ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis.

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KRP (KIP-RELATED PROTEIN) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with SHOOT MERISTEMLESS (STM), which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.

Glucose status within dark-grown etiolated cotyledons determines seedling de-etiolation upon light irradiation.

Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1-GRF5-phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation.

Mycorrhizal Fungal Effects on Plant Growth, Osmolytes, and CsHsp70s and CsPIPs Expression in Leaves of Cucumber under a Short-Term Heat Stress.

Arbuscular mycorrhizal (AM) fungi enhance plant stress tolerance, but it is unclear whether AM fungi affect heat tolerance in cucumbers. This study aimed to analyze how an AM fungus, Diversispora versiformis, affected growth, chlorophyll, five osmolytes, and plasma membrane intrinsic proteins (PIPs) and heat shock protein 70 (Hsp70) gene expression in cucumber leaves after a short-term (80 h) heat stress. Heat treatment significantly reduced root AM fungal colonization rate (0.26 folds). Heat treatment also distinctly suppressed plant height, stem diameter, and biomass, whereas AM fungal inoculation improved these growth variables as well as the chlorophyll index, with the benefit being more obvious under heat than under no-heat stress conditions. Heat treatment triggered differential changes in osmolytes (sucrose, fructose, and betaine) of inoculated and uninoculated cucumbers, whereas inoculation with AM fungus significantly raised leaf sucrose, fructose, glucose, betaine, and proline levels when compared to non-AM fungal inoculation. Heat treatment increased the expression of two (CsPIP1;6 and CsPIP2;1) of eight CsPIPs in inoculated and uninoculated plants, whereas AM fungal inoculation up-regulated the expression of CsPIP1;6, CsPIP2;1, and CsPIP2;6 under heat stress conditions. Hsp70s expressed differently in inoculated and uninoculated plants under heat versus no-heat stress, with 6 of 11 CsHsp70s down-regulated in inoculated plants. Under heat stress conditions, AM fungus only up-regulated CsHsp70-8 expression in 11 Hsp70s, while another eight CsHsp70s were down-regulated. Heat treatment and AM fungal inoculation both increased the expression of CsHsp70-8 and CsPIP1;6. It was concluded that AM fungus-inoculated cucumbers have high levels of growth, chlorophyll, and osmolytes under heat stress and do not require high CsPIPs and CsHsp70s expression to tolerate a short-term heat treatment.

Supramolecular Architectures Bearing Half-Sandwich Iridium- or Rhodium-Based Carboranes: Design, Synthesis, and Applications.

The utilization of carboranes in supramolecular chemistry has attracted considerable attention. The unique spatial configuration and weak interaction forces of carboranes can help to explore the properties of supramolecular complexes, particularly via host-guest chemistry. Additionally, certain difficulties encountered in carborane development─such as controlled B-H bond activation─can be overcome by judiciously selecting metal centers and their adjacent ligands. However, few studies are being conducted in this nascent research area. With advances in this field, novel carborane-based supramolecular complexes will likely be prepared, structurally characterized, and intrinsically investigated. To expedite these efforts, we present major findings from recent studies, including π-π interactions, host-guest associations, and steric effects, which have been leveraged to implement a regioselective process for activating B(2,9)-, B(2,8)-, and B(2,7)-H bonds of para-carboranes and B(4,7)-H bonds of ortho-carboranes. Future studies should clarify the unique weak interactions of carboranes and their potential for enhancing the utility of supramolecular complexes. Although carboranes exhibit several unique weak interactions (such as dihydrogen-bond [Bδ+-Hδ-···Hδ+-Cδ-], Bδ+-Hδ-···M+, and Bδ+-Hδ-···π interactions), the manner in which they can be utilized remains unclear. Supramolecular complexes, particularly those based on host-guest chemistry, can be utilized as a platform for demonstrating potential applications of these weak interactions. Owing to the importance of alkane separation, applications related to the recognition and separation of alkane isomers via dihydrogen-bond interactions are primarily summarized. Advances in the research of unique weak interactions in carboranes will certainly lead to more possibilities for supramolecular chemistry.

Walnut (Juglans regia L.) Oligopeptides Alleviate Alcohol-Induced Acute Liver Injury through the Inhibition of Inflammation and Oxidative Stress in Rats.

