Au@h-Al2O3 Analogic Yolk–Shell Nanocatalyst for Highly Selective Synthesis of Biomass-Derived D-xylonic Acid via Regulation of Structure Effects

Selective oxidation of biomass-based monosaccharides into value-added sugar acids is highly desired, but limited success of producing D-xylonic acid has been achieved. Herein, we report an efficient catalyst system, viz., Au nanoparticles anchored on the inner walls of hollow Al2O3 nanospheres (Au@h- Al2O3), which could catalyze the selective oxidation of D-xylose into D-xylonic acid under base-free conditions. The mesoporous Al2O3 shell as the adsorbent first adsorbed D-xylose. Then, the interface of Au nanoparticles and Al2O3 as active sites spontaneously dissociated O2, and the exposed Au nanoparticle surface as the catalytic site drove the transformation. With this catalyst system, the valuable D-xylonic acid was produced with excellent yields in the aerobic oxidation of D-xylose. Extensive investigation showed that Au@h- Al2O3 is an efficient catalyst with high stability and recyclability

Hirschsprung's disease prognosis: significance of the length of aganglionosis and reference value for the dilated segment resection length

BackgroundThe appropriate length of resection for the dilated segment in Hirschsprung's disease (HSCR) remains a subject of debate, and the correlation between postoperative clinical outcomes has yet to be elucidated. This study aimed to explore the relationship between the dilated segment resection length (DSRL) and the short-term clinical outcome of HSCR, as well as to determine the optimal DSRL value.MethodsThe clinical data of all children with HSCR who underwent a pull-through surgery at Shanxi Children's Hospital from May 2016 to September 2023 were analyzed retrospectively, the baseline characteristics such as sex, gestational age, family history, and complications such as soiling, perianal erosion, constipation were collected. The groups were stratified in recto-sigmoid aganglionosis (short-segment) and extended colonic (long-segment), and DSRL was divided into three groups: DSRL < 10 cm, 10 ≤ DSRL < 20 cm, and DSRL ≥ 20 cm. The Wingspread score system was used to evaluate anal function and analyze the short-term clinical outcome.ResultsA total of 223 children were included in the study, among which 104 cases had short-segment HSCR and 119 cases had long-segment HSCR. The median age at which pull-through surgery was performed was 4 months. In cases of short-segment HSCR, aside from preoperative anemia, baseline characteristics showed no statistically significant differences among the three groups. No statistically significant association was observed between DSRL, the total length of intestinal resection, the length of aganglionosis,and postoperative clinical outcomes.For short-segment HSCR, the best postoperative bowel function was observed when DSRL < 10 cm, with the optimal value being 7.25 cm. In cases of long-segment HSCR, no statistically significant differences in baseline characteristics were observed among the three groups. DSRL, the total length of intestinal resection and the length of aganglionosis all showed statistically significant differences in relation to soiling and perianal erosion. For long-segment HSCR, the best postoperative bowel function was observed when 10 ≤ DSRL < 20 cm, with the optimal value being 13.00 cm.ConclusionsNot only the dilated segment resection length matters for the outcome but also the length of aganglionosis. For short-segment HSCR, DSRL, the total length of intestinal resection and the length of aganglionosis showed no significant impact on short-term clinical outcomes. In contrast, these parameters in long-segment HSCR were significantly associated with soiling and perianal erosion, although overall patient quality of life remained satisfactory. Data from a single clinical center suggest that optimal clinical outcomes for children are achieved when the DSRL measurements are 7.25 cm for short-segment HSCR and 13.00 cm for long-segment HSCR

Efficacy and safety of small molecule drugs in the treatment of pityriasis rubra pilaris—A systematic review

