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Abstract Hashimoto’s thyroiditis (HT) is an autoimmune disease, characterized by abnormal elevation in thyroid peroxidase antibody (TPO-Ab) and/or thyroglobulin antibody (TG-Ab). Patients have multiple symptoms despite adequate hormone substitution. In the present study, we aimed to quantify the relationship between thyroid antibodies and multiple symptoms, inflammation and health-related life quality. A total of 108 HT patients with clinical euthyroid status and 57 heathy controls were recruited. Clinical parameters were determined by laboratory examination, and the symptoms burden and life quality were obtained by a Hashimoto’s Thyroiditis Symptom Questionnaire and a SF-36 Questionnaire, respectively. Compared with healthy controls, multiple extrathyroidal symptoms were significantly more serious in HT patients despite euthyroid status, mainly including that related to digestive system (abdominal distension, constipation and diarrhea), endocrine system (chilliness, gain weight and facial edema), neuropsychiatric system (forgetfulness, anxiety, depressed, fatigue, insomnia, irritability, and indifferent) and mucocutaneous system (dry skin, pruritus, and hair loss). Furthermore, serum TPO-Ab and TG-Ab were both inversely correlated with health-related life quality of general health and vitality parameters, and positively correlated with pro-inflammatory factors of TNF-α and IFN-γ, as well as severity of abdominal distension, diarrhea, chilliness, forgetfulness and fatigue. Moreover, TG-Ab level was positively associated with depressed, insomnia and indifferent. HT patients suffered from a variety of symptoms, and the elevated thyroid antibodies were inversely associated with health-related life quality and positively associated with inflammation and multiple extrathyroidal symptoms.

Chromium (Cr)-contaminated in irrigation water poses a significant threat to the safety of wheat (Triticum aestivum L.) production safety. Recent studies suggest that melatonin (MT) could enhance crop tolerance to Cr pollution. This study aimed to investigate the effects of foliar spraying MT on alleviating Cr toxicity and accumulation in wheat irrigated with K2Cr2O7 solution at concentrations of 5, 10, and 20 mg/kg Cr in the soil. Our results showed that Cr-contaminated water irrigation significantly reduced dry weight, grain numbers, grain weight, yield, harvest index, net photosynthetic rate (Pn), maximum and actual photochemical efficiency of photosystem II (Fv/Fm and ΦPSII), chlorophyll contents, and the a/b ratio. It also increased PSII photodamage and oxidative stress in wheat leaves, resulting in high Cr accumulation in roots, leaves, and grains. Foliar spraying of MT alleviated Cr toxicity by improving Pn, Fv/Fm, and ΦPSII, enhancing chlorophyll content, promoting dry matter accumulation and yield, and reducing oxidative stress and Cr translocation. Furthermore, MT application enhanced transcriptional regulation, alleviated oxidative stress by boosting antioxidant enzyme activities, and restricted Cr translocation from roots to leaves and grains by increasing the accumulation of secondary metabolites, such as lignin and metallothionein. These findings suggest that MT application could serve as a viable strategy for reducing Cr contamination in cereals and supporting phytoremediation efforts.

Objective The clinical characteristics, genetic mutation spectrum, treatment strategies and prognoses of 15 children with Dent disease were retrospectively analyzed to improve pediatricians’ awareness of and attention to this disease.Methods We analyzed the clinical and laboratory data of 15 Chinese children with Dent disease who were diagnosed and treated at our hospital between January 2017 and May 2023 and evaluated the expression of the CLCN5 and OCRL1 genes.Results All 15 patients were male and complained of proteinuria, and the incidence of low-molecular-weight proteinuria (LMWP) was 100.0% in both Dent disease 1 (DD1) and Dent disease 2 (DD2) patients. The incidence of hypercalciuria was 58.3% (7/12) and 66.7% (2/3) in DD1 and DD2 patients, respectively. Nephrocalcinosis and nephrolithiasis were found in 16.7% (2/12) and 8.3% (1/12) of DD1 patients, respectively. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 1 patient, minimal change lesion in 5 patients, and small focal acute tubular injury in 1 patient. A total of 11 mutations in the CLCN5 gene were detected, including 3 missense mutations (25.0%, c.1756C > T, c.1166T > G, and c.1618G > A), 5 frameshift mutations (41.7%, c.407delT, c.1702_c.1703insC, c.137delC, c.665_666delGGinsC, and c.2200delG), and 3 nonsense mutations (25.0%, c.776G > A, c.1609C > T, and c.1152G > A). There was no significant difference in age or clinical phenotype among patients with different mutation types (p > 0.05). All three mutations in the OCRL1 gene were missense mutations (c.1477C > T, c.952C > T, and c.198A > G).Conclusion Pediatric Dent disease is often misdiagnosed. Protein electrophoresis and genetic testing can help to provide an early and correct diagnosis.