The study was aimed at investigating the effects of walnut oligopeptides (WOPs) on alcohol-induced acute liver injury and its underlying mechanisms. Male Sprague Dawley (SD) rats were randomly assigned to six groups: normal control, alcohol control, whey protein (440 mg/kg.bw), and three WOPs (220 mg/kg.bw, 440 mg/kg.bw, 880 mg/kg.bw) groups. After 30 days of gavage, ethanol with a volume fraction of 50%, administered at a dose of 7 g/kg.bw., caused acute liver injury. A righting reflex experiment and a blood ethanol concentration evaluation were then performed. Serum biochemical parameters, inflammatory cytokines, liver alcohol metabolism enzymes, oxidative stress biomarkers, liver nuclear factor-κB (NF-κB p65), and cytochrome P4502E1 expression were determined. The results revealed that the intervention of 440 mg/kg and 880 mg/kg WOPs could alleviate the degree of intoxication, decrease blood ethanol concentration, alleviate alcohol-induced hepatic steatosis, enhance the activity of hepatic ethanol metabolizing enzymes and antioxidant capacity, reduce lipid oxidation products and pro-inflammatory factor contents, and inhibit the expression of NF-κBp65 in the livers of rats. The outcomes of the study suggest that WOPs have beneficial effects on liver damage caused by acute ethanol binge drinking, with the high-dose WOPs (880 mg/kg.bw) exerting the most pronounced hepatoprotective effect.

The Effects of Peanut Oligopeptides on Exercise-Induced Fatigue in Mice and Its Underlying Mechanism.

The aim of this study was to clarify the anti-fatigue effect of peanut oligopeptides (POPs) in mice and to investigate its possible underlying mechanism. A total of 150 male ICR mice were randomly assigned into five groups: control, whey protein (0.50 g/kg·bw), and three peanut peptide groups (0.25, 0.50, and 1.00 g/kg·bw). All the mice were treated with intra-gastric administration for 30 days. Following the intervention, a weight-loaded swimming test, blood lactate concentration, glycogen content, the activities of antioxidant factors and energy metabolism enzymes, and the function of mitochondria in the skeletal muscle were examined. The results show that POP intervention significantly prolonged the exhaustive swimming time, decreased blood lactate concentration levels, regulated the process of energy metabolism, and increased the level of antioxidant enzymes, muscle glycogen, and expressions of mtTFA and NRF-1 in the mitochondria of the gastrocnemius muscle. The results suggest that POPs produce an anti-fatigue effect in the animals, and they may exert this effect through the mechanism of improving the animals' antioxidant capacity to reduce oxidative damage levels and regulating the process of energy metabolism.

"Cage Walking" Synthetic Strategy for Unusual Unsymmetrical Supramolecular Cages.

Developing novel assembly methods for supramolecular compounds has long been a research challenge. Herein, we describe how to integrate the B-C coupling reaction and "cage walking" process into coordination self-assembly to construct supramolecular cages. In this strategy, dipyridine linkers containing alkynes react with the metallized carborane backbone through B-C coupling and then "cage walking" resulting in metallacages. However, dipyridine linkers without alkynyl groups can form only metallacycles. We can regulate the size of metallacages based on the length of the alkynyl bipyridine linkers. When tridentate-pyridine linkers participate in this reaction, a new type of ravel is formed. The metallization of carboranes, the B-C coupling reaction, and especially the "cage walking" process of carborane cages play a vital role in this reaction. This work provides a promising principle for the synthesis of metallacages and opens up a novel opportunity in the supramolecular field.

Plasma soluble tumor necrosis factor receptor I as a biomarker of lupus nephritis and disease activity in systemic lupus erythematosus patients.

OBJECTIVES: The goal of our study was to evaluate the potential role of sTNF-RI as a biomarker of renal involvement in SLE patients and active SLE. METHODS: The study sample consisted of two cohorts. The discovery cohort included 16 SLE patients without renal involvement (non-LN), 60 lupus nephritis (LN) patients and 21 healthy controls (HCs) and the replication cohort included 18 SLE non-LN patients, 116 LN patients and 36 HCs. RESULTS: The sTNF-RI levels differed significantly in the discovery cohort. The plasma sTNF-RI levels were higher in LN patients than in non-LN patients (p = .009) and HCs (p = 4 × 10-6). Plasma sTNF-RI levels were significantly higher in non-LN patients than in HCs (p = .03). The finding was confirmed in independent replication cohort (LNs vs. non-LN, p = 4.053 × 10-7; LNs vs. HCs, p = 2.395 × 10-18; non-LN vs. HCs, p = 2.51 × 10-4). The plasma sTNF-RI levels were associated with disease activity, renal function in SLE patients and urine protein in LN patients. The multivariate analysis revealed that high sTNF-RI was an independent risk factor for renal involvement. The multivariate logistic regression results suggested that high TNF-RI, high systolic blood pressure, high serum creatinine, low C4 and positive anti-dsDNA were independent risks of active SLE patients. A nomogram was constructed based on the results of multivariate logistic regression analysis and it was practical in predicting the risk of the active SLE patients. Immunohistochemistry suggested that the expression of TNF-RI in the kidney was increased. CONCLUSIONS: Plasma sTNF-RI might be a good biomarker of renal involvement and disease activity in SLE patients.

