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Primary membranous nephropathy （PMN） is a kidney-specific autoimmune disease mediated by autoantibodies. Although rituximab （RTX） has been widely applied as a first-line treatment for PMN, 20%-40% patients are non-responsive to RTX. High disease activity, severe renal lesions and low RTX bioavailability may be correlated with poor therapeutic response to RTX. Residual B cells in tissues, preservation of CD20 negative B cells, epitopic spreading, disorders of T cells and cytokines are potential mechanisms of RTX-refractory PMN. Elucidation of these factors and potential mechanisms shall help to boost the efficacy of RTX for PMN.

Abstract Background Patients with diabetes have an increased risk of developing heart failure with preserved ejection fraction (HFpEF). This study aimed to compare indices of myocardial deformation and perfusion between patients with type 2 diabetes mellitus (T2DM) with and without HFpEF and to investigate the relationship between myocardial strain and perfusion reserve. Methods This study included 156 patients with T2DM without obstructive coronary artery disease (CAD) and 50 healthy volunteers who underwent cardiac magnetic resonance (CMR) examination at our center. Patients with T2DM were subdivided into the T2DM–HFpEF (n = 74) and the T2DM–non-HFpEF (n = 82) groups. The parameters of left ventricular (LV) and left atrial (LA) strain as well as stress myocardial perfusion were compared. The correlation between myocardial deformation and perfusion parameters was also assessed. Mediation analyses were used to evaluate the direct and indirect effects of T2DM on LA strain. Results Patients with T2DM and HFpEF had reduced LV radial peak systolic strain rate (PSSR), LV circumferential peak diastolic strain rate (PDSR), LA reservoir strain, global myocardial perfusion reserve index (MPRI), and increased LA booster strain compared to patients with T2DM without HFpEF (all P

In the pursuit of environmental sustainability and food security, biochar has emerged as a promising soil conditioner to mitigate continuous cropping obstacles (CCOs). This study explored the use of engineered biochar (WP400) with high adsorption capacity for phenolic acids in celery cultivation. Using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) for both target and suspect analyses, along with Biolog EcoPlate™ to track the functional diversity of soil bacteria, the study examined chemical and microbiological interactions at varying WP400 application rates. WP400 enhanced celery growth, reduced disease severity, and adsorbed p-coumaric acid (COU), a potential autotoxin. Additionally, other potential allelochemicals, predominantly fatty acid-related, were identified, suggesting a broader role for fatty acids in allelopathy. WP400 also influenced soil bacterial carbon utilization and altered microbial communities. However, higher WP400 doses (0.8% w/w) may not be beneficial for celery growth and reduced bacterial metabolic potential, indicating limitations to its effectiveness. Proper application of WP400 provides a sustainable solution for alleviating continuous cropping issues, promoting both environmental sustainability and agricultural development.

Background Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin‐based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high‐dose and moderate‐dose statins for patients who had experienced mild ischemic stroke during the acute period. Methods and Results This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high‐intensity and moderate‐intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow‐up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high‐intensity statin and moderate‐intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85–1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86–1.34]; P=0.519). High‐intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00–3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10–3.16]; P=0.021). The results from the propensity score‐matched analyses were consistent with those from the Cox proportional hazards analysis. Conclusions Compared with moderate‐intensity statin therapy, high‐dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. Registration URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Abstract This study was designed to probe the effect of chaperone-assisted selective autophagy (CASA) on the maintenance of proteostasis during exhaustive exercise and uncover the alteration of CASA in muscle fibers with pre-high-intensity interval training (HIIT) intervention-induced muscle adaptation in response to exhaustive exercise. Rats were randomly divided into a control group; an exhaustive exercise group; and an HIIT + exhaustive exercise group. Results show myofibril damage and BiP levels were increased after exhaustive exercise, and the levels of the HSP70, BAG3, ubiquitin, autophagy-related proteins, and their interactions were increased. HIIT intervention before exhaustive exercise could decrease myofibril injury and BiP levels, accompanied by down-regulation of HSP70/BAG3 complex and selective autophagy. In conclusion, exhaustive exercise promotes CASA to clear protein aggregation for keeping proteostasis in muscle fibers; pre-HIIT intervention improves myofibril injury and unfold protein response caused by exhaustive exercise, which might contribute to inhibit the augmentation of CASA.

Abstract We compute the six-particle maximally-helicity-violating (MHV) amplitude in planar N $$ \mathcal{N} $$ = 4 super-Yang-Mills theory at eight loops, using antipodal duality and the recently computed eight-loop three-point form factor for the chiral stress energy tensor multiplet. Antipodal duality maps the form factor symbol to the amplitude symbol on a two-dimensional parity-preserving surface in the three-dimensional amplitude kinematics. There are remarkably few ambiguities in lifting from two to three dimensions, nor in promoting the symbol to a function. The amplitude passes many tests, including near-collinear, multi-Regge, factorization, self-crossing and origin limits. These checks also constitute a validation of antipodal duality at eight loops.

Purpose: To investigate the regulatory effect and mechanism of Vitamin D receptor (VDR) on mitochondrial function in renal tubular epithelial cell under diabetic status. Methods: The diabetic rats induced by streptozotocin (STZ) and HK-2 cells under high glocose(HG)/transforming growth factor beta (TGF-β) stimulation were used in this study. Calcitriol was administered for 24 weeks. Renal tubulointerstitial injury and some parameters of mitochondrial function including mitophagy, mitochondrial fission, mitochondrial ROS, mitochondrial membrane potential (MMP), mitochondrial ATP, Complex V activity and mitochondria-associated ER membranes (MAMs) integrity were examined. Additionally, paricalcitol, 3-MA (an autophagy inhibitor), VDR over-expression plasmid, VDR siRNA and Mfn2 siRNA were applied in vitro. Results: The expression of VDR, Pink1, Parkin, Fundc1, LC3II, Atg5, Mfn2, Mfn1 in renal tubular cell of diabetic rats were decreased significantly. Calcitriol treatment reduced the levels of urinary albumin, serum creatinine and attenuated renal tubulointerstitial fibrosis in STZ induced diabetic rats. In addition, VDR agonist relieved mitophagy dysfunction, MAMs integrity, and inhibited mitochondrial fission, mitochondrial ROS. Co-immunoprecipitation analysis demonstrated that VDR interacted directly with Mfn2. Mitochondrial function including mitophagy, mitochondrial membrane potential (MMP), mitochondrial Ca2+, mitochondrial ATP and Complex V activity were decreased dramatically in HK-2 cells under HG/TGF-β ambience. In vitro pretreatment of HK-2 cells with autophagy inhibitor 3-MA, VDR siRNA or Mfn2 siRNA negated the activating effects of paricalcitol on mitochondrial function. Pricalcitol and VDR over-expression plasmid activated Mfn2 and then partially restored the MAMs integrity. Additionally, VDR restored mitophagy was partially associated with MAMs integrity through Fundc1. Conclusion: Activated VDR could contribute to restore mitophagy through Mfn2-MAMs-Fundc1 pathway in renal tubular cell. VDR could recover mitochondrial ATP, complex V activity and MAMs integrity, inhibit mitochondrial fission and mitochondrial ROS. It indicating that VDR agonists ameliorate renal tubulointerstitial fibrosis in diabetic rats partially via regulation of mitochondrial function.

