Control of Kinetic Pathways toward Supramolecular Chiral Polymorphs for Tunable Circularly Polarized Luminescence.

An amphiphilic aza-BODIPY dye (S)-1 bearing two chiral hydrophilic side chains with S-stereogenic centers was synthesized. This dye exhibited kinetic-controlled self-assembly pathways and supramolecular chiral polymorphism properties in MeOH/H2O (9/1, v/v) mixed solvent. The (S)-1 monomers first aggregated into a kinetic controlled, off-pathway species Agg. A, which was spontaneously transformed into an on-pathway metastable aggregate (Agg. B) and subsequently into the thermodynamic Agg. C. The three aggregate polymorphs of dye (S)-1 displayed distinct optical properties and nanomorphologies. In particular, chiral J-aggregation characteristics were observed for both Agg. B and Agg. C, such as Davydov-split absorption bands (Agg. B), extremely sharp and intense J-band with large bathochromic shift (Agg. C), non-diminished fluorescence upon aggregation, as well as strong bisignated Cotton effects. Moreover, the AFM and TEM studies revealed that Agg. A had the morphology of nanoparticle while fibril or rod-like helical nanostructures with left-handedness were observed respectively for Agg. B and Agg. C. By controlling the kinetic transformation process from Agg. B to Agg. C, thin films consisting of Agg. B and Agg. C with different ratios were prepared, which displayed tunable CPL with emission maxima at 788 - 805 nm and g-factors between -4.2 × 10-2 and -5.1 × 10-2.

Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

Low platelet count at diagnosis of anti-neutrophil cytoplasmic antibody-associated vasculitis is correlated with the severity of disease and renal prognosis.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is an autoimmune disease that involves inflammation of blood vessels. There is increasing evidence that platelets play a crucial role not only in hemostasis but also in inflammation and innate immunity. In this study, we explored the relationship between platelet count, clinical characteristics, and the prognosis of patients with AAV. We divided 187 patients into two groups based on their platelet count. Clinicopathological data and prognostic information were retrospectively gathered from medical records. Univariate and multivariate regression analyses were used to identify risk factors for prognosis, including end-stage renal disease (ESRD) and mortality. The cutoff point for platelet count was set at 264.5 × 109/L, as determined by the receiver operating characteristic (ROC) curve for predicting progression to ESRD in patients with AAV. We observed patients with low platelet count (platelets < 264.5 × 109/L) had lower leukocytes, hemoglobin, complement, acute reactants, and worse renal function (P for eGFR < 0.001). They were also more likely to progress to ESRD or death compared to the high platelet count group (platelets > 264.5 × 109/L) (P < 0.0001, P = 0.0338, respectively). Low platelet count was potentially an independent predictor of poor renal prognosis in the multivariate regression analysis [HR 1.670 (95% CI 1.019-2.515), P = 0.014]. Lower platelet count at diagnosis is associated with more severe clinical characteristics and impaired renal function. Therefore, platelet count may be an accessible prognostic indicator for renal outcomes in patients with AAV.

Physiological and molecular mechanisms of ZnO quantum dots mitigating cadmium stress in Salvia miltiorrhiza.