Synthesis of Carborane-Backbone Metallacycles for Highly Selective Capture of n-Pentane.

The specific recognition and separation of alkanes with similar molecular structures and close boiling points face significant scientific challenges and industrial demands. Here, rectangular carborane-based metallacycles were designed to selectively encapsulate n-pentane from n-pentane, iso-pentane, and cyclo-pentane mixtures in a simple-to-operate and more energy-efficient way. Metallacycle 1, bearing 1,2-di(4-pyridyl) ethylene, can selectively separate n-pentane from these three-component mixtures with a purity of 97%. The selectivity is ascribed to the capture of the preferred guest with matching size, C-H···π interactions, and potential B-Hδ-···Hδ+-C interactions. Besides, the removal of n-pentane gives rise to original guest-free carborane-based metallacycles, which can be recycled without losing performance. Considering the variety of substituted carborane derivatives, metal ions, and organic linkers, these new carborane-based supramolecular coordination complexes (SCCs) may be broadly applicable to other challenging recognition and separation systems with good performance.

PRDX6 AS1 gene polymorphisms and SLE susceptibility in Chinese populations.

Background: Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease that is characterized by the production of autoantibodies. Although accumulated evidence suggests that the dysregulation of long non-coding RNAs (lncRNAs) is involved in the pathogenesis of SLE, the genetic contributions of lncRNA coding genes to SLE susceptibility remain largely unknown. Here, we aimed to provide more evidence for the role of lncRNA coding genes to SLE susceptibility. Methods: The genetic association analysis was first adopted from the previous genome-wide association studies (GWAS) and was then validated in an independent cohort. PRDX6-AS1 is located at chr1:173204199-173446294. It spans a region of approximately 240 kb, and 297 single nucleotide polymorphisms (SNPs) were covered by the previous GWAS. Differential expression at the mRNA level was analyzed based on the ArrayExpress Archive database. Results: A total of 33 SNPs were associated with SLE susceptibility, with a P<1.68×10-4. The strongest association signal was detected at rs844649 (P=2.12×10-6), according to the previous GWAS. Combining the results from the GWAS Chinese cohort and our replication cohort, we pursued a meta-analysis approach and found a pronounced genetic association between PRDX6-AS1 rs844649 and SLE susceptibility (pmeta=1.24×10-13, OR 1.50, 95% CI: 1.34-1.67). The mRNA expression of PRDX6 was elevated in peripheral blood cells, peripheral blood mononuclear cells (PBMCs), and multiple cell subpopulations, such as B cells, CD4+ T cells, CD3+ cells, and monocytes in patients with SLE. The PRDX6 protein expression level was also increased in patients with SLE compared with healthy donors. Conclusion: Our study provides new evidence that variants located in lncRNA coding genes are associated with SLE susceptibility.

Severe compression of left iliac vein is a protective factor for the risk of inferior vena cava thrombosis.