Abstract To investigate the effects and mechanism of Vitamin D receptor (VDR) signaling on arteriovenous fistula (AVF) endothelial cell injury. Venous tissues of AVF stenosis patients were collected and analyzed, vascular morphology, reactive oxygen species (ROS), and the expression of VDR, P66Shc, fibronectin (FN), collagen-1 (Col-1) were detected. In addition, human umbilical vein endothelial cells (HUVECs) was used in in vitro studies. HUVECs was incubated with transforming growth factor-beta (TGF-β, 50 ng/ml). Aditionally, paricalcitol, VDR overexpression plasmid and Pin1 inhibitor Juglone were used to investigate the regulatory mechanism of VDR in mitochondrial ROS. The parameters of ROS (e.g. MitoSox) and the expression of FN, Col-1 were tested. Moreover, the mitochondrial translocation of P66Shc was analyzed. The expression of VDR was obviously decreased in the venous tissues of AVF stenosis patients. On the contrary, the expression of P66Shc, P-P66Shc, FN, Col-1 and 8-OHdG were increased significantly in the venous tissues of AVF stenosis patients (P

In Bacillus thuringenesis (Bt) transgenic cotton, the cotton boll has the lowest insecticidal protein content when compared to the other organs. The present study investigated the effects of amino acid spray application at the peak flowering stage on the cotton boll Bt toxin concentration and yield formation. Boll protein synthesis and carbohydrate conversion were also studied to reveal the fundamental mechanism. Three treatments (i.e., CK, the untreated control; LA1, five amino acids; LA2, 21 amino acids) were applied to two Bt cultivars of G. hirsutum (i.e., the hybrid Sikang 3 and the conventional Sikang 1) in the cotton-growing seasons during 2017 and 2018. Amino acid spray application at the peak flowering stage resulted in an increase of 5.2–16.4% in the boll Bt protein concentration and an increase of 5.5–11.3% in the seed cotton yield, but there was no difference between the two amino acid treatments. In addition, amino acid applications led to increases in the amino acid content, soluble protein content, glutamate pyruvate transaminase (GPT) activity, glutamate oxaloacetate transaminase (GOT) activity, glucose content, fructose content and soluble acid invertase (SAI) activity. This study also found that Bt protein content, enhanced boll number and the weight of opened bolls were closely related to carbon and nitrogen metabolism. The Bt protein content had significant linear positive correlations with amino acid and soluble protein contents. Enhanced boll number had significant linear positive correlations with the GPT and GOT activities from 15–25 days after flowering (DAF). The weight of opened bolls from 55–65 DAF had a significant linear positive correlation with the SAI activity. These results indicate that the enhancement of boll protein synthesis and carbohydrate conversion by amino acid application resulted in a simultaneous increase in the boll Bt protein concentration and cotton lint yield.

Abstract Background Historically, malaria due to Plasmodium vivax has been epidemic in Henan Province, China, with Anopheles sinensis as the main vector. The most effective measures to prevent malaria transmission are based on vector control through the use of insecticides. However, insecticides exert a strong selective pressure on mosquito populations for insecticide resistance. The aim of this study was to investigate the susceptibility profile and population genetic characteristics of An. sinensis to provide basic data and scientific guidance for the study of resistance mechanisms and the control of An. sinensis in Henan Province. Methods Adult Anopheles mosquitoes were collected at sites near local farmers' sheepfolds, pigsties and/or cowsheds located in Pingqiao, Xiangfu, Xiangcheng and Tanghe counties/districts of Henan Province during July–September 2021 for insecticide susceptibility testing. Molecular identification of collected mosquitoes as belonging to genus Anopheles was by PCR, and the frequencies of mutations in the knockdown resistance gene (kdr) and acetylcholinesterase-1 gene (ace-1) were detected using gene amplification. The mitochondrial DNA cytochrome oxidase subunit I (COI) gene was amplified in deltamethrin-resistant and deltamethrin-sensitive mosquitoes to analyze the genetic evolutionary relationship. Results A total of 1409 Anopheles mosquitoes were identified by molecular identification, of which 1334 (94.68%) were An. sinensis, 28 (1.99%) were An. yatsushiroensis, 43 (3.05%) were An. anthropophagus and four (0.28%) were An. belenrae. The 24-h mortality rates of An. sinensis in Pingqiao, Tanghe, Xiangcheng and Xiangfu counties/districts exposed to deltamethrin were 85.85%, 25.38%, 29.73% and 7.66%, respectively; to beta-cyfluthrin, 36.24%, 70.91%, 34.33% and 3.28%, respectively; to propoxur, 68.39%, 80.60%, 37.62% and 9.29%, respectively; and to malathion, 97.43%, 97.67%, 99.21% and 64.23%, respectively. One mutation, G119S, was detected in the ace-1 gene. The frequencies of the main genotypes were 84.21% of specimens collected in Xiangfu (G/S), 90.63% of speciments collected in Xiangcheng (G/G) and 2.44% of speciments collected in Tanghe (S/S). Significantly higher G119S allele frequencies were observed in both propoxur- and malathion-resistant mosquitoes than in their sensitive counterparts in the Tanghe population (P 0.10), and each haplotype was interlaced and did not form two distinct branches. Conclusions High resistance to pyrethroids and propoxur was observed at four sites, but the resistance to malathion varied according to the location. Anopheles belenrae and the L1014W (TGG) mutation in An. sinensis were first discovered in Henan Province. The deltamethrin-resistant and deltamethrin-sensitive mosquito populations showed no genetic differentiation. The generation of resistance might be the result of the combination of multiple factors. Graphical Abstract

Scoring sleep stages is an essential procedure for the diagnosis of sleeping disorders. Conventional sleep staging is a laborious and costly procedure requiring multimodal biological signals and an expert for the assessment. There has always been a demand for approaches which can exempt the need to going through diagnostic procedures under specialized facilities and enable automated sleep staging. Herein, a high‐performance multitask learning model enabling high‐accuracy sleep staging using heart rate data is reported. The proposed algorithm exhibits superior performance with reduced computational resource in comparison with the competing machine and deep learning algorithms when trained and evaluated using electrocardiography and photoplethysmogram (PPG) data. The reported model consumes ≈7.5 times less training parameters and ≈75% less amount of input data than the previously reported models and yields better or comparable performance (mean per night accuracy of 77.5% and Cohen's kappa of 0.643). To demonstrate its potential for wearable electronics, the reported algorithm is implemented in a fully integrated watch. The reported integrated watch is a stand‐alone fully functional platform, which automatedly captures PPG data from the subject's wrist, predicts sleep stages, and displays the result on a screen as well as an associated smartphone application.

