Targeting histone deacetylase 1 (HDAC1) in the bone marrow stromal cells revers imatinib resistance by modulating IL-6 in Ph + acute lymphoblastic leukemia.

Bone marrow stromal cells (BMSCs) can promote the growth of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Histone deacetylases (HDACs) play essential roles in the proliferation and apoptosis resistance of Ph + ALL cells. In our previous study, inhibiting histone deacetylase 1 (HDAC1) decreases the proliferation of Ph + ALL cells. However, little is known regarding how HDAC1 in BMSCs of Ph + ALL patients affects the imatinib (IM) resistance. Therefore, the present work examined the roles of HDAC1 in BMSCs. Overexpression of HDAC1 was found in BMSCs of Ph + ALL patients with IM resistance. In addition, the Ph + ALL cell line SUP-B15 was co-cultured with BMSCs after lentivirus transfection for regulating HDAC1 expression. Knockdown of HDAC1 within BMSCs elevated the IM-mediated SUP-B15 cell apoptosis, while increasing HDAC1 expression had an opposite effect. IL-6 in BMSCs, which is an important factor for the microenvironment-associated chemoresistance, showed evident up-regulation in HDAC1-upregulated BMSCs and down-regulation in HDAC1-downregulated BMSCs. While recombinant IL-6 (rIL-6) can reversed the sensitivity of SUP-B15 cells to IM induced by downregulating HDAC1 expression in BMSCs. HDAC1 showed positive regulation on IL-6 transcription and secretion. Moreover, IL-6 secretion induced by HDAC1 in BMSCs might enhance IM resistance in Ph + ALL cells. With regard to the underlying molecular mechanism, NF-κB, an important signal responsible for IL-6 transcription in BMSCs, mediated the HDAC1-regulated IL-6 expression. Collectively, this study facilitated to develop HDAC1 inhibitors based not only the corresponding direct anti-Ph + ALL activity but also the regulation of bone marrow microenvironment.

Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

Randomized controlled trial of nalfurafine for refractory pruritus in hemodialysis patients.

Background: Chronic kidney disease-associated pruritus (CKD-aP) is very common and sometimes refractory to treatment in hemodialysis patients. In a trial conducted in Japan, nalfurafine, effectively reduced itching of treatment-resistant CKD-aP. Our present bridging study aimed to evaluate the efficacy and safety of nalfurafine in Chinese cohort with refractory CKD-aP.Methods: In this phase III, multicenter bridging study conducted at 22 sites in China, 141 Chinese cases with refractory CKD-aP were randomly (2:2:1) assigned to receive 5 µg, 2.5 µg of nalfurafine or a placebo orally for 14 days in a double-blind manner. The primary end point was the mean decrease in the mean visual analogue scale (VAS) from baseline.Results: A total of 141 patients were included. The primary endpoint analysis based on full analysis set (FAS), the difference of mean VAS decrease between 5 µg nalfurafine and placebo group was 11.37 mm (p = .041); the difference of mean VAS decrease between 2.5 µg and placebo group was 8.81 mm, but not statistically significantly different. Both differences were greater than 4.13 mm, which met its predefined success criterion of at least 50% efficacy of the key Japanese clinical trial. The per protocol set (PPS) analysis got similar results. The incidence of adverse drug reactions (ADRs) was 49.1% in 5µg, 38.6% in 2.5 µg and 33.3% in placebo group. The most common ADR was insomnia, seen in 21 of the 114 nalfurafine patients.Conclusions: Oral nalfurafine effectively reduced itching with few significant ADRs in Chinese hemodialysis patients with refractory pruritus.

Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis.

BACKGROUND: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis. METHODS: In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values. RESULTS: A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 µg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group. CONCLUSIONS: Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).

Telemedicine and Clinical Outcomes in Peritoneal Dialysis: A Propensity-Matched Study.