Abstract Introduction Congenital chloride diarrhoea (CCD) is an autosomal recessive condition that causes secretory diarrhoea and potentially deadly electrolyte imbalances in infants because of solute carrier family 26 member 3 (SLC26A3) gene mutations. Case presentation A 7-month-old Chinese infant with a history of maternal polyhydramnios presented with frequent watery diarrhoea, severe dehydration, hypokalaemia, hyponatraemia, failure to thrive, metabolic alkalosis, hyperreninaemia, and hyperaldosteronaemia. Genetic testing revealed a compound heterozygous SLC26A3 gene mutation in this patient (c.269_270dup and c.2006 C > A). Therapy was administered in the form of oral sodium and potassium chloride supplements, which decreased stool frequency. Conclusions CCD should be considered when an infant presents with prolonged diarrhoea during infancy, particularly in the context of maternal polyhydramnios and dilated foetal bowel loops.

Abstract Background Systemic lupus erythematosus (SLE) and Wilson’s disease (WD) are both systemic diseases that can affect multiple organs in the body. The coexistence of SLE and WD is rarely encountered in clinical practice, making it challenging to diagnose. Case report We present the case of a 9-year-old girl who initially presented with proteinuria, haematuria, pancytopenia, hypocomplementemia, and positivity for multiple autoantibodies. She was diagnosed with SLE, and her blood biochemistry showed elevated liver enzymes at the time of diagnosis. Despite effective control of her symptoms, her liver enzymes remained elevated during regular follow-up. Laboratory tests revealed decreased serum copper and ceruloplasmin levels, along with elevated urinary copper. Liver biopsy revealed chronic active hepatitis, moderate inflammation, moderate-severe fibrosis, and a trend towards local cirrhosis. Genetic sequencing revealed compound heterozygous mutations in the ATP7B gene, confirming the diagnosis of SLE with WD. The girl received treatment with a high-zinc/low-copper diet, but her liver function did not improve. Upon recommendation following multidisciplinary consultation, she underwent liver transplantation. Unfortunately, she passed away on the fourth day after the surgery. Conclusions SLE and WD are diseases that involve multiple systems and organs in the body, and SLE complicated with WD is rarely encountered in the clinic; therefore, it is easy to misdiagnose. Because penicillamine can induce lupus, it is not recommended. Liver transplantation is indicated for patients with liver disease who do not respond to medical treatment with WD. However, further research is needed to determine the optimal timing of liver transplantation for patients with SLE complicated with WD.

Abstract Background Joubert syndrome (JS) is a rare genetically heterogeneous primary ciliopathy characterized by a pathognomonic cerebellar and brainstem malformation, the “molar tooth sign”, and variable organ involvement (such as eye, kidney, liver, and skeleton). Here, we present a case of JS in a Chinese boy. Case presentation An 11-year-old Chinese boy presented with neonatal asphyxiation and hypoxia, strabismus, subsequent developmental delay, ataxia and end-stage kidney disease (ESKD). Routine blood tests showed severe anemia, increasing blood urea nitrogen and creatinine, elevated parathyroid hormone, hypocalcemia, hypokalemia and metabolic acidosis. Urine tests showed mild proteinuria. Ultrasound showed two small kidneys. Brain magnetic resonance imaging (MRI) showed dysplasia of the cerebellar vermis and extension of the upper cerebellar feet with the “molar tooth sign”. Genetic analysis showed novel compound heterozygous mutations in the RPGRIP1L gene [p.L447fs*7(p.Leu447fsTer7) and p.G908V (p.Gly908Val)]. Conclusion In the present study, we identified novel compound heterozygous mutations in the RPGRIP1L gene in a Chinese boy. The clinical and genetic findings of this study will expand the understanding of JS.