An unparalleled copper(I)-catalyzed synthesis of 1,3,4-oxadiazoles from tertiary amines in one step has been described. The one-pot reactions involving (N-isocyanimine)triphenylphosphorane, tertiary amines, and carboxylic acids resulted in the formation of 1,3,4-oxadiazoles in moderate to good yields through a consecutive oxidative Ugi/aza-Wittig reaction, enabling the direct functionalization of sp3 C-H bonds adjacent to the nitrogen atom. This method offered several notable advantages, including ligands-free, exceptional productivity and a high functional group tolerance. The preliminary biological evaluation demonstrated that compound 4f inhibited hepatoma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.

Abstract I present a conjecture that all two-loop MHV amplitudes in planar N $$ \mathcal{N} $$ = 4 super-Yang-Mills theory possess an antipodal symmetry when evaluated on parity-even kinematics. The symmetry acts as a change of basis on the symbol letters, followed by the antipode operation associated with the Hopf algebra structure of multiple polylogarithms. At the symbol level, I provide the symmetry map explicitly for amplitudes with up to eight external particles, and also provide evidence at all multiplicities. Intriguingly, the map acts as an isomorphism on the normal fans of the Newton polytopes of the symbol letters. The conjectured symmetry is one of the rare known cases where the antipode map shows up in physically important examples.

Summary: Purpose: Nowadays most children with congenital heart disease (CHD) are expected to survive to adulthood. The healthcare focus needs to pay close attention to the important developmental tasks during their growth process. The women with CHD face some challenges in their critically developmental stages during pregnancy, delivery, and even motherhood. The lived experience of being a mother needs to be further concerned. This study aimed to explore the lived experience of first-time mothers with CHD. Methods: Descriptive phenomenological design was adopted. Semi-structured interviews were conducted from April to August 2018 with 11 primiparous women with CHD, who were recruited from the pediatric and adult cardiology outpatient departments at a medical center and who had a child aged between 6 months and 3 years. Giorgi's phenomenological analysis method was employed. Results: Six main themes arose from the analysis: (1) recognizing pregnancy risks, (2) performing self-care for health, (3) building self-worth from my baby, (4) adapting to postpartum life and adjusting priorities, (5) enjoying being a first-time mother, and (6) the factors contributing to success in high-risk childbirth. Conclusions: The experiences that occurred prior to and after labor that were identified in this study can assist women with CHD to more capably prepare for and understand the process of becoming a mother, including recognition of the importance of a prepregnancy evaluation. The findings of this study can help women with CHD to better understand the path to becoming a mother and prepare themselves for the challenges that lie ahead.

Abstract Background Alternative splicing (AS) increases the diversity of transcriptome and could fine-tune the function of genes, so that understanding the regulation of AS is vital. AS could be regulated by many different cis-regulatory elements, such as enhancer. Enhancer has been experimentally proved to regulate AS in some genes. However, there is a lack of genome-wide studies on the association between enhancer and AS (enhancer-AS association). To bridge the gap, here we developed an integrative analysis on a genome-wide scale to identify enhancer-AS associations in human and mouse. Result We collected enhancer datasets which include 28 human and 24 mouse tissues and cell lines, and RNA-seq datasets which are paired with the selected tissues. Combining with data integration and statistical analysis, we identified 3,242 human and 7,716 mouse genes which have significant enhancer-AS associations in at least one tissue. On average, for each gene, about 6% of enhancers in human (5% in mouse) are associated to AS change and for each enhancer, approximately one gene is identified to have enhancer-AS association in both human and mouse. We found that 52% of the human significant (34% in mouse) enhancer-AS associations are the co-existence of homologous genes and homologous enhancers. We further constructed a user-friendly platform, named Visualization of Enhancer-associated Alternative Splicing (VEnAS, http://venas.iis.sinica.edu.tw/ ), to provide genomic architecture, intuitive association plot, and contingency table of the significant enhancer-AS associations. Conclusion This study provides the first genome-wide identification of enhancer-AS associations in human and mouse. The results suggest that a notable portion of enhancers are playing roles in AS regulations. The analyzed results and the proposed platform VEnAS would provide a further understanding of enhancers on regulating alternative splicing.

Abstract We compute all 2 → 5 gluon scattering amplitudes in planar N $$ \mathcal{N} $$ = 4 super-Yang-Mills theory in the multi-Regge limit that is sensitive to the non-trivial (“long”) Regge cut. We provide the amplitudes through four loops and to all logarithmic accuracy at leading power, in terms of single-valued multiple polylogarithms of two variables. To obtain these results, we leverage the function-level results for the amplitudes in the Steinmann cluster bootstrap. To high powers in the series expansion in the two variables, our results agree with the recently conjectured all-order central emission vertex used in the Fourier-Mellin representation of amplitudes in multi-Regge kinematics. Our results therefore provide a resummation of the Fourier-Mellin residues into single-valued polylogarithms, and constitute an important cross-check between the bootstrap approach and the all-orders multi-Regge proposal.

Abstract Renal tubulointerstitial fibrosis was a crucial pathological feature of diabetic nephropathy (DN), and renal tubular injury might associate with abnormal mitophagy. In this study, we investigated the effects and molecular mechanisms of AMPK agonist metformin on mitophagy and cellular injury in renal tubular cell under diabetic condition. The high fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice model and HK-2 cells were used in this study. Metformin was administered in the drinking water (200 mg/kg/d) for 24 weeks. Renal tubulointerstitial lesions, oxidative stress and some indicators of mitophagy (e.g., LC3II, Pink1, and Parkin) were examined both in renal tissue and HK-2 cells. Additionally, compound C (an AMPK inhibitor) and Pink1 siRNA were applied to explore the molecular regulation mechanism of metformin on mitophagy. We found that the expression of p-AMPK, Pink1, Parkin, LC3II, and Atg5 in renal tissue of diabetic mice was decreased obviously. Metformin reduced the levels of serum creatinine, urine protein, and attenuated renal oxidative injury and fibrosis in HFD/STZ induced diabetic mice. In addition, Metformin reversed mitophagy dysfunction and the over-expression of NLRP3. In vitro pretreatment of HK-2 cells with AMPK inhibitor compound C or Pink1 siRNA negated the beneficial effects of metformin. Furthermore, we noted that metformin activated p-AMPK and promoted the translocation of Pink1 from the cytoplasm to mitochondria, then promoted the occurrence of mitophagy in HK-2 cells under HG/HFA ambience. Our results suggested for the first time that AMPK agonist metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice via activating mitophagy through a p-AMPK-Pink1-Parkin pathway.