This study delved into the physiological and molecular mechanisms underlying the mitigation of cadmium (Cd) stress in the model medicinal plant Salvia miltiorrhiza through the application of ZnO quantum dots (ZnO QDs, 3.84 nm). A pot experiment was conducted, wherein S. miltiorrhiza was subjected to Cd stress for six weeks with foliar application of 100 mg/L ZnO QDs. Physiological analyses demonstrated that compared to Cd stress alone, ZnO QDs improved biomass, reduced Cd accumulation, increased the content of photosynthetic pigments (chlorophyll and carotenoids), and enhanced the levels of essential nutrient elements (Ca, Mn, and Cu) under Cd stress. Furthermore, ZnO QDs significantly lowered Cd-induced reactive oxygen species (ROS) content, including H2O2, O2-, and MDA, while enhancing the activity of antioxidant enzymes (SOD, POD, APX, and GSH-PX). Additionally, ZnO QDs promoted the biosynthesis of primary and secondary metabolites, such as total protein, soluble sugars, terpenoids, and phenols, thereby mitigating Cd stress in S. miltiorrhiza. At the molecular level, ZnO QDs were found to activate the expression of stress signal transduction-related genes, subsequently regulating the expression of downstream target genes associated with metal transport, cell wall synthesis, and secondary metabolite synthesis via transcription factors. This activation mechanism contributed to enhancing Cd tolerance in S. miltiorrhiza. In summary, these findings shed light on the mechanisms underlying the mitigation of Cd stress by ZnO QDs, offering a potential nanomaterial-based strategy for enhancing Cd tolerance in medicinal plants.

A new nomogram model for the individualized prediction of mild cognitive impairment in elderly patients with type 2 diabetes mellitus.

Background: A high risk of developing mild cognitive impairment (MCI) is faced by elderly patients with type 2 diabetes mellitus (T2DM). In this study, independent risk factors for MCI in elderly patients with T2DM were investigated, and an individualized nomogram model was developed. Methods: In this study, clinical data of elderly patients with T2DM admitted to the endocrine ward of the hospital from November 2021 to March 2023 were collected to evaluate cognitive function using the Montreal Cognitive Assessment scale. To screen the independent risk factors for MCI in elderly patients with T2DM, a logistic multifactorial regression model was employed. In addition, a nomogram to detect MCI was developed based on the findings of logistic multifactorial regression analysis. Furthermore, the accuracy of the prediction model was evaluated using calibration and receiver operating characteristic curves. Finally, decision curve analysis was used to evaluate the clinical utility of the nomogram. Results: In this study, 306 patients were included. Among them, 186 patients were identified as having MCI. The results of multivariate logistic regression analysis demonstrated that educational level, duration of diabetes, depression, glycated hemoglobin, walking speed, and sedentary duration were independently correlated with MCI, and correlation analyses showed which influencing factors were significantly correlated with cognitive function (p <0.05). The nomogram based on these factors had an area under the curve of 0.893 (95%CI:0.856-0.930)(p <0.05), and the sensitivity and specificity were 0.785 and 0.850, respectively. An adequate fit of the nomogram in the predictive value was demonstrated by the calibration plot. Conclusions: The nomogram developed in this study exhibits high accuracy in predicting the occurrence of cognitive dysfunction in elderly patients with T2DM, thereby offering a clinical basis for detecting MCI in patients with T2DM.

Comparison of novel PSMA-targeting [177Lu]Lu-P17-087 with its albumin binding derivative [177Lu]Lu-P17-088 in metastatic castration-resistant prostate cancer patients: a first-in-human study.