OBJECTIVE: The purpose of this study is to evaluate the association between left iliac vein (LIV) compression and inferior vena cava thrombosis (IVCT) in patients with LIV involvement of deep vein thrombosis (DVT). METHODS: A total of 263 consecutive patients with DVT were reviewed retrospectively and divided into a group with IVCT and a group without IVCT. The influences of LIV smallest diameter and percentage compression on the risk of IVCT were investigated using logistic regression analysis. RESULTS: The mean age of patients with IVCT was significantly younger than that of patients without IVCT (55.5 ± 1.8 vs 62.7 ± 1.1; P = .001). The percentage of provoked DVT in patients with IVCT was higher than that in patients without IVCT (67.1% vs 48.2%; P = .01). The smallest diameter of the LIV in patients with ICVT was larger than that in patients without IVCT (4.1 ± 0.3 vs 2.5 ± 0.2; P < .001). The mean percentage compression of LIV in patients with IVCT was significantly lower than that in patients without IVCT (63.5 ± 2.2 vs 74.3 ± 1.3; P < .001). Age was associated with a decreased odds of ICVT (odds ratio [OR], 0.965; 95% confidence interval [CI], 0.965-0.985; P = .001). Provoked DVT was associated with an increased odds of ICVT (OR, 2.011; 95% CI, 1.070-3.782; P = .03). LIV compression was associated with a decreased odds of ICVT for each 1-mm decrease in smallest diameter of the LIV (OR, 0.717; 95% CI, 0.627-0.820; P < .001), and for each 10% increase in percentage compression of the LIV (OR, 0.715; 95% CI, 0.612-0.835; P < .001). CONCLUSIONS: For LIV involvement in patients with DVT, patients without IVCT had more severe LIV compression than patients with IVCT. Severe LIV compression may be a protective factor for the risk of IVCT.

New progress in understanding roles of nitric oxide during hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (HIRI) is a major clinical cause of morbidity and mortality in liver surgery and transplantation. Many studies have found that nitric oxide (NO) plays an important role in the HIRI and its increase or decrease can affect the progression and outcome of HIRI. However, the role of NO in HIRI is controversial and complicated. NO derived by endothelial NO synthase (eNOS) shows a protective role in HIRI, while excessive NO derived by inducible NO synthase (iNOS) accelerates inflammation and increases oxidative stress, further aggravating HIRI. Nevertheless, the overexpression of eNOS may exacerbate HIRI and iNOS-derived NO in some cases reduces HIRI. Here we review the new progress in the understanding of the roles of NO during HIRI: (1) NO possesses different roles in HIRI by increasing NO bioavailability, down-regulating leukotriene C4 synthase, inhibiting the activation of the nuclear factorκB (NFκB) pathway, enhancing cell autophagy, and reducing inflammatory cytokines and reactive oxygen species (ROS). And NO has both protective and deleterious effects by regulating apoptotic factors; (2) eNOS promotes NO production and suppresses its own overexpression, exerting a hepatoprotective effect reversely. Its activation is regulated by the PI3K/Akt and KLF2/AMPK pathways; and (3) iNOS derived NO mainly has deteriorating effects on HIRI, while it may have a protective function under some conditions. Their expression should reach a balance to reduce the adverse side and make NO protective in the treatment of HIRI. Thus, it can be inferred that NO modulating drugs may be a new direction in the treatment of HIRI or may be used as an adjunct to mitigate HIRI for the purpose of protecting the liver.

The comprehensive analysis of clinical trials registration for IgA nephropathy therapy on ClinicalTrials.gov.

OBJECTIVES: IgA Nephropathy (IgAN) is common chronic kidney disease with a high incidence. This study aims to analyze comprehensively therapeutic clinical trials for IgAN registered on ClinicalTrials.gov. METHODS: Therapeutic trials for IgAN registered on ClinicalTrials.gov. up to 15 August 2021 were obtained. The general characteristics, features of experimental design, treatment strategies, and some main inclusion criteria and outcome measures were accessed. RESULTS: A total of 104 therapeutic clinical trials for IgAN were extracted on ClinicalTrials.gov up to 15 August 2021. Most of these trials explored the treatment for primary IgAN confirmed by renal biopsy in adults. Only 9% of all selected trials had results. Forty-five percent of trials recruited 50 or fewer participants, and 73% were adults or older adults. 99% of trials were interventional studies, and of all the interventional trials, 70% of trials were randomized, and 68% exercised a parallel assignment of intervention model. Immunosuppression was the most studied for the treatment of IgAN. Moreover, many novel agents had been increasingly studied in recent years. Furthermore, the inclusion criteria and primary outcome measures in these trials were diverse, and the level of proteinuria and change of proteinuria levels were the most used as inclusion criteria and primary outcome, respectively. CONCLUSIONS: The majority of therapeutic trials for IgAN were randomized, none masking and parallel-assignment interventional studies, primarily recruiting adult patients as research subjects. These trials had relatively small sample sizes and short observation. Thus, more large-scale, multicenter, and randomized controlled trials are still needed to improve the management for IgAN.

