Intercropping Gramineae Herbage in Semiarid Jujube Cultivar ‘LingwuChangzao’ (<i>Ziziphus jujuba</i> Mill. <i>cv</i>. LingwuChangzao) Orchard Improves Productivity, Plant Nutritional Quality, and Soil Quality

Forest-grass intercropping has great advantages in exploiting the potential of biological resources, improving the productivity of agriculture. Nevertheless, research on intercropping of ‘LingwuChangzao’ (Ziziphus jujuba Mill. cv. LingwuChangzao) with Gramineae herbage is less frequently reported. In this study, we measured the land equivalent ratio (LER), the nutritional quality of fruit and forage, and soil properties when ‘LingwuChangzao’ jujube was intercropped with Gramineae herbage compared to when grown in a corresponding monoculture, using clean tillage as a control. The results indicated that ‘LingwuChangzao’ jujube/Gramineae herbage intercropping significantly improved the LER in the system, the appearance traits, and the quality of jujube fruit (e.g., the total soluble solids, soluble sugar, vitamin C, anthocyanin, and flavonoids). Conversely, some nutritional quality indicators, such as dry matter, crude protein, crude fat, and neutral detergent fiber of forage, were lower than the corresponding monoculture. The physical properties in the soil improved with increased soil water content, electrical conductivity, total nitrogen, available phosphorus, etc. Further, intercropping systems had significant effects on soil organic carbon fractions and most of the C-N cycling enzyme activities. Redundancy analyses (RDA) revealed that electrical conductivity and total nitrogen were the dominant soil factors that influenced the C-N cycling enzyme activities and four soil organic carbon fractions correlated with C-N cycling soil enzyme activities. In conclusion, these results demonstrated that ‘LingwuChangzao’ jujube/Gramineae herbage intercropping significantly altered C-N cycling enzyme activities by driving the soil physicochemical properties and soil organic carbon fractions. Our findings show how to improve the productivity of ‘LingwuChangzao’ jujube and they provide insights into the mechanisms underlying healthy, biodiverse soils in agroecosystems

Decitabine plus CLAG chemotherapy as a bridge to haploidentical transplantation in the setting of acute myeloid leukemia relapse after HLA-matched sibling transplantation: a case report

Abstract Background Patients with relapsed/refractory acute myeloid leukemia after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, with a 2-year survival rate of 14%. The optimal treatment for these patients remains unclear. To treat these patients, we designed a new salvage regimen consisting of decitabine, cladribine, cytarabine, and granulocyte-stimulating factor (D-CLAG). Case presentation Here, we describe a case of acute monocytic leukemia with a complex karyotype in a 38-year-old female patient who relapsed after her first HSCT, which was performed using a matched sibling donor. The patient did not respond to standard induction chemotherapy and subsequently achieved complete remission with the D-CLAG regimen. No severe hematological or extramedullary toxicity was observed. Subsequently, the patient received a second D-CLAG regimen as a bridge therapy and directly underwent haploidentical related HSCT. Following HSCT, the marrow showed complete hematologic and cytogenetic remission. Currently, 1 year after transplantation, the patient’s general condition remains good. Conclusions This case suggests that the D-CLAG regimen can be an option for reinduction in relapsed refractory AML patients as a bridge to transplantation. Nevertheless, further research will be required in the future as this report describes only a single case

The gene knockout of angiotensin II type 1a receptor improves high-fat diet-induced obesity in rat via promoting adipose lipolysis.

AimsThe renin-angiotensin system (RAS) is over-activated and the serum angiotensin II (Ang II) level increased in obese patients, while their correlations were incompletely understood. This study aims to explore the role of Ang II in diet-induced obesity by focusing on adipose lipid anabolism and catabolism.MethodsRat model of AT1aR gene knockout were established to investigate the special role of Ang II on adipose lipid metabolism. Wild-type (WT) and AT1aR gene knockout (AT1aR-/-) SD rats were fed with normal diet or high-fat diet for 12 weeks. Adipose morphology and adipose lipid synthesis and lipolysis were examined.ResultsAT1aR deficiency activated lipolysis-related enzymes and increased the levels of NEFAs and glycerol released from adipose tissue in high-fat diet rats, while did not affect triglycerides synthesis. Besides, AT1aR knockout promoted energy expenditure and fatty acids oxidation in adipose tissue. cAMP levels and PKA phosphorylation in the adipose tissue were significantly increased in AT1aR-/- rats fed with high-fat. Activated PKA could promote adipose lipolysis and thus improved adipose histomorphology and insulin sensitivity in high-fat diet rats.ConclusionsAT1aR deficiency alleviated adipocyte hypertrophy in high-fat diet rats by promoting adipose lipolysis probably via cAMP/PKA pathway, and thereby delayed the onset of obesity and related metabolic diseases