PURPOSE: Prostate-specific membrane antigen (PSMA) is a promising target for diagnosis and radioligand therapy (RLT) of prostate cancer. Two novel PSMA-targeting radionuclide therapy agents, [177Lu]Lu-P17-087, and its albumin binder modified derivative, [177Lu]Lu-P17-088, were evaluated in metastatic castration-resistant prostate cancer (mCRPC) patients. The primary endpoint was dosimetry evaluation, the second endpoint was radiation toxicity assessment (CTCAE 5.0) and PSA response (PCWG3). METHODS: Patients with PSMA-positive tumors were enrolled after [68Ga]Ga-PSMA-11 PET/CT scan. Five mCRPC patients received [177Lu]Lu-P17-087 and four other patients received [177Lu]Lu-P17-088 (1.2 GBq/patient). Multiple whole body planar scintigraphy was performed at 1.5, 4, 24, 48, 72, 120 and 168 h after injection and one SPECT/CT imaging was performed at 24 h post-injection for each patient. Dosimetry evaluation was compared in both patient groups. RESULTS: Patients showed no major clinical side-effects under this low dose treatment. As expected [177Lu]Lu-P17-088 with longer blood circulation (due to its albumin binding) exhibited higher effective doses than [177Lu]Lu-P17-087 (0.151 ± 0.036 vs. 0.056 ± 0.019 mGy/MBq, P = 0.001). Similarly, red marrow received 0.119 ± 0.068 and 0.048 ± 0.020 mGy/MBq, while kidney doses were 0.119 ± 0.068 and 0.046 ± 0.022 mGy/MBq, respectively. [177Lu]Lu-P17-087 demonstrated excellent tumor uptake and faster kinetics; while [177Lu]Lu-P17-088 displayed a slower washout and higher average dose (7.75 ± 4.18 vs. 4.72 ± 2.29 mGy/MBq, P = 0.018). After administration of [177Lu]Lu-P17-087 and [177Lu]Lu-P17-088, 3/5 and 3/4 patients showed reducing PSA values, respectively. CONCLUSION: [177Lu]Lu-P17-088 and [177Lu]Lu-P17-087 displayed different pharmacokinetics but excellent PSMA-targeting dose delivery in mCRPC patients. These two agents are promising RLT agents for personalized treatment of mCRPC. Further studies with increased dose and frequency of RLT are warranted to evaluate the potential therapeutic efficacy. TRIAL REGISTRATION: 177Lu-P17-087/177Lu-P17-088 in Patients with Metastatic Castration-resistant Prostate Cancer (NCT05603559, Registered at 25 October, 2022). URL OF REGISTRY: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05603559 .

Direct and Inverse Spin Splitting Effects in Altermagnetic RuO2.

Recently, the altermagnetic materials with spin splitting effect (SSE), have drawn significant attention due to their potential to the flexible control of the spin polarization by the Néel vector. Here, the direct and inverse altermagnetic SSE (ASSE) in the (101)-oriented RuO2 film with the tilted Néel vector are reported. First, the spin torque along the x-, y-, and z-axis is detected from the spin torque-induced ferromagnetic resonance (ST-FMR), and the z-spin torque emerges when the electric current is along the [010] direction, showing the anisotropic spin splitting of RuO2. Further, the current-induced modulation of damping is used to quantify the damping-like torque efficiency (ξDL) in RuO2/Py, and an anisotropic ξDL is obtained and maximized for the current along the [010] direction, which increases with the reduction of the temperature, indicating the present of ASSE. Next, by way of spin pumping measurement, the inverse altermagnetic spin splitting effect (IASSE) is studied, which also shows a crystal direction-dependent anisotropic behavior and temperature-dependent behavior. This work gives a comprehensive study of the direct and inverse ASSE effects in the altermagnetic RuO2, inspiring future altermagnetic materials and devices with flexible control of spin polarization.

Columbianadin suppresses glioblastoma progression by inhibiting the PI3K-Akt signaling pathway.

Glioblastoma (GBM) is the most common malignant glioma among brain tumors with low survival rate and high recurrence rate. Columbianadin (CBN) has pharmacological properties such as anti-inflammatory, analgesic, thrombogenesis-inhibiting and anti-tumor effects. However, it remains unknown that the effect of CBN on GBM cells and its underlying molecular mechanisms. In the present study, we found that CBN inhibited the growth and proliferation of GBM cells in a dose-dependent manner. Subsequently, we found that CBN arrested the cell cycle in G0/G1 phase and induced the apoptosis of GBM cells. In addition, CBN also inhibited the migration and invasion of GBM cells. Mechanistically, we chose network pharmacology approach by screening intersecting genes through targets of CBN in anti-GBM, performing PPI network construction followed by GO analysis and KEGG analysis to screen potential candidate signaling pathway, and found that phosphatidylinositol 3-kinase/Protein Kinase-B (PI3K/Akt) signaling pathway was a potential target signaling pathway of CBN in anti-GBM. As expected, CBN treatment indeed inhibited the PI3K/Akt signaling pathway in GBM cells. Furthermore, YS-49, an agonist of PI3K/Akt signaling, partially restored the anti-GBM effect of CBN. Finally, we found that CBN inhibited GBM growth in an orthotopic mouse model of GBM through inhibiting PI3K/Akt signaling pathway. Together, these results suggest that CBN has an anti-GBM effect by suppressing PI3K/Akt signaling pathway, and is a promising drug for treating GBM effectively.