Hexavalent chromium [Cr(VI)] and arsenite [As(III)] are hazardous to both human and ecosystem. While their cross-redox reaction decreases both their toxicities, the interferences from ubiquitous substances like Fe (Fe(II) and Fe(III)) and organic compounds (oxalic acid and soil-extracted dissolved organic carbon (DOC)) on such interaction are rarely reported; thence, inspires the investigation in this study. Results showed that the cross-redox, in the absence of interfering substances, only occurred at pH≤2.0, with reaction orders of 0.676 and 0.783 in respect to the concentration of Cr(VI) and As(III). The pseudo-reaction constant, k′, of such reaction was recorded at 0.087 m1.377/(mmol0.459 min). With the addition of Fe(II), the rate of Cr(VI) reduction is promoted in conjunction with suppressed As(III) oxidation. Upon neutralizing to pH 6.0, such reduced Cr can be entirely removed via Fe(II)-assisted adsorption and/or co-precipitation. Meanwhile, the elimination of aqueous As is relatively inferior (36 %), attributed to the largely preserved As(III), which is less susceptible to adsorptive/co-precipitative removal. Unlike Fe(II), Fe(III) did not alter Cr(VI)-As(III) cross-redox path, but triggered high adsorptive and/or co-precipitative removals of Cr and As (90 %). In contrast, both organically-altered systems exhibits plummeted As(III) oxidation, under distinctive mechanisms: oxalic acid competes with As(III) in the redox interactions while DOC reduces As(V) into As(III). Also, DOC would undergo complexion with metals and/or blocked the adsorption or co-precipitation sites, leading to even lower Cr and As precipitation. This study unravelled the interference from ubiquitous species in the co-removal of Cr(VI) and As(III), which provides insightful remediation for heavy metal contaminations.

Abstract Lung squamous cell carcinoma (LUSC) possesses a poor prognosis even for stages I–III resected patients. Reliable prognostic biomarkers that can stratify and predict clinical outcomes for stage I–III resected LUSC patients are urgently needed. Based on gene expression of LUSC tissue samples from five public datasets, consisting of 687 cases, we developed an immune-related prognostic model (IPM) according to immune genes from ImmPort database. Then, we comprehensively analyzed the immune microenvironment and mutation burden that are significantly associated with this model. According to the IPM, patients were stratified into high- and low-risk groups with markedly distinct survival benefits. We found that patients with high immune risk possessed a higher proportion of immunosuppressive cells such as macrophages M0, and presented higher expression of CD47, CD73, SIRPA, and TIM-3. Moreover, When further stratified based on the tumor mutation burden (TMB) and risk score, patients with high TMB and low immune risk had a remarkable prolonged overall survival compared to patients with low TMB and high immune risk. Finally, a nomogram combing the IPM with clinical factors was established to provide a more precise evaluation of prognosis. The proposed immune relevant model is a promising biomarker for predicting overall survival in stage I–III LUSC. Thus, it may shed light on identifying patient subset at high risk of adverse prognosis from an immunological perspective.

AIM: To observe and compare the changes of macular vascular density and retinal thickness in children and adolescents with different degrees using optical coherence tomography angiography(OCTA), then analyze their correlation.METHODS: Our prospective cross-sectional study included 230 eyes of 115 children and adolescents aged 6-18a. According to spherical equivalent power(SE), they were divided into four groups: emmetropia group(32 eyes of 16 cases), mild myopia group(94 eyes of 47 cases), moderate myopia group(68 eyes of 34 cases), and high myopia group(36 eyes of 18 cases). Using RTVue XR scans of the 6mm×6mm region of the macula, the system automatically divided it into three rings: 1mm(fovea)ring, 1mm-3mm(parafovea)ring, and 3mm-6mm(perifovea)ring. And each ring was further divided into four quadrants: temporal(T), superior(S), nasal(N), and inferior(I). Quantitatively analysis was performed for the superficial and deep capillary densities and retinal thickness of each sector.RESULTS: The superficial capillary density in the macula was in turn significantly decreased as in emmetropia(44.4±3.5)%, mild myopia(44.8±3.8)%, moderate myopia(44.3±3.8)%, and high myopia(42.6±4.5)% groups(F=2.963,P=0.033). The superficial capillary density of parafovea's temporal side were(46.1±3.5)%,(46.8±5.1)%,(46.2±4.3)%, and(43.8±5.5)% in the four groups, respectively(F=3.436, P=0.018). Similarly, the deep capillary density of the four groups was(49.9±4.1)%,(48.4±4.7)%,(47.9±5.5)%, and(45.3±4.7)%, respectively(F=4.806, P=0.003). The deep capillary density of the perifovea was(49±4.4)%,(47.2±5.2)%,(46.6±6)%, and(43.6±5.1)% in the 4 groups, respectively(F=5.495, P=0.001). The retinal thickness of the four groups was 293.9±12.9, 295.5±13.0, 290.9±12.0, and 284.5±10.7 μm(F=6.606, P

Abstract The challenge of decoding information about complex diseases hidden in huge number of single nucleotide polymorphism (SNP) genotypes is undertaken based on five dbGaP studies. Current genome-wide association studies have successfully identified many high-risk SNPs associated with diseases, but precise diagnostic models for complex diseases by these or more other SNP genotypes are still unavailable in the literature. We report that lung cancer, breast cancer and prostate cancer as the first three top cancers worldwide can be predicted precisely via 240–370 SNPs with accuracy up to 99% according to leave-one-out and 10-fold cross-validation. Our findings (1) confirm an early guess of Dr. Mitchell H. Gail that about 300 SNPs are needed to improve risk forecasts for breast cancer, (2) reveal an incredible fact that SNP genotypes may contain almost all information that one wants to know, and (3) show a hopeful possibility that complex diseases can be precisely diagnosed by means of SNP genotypes without using phenotypical features. In short words, information hidden in SNP genotypes can be extracted in efficient ways to make precise diagnoses for complex diseases.

Abstract Seven-point amplitudes in planar N $$ \mathcal{N} $$ = 4 super-Yang-Mills theory have previously been constructed through four loops using the Steinmann cluster bootstrap, but only at the level of the symbol. We promote these symbols to actual functions, by specifying their first derivatives and boundary conditions on a particular two-dimensional surface. To do this, we impose branch-cut conditions and construct the entire heptagon function space through weight six. We plot the amplitudes on a few lines in the bulk Euclidean region, and explore the properties of the heptagon function space under the coaction associated with multiple polylogarithms.