Abstract In this study, we investigated the nephroprotective effects of Umbelliferone (UMB) against cisplatin‐induced acute kidney injury (AKI). C57BL/6J mice were treated with cisplatin via a single intraperitoneal injection (25 mg/kg) with or without UMB (40 mg/kg/day) by gavage. Renal function, apoptosis, oxidative stress, inflammation, and mitochondrial function were analyzed to evaluate kidney injury. In vitro, human proximal tubule epithelial cells were treated with cisplatin, with or without UMB, for 24 h. Western blotting and immunohistochemistry were performed to explore the mechanisms underlying the nephroprotective effects of UMB. Cisplatin‐induced renal dysfunction, including increases in blood urea nitrogen, serum creatinine, and renal tubular injury indices (NGAL and KIM‐1), were significantly attenuated by UMB treatment, along with renal phenotypic changes and renal tubular injury, as evidenced by improved renal histology. Moreover, NRF2 was activated by UMB pretreatment, along with the inhibition of oxidative stress and inflammatory response, as evidenced by decreased levels of antioxidant genes and inflammatory cytokines in cisplatin‐induced AKI. Our results demonstrate that UMB can protect against cisplatin‐induced nephrotoxicity, which is mediated by the NRF2 signaling pathway via antioxidant and anti‐inflammatory activities, suggesting the clinical potential of UMB for the treatment of AKI.

Objective To explore the clinical characteristics, treatment protocol and prognosis of children with anti-complement factor H (CFH) autoantibody (Ab)-associated hemolytic uremic syndrome (HUS).Methods Clinical data of 8 patients with anti-CFH Ab-associated HUS who were admitted to Shandong Provincial Hospital from January 2011 to December 2020 were collected retrospectively.Results The age at disease onset ranged between 5.83 and 13.5 years, with a male: female ratio of 1.67:1. The time of onset was distributed from May to June and November to December. Digestive and upper respiratory tract infections were common prodromal infections. Positivity for anti-CFH Ab and reduced C3 levels were observed among all patients. Heterozygous mutation of the CHFR5 gene (c.669del A) and homozygous loss of the CFHR1 gene [loss2(EXON:2-6)] were found in two patients. All patients received early treatment with plasma exchange and corticosteroid therapy. Six patients were given immunosuppressive agents (cyclophosphamide and/or mycophenolate mofetil) for persistent proteinuria. The follow-up period was 12–114 months. Four of 8 patients achieved complete remission, 3 achieved partial remission, and 1 died. Relapse occurred in two patients.Conclusion Children with anti-CFH Ab-associated HUS were mainly school-aged and predominantly male, with onset times of summer and winter. Digestive and upper respiratory tract infections were common prodromal infections. Plasma exchange combined with methylprednisolone pulse therapy in the acute phase and cyclophosphamide or mycophenolate mofetil treatment for maintenance can be utilized in children with anti-CFH Ab-associated HUS if eculizumab is not available.

