBUT), corneal fluorescein score (CFS), Schirmer I test. DED was diagnosed according to the Tear Film and Ocular Surface Society Dry Eye Workshop II Criteria. SLE patients were further divided into DED group and non-DED group, the disease activity, clinical manifestations and laboratory investigations were compared between the two groups. The disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Receiver operative characteristic (ROC) curve and multiple-factor binary logistic regression were performed. RESULTS: SLE patients showed higher OSDI [9.1 (2.8-15.9) vs 6.3 (2.2-7.5), P=0.035], higher OSI [1.67 (1.09-2.60) vs 0.96 (0.87-1.60), P=0.001], higher CFS [1 (0-2) vs 0 (0-1), P=0.001], lower LLT [65 (42-100) vs 100 (79.5-100), P=0.010], and lower NIKBUT [8.03 (4.02-9.73) vs 9.67 (5.26-12.71), P=0.030] than controls. The 32.6% of SLE patients had DED, which was higher than 12.2% of healthy controls. DED group showed higher SLEDAI-2K score [9.7±6.1 vs 5.4±3.4, P=0.025], higher anti-cardiolipin antibody (ACL) [8.7 (3.5-13.2) vs 3.6 (2.0-6.9), P=0.035], and higher proportion of patients with cutaneous eruption [42.9% vs 6.9%, P=0.015] than non-DED group. According to multiple-factor binary logistic regression analysis, the SLEDAI-2K score (OR=1.194, P=0.041) and cutaneous eruption (OR=7.094, P=0.045) could be consider as risk factors for DED in SLE patients. The ROC curve of the combined factors including age, disease duration, SLEDAI-2K score, ACL, and cutaneous eruption was analyzed, with a sensitivity of 0.786, a specificity of 0.793, and an area under curve of 0.820. CONCLUSION: Ocular surface affection is frequent in SLE patients, and patients with high disease activity and cutaneous eruption show increased risk of DED.

Improved marine predators algorithm for engineering design optimization problems.

The Marine Predator Algorithm (MPA) has unique advantages as an important branch of population-based algorithms. However, it emerges more disadvantages gradually, such as traps to local optima, insufficient diversity, and premature convergence, when dealing with complex problems in practical industrial engineering design applications. In response to these limitations, this paper proposes a novel Improved Marine Predator Algorithm (IMPA). By introducing an adaptive weight adjustment strategy and a dynamic social learning mechanism, this study significantly improves the encounter frequency and efficiency between predators and preys in marine ecosystems. The performance of the IMPA was evaluated through benchmark functions, CEC2021 suite problems, and engineering design problems, including welded beam design, tension/compression spring design, pressure vessel design, and three-bar design. The results indicate that the IMPA has achieved significant success in the optimization process over other methods, exhibiting excellent performance in both solving optimal parameter solutions and optimizing objective function values. The IMPA performs well in terms of accuracy and robustness, which also proves its efficiency in successfully solving complex industrial engineering design problems.

Evaluation of the impact of weak end feedback on the SBS threshold in high-power narrow-linewidth fiber amplifiers.

In this work, we quantitatively investigate the SBS threshold in high-power narrow-linewidth fiber amplifiers seeded with phase-modulated single-frequency lasers in presence of weak end feedback. The impacts of the end feedback and spectral linewidths on the SBS threshold are demonstrated in detail through comparative experiments and numerical simulations, respectively. In the experiment, we have pointed out a practical method to estimate the end reflectivity in high-power fiber amplifiers. Based on this estimation, the SBS threshold characters of the high-power narrow-linewidth fiber amplifiers with different end reflectivity and seed linewidths are investigated. By reducing the end reflectivity, a 2.85 times SBS threshold enhancement has been achieved at the most susceptible linewidth (16.8 GHz). Furthermore, we propose a spectral evolution model to investigate the SBS threshold in high-power narrow-linewidth fiber amplifiers, which is even capable for calculating SBS thresholds of the systems with tens of GHz linewidth while weak end reflection is considered. The simulation results demonstrate that end reflection will obviously affect the SBS threshold when the linewidth of the seed laser is broadened beyond 5 GHz, especially for the spectral linewidth of seed lasers nearing the Brillouin frequency shift. Besides, when the end reflectivity is set to be stronger than -65 dB, the SBS threshold performs a tendency to decline and then rise with the growth of seed linewidth. The experiment and simulation results provide a new optimization sight for the SBS effect suppression in high-power narrow-linewidth fiber amplifiers.

A new multifunctional phenanthroline-derived probe for colorimetric sensing of Fe2+ and fluorometric sensing of Zn2.

A new phenanthroline derivative bearing imidazole group, (2-(3,5-di(pyridin-4-yl)phenyl)-1-p-tolyl-1H-imidazo[4,5-f][1,10]phenanthroline) (1), has been devised. 1 can be used as a multifunctional probe exhibiting a highly sensitive colorimetric response to Fe2+ and a selectively ratiometric fluorescent response to Zn2+ in a buffer-ethanol solution. The absorption enhancement accompanied by a visual color change from colorless to red upon addition of Fe2+, makes 1 a suitable naked-eye sensor for Fe2+. Moreover, 1 displayed a Zn2+-induced red-shift of emission (44 nm) showing a color change from blue to light cyan under a 365-nm UV lamp. Its practical imaging applicability for intracellular Zn2+ was confirmed in HeLa cells using a confocal microscope. The improved emission properties and cell imaging capability would provide a new approach for fluorescence sensation for Zn2+.