Thriving at work as a mediator of the relationship between psychological resilience and the work performance of clinical nurses.

OBJECTIVE: This study aims to investigate the relationship between psychological resilience, thriving at work, and work performance among nurses, as well as analyse the mediating role of thriving at work in the relationship between psychological resilience and the work performance of nurses. The findings are intended to serve as a reference for nursing managers to design tailored work performance intervention programs. METHOD: Using convenience sampling, 308 clinical nurses were selected from a tertiary hospital in Changsha City, Hunan Province, China, from February to April 2023. The Connor-Davidson Resilience Scale (CD-RISC), the Thriving at Work Scale, and the Work Performance Scale were employed for the questionnaire survey. Pearson correlation analysis was used to explore the relationship between psychological resilience, thriving at work and work performance. The SPSS 26.0 software's 'Process' plugin was utilised for mediation effect analysis. RESULTS: Significantly positive correlations were found between psychological resilience and thriving at work (r = 0.806, P < 0.01), thriving at work and work performance (r = 0.571, P < 0.01) as well as psychological resilience and work performance (r = 0.572, P < 0.01). Psychological resilience significantly predicted work performance positively (ß = 0.558, t = 11.165, P < 0.01), and this prediction remained significant when thriving at work (the mediating variable), was introduced (ß = 0.371, t = 4.772, P < 0.01). Psychological resilience significantly predicted thriving at work positively (ß = 0.731, t = 20.779, P < 0.01), and thriving at work significantly predicted work performance positively (ß = 0.256, t = 3.105, P < 0.05). The mediating effect size of thriving at work between psychological resilience and work performance was 33.49% (P < 0.05). CONCLUSION: Thriving at work plays a partial mediating role between psychological resilience and work performance. The level of work performance among clinical nurses was relatively high. Nursing managers can enhance thriving at work by fostering psychological resilience among clinical nurses, thereby further improving their work performance to ensure high-quality and efficient nursing care.

Chemical Synthesis of a Branched Nonasaccharide Fragment from Helicobacter pylori Lipopolysaccharide.

A chemical synthesis of a unique nanosaccharide fragment from Helicobacter pylori lipopolysaccharide was achieved via a convergent glycosylation method. Challenges involved in the synthesis include the highly stereoselective construction of ß-3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) and two 1,2-cis-glycosidic linkages, as well as the formation of a branched 2,7-disubstituted heptose subunit. Hydrogen-bond mediated aglycone delivery strategy and benzoyl-directing remote participation effect were employed, respectively, for the efficient generation of the desired ß-Kdo glycoside and 1,2-cis-α-l-fucoside/d-glucoside. Moreover, the key branched framework was successfully established through a [(7 + 1) + 1] assembly approach involving the stepwise glycosylation of the heptasaccharide alcohol with two monosaccharide donors. The synthesized 1 containing a propylamine linker at the reducing end can be covalently bound to a carrier protein for further immunological studies.

High Open-Circuit Voltage Organic Solar Cells with 19.2% Efficiency Enabled by Synergistic Side-Chain Engineering.