Background and Aims: Hereditary nephropathy, including monogenic nephropathy, is an important cause of renal insufficiency and end-stage renal disease. Therefore, genetic blockade is necessary for couples with monogenic nephropathy. Following routine application of prenatal diagnosis, preimplantation genetic testing for monogenic disorders (PGT-M) has been applied to the genetic blockade of monogenic disease patients. The purpose of this study is to retrospectively analyze genetic counseling process for patients with nephropathy-related disease and provide clinical overviews of patients with monogenic nephropathy who underwent PGT-M. Method: A single-center retrospective cohort study was conducted at Center for Reproductive Medicine, Shandong University from January 2014 to December 2022. 352 couples with nephropathy-related disease were included in the cohort totally. Statistical analysis was performed using Statistical Package for Social Science software 26.0. Results: Of the 352 couples with nephropathy-related disease, 291 underwent genetic counseling, followed by 180 accepting genetic screening. 104 couples with monogenic nephropathy indications proceeded with PGT-M, including 91 of autosomal dominant inheritance, 9 of autosomal recessive inheritance, 3 of X-linked dominant inheritance, and one of X-linked recessive inheritance. 498 blastocysts were tested by PGT-M combined with preimplantation genetic testing for aneuploidy (PGT-A), making 72 transferable embryos, 249 non-transferable embryos, 72 genetic counseling embryos and 7 amplification failedembryos. Finally, 80 vitrified-thawed single blastocyst transfer cycles were performed. Live births occurred in 38 women, of which 37 transferred embryos with non-pathogenic genotypes. The results of prenatal diagnosis of all newborns were consistent with the testing results for embryos transferred. The cumulative live birth, biochemical pregnancy, clinical pregnancy, ongoing pregnancy and pregnancy loss rates were 36.54%, 56.73%, 49.04%, 7.69%, and 22.03% respectively. Conclusion: PGT-M is an effective means of genetic blockade for couples with monogenic nephropathy. The absence of genetic abnormalities detected by prenatal diagnosis in healthy newborns without monogenic nephropathy also underscore its validity.

ObjectiveTo summarize the clinical features, diagnosis and enzyme replacement therapy(ERT) of Fabry disease (FD) in children.MethodsThe clinical data, laboratory tests, genetic variations and treatment of 10 FD children diagnosed in Shandong Provincial Hospital from September 2020 to June 2022 were retrospectively analyzed.ResultsAmong the 10 cases from 6 families, 7 patients were boys of 4 to 13 years of age, and 3 were girls of 12 to 15 years of age. There were 7 symptomatic patients, including 6 boys and 1 girl. All 7 patients presented with acral neuralgia. Five patients had little or no sweating. Five patients presented with cutaneous angiokeratoma. Two patients had abdominal pain. One patient developed joint symptoms. Four patients had corneal opacity. One patient had hearing loss; one patient had short stature. One patient had mild proteinuria and 1 patient had dysplasia of the right kidney with decreased eGFR (55.28 ml/min.1.73 m2). The left ventricular mass index was slightly elevated in 1 patient. Three patients had mild obstructive ventilatory dysfunction; a small amount of effusion in the intestinal space of the lower abdomen or mild fatty liver was found in 2 patients. Partial empty sella turcica in 1 patient. A total of 6 GLA gene variants were detected in 10 children, among which C.1059_1061delGAT (p.met353del) was a newly discovered mutation. Five children received ERT, of which 4 were treated with agalsidase beta and 1 was treated with agalsidase alpha. Only 1 patient had anaphylaxis. Lyso-GL-3 levels decreased significantly in the first 3 months of ERT initiation and remained relatively stable thereafter in 3 patients. The Lyso-GL-3 level was decreased, but renal impairment continued to progress in 1 patient treated with agalsidase alpha.ConclusionThe clinical manifestations of FD in childhood are diverse, and it is necessary to make a definite diagnosis by combining family history, enzyme activity, biomarkers, gene testing and other indicators. Pedigree screening and high-risk population screening are helpful for early identification, early diagnosis and early treatment. No serious adverse reactions were found during the short-term treatment with agalsidase alpha and beta.

Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes of end-stage kidney disease (ESKD) in children and young adults. For approximately 30% of children with SRNS results from a genetic cause. In this study, genotype-phenotype correlations in a cohort of 283 pediatric patients with SRNS or early-onset NS (nephrotic syndrome presenting within the first year of life) from 23 major pediatric nephrology centers in China were analyzed. All patients were performed with next-generation sequencing and Sanger sequencing. The overall mutation detection rate was 37.5% (106 of 283 patients). WT1 was the most frequently detected mutation, followed by NPHS1, NPHS2, and ADCK4, and these four major causative genes (WT1, NPHS1, NPHS2, and ADCK4) account for 73.6% of patients with monogenic SRNS. Thirteen of 106 individuals (12.3%) carried mutations in ADCK4 that function within the coenzyme Q10 biosynthesis pathway. In the higher frequently ADCK4-related SRNS, two mutations, c.737G>A (p.S246N) and c.748G>C (p.D250H), were the most prevalent. Our study provides not only definitive diagnosis but also facilitate available targeted treatment for SRNS, and prediction of prognosis and renal outcome. Our indications for genetic testing are patients with FSGS, initial SRNS, cases of positive family history or those with extra-renal manifestations.

Chromium (Cr) pollution has serious harm to crop growth, while little is known on the role of melatonin (MT) on seed germination and physiology in Cr-stressed wheat. The effects of seed soaking with MT on growth, reserve mobilization, osmotic regulation and antioxidant capacity of wheat seeds during germination under hexavalent chromium (100 μM) stress were investigated. The results indicated that Cr toxicity decreased the seed germination rate by 16% and suppressed the growth of germinated seeds compared to unstressed seeds. MT in the concentration-dependent manner increased germination rate and promoted subsequent growth when seeds were exposed to Cr stress, but the effect could be counteracted at high concentration. Seed soaking with MT (100 μM) markedly decreased Cr accumulation in seeds, radicals and coleoptiles by 15%, 6% and 15%, respectively, and enhanced α-amylase activity and soluble sugar and free amino acids content in seeds to improve reserve mobilization under Cr stress, compared with Cr treatment. Furthermore, decreasing the level of osmotic regulators (soluble sugar and soluble protein) in radicles under MT combined with Cr treatment confirmed the reduction of osmotic stress caused by Cr stress. Importantly, MT pretreatment reduced H2O2 content by 19% and O2·− release rate by 45% in radicles under Cr toxicity compared with Cr-stressed wheat, in terms of promoting scavenging ability and decreasing production ability, which was to upregulate the activities and encoding genes expression levels of superoxide dismutase (SOD), catalase (CAT), ascorbic acid peroxidase (APX) and peroxidase (POD) and to downregulate plasma membrane-bound NADPH oxidase (NOX) encoding genes (TaRbohD, TaRbohF) expression, respectively. In all, these results provided evidence that seed soaking with MT could be a potentially method to protect wheat seeds from Cr toxicity, which effectively ameliorated germination under Cr stress by enhancing reserve mobilization and antioxidant metabolism in wheat.

Abstract Behavioral barriers to gene flow often evolve faster than intrinsic incompatibilities and can eliminate the opportunity for hybridization between interfertile species. While acoustic signal divergence is a common driver of premating isolation in birds and insects, its contribution to speciation in mammals is less studied. Here we characterize the incidence of, and potential barriers to, hybridization among three closely related species of grasshopper mice (genus Onychomys). All three species use long‐distance acoustic signals to attract and localize mates; Onychomys arenicola and Onychomys torridus are acoustically similar and morphologically cryptic whereas Onychomys leucogaster is larger and acoustically distinct. We used genotyping‐by‐sequencing (GBS) to test for evidence of introgression in 227 mice from allopatric and sympatric localities in the western United States and northern Mexico. We conducted laboratory mating trials for all species pairs to assess reproductive compatibility, and recorded vocalizations from O. arenicola and O. torridus in sympatry and allopatry to test for evidence of acoustic character displacement. Hybridization was rare in nature and, contrary to prior evidence for O. torridus/O. arenicola hybrids, only involved O. leucogaster and O. arenicola. In contrast, laboratory crosses between O. torridus and O. arenicola produced litters whereas O. leucogaster and O. arenicola crosses did not. Call fundamental frequency in O. torridus and O. arenicola was indistinguishable in allopatry but significantly differentiated in sympatry, a pattern consistent with reproductive character displacement. These results suggest that assortative mating based on a long‐distance signal is an important isolating mechanism between O. torridus and O. arenicola and highlight the importance of behavioral barriers in determining the permeability of species boundaries.