BackgroundPityriasis rubra pilaris is a chronic, scaly, keratotic skin disease, mainly manifested as scaly plaques and keratinized hair follicles. This condition significantly impacts the patient’s quality of life and is considered one of the intractable diseases in dermatology. Currently, no satisfactory clinical treatment options are available for this condition, presenting a considerable challenge for dermatologists. We conducted this systematic evaluation to assess the therapeutic potential of existing small molecule drugs for this disease.ObjectivesTo conduct a systematic review of the existing literature on the use of small molecule drugs for treating pityriasis rubra pilaris and to evaluate their clinical effectiveness and safety.MethodsWe conducted a systematic review of all the literature on small molecule drugs for the treatment of Pityriasis rubra pilaris and searched several databases until November 2024, including PubMed, Embase, Web of Science, and the Cochrane Library.ResultsA total of 16 patients with pityriasis rubra pilaris from 11 publications were included. The small molecule drugs, including apremilast, upadacitinib, abrocitinib, and tofacitinib, demonstrate good efficacy and safety in the treatment of pityriasis rubra pilaris across all ages, particularly in patients who have failed systemic therapy and have a poor response to biological agents. However, the conclusions are limited by the small sample size and need to be further confirmed through large-scale randomized controlled clinical trials.ConclusionSmall molecule drugs demonstrate favorable clinical efficacy and safety in the treatment of refractory pityriasis rubra pilaris, exhibiting a relatively rapid onset and a high safety profile. However, the findings in the literature may be affected by publication bias

Increased neutrophil extracellular trap formation in oligoarticular, polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis: biomarkers for diagnosis and disease activity

ObjectiveNeutrophil extracellular traps (NETs) are important factors in initiating and perpetuating inflammation. However, the role of NETs in different subtypes of juvenile idiopathic arthritis (JIA) has been rarely studied. Therefore, we aimed to explore the ability of JIA-derived neutrophils to release NETs and the effect of TNF-α (tumor necrosis factor-alpha) inhibitors on NET formation both in vitro and in vivo, and evaluate the associations of NET-derived products with clinical and immune-related parameters.MethodsThe ability of neutrophils to release NETs and the effect of adalimumab on NET formation was assessed via in vitro stimulation and inhibition studies. Plasma NET-derived products were detected to assess the incidence of NET formation in vivo. Furthermore, flow cytometry and western blotting were used to detect NET-associated signaling components in neutrophils.ResultsCompared to those derived from HCs, neutrophils derived from patients with oligoarticular-JIA, polyarticular-JIA and enthesitis-related arthritis were more prone to generate NETs spontaneously and in response to TNF-α or PMA in vitro. Excessive NET formation existed in peripheral circulation of JIA patients, and elevated plasma levels of NET-derived products (cell-free DNA and MPO-DNA complexes) could accurately distinguish JIA patients from HCs and were positively correlated with disease activity. Multiple linear regression analysis showed that erythrocyte sedimentation rate and TNF-α levels were independent variables and were positively correlated with cell-free DNA concentration. Notably, TNF-α inhibitors could effectively prevent NET formation both in vitro and in vivo. Moreover, the phosphorylation levels of NET-associated kinases in JIA-derived neutrophils were markedly increased.ConclusionOur data suggest that NETs might play pathogenic roles and may be involved in TNF-α-mediated inflammation in JIA. Circulating NET-derived products possess potential diagnostic and disease monitoring value. Furthermore, the preliminary results related to the molecular mechanisms of NET formation in JIA patients provide a theoretical basis for NET-targeted therapy

Independent and joint association of N-terminal pro-B-type natriuretic peptide and left ventricular mass index with heart failure risk in elderly diabetic patients with right ventricular pacing

BackgroundElevated levels of N-terminal pro-B natriuretic peptide (NT-proBNP) and left ventricular hypertrophy (LVH) are independent risk factors for heart failure (HF). In addition, right ventricular pacing (RVP) is an effective treatment strategy for bradyarrhythmia, but long-term RVP is associated with HF. However, there is limited evidence on the independent and combined association of NT-proBNP and left ventricular mass index (LVMI) with HF risk in elderly diabetic patients with long-term RVP.MethodsBetween January 2017 and January 2018, a total of 224 elderly diabetic patients with RVP at Fuwai Hospital were consecutively included in the study, with a 5-year follow-up period. The study endpoint was the first HF readmission during follow-up. This study aimed to explore the independent and joint relationship of NT-proBNP and LVMI with HF readmission in elderly diabetic patients with long-term RVP, using a multivariate Cox proportional hazards regression model.ResultsA total of 224 (11.56%) elderly diabetic patients with RVP were included in the study. During the 5-year follow-up period, a total of 46 (20.54%) patients suffered HF readmission events. Multivariate Cox proportional hazards regression analysis showed that higher levels of NT-proBNP and LVMI were independent risk factors for HF readmission [NT-proBNP: hazard risk (HR) = 1.05, 95% confidence interval (CI): 1.01–1.10; LVMI: HR = 1.14, 95% CI: 1.02–1.27]. The optimal cut-off point of NT-proBNP was determined to be 330 pg/ml by receiver operating characteristic (ROC) curve analysis. Patients with NT-proBNP > 330 pg/ml and LVH had a higher risk of HF readmission compared to those with NT-proBNP ≤ 330 pg/ml and non-LVH (39.02% vs. 6.17%; HR = 7.72, 95% CI: 1.34–9.31, P < 0.001).ConclusionIn elderly diabetic patients with long-term RVP, NT-proBNP and LVMI were associated with the risk of HF readmission. Elevated NT-proBNP combined with LVH resulted in a significantly higher risk of HF readmission