INTRODUCTION: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure. METHODS: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016. Patient and practice data were collected through the doctor-end of the TM app (Manburs) for all participants. TM including self-monitoring records, on-line education materials, and real-time physician-patient contact was only performed for the patient-end users of the Manburs. The primary outcome was all-cause mortality. The secondary outcomes were cause-specific mortality and all-cause and cause-specific permanent transfer to hemodialysis. RESULTS: A total of 7,539 PD patients were enrolled between June 2016 and April 2019, with follow-up till December 2020. Patients were divided into two cohorts: TM group (39.1%) and non-TM group (60.9%). A propensity score was used to create 2,160 matched pairs in which the baseline covariates were well-balanced. There were significantly lower risks of all-cause mortality (HR 0.59 [0.51, 0.67], p < 0.001), CVD mortality (HR 0.59 [0.49, 0.70], p < 0.001), all-cause transfer to hemodialysis (0.57 [0.48, 0.67], p < 0.001), transfer to hemodialysis from PD-related infection (0.67 [0.51, 0.88], p = 0.003), severe fluid overload (0.40 [0.30, 0.55], p < 0.001), inadequate solute clearance (0.49 [0.26, 0.92], p = 0.026), and catheter-related noninfectious complications (0.41 [0.17, 0.97], p = 0.041) in the TM group compared with the non-TM group. CONCLUSION: This study indicated real-world associations between TM usage and reduction in patient survival and technique survival through a multicenter prospective cohort.

Relationships among the Dosage of Erythropoiesis-Stimulating Agents, Erythropoietin Resistance Index, and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. METHODS: This multicenter observational retrospective study included MHD patients from 16 blood purification centers (n = 824) who underwent HD in 2011-2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either > or ≤12.80. RESULTS: In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage >10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and p = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI > 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and p = 0.010). CONCLUSIONS: Our data suggested that ESA dosages >10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.

Randomized Control Study on Hemoperfusion Combined with Hemodialysis versus Standard Hemodialysis: Effects on Middle-Molecular-Weight Toxins and Uremic Pruritus.

INTRODUCTION: Classic hemodialysis schedules present inadequate middle-molecular-weight toxin clearance due to limitations of membrane-based separation processes. Accumulation of uremic retention solutes may result in specific symptoms (e.g., pruritus) and may affect clinical outcome and patient's quality of life. Hemoperfusion (HP) is a blood purification modality based on adsorption that can overcome such limitations, and thus, it may be interesting to test the efficacy of at least one session per week of HP combined with hemodialysis. This is a randomized, open-label trial, controlled, multicenter clinical study to investigate the effect of long-term HP combined with hemodialysis on middle-molecular-weight toxins and uremic pruritus in maintenance hemodialysis (MHD) patients. METHODS: 438 MHD patients from 37 HD centers in China with end-stage kidney disease (63.9% males, mean age 51 years) suffering from chronic intractable pruritus were enrolled in the study. Eligible patients were randomized into four groups: low-flux hemodialysis (LFHD), high-flux hemodialysis (HFHD), HP + LFHD, and HP + HFHD at a 1:1:1:1 ratio. Beta-2 microglobulin (ß2M) and parathyroid hormone (PTH) were measured at baseline, 3-6, and 12 months. At the same time points, the pruritus score was evaluated. The primary outcome was the reduction of ß2M and PTH, while the secondary outcome was the reduction of the pruritus score. RESULTS: In the two groups HP + LFHD and HP + HFHD, there was a significant decrease of ß2M and PTH levels after 12 months compared to the control groups. No significant differences were noted between HP + LFHD and HP + HFHD. Pruritus score reduction was 63% in the HP + LFHD group and 51% in the HP + HFHD group, respectively. CONCLUSION: The long-term HP + HD can reduce ß2M and PTH levels and improve pruritus in MHD patients independently on the use of high- or low-flux dialyzers, showing that the results are linked to the effect of adsorption.

Evaluation of factors that predict the success rate of trial of labor after the cesarean section.