Restricted by the energy-gap law, state-of-the-art organic solar cells (OSCs) exhibit relatively low open-circuit voltage (VOC) because of large nonradiative energy losses (ΔEnonrad). Moreover, the trade-off between VOC and external quantum efficiency (EQE) of OSCs is more distinctive; the power conversion efficiencies (PCEs) of OSCs are still <15% with VOCs of >1.0 V. Herein, the electronic properties and aggregation behaviors of non-fullerene acceptors (NFAs) are carefully considered and then a new NFA (Z19) is delicately designed by simultaneously introducing alkoxy and phenyl-substituted alkyl chains to the conjugated backbone. Z19 exhibits a hypochromatic-shifted absorption spectrum, high-lying lowest unoccupied molecular orbital energy level and ordered 2D packing mode. The D18:Z19-based blend film exhibits favorable phase separation with face-on dominated molecular orientation, facilitating charge transport properties. Consequently, D18:Z19 binary devices afford an exciting PCE of 19.2% with a high VOC of 1.002 V, surpassing Y6-2O-based devices. The former is the highest PCE reported to date for OSCs with VOCs of >1.0 V. Moreover, the ΔEnonrad of Z19- (0.200 eV) and Y6-2O-based (0.155 eV) devices are lower than that of Y6-based (0.239 eV) devices. Indications are that the design of such NFA, considering the energy-gap law, could promote a new breakthrough in OSCs.

Distinct characteristics and prognosis of IgA nephropathy patients with nephrotic syndrome: a propensity score-matched cohort study.

Introduction: IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally. While nephrotic syndrome (NS) is uncommon in IgAN, its significance remains unclear. Methods: We conducted a retrospective analysis of 170 IgAN patients, classifying them into NS (n = 85) and non-NS (n = 5) groups. Our study aims to compare their clinical characteristics, treatment responses, and prognoses. Patients were selected based on renal biopsy from 2003 to 2020. Propensity score matching ensured comparability. Clinical, pathological, and immunological data were analyzed. Composite endpoints were defined as end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR). Results: NS patients showed higher eGFR (74.3 ± 36.8 vs. 61.5 ± 33.6 mL/min.1.73 m2, p = 0.02), severe hematuria (35.0 (4.7,147.5) vs. 4.0 (1.8,45,0) cells/µl, p < 0.001), severe foot process effacement (p = 0.01), and lower C3 levels (1.0 ± 0.3 vs. 1.1 ± 0.2 g/L, p = 0.03). In contrast, the non-NS group had higher BMI (24.3 ± 4.0 vs. 26.8 ± 3.7 kg/m2, p < 0.001) and elevated serum uric acid levels (376 (316,417) vs. 400 (362, 501) mmol/L, p = 0.001), suggesting metabolic factors might contribute to their condition. Both groups exhibited similar MESTC scores. NS patients had higher complete remission rates (26.2% vs. 14.1%, p = 0.04). Cox regression revealed NS independently associated with a higher risk of composite endpoints (HR = 1.97, 95% CI 1.05-3.72, p = 0.04). Linear mixed models did not show significant eGFR trajectory differences. Discussion: This study has established that IgAN patients with NS exhibit distinct characteristics, including active disease and increased complement activation. NS is independently associated with a poorer prognosis, emphasizing the need for targeted interventions in this subgroup.

Dectin-1 aggravates neutrophil inflammation through caspase-11/4-mediated macrophage pyroptosis in asthma.