The study aimed to investigate the hepatoprotective effects of Capparis spinosa fruit extract (CSE) on triptolide (TP)-induced hepatotoxicity in vitro and in vivo. In vitro, we used a TP-induced AML-12 cell injury model and flow cytometry to determine the cell survival rate after intervention with CSE. In vivo, acute liver injury was induced by intragastric administration of TP (1000 μg/kg) to C57BL/6 mice. Two experimental groups received CSE treatment at 0.9 g/kg (CSE-Low (L)) or 2.8 g/kg (CSE-high (H)). CSE-H can significantly decrease liver cell apoptosis and ameliorated TP-induced liver injury. Furthermore, 19 metabolites identified in serum were associated with TP treatment and the levels of 13 metabolites were altered relative to TP treatment after CSE-H intervention. TP increased the activities of arachidonate 5-lipoxygenase-activating protein and choline kinase alpha in the liver, while CSE-H inhibited their activity. In conclusion, the CSE has good hepatoprotective effects on TP-induced hepatotoxicity.

Introduction Periodontal disease and osteoporosis are common chronic diseases, especially for the postmenopausal women. Several original studies explore the association, but there still controversial. Therefore, we will conduct this systematic review and meta-analysis to assess the association between periodontal disease and osteoporosis in postmenopausal women.Methods and analysis This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Protocols. We will systematically search Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and Scopus from inception to August 2021 to collect all relevant publications, with no restrictions on publication date or languages. Study selection, data extraction and risk of bias assessment will be conducted independently by two trained reviewers independently. The Cochrane’s tool for assessing risk of bias, Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality will be used for the risk of bias assessment. OR, HR and risk ratio with 95% CI were considered as the effect size for dichotomous outcomes, weighted mean difference with 95% CI were calculated as the effect size for continuous outcomes. Random-effects models will be used. Heterogeneity between studies will be assessed via the forest plot and I². Publication bias will detected by funnel plots, Begg’s test and Egger’s test. The subgroup analyses and sensitivity ananlyses will also be used to explore and interpret the heterogeneity.Ethics and dissemination This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal.PROSPERO registration number CRD42021225746.

Abstract Background Sleep problem or disturbance often exists in pain or neurological/psychiatric diseases. However, sleep scoring is a time-consuming tedious labor. Very few studies discuss the 5-stage (wake/NREM1/NREM2/transition sleep/REM) automatic fine analysis of wake–sleep stages in rodent models. The present study aimed to develop and validate an automatic rule-based classification of 5-stage wake–sleep pattern in acid-induced widespread hyperalgesia model of the rat. Results The overall agreement between two experts’ consensus and automatic scoring in the 5-stage and 3-stage analyses were 92.32% (κ = 0.88) and 94.97% (κ = 0.91), respectively. Standard deviation of the accuracy among all rats was only 2.93%. Both frontal–occipital EEG and parietal EEG data showed comparable accuracies. The results demonstrated the performance of the proposed method with high accuracy and reliability. Subtle changes exhibited in the 5-stage wake–sleep analysis but not in the 3-stage analysis during hyperalgesia development of the acid-induced pain model. Compared with existing methods, our method can automatically classify vigilance states into 5-stage or 3-stage wake–sleep pattern with a promising high agreement with sleep experts. Conclusions In this study, we have performed and validated a reliable automated sleep scoring system in rats. The classification algorithm is less computation power, a high robustness, and consistency of results. The algorithm can be implanted into a versatile wireless portable monitoring system for real-time analysis in the future.

Agricultural lands adjacent to industrial activities are vulnerable due to the risk of trace elements (TEs) being accumulated into crops and subsequently humans. One such case concerns the industrial area of Volos, Greece, a suspected contaminated area which has never been studied. We measured Ag, Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sb, Se, Sn, Tl, V, and Zn in soil and maize (leaves and grains) and assessed health risk of human exposure via soil ingestion and grain consumption. We found that the most highly enriched elements in soils were Tl (enrichment factor = 19), Se (17.68), Sb (14.81), As (7.89), Ni (6.91), Mo (5.22) and Cr (4.33); they all likely derived from anthropogenic activities and in particular from a nearby major steel factory, except for Ni which is known to be lithogenically elevated in that area. Synchrotron XANES spectra analysis revealed that As species were associated with ferrihydrite, and predominant species were As(V) (at ca. 85%) and As(III) (at ca. 15%). Although the total content of the studied elements was high, the ammonium bicarbonate-DTPA extractions recovered very low element concentrations, probably due to the fact that soil conditions decelerated solubility (i.e., soils were alkaline, clayey, and with high Fe oxides content). This was confirmed by the soil-to-grain transfer index, which was particularly low for all studied elements. In 5% of sampled grains concerning Cd, and in 40% concerning Pb, the European food-related regulation limits were surpassed. Health risk assessment showed a dramatically elevated risk for Tl via soil ingestion (hazard quotient, HQ = 2.399), a value that contributed 74% of the total risk. Similarly, concerning the grain consumption-related health risk, Tl was the predominant contributor (HQ = 0.128, contributing 40% of the total risk). Such elevated Tl risk which has rarely been reported previously, led to a considerably high hazard index (HI) well above the threshold of HI = 1. Cancer risk was below the 1 × 10−4 risk threshold for As and Pb. Our findings indicate that this study should be pivotal concerning similar industrially-affected agricultural soils of suspected contamination, since less-expected toxic elements such as Tl here may be primary contributors to health risk. Keywords: Heavy metals, Steel factory, Pollution indices, Corn

Objectives: We studied patients who underwent extracorporeal shock wave lithotripsy (SWL) to investigate the factors influencing the outcome, and built a logistic regression model to estimate the stone-free rate (SFR) after SWL. Material and methods: From January 2013 to December 2013, we retrospectively reviewed the clinical status of 641 patients with a solitary urinary calculus who underwent SWL in our hospital. Univariate logistic regression was used to identify the factors leading to a high SFR, and significant factors were further analyzed by multivariate logistic regression. After the optimal model had been developed, we placed it on the website so others could calculate the SFR at their institutions. Results: The overall SFR for all patients, patients with ureteral stones, and patients with renal stones were 54.8%, 67.8%, and 46.7%, respectively. Multivariate logistic regression showed that body mass index (BMI), stone length, stone width, and stone location were the independent factors that affected the overall successful rate. Stone length was the only significant factor to predict SFR for ureteral stones. BMI, stone length, and stone width were significant SFR predictors for renal stones. A logistic regression model was designed to estimate SFR, which has a sensitivity of 77.8% and specificity of 75.5%. Conclusion: BMI, stone length, stone width, and kidney and ureteral stones were all prognostic factors influencing the outcome of SWL. We built a logistic regression formula to predict the SFR, which helps urologists to select patients for SWL.