BACKGROUND: For most women who have had a previous cesarean section, vaginal birth after cesarean section (VBAC) is a reasonable and safe choice, but which will increase the risk of adverse outcomes such as uterine rupture. In order to reduce the risk, we evaluated the factors that may affect VBAC and and established a model for predicting the success rate of trial of the labor after cesarean section (TOLAC). METHODS: All patients who gave birth at Northwest Women's and Children's Hospital from January 2016 to December 2018, had a history of cesarean section and voluntarily chose the TOLAC were recruited. Among them, 80% of the population was randomly assigned to the training set, while the remaining 20% were assigned to the external validation set. In the training set, univariate and multivariate logistic regression models were used to identify indicators related to successful TOLAC. A nomogram was constructed based on the results of multiple logistic regression analysis, and the selected variables included in the nomogram were used to predict the probability of successfully obtaining TOLAC. The area under the receiver operating characteristic curve was used to judge the predictive ability of the model. RESULTS: A total of 778 pregnant women were included in this study. Among them, 595 (76.48%) successfully underwent TOLAC, whereas 183 (23.52%) failed and switched to cesarean section. In multi-factor logistic regression, parity = 1, pre-pregnancy BMI < 24 kg/m2, cervical score ≥ 5, a history of previous vaginal delivery and neonatal birthweight < 3300 g were associated with the success of TOLAC. The area under the receiver operating characteristic curve in the prediction and validation models was 0.815 (95% CI: 0.762-0.854) and 0.730 (95% CI: 0.652-0.808), respectively, indicating that the nomogram prediction model had medium discriminative power. CONCLUSION: The TOLAC was useful to reducing the cesarean section rate. Being primiparous, not overweight or obese, having a cervical score ≥ 5, a history of previous vaginal delivery or neonatal birthweight < 3300 g were protective indicators. In this study, the validated model had an approving predictive ability.

Protocol for a prospective, cluster randomized trial to evaluate routine and deferred dialysis initiation (RADDI) in Chinese population.

BACKGROUND: The timing of when to initiate dialysis for progressive chronic kidney disease (CKD) patients has not been well established. There has been a strong trend for early dialysis initiation for these patients over the past decades. However, the perceived survival advantage of early dialysis has been questioned by a series of recent observational studies. The only randomized controlled trial (RCT) research on this issue found the all-cause mortality, comorbidities, and quality of life showed no difference between early and late dialysis starters. To better understand optimal timing for dialysis initiation, our research will evaluate the efficacy and safety of deferred dialysis initiation in a large Chinese population. METHODS: The trial adopts a multicenter, cluster randomized, single-blind (outcomes assessor), and endpoint-driven design. Eligible participants are 18-80 years old, in stable CKD stages 4-5 (eGFR > 7 ml/min /1.73 m2), and with good heart function (NYHA grade I or II). Participants will be randomized into a routine or deferred dialysis group. The reference eGFR at initiating dialysis for asymptomatic patients is 7 ml/min /1.73 m2 (routine dialysis group) and 5 ml/min/1.73 m2 or less (deferred dialysis group) in each group. The primary endpoint will be the difference of all-cause mortality and acute nonfatal cerebro-cardiovascular events between the two groups. The secondary outcomes include hospitalization rate and other safety indices. The primary and secondary outcomes will be analyzed by appropriate statistical methods. DISCUSSION: This study protocol represents a large, cluster randomized study evaluating deferred and routine dialysis intervention for an advanced CKD population. The reference eGFR to initiate dialysis for both treatment groups is targeted at less than 7 ml/min/1.73m2. With this design, we aim to eliminate lead-time and survivor bias and avoid selection bias and confounding factors. We acknowledge that the study has limitations. Even so, given the low-targeted eGFR values of both arms, this study still has potential economic, health, and scientific implications. This research is unique in that such a low targeted eGFR value has never been studied in a clinical trial. TRIAL REGISTRATION: The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT02423655). The date of registration was April 22, 2015.

HBxAg suppresses cell apoptosis and promotes the secretion of placental hormones in human placental trophoblasts via activation of the EGFR/Akt pathway.