Purification and analysis of kidney-infiltrating leukocytes in a mouse model of lupus nephritis.

Renal injury often occurs as a complication in autoimmune diseases such as systemic lupus erythematosus (SLE). It is estimated that a minimum of 20% SLE patients develop lupus nephritis, a condition that can be fatal when the pathology progresses to end-stage renal disease. Studies in animal models showed that incidence of immune cell infiltrates in the kidney was linked to pathological injury and correlated with severe lupus nephritis. Thus, preventing immune cell infiltration into the kidney is a potential approach to impede the progression to an end-stage disease. A requirement to investigate the role of kidney-infiltrating leukocytes is the development of reproducible and efficient protocols for purification and characterization of immune cells in kidney samples. This chapter describes a detailed methodology that discriminates tissue-resident leukocytes from blood-circulating cells that are found in kidney. Our protocol was designed to maximize cell viability and to reduce variability among samples, with a combination of intravascular staining and magnetic bead separation for leukocyte enrichment. Experiments included as example were performed with FcγRIIb[KO] mice, a well-characterized murine model of SLE. We identified T cells and macrophages as the primary leukocyte subsets infiltrating into the kidney during severe nephritis, and we extensively characterized them phenotypically by flow cytometry.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial.

Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-t) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3',5'-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension. Systematic Review Registration: http://www.chinadrugtrials.org.cn, identifier CTR20210064.

Association of point-of-care testing for sST2 with clinical outcomes in patients hospitalized with heart failure.

AIMS: This study aimed to investigate the association of soluble suppression of tumorigenicity-2 (sST2) measured by point-of-care testing assay with clinical outcomes in patients hospitalized with heart failure after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). METHODS: A total of 1726 consecutive patients hospitalized with heart failure from July 2015 to December 2021 were enrolled. Baseline serum sST2 concentrations were measured by immunofluorescence assay. Primary endpoint event was the composite of all-cause death, heart transplantation, or left ventricular assist device. RESULTS: During the median follow-up duration of 682 days, 434 patients (25.1%) suffered from primary endpoint events. Baseline sST2 remained an independent predictor of the primary endpoint event in patients hospitalized with heart failure after adjusting for other predictors including NT-proBNP and hs-cTnT [per log (unit) increase, adjusted hazard ratio (HR) (95% confidence interval) (CI): 1.20 (1.09, 1.32), P < 0.001]. And baseline sST2 had a better prognostic value for patients with chronic decompensated heart failure [per log (unit) increase, adjusted HR (95% CI): 1.19 (1.07, 1.31)] than for those with acute new onset heart failure [per log (unit) increase, adjusted HR (95% CI): 1.28 (0.94, 1.75), P value for interaction <0.001], as well as a better prognostic value for patients with New York Heart Association (NYHA) functional class I-II [per log (unit) increase, adjusted HR (95% CI): 1.67 (1.11, 2.52)] than for those with NYHA functional class III-IV [per log (unit) increase, adjusted HR (95% CI): 1.18 (1.07, 1.31), P value for interaction <0.001]. Baseline sST2 was also a good predictor of the primary endpoint event in patients hospitalized with heart failure at 1 month, 3 months, 1 year and 2 years (area under the curve: 0.789, 0.775, 0.736 and 0.733, respectively), and the best cut-off values were 27.2 ng/ml, 27.1 ng/ml, 27.1 ng/ml and 25.1 ng/ml, respectively. Furthermore, baseline sST2 could provide additional prognostic value when added to baseline NT-proBNP and hs-cTnT (all P values <0.05). According to the category of elevated biomarkers (including NT-proBNP, hs-cTnT, and sST2), patients with three elevated biomarkers had a higher risk of the primary endpoint event compared with those with one or two elevated biomarkers (all P values <0.05). CONCLUSIONS: Baseline sST2 remained an independent predictor of adverse events after adjusting for other predictors including NT-proBNP and hs-cTnT, particularly in patients with chronic decompensated heart failure and NYHA functional class I-II. And in the basis of baseline NT-proBNP and hs-cTnT, adding baseline sST2 could provide additional prognostic value for patients hospitalized with heart failure.

Influence factors of metagenomic next-generation sequencing negative results in diagnosed patients with spinal infection.

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.

Altered functional connectivity strength of primary visual cortex in subjects with thyroid-associated ophthalmopathy.