Objective Rheumatoid arthritis is an autoimmune disease characterised by inflammation and bone loss, leading to joint destruction and deformity. The cervus and cucumis polypeptide (CCP) injection, one of the traditional Chinese medicine injections combined extracts from deer horn and sweet melon seeds, is widely used to treat arthritis and bone fracture in China. The present study investigated the therapeutic efficacy and mechanism of CCP on pathological immune cells and bone homoeostasis in rodent experimental arthritis.Methods The effects of CCP (4 mg/kg and 2 mg/kg) on clinical arthritis symptoms, bone erosion, proinflammatory cytokines and pathological immune cells induced by complete Freund’s adjuvant was evaluated in male Sprague-Dawley rats. The impacts of CCP (2 mg/kg) on joint erythema and swelling, production of pathogenic antibodies and the proportion of inflammatory cells were assessed in collagen-induced arthritis (CIA) in DBA/1J mice. Regulation of osteoclastogenesis by CCP was observed in the murine macrophage-like RAW264.7 cells treated with receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF).Results CCP administration significantly prevented disease progression in both adjuvant-induced arthritis (AIA) rats and CIA mice. The therapeutic benefits were accompanied by reduction of paw oedema, reversed bone destruction, decreased pathological changes and osteoclast numbers in joints in AIA rats, as well as attenuated clinical manifestation and autoantibodies production in CIA mice. Meanwhile, in vitro supplemented of CCP concentration dependently inhibited RANKL/M-CSF-induced osteoclast differentiation, without showing cytotoxicity in RAW264.7 cells. Further, the presence of CCP dampened the augmented downstream signalling transduction as well as activation of osteoclast-specific genes and transcription factors induced by RANKL/M-CSF in RAW264.7 cells.Conclusion Our study suggested that the therapeutic effects of CCP in experimental arthritis could be attributed to its intervention on RANKL-induced osteoclastogenesis signalling pathway in osteoclast precursor cells.

The Keap1-Nrf2-ARE pathway regulates the constitutive and inducible transcription of various genes that encode detoxification enzymes, antioxidant proteins and anti-inflammatory proteins and has pivotal roles in the defence against cellular oxidative stress. In this study, we investigated the therapeutic potential of CPUY192018, a potent small-molecule inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI), in renal inflammation. In human proximal tubular epithelial HK-2 cells, CPUY192018 treatment significantly increased Nrf2 protein level and Nrf2 nuclear translocation, which enhanced Nrf2-ARE transcription capacity and the downstream protein content in a Nrf2 dependent manner. In lipopolysaccharide (LPS)-challenged human HK-2 cells, CPUY192018 exhibited cytoprotective effects by enhancing the Nrf2-ARE regulated antioxidant system and diminished the LPS-induced inflammatory response by hindering the ROS-mediated activation of the NF-κB pathway. In the LPS-induced mouse model of chronic renal inflammation, by activating Nrf2, CPUY192018 treatment balanced renal oxidative stress and suppressed inflammatory responses. Hence, administration of CPUY192018 reduced kidney damage and ameliorated pathological alterations of the glomerulus. Taken together, our study suggested that small-molecule Keap1-Nrf2 PPI inhibitors can activate the Nrf2-based cytoprotective system and protect the kidney from inflammatory injury, raising a potential application of Keap1-Nrf2 PPI inhibitors in the treatment of inflammatory kidney disorders. Keywords: Keap1-Nrf2 pathway, Protein-protein interaction inhibitors, ROS, NF-κB, Renal inflammation

The heavy metal cadmium (Cd), as one of the major environmentally toxic pollutants, has serious impacts on the growth, development, and physiological functions of plants and animals, leading to deterioration of environmental quality and threats to human health. Research on how plants absorb and transport Cd, as well as its enrichment and detoxification mechanisms, is of great significance to the development of phytoremediation technologies for ecological and environmental management. This article summarises the research progress on the enrichment of heavy metal cadmium in plants in recent years, including the uptake, transport, and accumulation of Cd in plants. The role of plant roots, compartmentalisation, chelation, antioxidation, stress, and osmotic adjustment in the process of plant Cd enrichment are discussed. Finally, problems are proposed to provide a more comprehensive theoretical basis for the further application of phytoremediation technology in the field of heavy metal pollution.

There are current limitations in the recording technologies for measuring EEG activity in clinical and experimental applications. Acquisition systems involving wet electrodes are time-consuming and uncomfortable for the user. Furthermore, dehydration of the gel affects the quality of the acquired data and reliability of long-term monitoring. As a result, dry electrodes may be used to facilitate the transition from neuroscience research or clinical practice to real-life applications. EEG signals can be easily obtained using dry electrodes on the forehead, which provides extensive information concerning various cognitive dysfunctions and disorders. This paper presents the usefulness of the forehead EEG with advanced sensing technology and signal processing algorithms to support people with healthcare needs, such as monitoring sleep, predicting headaches, and treating depression. The proposed system for evaluating sleep quality is capable of identifying five sleep stages to track nightly sleep patterns. Additionally, people with episodic migraines can be notified of an imminent migraine headache hours in advance through monitoring forehead EEG dynamics. The depression treatment screening system can predict the efficacy of rapid antidepressant agents. It is evident that frontal EEG activity is critically involved in sleep management, headache prevention, and depression treatment. The use of dry electrodes on the forehead allows for easy and rapid monitoring on an everyday basis. The advances in EEG recording and analysis ensure a promising future in support of personal healthcare solutions.

Recently, plant bioreactors have flourished into an exciting area of synthetic biology because of their product safety, inexpensive production cost, and easy scale-up. Duckweed is the smallest and fastest-growing aquatic plant, and has advantages including simple processing and the ability to grow high biomass in smaller areas. Therefore, duckweed could be used as a new potential bioreactor for biological products such as vaccines, antibodies, pharmaceutical proteins, and industrial enzymes. Duckweed has made a breakthrough in biosynthesis as a chassis plant and is being utilized for the production of plenty of biological products or bio-derivatives with multiple uses and high values. This review summarizes the latest progress on genetic background, genetic transformation system, and bioreactor development of duckweed, and provides insights for further exploration and application of duckweed.