The aim of this study is to investigate the role of Hepatitis B virus x (HBx) in the growth and secretion of human placental trophoblasts. Firstly, placenta tissues were collected from pregnant HBV carriers with various viral loads. The results of immunohistochemical technique showed that the HBx protein and pEGFR protein levels were both markedly increased with the viral load elevation. Then, a placental trophoblast cell strain (JEG-3-HBx), which stably expressed HBx mRNA and protein, was established with the pcDNA-HBx transfection followed by the G418 selection. The JEG-3-HBx strain displayed distinct activation of the EGFR/AKT pathway, a lower level of cell apoptosis, and higher secretion levels of placental hormones, including human chorionic gonadotropin (hCG), progesterone, estrogen and ß-endorphin. Subsequently, HBx siRNA was used to silence the HBx gene in the JEG-3-HBx strain. Our data showed that the HBx siRNA transfection markedly suppressed the activation of the EGFR/AKT pathway, promoted cell apoptosis, and reduced the secretion of the placental hormones. Finally, EGF was applied to simulate the JEG-3-HBx strain with or without the HBx siRNA transfection. EGF treatment counteracted the reduction of cell apoptosis and the suppression of hormone secretion caused by HBx siRNA in the cell strain. In conclusion, the pEGFR protein was robustly upregulated in HBx-infected human placenta tissues and trophoblast cells. HBx reduces cell apoptosis and promotes the secretion of placental hormones in human placental trophoblast cells via activation of the EGFR/Akt pathway.

Distinct transgenic effects of poplar TDIF genes on vascular development in Arabidopsis.

KEY MESSAGE: Poplar CLE genes encoding TDIF motifs differentially regulate vascular cambial cell division and woody tissue organization in transgenic Arabidopsis. In Arabidopsis, CLE41 and CLE44 genes encode the tracheary element differentiation inhibitory factor (TDIF) peptide, which functions as a non-cell autonomous signal to regulate vascular development, and overexpression of AtCLE41/CLE44 generate similar phenotypic defects. In poplar, there are six CLE genes (PtTDIF1-4 and PtTDIF-like1-2) encoding two TDIF peptides (TDIF and TDIF-like peptide), which exhibit nearly same activities when exogenously applied to Arabidopsis seedlings. In this work, for each TDIF peptide, we chose two poplar CLE genes (PtTDIF2 and 3 for TDIF, and PtTDIF-like1-2 for TDIF-like peptide) to compare their in vivo effects in transgenic Arabidopsis. Our results showed that transgenic Arabidopsis lines overexpressing each individual PtTDIF gene exhibited dramatically distinct phenotypes associated with vascular development, demonstrating that TDIF motif is not the only functional determinant after genetic transformation. Moreover, we revealed that overexpressed poplar TDIFs enhanced the proliferation of (pro)cambial cells only in hypocotyls, but not in inflorescence stems by differentially regulating the transcriptional levels of WOX4 and WOX14 in these two tissues.

Association of MYH9 Polymorphisms with Hypertension in Patients with Chronic Kidney Disease in China.

BACKGROUND/AIMS: This study explored the correlation between hypertension and non-muscle myosin heavy chain 9 (MYH9) gene polymorphisms in Chinese chronic kidney disease (CKD) patients. METHODS: This case-control study included 301 patients with CKD and 293 healthy controls. The E1 haplotype single nucleotide polymorphisms (SNPs) rs3752462 and rs4821480 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The association between MYH9 polymorphisms and high systolic blood pressure (SBP ≥ 140 mmHg) susceptibility in CKD patients was analysed. RESULTS: The cases and controls had similar genotype and allele distributions at rs3752462 and rs4821480. No GG genotype at rs4821480 was observed. Patients with SBP < 140 mmHg were more likely to have the CC genotype (17.1%) than patients with SBP ≥ 140 mmHg (4.3%) (P = 0.001). Creatinine clearance (OR = 0.99, 95% CI = 0.98-0.10, P = 0.01) was associated with SBP in patients with CKD. The risk of SBP ≥ 140 mmHg was 0.24-fold greater among patients with the CC genotype than among patients with the TT genotype (P = 0.002). CONCLUSION: The rs3752462 polymorphism of MYH9 is associated with SBP in patients with CKD. The T allele in the dominant model was associated with an elevated risk for high SBP.