Highly Selective Separation of Benzene and Cyclohexane in a Spatially Confined Carborane Metallacage.

Separation of light hydrocarbons (C1-C9) represents one of the "seven chemical separations to change the world". Boron clusters can potentially play an important role in chemical separation, due to their unique three-dimensional structures and their ability to promote a potentially rich array of weak noncovalent interactions. Herein, we report the rational design of metallacages with carborane functionality and cooperative dihydrogen binding sites for the highly selective capture of cyclohexane molecules. The metallacage 1, bearing the ligand 2,4,6-tris(4-pyridyl)-1,3,5-triazine (TPT), can produce cyclohexane with a purity of 98.5% in a single adsorption-desorption cycle from an equimolar mixture of benzene and cyclohexane. In addition, cyclohexene molecules can be also encapsulated inside the metallacage 1. This selective encapsulation was attributed to spatial confinement effects, C-H···π interactions, and particularly dihydrogen-bond interactions. This work suggests exciting future applications of carborane cages in supramolecular chemistry for the selective adsorption and separation of alkane molecules and may open up a new research direction in host-guest chemistry.

Lupus susceptibility region containing CTLA4 rs17268364 functionally reduces CTLA4 expression by binding EWSR1 and correlates IFN-α signature.

BACKGROUND: Dysregulation of T cells mediated immune responses is a hallmark in the development of systemic lupus erythematosus (SLE). Recent genome wide association study (GWAS) revealed the genetic contribution of variants located in the cytotoxic T lymphocyte-associated protein-4 (CTLA4)-inducible T cell co-stimulator (ICOS) intergenic region to SLE susceptibility. Our aim is to find a functional variant in this region. METHODS: The genetic association results in the CTLA4-ICOS region from previous GWAS were adopted to select the potential variant which was further replicated in two independent cohorts (Henan cohort 2053 SLE patients and 1845 healthy controls, Beijing cohort 2303 SLE patients and 19,262 healthy). In order to explore the functional significance in SLE, bioinformatics with validation experiments (including electrophoretic mobility shift assay and luciferase reporter assay) and mRNA expression analysis were also performed. RESULTS: A variant located in the CTLA4-ICOS intergenic region, rs17268364, was associated with susceptibility to SLE patients in Chinese populations (risk allele, pmeta = 7.02×10-11, OR 1.19, 95%CI 1.13-1.26). The bioinformatics suggested that rs17268364 might affect the expression of CTLA4, not ICOS. The rs17268364 risk G allele containing sequence reduced the expression of the reporter gene by binding transcriptional repressor Ewing sarcoma breakpoint region 1 (EWSR1). Following genotype-mRNA expression, the analysis also showed the risk allele of rs17268364 was associated with low CTLA4 expression in lupus nephritis (LN) patients. Healthy individuals carrying rs17268364 risk G allele was significantly correlated with higher levels of IFN-α signature including increased lymphocyte antigen 6E (LY6E) (p=0.031), interferon-stimulated gene 15 (ISG15) (p=0.038), interferon regulatory factor 9 (IRF9) (p=0.028), and interferon regulatory factor 5 (IRF5) (p=0.040) mRNA expression. CONCLUSIONS: The present study confirmed the functional role of rs17268364 in the CTLA4-ICOS intergenic region that increased SLE susceptibility in the Chinese population.

A safe and efficient synthetic method for alkali metal octahydrotriborates, unravelling a general mechanism for constructing the delta B3 unit of polyhedral boranes.

A safe and efficient synthetic method for MB3H8 (M = Na, K, Rb and Cs) has been developed with excellent yields by directly reacting the corresponding MBH4 with the dimethyl sulfide borane complex (DMS·BH3). A general mechanism for constructing B3H8-, a basic unit for building polyhedral boranes, has been unravelled.

Association of the PINX1 Variant rs6984094, Which Lengthens Telomeres, with Systemic Lupus Erythematosus Susceptibility in Chinese Populations.