TXNIP inhibition in the treatment of type 2 diabetes mellitus: design, synthesis, and biological evaluation of quinazoline derivatives

AbstractThioredoxin interacting protein (TXNIP) is a potential drug target for type 2 diabetes mellitus (T2DM) treatment. A series of quinazoline derivatives were designed, synthesised, and evaluated to inhibit TXNIP expression and protect from palmitate (PA)-induced β cell injury. In vitro cell viability assay showed that compounds D-2 and C-1 could effectively protect β cell from PA-induced apoptosis, and subsequent results showed that these two compounds decreased TXNIP expression by accelerating its protein degradation. Mechanistically, compounds D-2 and C-1 reduced intracellular reactive oxygen species (ROS) production and modulated TXNIP-NLRP3 inflammasome signalling, and thus alleviating oxidative stress injury and inflammatory response under PA insult. Besides, these two compounds were predicted to possess better drug-likeness properties using SwissADME. The present study showed that compounds D-2 and C-1, especially compound D-2, were potent pancreatic β cell protective agents to inhibit TXNIP expression and might serve as promising lead candidates for the treatment of T2DM

New ECG Compression Method for Portable ECG Monitoring System Merged with Binary Convolutional Auto-Encoder and Residual Error Compensation

In the past few years, deep learning-based electrocardiogram (ECG) compression methods have achieved high-ratio compression by reducing hidden nodes. However, this reduction can result in severe information loss, which will lead to poor quality of the reconstructed signal. To overcome this problem, a novel quality-guaranteed ECG compression method based on a binary convolutional auto-encoder (BCAE) equipped with residual error compensation (REC) was proposed. In traditional compression methods, ECG signals are compressed into floating-point numbers. BCAE directly compresses the ECG signal into binary codes rather than floating-point numbers, whereas binary codes take up fewer bits than floating-point numbers. Compared with the traditional floating-point number compression method, the hidden nodes of the BCAE network can be artificially increased without reducing the compression ratio, and as many hidden nodes as possible can ensure the quality of the reconstructed signal. Furthermore, a novel optimization method named REC was developed. It was used to compensate for the residual between the ECG signal output by BCAE and the original signal. Complemented with the residual error, the restoration of the compression signal was improved, so the reconstructed signal was closer to the original signal. Control experiments were conducted to verify the effectiveness of this novel method. Validated by the MIT-BIH database, the compression ratio was 117.33 and the root mean square difference (PRD) was 7.76%. Furthermore, a portable compression device was designed based on the proposed algorithm using Raspberry Pi. It indicated that this method has attractive prospects in telemedicine and portable ECG monitoring systems

TXNIP aggravates cardiac fibrosis and dysfunction after myocardial infarction in mice by enhancing the TGFB1/Smad3 pathway and promoting NLRP3 inflammasome activation

Myocardial infarction (MI) results in high mortality. The size of fibrotic scar tissue following MI is an independent predictor of MI outcomes. Thioredoxin-interacting protein (TXNIP) is involved in various fibrotic diseases. Its role in post-MI cardiac fibrosis, however, remains poorly understood. In the present study, we investigate the biological role of TXNIP in post-MI cardiac fibrosis and the underlying mechanism using mouse MI models of the wild-type (WT), Txnip-knockout (Txnip-KO) type and Txnip-knock-in (Txnip-KI) type. After MI, the animals present with significantly upregulated TXNIP levels, and their fibrotic areas are remarkably expanded with noticeably impaired cardiac function. These changes are further aggravated under Txnip-KI conditions but are ameliorated in Txnip-KO animals. MI also leads to increased protein levels of the fibrosis indices Collagen I, Collagen III, actin alpha 2 (ACTA2), and connective tissue growth factor (CTGF). The Txnip-KI group exhibits the highest levels of these proteins, while the lowest levels are observed in the Txnip-KO mice. Furthermore, Txnip-KI significantly upregulates the levels of transforming growth factor (TGF)B1, p-Smad3, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), Cleaved Caspase-1, and interleukin (IL)1B after MI, but these effects are markedly offset by Txnip-KO. In addition, after MI, the Smad7 level significantly decreases, particularly in the Txnip-KI mice. TXNIP may aggravate the progression of post-MI fibrosis and cardiac dysfunction by activating the NLRP3 inflammasome, followed by IL1B generation and then the enhancement of the TGFB1/Smad3 pathway. As such, TXNIP might serve as a novel potential therapeutic target for the treatment of post-MI cardiac fibrosis