Theoretical model predictions and experimental results for a wavelength switchable Tm:YAG laser.

We present a theoretical model study of a quasi-three-level laser with particular attention given to the Tm:YAG laser. The oscillating conditions of this laser were theoretically analyzed from the point of the pump threshold while taking into account reabsorption loss. The laser oscillation at 2.02 µm with large stimulated emission sections was suppressed by selecting the appropriate coating for the cavity mirrors, then an efficient laser-diode side-pumped continuous-wave Tm:YAG crystal laser operating at 2.07 µm was realized. Experiments with the Tm:YAG laser confirmed the accuracy of the model, and the model was able to accurately predict that the high Stark sub-level within the H36 ground state manifold has a low laser threshold and long laser wavelength, which was achieved by decreasing the transmission of the output coupler.

Prediction of outcomes in crescentic IgA nephropathy in a multicenter cohort study.

Crescentic IgA nephropathy (IgAN), defined as >50% crescentic glomeruli on kidney biopsy, is one of the most common causes of rapidly progressive GN. However, few studies have characterized this condition. To identify risk factors and develop a prediction model, we assessed data from patients ≥ 14 years old with crescentic IgAN who were followed ≥ 12 months. The discovery cohort comprised 52 patients from one kidney center, and the validation cohort comprised 61 patients from multiple centers. At biopsy, the mean serum creatinine (SCr) level ± SD was 4.3 ± 3.4 mg/dl, and the mean percentage of crescents was 66.4%± 15.8%. The kidney survival rates at years 1, 3, and 5 after biopsy were 57.4%± 4.7%, 45.8%± 5.1%, and 30.4%± 6.6%, respectively. Multivariate Cox regression revealed initial SCr as the only independent risk factor for ESRD (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.10 to 1.57; P=0.002). Notably, the percentage of crescents did not associate independently with ESRD. Logistic regression showed that the risk of ESRD at 1 year after biopsy increased rapidly at SCr>2.7 mg/dl and reached 90% at SCr>6.8 mg/dl (specificity=98.5%, sensitivity=64.6% for combined cohorts). In both cohorts, patients with SCr>6.8 mg/dl were less likely to recover from dialysis. Analyses in additional cohorts revealed a similar association between initial SCr and ESRD in patients with antiglomerular basement membrane disease but not ANCA-associated systemic vasculitis. In conclusion, crescentic IgAN has a poor prognosis, and initial SCr concentration may predict kidney failure in patients with this disease.

Carotenoid biosynthesis genes LcLCYB, LcLCYE, and LcBCH from wolfberry confer increased carotenoid content and improved salt tolerance in tobacco.

Carotenoids play essential roles in plant growth and development and provide plants with a tolerance to a series of abiotic stresses. In this study, the function and biological significance of lycopene ß-cyclase, lycopene ε-cyclase, and ß-carotene hydroxylase, which are responsible for the modification of the tetraterpene skeleton procedure, were isolated from Lycium chinense and analyzed. The overexpression of lycopene ß-cyclase, lycopene ε-cyclase, and ß-carotene hydroxylase promoted the accumulation of total carotenoids and photosynthesis enhancement, reactive oxygen species scavenging activity, and proline content of tobacco seedlings after exposure to the salt stress. Furthermore, the expression of the carotenoid biosynthesis genes and stress-related genes (ascorbate peroxidase, catalase, peroxidase, superoxide dismutase, and pyrroline-5-carboxylate reductase) were detected and showed increased gene expression level, which were strongly associated with the carotenoid content and reactive oxygen species scavenging activity. After exposure to salt stress, the endogenous abscisic acid content was significantly increased and much higher than those in control plants. This research contributes to the development of new breeding aimed at obtaining stronger salt tolerance plants with increased total carotenoids and vitamin A content.