BACKGROUND: The pattern recognition receptor Dectin-1 was initially discovered to play a pivotal role in mediating pulmonary antifungal immunity and promoting neutrophil-driven inflammation. Recent studies have revealed that Dectin-1 is overexpressed in asthma, but the specific mechanism remains elusive. Additionally, Dectin-1 has been implicated in promoting pyroptosis, a hallmark of severe asthma airway inflammation. Nevertheless, the involvement of the non-classical pyroptosis signal caspase-11/4 and its upstream regulatory mechanisms in asthma has not been completely explored. METHODS: House dust mite (HDM)-induced mice was treated with Dectin-1 agonist Curdlan, Dectin-1 inhibitor Laminarin, and caspase-11 inhibitor wedelolactone separately. Subsequently, inflammatory cells in bronchoalveolar lavage fluid (BALF) were analyzed. Western blotting was performed to measure the protein expression of caspase-11 and gasdermin D (GSDMD). Cell pyroptosis and the expression of chemokine were detected in vitro. The correlation between Dectin-1 expression, pyroptosis factors and neutrophils in the induced sputum of asthma patients was analyzed. RESULTS: Curdlan appeared to exacerbate neutrophil airway inflammation in asthmatic mice, whereas wedelolactone effectively alleviated airway inflammation aggravated by Curdlan. Moreover, Curdlan enhanced the release of caspase-11 activation fragments and N-terminal fragments of gasdermin D (GSDMD-N) stimulated by HDM both in vivo or in vitro. In mouse alveolar macrophages (MH-S cells), Curdlan/HDM stimulation resulted in vacuolar degeneration and elevated lactate dehydrogenase (LDH) release. In addition, there was an upregulation of neutrophil chemokines CXCL1, CXCL3, CXCL5 and their receptor CXCR2, which was suppressed by wedelolactone. In asthma patients, a positive correlation was observed between the expression of Dectin-1 on macrophages and caspase-4 (the human homology of caspase-11), and the proportion of neutrophils in induced sputum. CONCLUSION: Dectin-1 activation in asthma induced caspase-11/4 mediated macrophage pyroptosis, which subsequently stimulated the secretion of chemokines, leading to the exacerbation of airway neutrophil inflammation.

Mental health status among children and adolescents in one-child and multichild families: a meta-analysis of comparative studies.

PURPOSE OF REVIEW: Controversy remains about the difference in mental health status among children and adolescents between one-child and multichild families in China. Thus, we conducted a meta-analysis of studies comparing mental health status between both groups and explored their potential moderating factors. RECENT FINDINGS: Totally, 113 eligible studies encompassing 237 899 participants (one-child families: 83 125; multichild families: 154 774) were included. The pooled SMD of SCL-90 total score was -0.115 [95% confidence interval (95% CI): -0.152; -0.078; I2  = 86.9%]. Specifically, children and adolescents from one-child families exhibited lower scores in terms of somatization (SMD = -0.056; 95% CI: -0.087; -0.026), obsessive-compulsive symptoms (SMD = -0.116; 95% CI: -0.154; -0.079), interpersonal sensitivity (SMD = -0.140; 95% CI: -0.171; -0.109), depression (SMD = -0.123; 95% CI: -0.159; -0.088); anxiety (SMD = -0.121; 95% CI: -0.151; -0.092); phobic anxiety (SMD = -0.124; 95% CI: -0.166; -0.081); paranoid ideation (SMD = -0.040; 95% CI: -0.070; -0.009); and psychoticism (SMD = -0.119; 95% CI: -0.148; -0.089). Study publication year was significantly associated with differences in mental health status between both groups ( P  = 0.015). SUMMARY: Children and adolescents from one-child families had better mental health status compared to those from multichild families in China. Future studies should investigate the underlying factors contributing to such mental health differences, and the potential interventions that could address these mental health problems.

Effects of natural extract from medicinal herbs on broilers experimentally infected with Eimeria tenella.