Renal cell carcinoma (RCC) accounts for 2–3% of adult malignant tumors, and the incidence of RCC worldwide has increased by about 2% over the past two decades. The homeobox protein Six2 has been shown to promote the stemness of breast cancer cells and play a role in kidney development, but its involvement in RCC progression has not previously been investigated. Here, we found that six2 expression was significantly increased in RCC tissues and negatively correlated with the overall survival of patients with RCC. In addition, six2 expression exhibited a remarkably higher level relative to that in normal renal cells. Functional experiments showed that six2 knockdown attenuated the stemness of RCC cells, which was evident by decreased spheroid formation ability and stemness marker (sox2 and nanog) expression. Mechanistic studies indicated that Six2 directly bound to the enhancer of sox2, promoting sox2 expression and downstream effector expression of nanog. Furthermore, overexpression of sox2 rescued the inhibitory effects of six2 on the stemness of RCC cells. Notably, six2 expression is positively correlated with sox2 and nanog expression in RCC tissues. Collectively, our results point toward a six2/sox2 axis responsible for RCC cell stemness.

Abstract To quickly solve the fractional Black–Scholes (B–S) equation in the option pricing problems, in this paper, we construct pure alternative segment explicit–implicit (PASE-I) and pure alternative segment implicit–explicit (PASI-E) difference schemes for time-space fractional B–S equation. It is a kind of intrinsic parallel difference schemes constructed on the basis of classic explicit scheme and classic implicit scheme combined with alternate segmentation technique. PASE-I and PASI-E schemes are analyzed to be unconditionally stable, convergent with second-order spatial accuracy and (2−α) $(2-\alpha)$th-order time accuracy, and they have a unique solution. The numerical experiments show that the two schemes have obvious parallel computing properties, and the computation time is greatly improved compared to Crank–Nicolson (C–N) scheme. The PASE-I and PASI-E intrinsic parallel difference methods are efficient to solve the time-space fractional B–S equation.

Objective: To investigate the effect of simvastatin on lipid accumulation and the expression of CXCL16 and Nephrin in murine podocytes induced by oxidized LDL (OxLDL) in order to explore the mechanism of protection. Methods: Murine podocytes (MPC5) were incubated with OxLDL (80 μg/ml) at different concentrations of simvastatin (0, 1.0, and 2.0 μg/ml) for 48 hours. Oil red O staining was used for the assessment of lipid accumulation in podocytes, and colorimetric cholesterol detection kit was used for the quantitative measurement. CXCL16 and Nephrin expression were detected by using Western blot. Results: OxLDL-treated MPC5 cells exhibited significantly higher intracellular lipid accumulations compared with the untreated group. Colorimetric detection found that total cholesterol was 90.3 ± 30.1 μg/ml in untreated cells and 226.5 ± 21.6 μg/ml in OxLDL-treated cells. The difference was statistically significant (p < .01). While cells were treated with both OxLDL and simvastatin, we observed little lipid accumulation. Total cholesterol in OxLDL + simvastatin cells were 151.8 ± 6.8 μg/ml and 135.5 ± 26.9 μg/ml under 1.0 μg/ml or 2.0 μg/ml of simvastatin treatment, respectively. Both were statistically significantly lower than that of the OxLDL treated cells (p < .05). Western blot analysis showed that CXCL16 expression was significantly increased (p < .05) in OxLDL-treated cells compared with the untreated cells, and was significantly inhibited by application of simvastatin (p < .05). The analysis of nephrin expression showed that there were no changes in group simvastatin compared with that of control group (p > .05). Nephrin expression was significantly reduced by treatment with OxLDL (p < .01), and was significantly increased by application of simvastatin (p < .05). Conclusion: Simvastatin treatment could significantly decrease lipid accumulation in murine podocytes and this protective effect was realized through inhibition of the expression of CXCL16 and increase in the expression of nephrin.