Preparation of Antimony-Doped Tin Oxide Fly Ash Antistatic Composite and Its Properties in Filling EVA.

As a common coal-based solid waste, fly ash is widely used in material filling. However, due to the high resistivity of fly ash itself, the antistatic performance of the filling material is poor. Therefore, antistatic composite powder was prepared by coating nano-sized antimony-doped tin oxide (ATO) on the surface of fly ash, and its preparation mechanism was discussed. The composite powders were characterized by SEM, EDS, XRD and FTIR. The results show that the interaction between SiO2 and SnO2 appears at the wave number of 727.12 cm-1, and the obvious SnO2 crystal phase appears on the surface of fly ash. The volume resistivity of calcined fly ash is 1.72 × 1012 Ω·cm, and the volume resistivity of ATO fly ash is reduced to 6 × 103 Ω·cm. By analyzing the limiting oxygen index, melt index, tensile strength, elongation at break, cross-section morphology and surface electrical resistivity of EVA, it was found that the addition of antistatic powder to EVA can improve its antistatic performance without deteriorating the mechanical properties of EVA.

Profiles in neglect of older adult care workers in a long-term care facility: a latent profile analysis.

Background: Neglect is a common form of abuse, and long-term care facilities record higher incidences of this abuse. Given that older adult care workers are the main workforce in these facilities, their neglectful behavior requires public health attention. Internal individual characteristics can lead to older adult abuse, and managing workers who abuse older adults may require various methods. This study aimed to identify the profiles of neglect among older adult care workers in long-term care facilities and explore the influencing factors of neglect. Methods: In this cross-sectional study, a convenience sample of older adult care workers from 15 long-term care facilities in Shandong Province (N = 421) completed a questionnaire on the characteristics associated with neglect. Latent profile analysis was used to identify distinct neglect profiles and promote the understanding of individual characteristics associated with varying levels of neglect. One-way analysis of variance and multivariate logistic regression analyses were used to examine the population characteristic differences. Results: Older adult care workers exhibited three neglect profiles, namely, the "low-risk group," "medium-risk group," and "high-risk group." Males, participants with no employment qualification certificate, and those who did not attend regular training represented the majority of those in the "high-risk group." Participants with a monthly income of more than ¥ 4,000 and nursing 1-2 older adults simultaneously represented the majority of those in the "low-risk group." Conclusion: Long-term care facility administrators should tailor interventions to individual care worker profiles to reduce neglect behaviors and improve care levels.

Development of pea protein nanoparticle/hydrolyzed rice glutelin fibril emulsion gels for encapsulation of curcumin.

The potential of using emulsion gels stabilized by binary plant protein nanoparticle mixtures for the encapsulation and delivery of lipophilic nutraceuticals was evaluated. The particle characteristics, physical stability, water diffusivity, microrheology, large amplitude oscillating shear (LAOS) properties, and in vitro digestion of emulsion gels prepared by different ratios of hydrolyzed rice glutelin fibrils (HRGFs) and pea protein nanoparticle (PNP) were characterized. The emulsion gel with P/H = 2:1 (0.84 µm) exhibited the best storage stability and freeze-thaw stability, as seen by the smaller oil droplet size (1.02 and 1.42 µm, respectively). Low-field pulsed NMR indicated that the majority of water in samples was highly mobile. All the samples were predominantly elastic-like materials. The P/H 2:1 emulsion gel had the lowest FI value (6.21 × 10-4 Hz), the highest MVI value (5.57 s/nm2), G'/ G″ values and enclosed area, showing that it had denser 3D network structures, higher stiffness values, and a high sensitivity to changes in strain. Additionally, P/H 2:1 emulsion gel had a relatively high lipid digestibility (96.1 %), curcumin bioaccessibility (58.9 %), and curcumin stability (94.2 %). This study showed that emulsion gels stabilized by binary protein nanoparticle mixtures (PNP/HRGF) have potential as edible delivery systems for lipophilic nutraceuticals.