This study aimed to evaluate the effects of natural extracts from nine medicinal herbs (SMA) on the growth performance, immunity, and intestinal integrity of broilers experimentally infected with Eimeria tenella. A total of 252 one-day-old broiler chicks were divided into 7 groups with 3 replicates per group and 12 broilers per cage. The groups were uninfected-untreated blank control group (BC), infected-untreated negative control group (NC), SMA treatment groups, Chinese medicine positive control group (CM), and chemical drug positive control group (CD). The SMA groups were infected and fed a basal diet supplemented with 0.6 (SMA-L), 0.8 (SMA-M), and 1.0 (SMA-H) g/kg SMA. The CM and CD groups were infected and fed a basal diet supplemented with 15 g/kg Jiqiuchong San and 0.2 g/kg Diclazuril, respectively. Results showed that feeding SMA could significantly reduce the number of oocysts in infected chickens, especially 1.0 g/kg SMA, which exhibited moderate anticoccidial efficacy. When infected with E. tenella, the supplementation of 1.0 g/kg SMA increased the renal index; restored the hepatic, splenic, and bursal indexes to BC levels; increased the levels of immunoglobulin A (IgA), IgM, and IgY; and reduced the contents of tumor necrosis factor (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), and IL-10 of the infected chickens. Moreover, treatment with 1.0 g/kg SMA alleviated the pathological changes in cecal tissue and increased the contents of zonula occludens-1 (ZO-1), occludin, claudin-1, and mucoprotein 2 (mucin-2) in cecal tissues of E. tenella-infected chickens. We found that 1.0 g/kg SMA reduced the number of oocysts, improved immunity, and alleviated intestinal barrier damage, which could improve the growth performance of infected chickens. Thus, SMA proved to be an effective natural extract against E. tenella and has the potential to be used as an efficient anticoccidial drug or additive.

Tenacissoside H repressed the progression of glioblastoma by inhibiting the PI3K/Akt/mTOR signaling pathway.

Glioblastoma (GBM) is one of the most common intracranial primary malignancies with the highest mortality rate, and there is a lack of effective treatments. In this study, we examined the anti-GBM activity of Tenacissoside H (TH), an active component isolated from the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Wight & Arn (MT), and investigated the potential mechanism. Firstly, we found that TH decreased the viability of GBM cells by inducing cell cycle arrest and apoptosis, and inhibited the migration of GBM cells. Furthermore, combined with the Gene Expression Omnibus database (GEO) and network pharmacology as well as molecular docking, TH was shown to inhibit GBM progression by directly regulating the PI3K/Akt/mTOR pathway, which was further validated in vitro. In addition, the selective PI3K agonist 740 y-p partially restored the inhibitory effects of TH on GBM cells. Finally, TH inhibited GBM progression in an orthotopic transplantation model by inactivating the PI3K/Akt/mTOR pathway in vivo. Conclusively, our results suggest that TH represses GBM progression by inhibiting the PI3K/Akt/mTOR signaling pathway in vitro and in vivo, and provides new insight for the treatment of GBM patients.

Construction of site-specific magnetic Z-scheme CdS/Fe3O4@N-doped graphene aerogel microtube/N-doped TiO2 with porous structure: enhanced catalytic performance in photo-Fenton reaction.

The development of composite photocatalysts with high charge transfer efficiency, great visible light absorption, and quick recovery has aroused the interest of many researchers. Herein, based on the hydrothermal assisted vacuum freeze drying method, CdS, Fe3O4, and N-TiO2 were, respectively, fixed in the inner, middle, and outer layers of nitrogen-doped graphene aerogel for preparation of the site-specific magnetic porous Z-scheme CdS/Fe3O4@N-doped graphene aerogel microtube/N-doped TiO2 (CdS/Fe3O4@NGAM/N-TiO2) photocatalyst. For the composite, Fe3O4@NGAM carrier with porous and tubular structure not only helps the recycle and reactants/productions mass transport in the photocatalytic process but also ensures the well-steered transfer of electrons and holes from CdS and N-TiO2 in the Z-type heterojunction system, greatly improving the separation of photogenerated carriers. Besides, Fe3O4 can also work as a Fenton catalyst to activate hydrogen peroxide which is generated in situ by CdS. Thus, the CdS/Fe3O4@NGAM/N-TiO2 composite presents excellent degradation efficiencies towards methyl orange ((MO) 98% removal rate within 50 min), bisphenol A ((BPA) 96% removal rate within 50 min), tetracycline hydrochloride ((TCH) 96% removal rate within 120 min) and strong stabilities after 6 cycles. The free radical removal experiments show that ·O2- and ·OH are the main active substances of catalysis, which further confirms the synergistic effect of photocatalysis and Fenton catalysis.