Our objective was to explore the disparities in the intrinsic functional connectivity (FC) patterns of primary visual cortex (V1) between patients with thyroid-associated ophthalmopathy (TAO) and healthy controls (HCs) utilizing resting-state functional MRI. Twenty-one patients with TAO (14 males and 7 females; mean age: 54.17 ±â€…4.83 years) and 21 well-matched HCs (14 males and 7 females; mean age: 55.17 ±â€…5.37 years) underwent functional MRI scans in the resting-state. We assessed modifications in the intrinsic FC patterns of the V1 in TAO patients using the FC method. Subsequently, the identified alterations in FC regions in the analysis were selected as classification features to distinguish TAO patients from HCs through the support vector machine (SVM) method. The results indicated that, in comparison to HCs, patients with TAO exhibited notably reduced FC values between the left V1 and the bilateral calcarine (CAL), lingual gyrus (LING) and superior occipital gyrus, as well as between the right V1 and the bilateral CAL/LING and the right cerebellum. Furthermore, the SVM classification model based on FC maps demonstrated effective performance in distinguishing TAO patients from HCs, achieving an accuracy of 61.9% using the FC of the left V1 and 64.29% using the FC of the right V1. Our study revealed that patients with TAO manifested disruptions in FC between the V1 and higher visual regions during rest. This might indicate that TAO patients could present with impaired top-down modulations, visual imagery and vision-motor function. These insights could be valuable in understanding the underlying neurobiological mechanisms of vision impairment in individuals with TAO.

Nitrate and oxygen significantly changed the abundance rather than structure of sulphate-reducing and sulphur-oxidising bacteria in water retrieved from petroleum reservoirs.

Sulphate-reducing bacteria (SRB) are the main culprits of microbiologically influenced corrosion in water-flooding petroleum reservoirs, but some sulphur-oxidising bacteria (SOB) are stimulated when nitrate and oxygen are injected, which control the growth of SRB. This study aimed to determine the distributions of SRB and SOB communities in injection-production systems and to analyse the responses of these bacteria to different treatments involving nitrate and oxygen. Desulfovibrio, Desulfobacca, Desulfobulbus, Sulfuricurvum and Dechloromonas were commonly detected via 16S rRNA gene sequencing. Still, no significant differences were observed for either the SRB or SOB communities between injection and production wells. Three groups of water samples collected from different sampling sites were incubated. Statistical analysis of functional gene (dsrB and soxB) clone libraries and quantitative polymerase chain reaction showed that the SOB community structures were more strongly affected by the nitrate and oxygen levels than SRB clustered according to the sampling site; moreover, both the SRB and SOB community abundances significantly changed. Additionally, the highest SRB inhibitory effect and the lowest dsrB/soxB ratio were obtained under high concentrations of nitrate and oxygen in the three groups, suggesting that the synergistic effect of nitrate and oxygen level was strong on the inhibition of SRB by potential SOB.

Use of ultrasound to increase the catalytic activity of α-L-rhamnosidase.

α-L-rhamnosidase (Rha) is ubiquitous in nature and has high feasibility in the food and biotechnology industries. A green and environmentally friendly method was used to improve the activity of Rha. Here, we show that the effects of ultrasound treatment on the Rha. Ultrasonic treatment at 80 W for 10 min yielded the highest enzyme activity. Treatment increased enzyme activity by 26.3% and half-life by 124 min. Further, treatment increased the catalytic efficiency of Rha and increased the substrate conversion rate by 33.88%. These results demonstrate that ultrasound increases the catalytic activity and stability of Rha. Thus, ultrasonic treatment of Rha is cost-effective on the industrial scale.

Textbook oncological outcomes and prognosis after curative gastrectomy in advanced gastric cancer: A multicenter study.

BACKGROUND: The impact of achieving textbook oncological outcome (TOO) as a multimodal therapy quality indicator on the prognosis of advanced gastric cancer (AGC) remains inadequately assessed. METHODS: Patients with AGC who underwent curative gastrectomy between January 2010 and December 2017 at two East Asian medical centers were included. TOO was defined as achieving the textbook outcome (TO) and receiving neoadjuvant and/or adjuvant chemotherapy (NCT or ACT). Cox and logistic regression models were used to identify prognostic and non-TOO-associated risk factors. RESULTS: Among 3626 patients, 57.6% achieved TOO (TOO group), exhibiting significantly better 5-year overall survival (OS) and disease-free survival (DFS) than the non-TOO group (both p < 0.05). Multivariate Cox regression identified TOO as an independent prognostic factor for 5-year OS (HR, 0.67; 95% CI, 0.61-0.74; p < 0.001) and DFS (HR, 0.73; 95% CI, 0.66-0.81; p < 0.001). Multivariate logistic regression showed that open gastrectomy, lack of health insurance, age ≥65 years, ASA score ≥ Ⅲ, and tumor size ≥50 mm are independent risk factors for non-achievement of TOO (all p < 0.05). On a sensitivity analysis of TOO's prognostic value using varying definitions of chemotherapy parameters, a stricter definition of chemotherapy resulted in a decrease in the TOO achievement rate from 57.6 to 22.3%. However, the associated reductions in the risk of death and recurrence fluctuated within the ranges of 33-39% and 28-37%, respectively. CONCLUSIONS: TOO is a reliable and stable metric for favorable prognosis in AGC. Optimizing the surgical approach and improving health insurance status may enhance TOO achievement.