Previous work has explored link between mitochondrial biology and fungal pathogenicity in F1Fo-ATP synthase in Candida albicans. In this work we have detailed the more specific roles of the F1Fo-ATP synthase β subunit, a key protein subunit of F1Fo-ATP synthase. The ability to assimilate alternative carbons in glucose-limited host niches is known to be a critical factor for infection caused by opportunistic pathogens including C. albicans. The function of the F1Fo-ATP synthase β subunit was characterized through the construction of an ATP2 gene null mutant (atp2Δ/Δ) and the gene-reconstituted strain (atp2Δ/ATP2) in order to understand the link between carbon metabolism and C. albicans pathogenesis. Cell growth, viability, cellular ATP content, mitochondrial membrane potential (ΔΨm), and intracellular ROS were compared between null mutant and control strain. Results showed that growth of the atp2Δ/Δ mutant in synthetic medium was slower than in complex medium. However, the synthetic medium delayed the onset of reduced cell viability and kept cellular ATP content from becoming fully depleted. Consistent with these observations, we identified transcriptional changes in metabolic response that activated other ATP-generating pathways, thereby improving cell viability during the initial phase. Unlike glucose effects, the atp2Δ/Δ mutant exhibited an immediate and sharp reduction in cell viability on non-fermentable carbon sources, consistent with an immediate depletion of cellular ATP content. Along with a reduced viability in non-fermentable carbon sources, the atp2Δ/Δ mutant displayed avirulence in a murine model of disseminated candidiasis as well as lower fungal loads in mouse organs. Regardless of the medium, however, a decrease in mitochondrial membrane potential (ΔΨm) was found in the atp2Δ/Δ mutant but ROS levels remained in the normal range. These results suggest that the F1Fo-ATP synthase β subunit is required for C. albicans pathogenicity and operates by affecting metabolic flexibility in carbon consumption.

ObjectiveTo determine the changes in interhemispheric functional coordination in patients with obstructive sleep apnea–hypopnea syndrome (OSAHS) relative to controls, using a recently introduced method of analysis: voxel-mirrored homotopic connectivity (VMHC).MethodsTwenty-nine patients with OSAHS and twenty-six normal sex-, age-, and education-matched controls were recruited and resting-state functional magnetic resonance imaging data were obtained. We employed VMHC to analyze the interhemispheric functional connectivity differences between groups. The z-values of alterations in VMHC in brain region were correlated with clinical characteristics.ResultsCompared with controls, patients with OSAHS had significantly higher scores for body mass index (t = 5.749, P

The Notch signaling pathway is a highly evolutionarily-conserved cell-cell signaling pathway that regulates many events during development. It plays a pivotal role in the regulation of fundamental cellular processes, such as cell proliferation, stem cell maintenance, and differentiation during embryonic and adult development. However, functions of Notch signaling in Aedes aegypti, the major mosquito vector for dengue, are largely unknown. In this study, we identified a unique feature of A. aegypti Notch (AaNotch) in the control of the sterile-like phenotype in female mosquitoes. Silencing AaNotch with a reverse genetic approach significantly reduced the fecundity and fertility of the mosquito. Silencing AaNotch also resulted in the prevention of micropyle formation, which led to impaired fertilization. In addition, JNK phosphorylation (a signaling molecule in the non-canonical Notch signaling pathway) was inhibited in the absence of AaNotch. Furthermore, treatment with a JNK inhibitor in the mosquito resulted in impaired fecundity and fertility. Taken together, our results demonstrate that non-canonical Notch signaling is essential for controlling fertility in the A. aegypti mosquito.

Iron (Fe) (hydr)oxides control the mobility and bioavailability of tetracycline (TC) in waters and soils. Adsorption of TC on Fe (hydr)oxides is greatly affected by polyvalent metals; however, impacts of molar metal/TC ratios on TC adsorptive behaviours on Fe (hydr)oxides remain unclear. Results showed that maximum TC adsorption on ferrihydrite and goethite occurred at pH 5–6. Such TC adsorption was generally promoted by the addition of Cu2+, Zn2+ and Al3+. The greatest increase in TC adsorption was found in the system with molar Cu/TC ratio of 3 due to the formation of Fe hydr(oxide)–Cu–TC ternary complexes. Functional groups on TC that were responsible for the complexation with Cu2+shifted from phenolic diketone groups at Cu/TC molar ratio 1 as excess Al3+ led to the competitive adsorption with Al/TC complexes. For the Zn2+ addition, no significant correlation was found between TC adsorption capacity and molar Zn/TC ratios.

Histone tail modifications can greatly influence chromatin-associated processes. Asymmetrically modified nucleosomes exist in multiple cell types, but whether modifications on both sister histones contribute equally to chromatin dynamics remains elusive. Here, we devised a bivalent nucleosome system that allowed for the constitutive assembly of asymmetrically modified sister histone H3s in nucleosomes in Saccharomyces cerevisiae. The sister H3K36 methylations independently affected cryptic transcription in gene coding regions, whereas sister H3K79 methylation had cooperative effects on gene silencing near telomeres. H3K4 methylation on sister histones played an independent role in suppressing the recruitment of Gal4 activator to the GAL1 promoter and in inhibiting GAL1 transcription. Under starvation stress, sister H3K4 methylations acted cooperatively, independently or redundantly to regulate transcription. Thus, we provide a unique tool for comparing symmetrical and asymmetrical modifications of sister histone H3s in vivo.

A brain-computer interface (BCI) creates a direct communication pathway between the human brain and an external device or system. In contrast to patient-oriented BCIs, which are intended to restore inoperative or malfunctioning aspects of the nervous system, a growing number of BCI studies focus on designing auxiliary systems that are intended for everyday use. The goal of building these BCIs is to provide capabilities that augment existing intact physical and mental capabilities. However, a key challenge to BCI research is human variability; factors such as fatigue, inattention, and stress vary both across different individuals and for the same individual over time. If these issues are addressed, autonomous systems may provide additional benefits that enhance system performance and prevent problems introduced by individual human variability. This study proposes a human-machine autonomous (HMA) system that simultaneously aggregates human and machine knowledge to recognize targets in a rapid serial visual presentation (RSVP) task. The HMA focuses on integrating an RSVP BCI with computer vision techniques in an image-labeling domain. A fuzzy decision-making fuser (FDMF) is then applied in the HMA system to provide a natural adaptive framework for evidence-based inference by incorporating an integrated summary of the available evidence (i.e., human and machine decisions) and associated uncertainty. Consequently, the HMA system dynamically aggregates decisions involving uncertainties from both human and autonomous agents. The collaborative decisions made by an HMA system can achieve and maintain superior performance more efficiently than either the human or autonomous agents can achieve independently. The experimental results shown in this study suggest that the proposed HMA system with the FDMF can effectively fuse decisions from human brain activities and the computer vision techniques to improve overall performance on the RSVP recognition task. This conclusion demonstrates the potential benefits of integrating autonomous systems with BCI systems.

This study investigates the temperature-drift effect on strain measurement of concrete beams and proposes a method for determination of the mechanical strain of stressed concrete beams. In the study, wireless electrical resistance strain gauges were used to measure the strain of concrete beams. This study first examined how temperature changes affected the strain gauge attached to concrete beams. Subsequently, a concrete beam experiencing changes in temperature and load was monitored for six consecutive days. The test results showed that the apparent strain response of the concrete beam was significantly affected by temperature changes. After adjusting for the temperature effect, the mechanical strain generated by a load could be obtained. However, temperature-induced drift was still observed in the mechanical strain response. Based on the assumption that temperature changes are slow and gradual, and mechanical strain changes are momentary, an adjacent data subtraction method can be used to eliminate the temperature-induced drift present in the mechanical strain data. The subtraction results show that the mechanical strain generated by a load was accurately obtained. The proposed data-processing method could also be used to find the residual strain of the nonelastic response of a beam subjected to substantial short-term forces.