Natural Enzyme-Inspired Design of the Single-Atom Cu Nanozyme as Dual-Enzyme Mimics for Distinguishing Total Antioxidant Capacity and the Ascorbic Acid Level.

Although various oxidase mimetic or peroxidase (POD) mimetic nanozymes have been extensively studied, their poor substrate selectivity significantly inhibits their practical applications. Nanozymes with specific biomolecules as substrates, especially ascorbic acid oxidase (AAO) mimetic nanozymes with ascorbic acid (AA) as a substrate, have scarcely been studied. Herein, inspired by the multi-Cu atom sites and the redox electron transfer pathway of Cu2+/Cu+ in the natural AAO, atomically dispersed Cu sites immobilized on N-doped porous carbon (Cu-N/C) are artificially designed to simulate the function of natural AAO. Compared with their natural counterparts, the Cu-N/C catalysts exhibited higher catalytic efficiency and superior stability. Combined theoretical calculation and experimental characterizations reveal that the Cu-N/C nanozymes could catalyze the AA oxidation through a 2e- oxygen reduction pathway with H2O2 as the product. Moreover, the Cu-N/C nanozymes also possess high POD activity. As a proof-of-concept application, Cu-N/C can simultaneously realize AA detection in fluorescent mode based on its AAO activity and total antioxidant capacity detection in colorimetric mode utilizing its POD activity.

Classical famous prescription of Jichuan decoction improved loperamide-induced slow transit constipation in rats through the cAMP/PKA/AQPs signaling pathway and maintained inflammatory/intestinal flora homeostasis.

Introduction: Jichuan decoction (JCD) is a well-known traditional Chinese medicinal formula that moistens the intestines and is widely used for the treatment of constipation in China. However, its effects and mechanisms in alleviating slow transit constipation (STC) in vivo remain unclear. We attempted to demonstrate the effect of JCD, with and without essential oil (VO), on intestinal transit and its underlying molecular mechanisms in rats with loperamide-induced STC. Materials and methods: Water consumption, body weight, fecal water content, time to first melena excretion, and intestinal transit ratio of the animals were measured. 5-Hydroxytryptamine (5-HT), substance P (SP), vasoactive intestinal peptide (VIP), and interleukin-6 (IL-6) levels in the sera of rats were evaluated using ELISA. Hematoxylin and eosin and Periodic Acid-Schiff staining were used to determine intestinal tissue histology, while quantitative real-time PCR, western blotting, and immunohistochemical analysis were used to assess the relative expression levels of cAMP/PKA/AQPs pathway- and inflammation-related proteins. 16 S rDNA sequence analysis of rat feces was used to determine the diversity and abundance of the intestinal flora. Results: The JCD groups showed reduced time to first melena excretion and expression of VIP and IL-6. The JCD groups, specifically JCD + VO groups, showed increased fecal water content, intestinal transit rate, and SP expression. Further, these groups showed improved histological characteristics of the colon, with no significant change in the index of immune organs or morphological characteristics of other organs. In addition, a significant decrease in the activation of the cAMP/PKA/AQPs signaling pathway in the colon tissue was observed in these groups, specifically the JCD + VO groups. Moreover, treatment with JCD, with or without VO, downregulated the expression of inflammatory factors and enriched the diversity of intestinal flora as evidenced by polymorphism analysis and the contents of Bacteroides, Lactobacillus, and Erysipelas, with the JCD + VO groups showing better therapeutic outcomes. Conclusion: JCD improved loperamide-induced STC, and co-administration with VO exhibited better activity than sole JCD therapy. JCD may improve STC by inhibiting the cAMP/PKA/AQPs signaling pathway and maintaining inflammatory/intestinal flora homeostasis.