A recent genome-wide association study (GWAS) of Asian ancestry reported that single nucleotide polymorphism (SNP) in TERT (telomerase reverse transcriptase) was associated with systemic lupus erythematosus (SLE). TERT has a critical role in maintaining the chromosomal stability and the length of telomere. Given that only a small portion of the genetic heritability of SLE has been explained so far, we aimed to identify novel loci in telomere-related genes responsible for SLE susceptibility in Chinese populations. We performed a comprehensive genetic association analysis of SLE with telomere-related genes. To identify functional significance, we analyzed the publicly available HaploReg v4.1 and RegulomeDB databases. Differential gene expression analysis was also performed using ArrayExpress. A novel signal of PINX1 rs6984094 was identified (P discovery = 4.13 × 10-2, OR = 0.58, 95% CI 0.35-0.98) and successfully replicated (P replication = 5.73 × 10-3, OR = 0.45, 95% CI 0.26-0.81). Multiple layers of functional analysis suggested that the PINX1 rs6984094 risk T allele exhibited increased nuclear protein binding. We also observed an increased expression of PINX1 mRNA in peripheral blood mononuclear cells from SLE patients compared with healthy controls. Overall, we observed a novel genetic association between PINX1 (encodes the PinX1 protein, an inhibitory telomerase enzyme that lengthens telomeres) and SLE susceptibility in Chinese populations.

The Antioxidant Effects of Whey Protein Peptide on Learning and Memory Improvement in Aging Mice Models.

This study investigated the antioxidant effects of whey protein peptide on learning and memory in aging C57BL/6N mice. A total of 72 SPF male C57BL/6N mice were used. Twelve mice were randomly selected as the control group, and the other mice were intraperitoneally injected with D-galactose (100 mg/kg body weight for 6 weeks), during which, the mice in the control group were intraperitoneally injected with the same amount of normal saline. After 6 weeks, the blood was taken from the epicanthus and the serum MDA level was measured, according to which, the mice were randomly divided into the model control group, the whey protein group (1.5 g/kg body weight), and three Whey protein peptide (WHP) intervention groups (0.3 g/kg body weight, 1.5 g/kg body weight, 3.0 g/kg body weight). The water solution of the test sample was administered by oral gavage every day. The intervention period was 30 days, during which, the model control group, the whey protein group, and the whey protein peptide group continued receiving intraperitoneal injections of D-galactose, while the control group continued receiving intraperitoneal injections of normal saline. After the intervention, behavioral experiments were conducted in the following order: open field test, water maze test, and new object recognition test. After the behavioral experiment, the morphology of hippocampal formation was observed by HE staining and TUNEL labeling. Oxidative stress-related indexes in the serum, liver, and brain were detected. Expression levels of the cholinergic system-related enzymes and proinflammatory cytokines in brain tissue were detected. Western blot was used to detect the expression of synaptic plasticity-related proteins in the mouse brain. The results showed that WHP could significantly improve the accumulation of MDA and PC, increase the activities of SOD and GSH-Px, resist oxidative stress injury, and enhance the potential of endogenous antioxidant defense mechanisms. WHP can significantly improve the decline of aging-related spatial exploration, body movement, and spatial and non-spatial learning/memory ability. Its specific mechanism may be related to reducing the degeneration of hippocampal nerve cells, reducing the apoptosis of nerve cells, improving the activity of AChE, reducing the expression of inflammatory factors (TNF-α and IL-1ß) in brain tissue, reducing oxidative stress injury, and improving the expression of p-CaMKⅡ and BDNF synaptic plasticity protein. These results indicate that WHP can improve aging-related oxidative stress, as well as learning and memory impairment.

Radioprotective Effect of Whey Hydrolysate Peptides against γ-Radiation-Induced Oxidative Stress in BALB/c Mice.

Radiation therapy is widely used in the treatment of tumor diseases, but it can also cause serious damage to the body, so it is necessary to find effective nutritional supplements. The main purpose of this study is to evaluate the protective effect of whey hydrolysate peptides (WHPs) against 60Coγ radiation damage in mice and explore the mechanism. BALB/c mice were given WHPs by oral gavage administration for 14 days. Then, some mice underwent a 30-day survival test after 8 Gy radiation, and other mice received 3.5 Gy radiation to analyze the changes in body weight, hematology and bone marrow DNA after three and 14 days. In addition, through further analysis of the level of oxidative stress and intestinal barrier function, the possible mechanism of the radioprotective effect of WHPs was explored. The study found WHPs can prolong survival time, restore body weight, and increase the number of peripheral blood white blood cells and bone marrow DNA content in irradiated mice. In addition, WHPs can significantly improve the antioxidant capacity, inhibit pro-inflammatory cytokines and protect the intestinal barrier. These results indicate that WHPs have a certain radioprotective effect in mice, and the main mechanism is related to reducing oxidative damage.