Effect of Telitacicept on Circulating Gd-IgA1 and IgA-Containing Immune Complexes in IgA Nephropathy.

Introduction: Telitacicept, a transmembrane activator and cyclophilin ligand interactor (TACI) fusion protein targeting B cell activating factor and a proliferation-inducing ligand (APRIL), has proven efficacy in treating Immunoglobulin A (IgA) nephropathy (IgAN). However, serum biomarkers that could predict the clinical response during the treatment remain unclear. Methods: Plasma samples from 24 participants in the phase 2 clinical trial were collected at baseline and after 4, 12, and 24 weeks; with 8 participants in the placebo group, 9 in the 160 mg group, and 7 in the 240 mg group. We measured the levels of galactose-deficient-IgA1 (Gd-IgA1), IgA-containing immune complexes, C3a, C5a, and sC5b-9. The association between the changes in these markers and proteinuria reduction was analyzed. Results: After 24 weeks of treatment, Gd-IgA1 decreased by 43.9% (95% confidence interval: 29.8%, 55.1%), IgG-IgA immune complex by 31.7% (14.4%, 45.5%), and poly-IgA immune complex by 41.3% (6.5%, 63.1%) in the 160 mg group; Gd-IgA1 decreased by 50.4% (38.6%, 59.9%), IgG-IgA immune complex decreased by 42.7% (29.5%, 53.4%), and poly-IgA immune complex decreased by 67.2% (48.5%,79.1%) in the 240 mg group. There were no significant changes in the circulatory C3a, C5a, or sC5b-9 levels during telitacicept treatment. Decreases in both plasma Gd-IgA1 and IgG-IgA or poly-IgA immune complexes were associated with proteinuria reduction. In turn, IgG-IgA or poly-IgA immune complexes showed a dose-dependent effect, consistent with proteinuria reduction during telitacicept treatment. Conclusion: Telitacicept lowered both circulating Gd-IgA1 and IgA-containing immune complexes, whereas IgA immune complex levels were more consistent with decreased proteinuria.

Roxadustat and Oral Iron Absorption in Chinese Patients with Anemia of Chronic Kidney Disease: A Randomized, Open-Label, Phase 4 Study (ALTAI).

INTRODUCTION: Anemia of chronic kidney disease (CKD) has a high incidence and is associated with many disease conditions. Iron dysmetabolism is an important contributor to anemia in CKD patients. METHODS: ALTAI, a randomized, active-controlled, phase 4 trial, investigated the efficacy of roxadustat versus recombinant human erythropoietin (rHuEPO) on gastrointestinal iron absorption in patients with anemia of CKD (stage 4/5). The primary endpoint was change from baseline to day 15 in gastrointestinal iron absorption (serum iron area under the concentration-time curve; AUC0-3h) following single-dose oral iron. RESULTS: Twenty-five patients with a mean age of 55.1 years were randomized 1:1 to roxadustat (n = 13) or rHuEPO (n = 12). Baseline iron profiles were similar between treatment groups. Change from baseline to day 15 in serum iron AUC0-3h was not statistically significantly different between the roxadustat and rHuEPO groups. Mean (SD) change from baseline in serum iron AUC0-3h was 11.3 (28.2) g × 3 h/dl in the roxadustat group and - 0.3 (9.7) g × 3 h/dl in the rHuEPO group. Roxadustat treatment was associated with decreased hepcidin and also increased transferrin, soluble transferrin receptor, and total iron-binding capacity (TIBC), with nominal significance. The proportion of patients experiencing one or more adverse events was 38.5% when treated with roxadustat and 16.7% with rHuEPO. CONCLUSIONS: The study showed no significant difference between roxadustat and rHuEPO in iron absorption but was underpowered because of recruitment challenges. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04655027.