Intestinal segment and vitamin D3 concentration affect gene expression levels of calcium and phosphorus transporters in broiler chickens

Two experiments were conducted in this research. Experiment 1 investigated the spatial expression characteristics of calcium (Ca) and phosphorus (P) transporters in the duodenum, jejunum, and ileum of 21-day-old broilers provided with adequate nutrient feed. Experiment 2 evaluated the effects of dietary vitamin D3 (VD3) concentration (0, 125, 250, 500, 1,000, and 2,000 IU/kg) on growth performance, bone development, and gene expression levels of intestinal Ca and P transporters in 1–21-day-old broilers provided with the negative control diet without supplemental VD3. Results in experiment 1 showed that the mRNA levels of calcium-binding protein 28-kDa (CaBP-D28k), sodium-calcium exchanger 1 (NCX1), plasma membrane calcium ATPase 1b (PMCA1b), and IIb sodium-phosphate cotransporter (NaPi-IIb) were the highest in the broiler duodenum. By contrast, the mRNA levels of inorganic phosphate transporter 1 (PiT-1) and 2 (PiT-2) were the highest in the ileum. Results in experiment 2 showed that adding 125 IU/kg VD3 increased body weight gain (BWG), feed intake (FI), bone weight, and percentage and weight of Ca and P in the tibia and femur of 1–21-day-old broilers compared with the negative control diet (p < 0.05). The rise in dietary VD3 levels from 125 to 1,000 IU/kg further increased the BWG, FI, and weights of the bone, ash, Ca, and P (p < 0.05). No difference in growth rate and leg bone quality was noted in the broilers provided with 1,000 and 2,000 IU/kg VD3 (p > 0.05). Supplementation with 125–2,000 IU/kg VD3 increased the mRNA abundances of intestinal Ca and P transporters to varying degrees. The mRNA level of CaBP-D28k increased by 536, 1,161, and 28 folds in the duodenum, jejunum, and ileum, respectively, after adding 1,000 IU/kg VD3. The mRNA levels of other Ca and P transporters (PMCA1b, NCX1, NaPi-IIb, PiT-1, and PiT-2) increased by 0.57–1.74 folds by adding 1,000–2,000 IU/kg VD3. These data suggest that intestinal Ca and P transporters are mainly expressed in the duodenum of broilers. Moreover, the addition of VD3 stimulates the two mineral transporter transcription in broiler intestines

Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation

Many cancers evade immune rejection by suppressing major histocompatibility class I (MHC-I) antigen processing and presentation (AgPP). Such cancers do not respond to immune checkpoint inhibitor therapies (ICIT) such as PD-1/PD-L1 [PD-(L)1] blockade. Certain chemotherapeutic drugs augment tumor control by PD-(L)1 inhibitors through potentiation of T-cell priming but whether and how chemotherapy enhances MHC-I-dependent cancer cell recognition by cytotoxic T cells (CTLs) is not entirely clear. We now show that the lysine acetyl transferases p300/CREB binding protein (CBP) control MHC-I AgPPM expression and neoantigen amounts in human cancers. Moreover, we found that two distinct DNA damaging drugs, the platinoid oxaliplatin and the topoisomerase inhibitor mitoxantrone, strongly up-regulate MHC-I AgPP in a manner dependent on activation of nuclear factor kappa B (NF-κB), p300/CBP, and other transcription factors, but independently of autocrine IFNγ signaling. Accordingly, NF-κB and p300 ablations prevent chemotherapy-induced MHC-I AgPP and abrogate rejection of low MHC-I-expressing tumors by reinvigorated CD8+ CTLs. Drugs like oxaliplatin and mitoxantrone may be used to overcome resistance to PD-(L)1 inhibitors in tumors that had "epigenetically down-regulated," but had not permanently lost MHC-I AgPP activity