Polyphenol polymerization receives much scientific attentions because it is an important reaction of humification processes. Through an oxidative polymerization reaction (OPR), hydroquinone (H2Q), a naturally occurring compound, has been found to be a vital precursor of humic substances in soils. Chromate (Cr(VI)), a strong oxidant, is widely distributed in the environment due to the inappropriate disposal of Cr-containing wastes. The OPR of H2Q in the presence of Cr(VI) may occur naturally. In the study, it was found that 400 mg L−1 H2Q could be polymerized at pH 3.0 with 105 mg L−1 Cr(VI). The results of FT-IR revealed the presence of both hydroquinone and benzoquinone nuclei in the polymer. The spectra of X-ray absorption near edge structure (XANES) demonstrated a decrease in Cr(VI) content during the OPR of H2Q. Based on the results of linear combination fitting (LCF) for the spectra of XANES, the proportions of Cr species in the precipitates mainly consisted of Cr(OH)3, and Cr-carboxylate contents increased gradually from 15.3 to 25.5% over the reaction time. After acidizing the supernatants at pH 1.0 for 1 d, Cr(III)-HA dominated Cr(III) species. This suggested that humic-like substances were formed during OPR of H2Q, possibly through the formation of Cr(III)-organic complex.

DNA double strand break (DSB) is one of the major damages that cause genome instability and cellular aging. The homologous recombination (HR)-mediated repair of DSBs plays an essential role in assurance of genome stability and cell longevity. Telomeres resemble DSBs and are competent for HR. Here we show that in budding yeast Saccharomyces cerevisiae telomere recombination elicits genome instability and accelerates cellular aging. Inactivation of KEOPS subunit Cgi121 specifically inhibits telomere recombination, and significantly extends cell longevity in both telomerase-positive and pre-senescing telomerase-negative cells. Deletion of CGI121 in the short-lived yku80(tel) mutant restores lifespan to cgi121Δ level, supporting the function of Cgi121 in telomeric single-stranded DNA generation and thus in promotion of telomere recombination. Strikingly, inhibition of telomere recombination is able to further slow down the aging process in long-lived fob1Δ cells, in which rDNA recombination is restrained. Our study indicates that HR activity at telomeres interferes with telomerase to pose a negative impact on cellular longevity.

Two new p-hydroxybenzoic acid glycosides, namely p-hydroxybenzoic acid-4-O-α-d-manopyranosyl-(1 → 3)-α-l-rhamnopyranoside (compound 1) and 4-O-α-l-rhamnopyran-osyl-(1 → 6)-α-d-manopyranosyl-(1 → 3)-α-l-rhamnopyranoside (compound 2), and seven known compounds, compound 3, 6, 7 (acid components), compound 8, 9 (flavonoids), compound 4 (a coumarin) and compound 5 (an alkaloid), were isolated from the 70% ethanol aqueous extract of the aerial parts of Melilotus officinalis (Linn.) Pall. The structures of all compounds were elucidated by use of extensive spectroscopic methods Infrared Spectroscopy (IR), High resolution electrospray ionization mass spectrometry (HR-ESI-MS), and 1H and 13C-NMR). Sugar residues obtained after acid hydrolysis were identified by high-performance liquid chromatography (HPLC). The antioxidant activity of all the compounds was evaluated by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) and 1,1-diphenyl-2-picrylhydrazyl (DPPH). The anti-inflammatory effects of the compounds were also evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. All compounds were shown to inhibit LPS-induced nitric oxide (NO) and prostaglandin E 2 (PGE 2) production by suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, in LPS-stimulated RAW 264.7 cells. The inhibitory effect of all the compounds on MCF-7 cells was determined by Cell Counting Kit-8 (CCK-8) method. The results showed that compounds 1, 2, 7, 8, 9 exhibited better antioxidant activity compared to the other compounds. compounds 1–9 had different inhibitory effects on the release of NO, TNF-α and IL-6 in LPS-stimulated RAW264.7 cells by LPS, of which compound 7 was the most effective against inflammatory factors. compounds 1 and 2 have better antitumor activity compared to other compounds. Further research to elucidate the chemical composition and pharmacological effects of Melilotus officinalis (Linn.) Pall is of major importance towards the development and foundation of clinical application of the species.

In telomerase negative yeast cells, Rad52-dependent recombination is activated to maintain telomeres. This recombination-mediated telomere elongation usually involves two independent pathways, type I and type II, and leads to generation of type I and type II survivors. It remains elusive whether the recombination-mediated telomere elongation prefers to take place on shorter or longer telomeres. In this study, we exploited the de novo telomere addition system to examine the telomere recombination event in telomerase negative cells. We show that recombination preferentially occurs on shorter rather than longer telomeres in both pre-survivors and established type II survivors. In type II survivors, the short VII-L telomeres could invade either terminal TG1-3 sequence or short tracts of TG1-3 sequence in subtelomeric Y'-X and Y'-Y' junction to initiate recombination. Unexpectedly, short VII-L telomere recombination still takes place in type II survivors lacking either Rad50 or Rad59, which are required for type II survivor generation in senescing telomerase-null cells. Our results support the notion that Rad50 and Rad59 are not essential for the maintenance of type II survivors once established.

Iron overload has been associated with carcinogenesis in humans. Intraperitoneal administration of ferric nitrilotriacetate initiates a Fenton reaction in renal proximal tubules of rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC) after repeated treatments. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of this oxidative stress-induced rat RCCs. The results revealed extensive large-scale genomic alterations with a preference for deletions. Deletions and amplifications were numerous and sometimes fragmented, demonstrating that a Fenton reaction is a cause of such genomic alterations in vivo. Frequency plotting indicated that two of the most commonly altered loci corresponded to a Cdkn2a/2b deletion and a Met amplification. Tumor sizes were proportionally associated with Met expression and/or amplification, and clustering analysis confirmed our results. Furthermore, we developed a procedure to compare whole genomic patterns of the copy number alterations among different species based on chromosomal syntenic relationship. Patterns of the rat RCCs showed the strongest similarity to the human RCCs among five types of human cancers, followed by human malignant mesothelioma, an iron overload-associated cancer. Therefore, an iron-dependent Fenton chemical reaction causes large-scale genomic alterations during carcinogenesis, which may result in distinct genomic profiles. Based on the characteristics of extensive genome alterations in human cancer, our results suggest that this chemical reaction may play a major role during human carcinogenesis.