Cytokine release syndrome was an independent risk factor associated with hypoalbuminemia for patients with relapsed/refractory hematological malignancies after CAR-T cell therapy

Abstract Background & aims This study aims to assess the nutritional status of patients during the different phases of the Chimeric Antigen Receptor (CAR)-T cell therapy and to identify prominent risk factors of hypoalbuminemia in patients after CAR-T treatment. The clinical consequences of malnutrition in cancer patients have been highlighted by growing evidence from previous clinical studies. Given CAR-T cell therapy's treatment intensity and possible side effects, it is important to provide patients with sufficient medical attention and support for their nutritional well-being. Methods This study was conducted from May 2021 to December 2021 among patients undergoing CAR-T cell therapy at the Bone Marrow Transplantation Center in The First Affiliated Hospital of Zhejiang University School of Medicine. Logistic regression analysis was performed to investigate the risk factors associated with hypoalbuminemia. Participants were divided into the cytokine release syndrome (CRS) group (n = 60) and the non-CRS group (n = 11) to further analyze the relationship between hypoalbuminemia and CRS. Results CRS (OR = 13.618; 95% CI = 1.499–123.709; P = 0.013) and baseline albumin (ALB) (OR = 0.854; 95% CI = 0.754–0.967; P = 0.020) were identified as the independent clinical factors associated with post-CAR-T hypoalbuminemia. According to the nadir of serum albumin, hypoalbuminemia occurred most frequently in patients with severe CRS (78.57%). The nadir of serum albumin (r =  − 0.587, P < 0.001) and serum albumin at discharge (r =  − 0.315, P = 0.01) were negatively correlated for the duration of CRS. Furthermore, patients with hypoalbuminemia deserved longer hospitalization (P = 0.04). Conclusions CRS was identified as a significant risk factor associated with post-CAR-T hypoalbuminemia. An obvious decline in serum albumin was observed as the grade and duration of CRS increase. However, further research is still needed to elucidate the mechanisms of CRS-associated hypoalbuminemia

Safety, Tolerability, and Pharmacokinetics of a Novel Human Hepatitis B Virus Capsid Assembly Modulator Canocapavir: A Randomized First-in-Human Study

Background and Aims: Canocapavir (ZM-H1505R) is a small-molecule hepatitis B virus capsid assembly modulator with a novel pyrazole structure. This is the first-in-human study to investigate its safety, tolerability, and pharmacokinetics (PK) following oral administration in healthy subjects. Methods: This was a randomized, double-blind, placebo-controlled study including single ascending dose (SAD) study with an additional crossover food-effect arm, and multiple ascending dose study. In SAD, 40 subjects, 8 in each cohort, were randomized in a 3:1 ratio to receive a single dose of 25, 75, 150, 300, and 450 mg of Canocapavir or placebo in fasted state. For food-effect study, subjects in the 150 mg cohort of SAD received a second dose (150 mg) of Canocapavir in the fed state after a 7-day washout period. In multiple ascending dose, 24 subjects, 8 in each cohort, were randomized in a 3:1 ratio to receive 75, 150, and 300 mg of Canocapavir or placebo once daily for 14 days. The safety and tolerability were assessed using vital signs, physical evaluation, electrocardiogram, laboratory investigations, and adverse events (AEs). Plasma PK parameters measured included area under the curves, Cmax, Cmin, Tmax, and T1/2. Results: Oral administration of single doses (25–450 mg) and multiple doses (75–300 mg) of Canocapavir was well tolerated. The most common AE seen was increased alanine aminotransferase. No dose dependency was observed in incidence and intensity of AEs. Mean plasma area under the curve and Cmax of Canocapavir increased dose-proportionally. A significant margin was observed between plasma exposure of Canocapavir and its in vitro anti-hepatitis B virus activity. Food had an effect on its absorption. Conclusion: The safety and PK profile of Canocapavir support its further evaluation in chronic hepatitis B patients. The study was registered on ClinicalTrial.gov with the number NCT04220801