To develop efficient N management strategies for high wheat NUE and minimizing the environmental impact of N losses under asymmetric warming, 15N micro-plot experiments were conducted to investigate the effects of night-warming during winter (warming by 1.47–1.56°C from tillering to jointing), spring (warming by 1.68–1.82°C from jointing to booting), and winter + spring (warming by 1.53–1.64°C from tillering to booting) on root growth and distribution of winter wheat, the fates of 15N-labeled fertilizer, and their relationships in 2015–2017. The results showed that night-warming increased the recovery of basal 15N and top-dressed 15N, while reduced the residual and loss of basal 15N and top-dressed 15N. The losses decreases of top-dressed 15N were higher than those of basal 15N, indicating that night-warming reduced losses of fertilizer 15N mainly by reducing losses of top–dressed 15N. Moreover, pre-anthesis root dry matter accumulation rate in 0–60 cm soil layer were promoted, resulted in improved root biomass and root/shoot ratio, which favored increasing recovery of fertilizer 15N and reducing losses of fertilizer 15N. Furthermore, residual fertilizer 15N content in 0–100 cm soil layer was reduced, which was associated with improved root weight density in 0–60 cm soil layer, resulted in reduced leaching losses of fertilizer 15N. The path analysis showed that root dry matter distribution in 0–20 cm soil layer was the most important in contributing to reducing losses of total fertilizer 15N compared with other soil layers. Two years data showed that winter and spring night-warming gave better root growth and distribution in 0–20 cm soil layer, resulted in reduced the losses of fertilizer 15N and improved the recovery of fertilizer 15N, while maximizing grain yield of winter wheat, and winter + spring night-warming resulted in higher advantages than winter night-warming and spring night-warming.

BACKGROUND:High-throughput sequencing technology has revolutionized both medical and biological research by generating exceedingly large numbers of genetic variants. The resulting datasets share a number of common characteristics that might lead to poor generalization capacity. Concerns include noise accumulated due to the large number of predictors, sparse information regarding the p≫n problem, and overfitting and model mis-identification resulting from spurious collinearity. Additionally, complex correlation patterns are present among variables. As a consequence, reliable variable selection techniques play a pivotal role in predictive analysis, generalization capability, and robustness in clustering, as well as interpretability of the derived models. METHODS AND FINDINGS:K-dominating set, a parameterized graph-theoretic generalization model, was used to model SNP (single nucleotide polymorphism) data as a similarity network and searched for representative SNP variables. In particular, each SNP was represented as a vertex in the graph, (dis)similarity measures such as correlation coefficients or pairwise linkage disequilibrium were estimated to describe the relationship between each pair of SNPs; a pair of vertices are adjacent, i.e. joined by an edge, if the pairwise similarity measure exceeds a user-specified threshold. A minimum k-dominating set in the SNP graph was then made as the smallest subset such that every SNP that is excluded from the subset has at least k neighbors in the selected ones. The strength of k-dominating set selection in identifying independent variables, and in culling representative variables that are highly correlated with others, was demonstrated by a simulated dataset. The advantages of k-dominating set variable selection were also illustrated in two applications: pedigree reconstruction using SNP profiles of 1,372 Douglas-fir trees, and species delineation for 226 grasshopper mouse samples. A C++ source code that implements SNP-SELECT and uses Gurobi optimization solver for the k-dominating set variable selection is available (https://github.com/transgenomicsosu/SNP-SELECT).

Synovitis is an important disease that causes intractable pain in TMJ. Some investigations suggested that the increasing expression of IL-1β secreted by synovial lining cells plays an important role in synovial inflammation and cartilage destruction in TMJ. In our previous research, the results demonstrated that TLR4 is involved in the expression of IL-1β in SFs from TMJ with lipopolysaccharide stimulation. However, the inflammatory response that occurred in synovial membrane is not caused by bacterial infection. In the current study, we investigated whether or not TLR4 participates in the inflammatory responses and the expression of IL-1β in synovial membrane of rats induced by occlusal interference. The results showed that obvious inflammation changes were observed in the synovial membranes and the expression of TLR4 and IL-1β was increased at both mRNA and protein levels in the occlusal interference rats. In addition, the inflammation reactions and the increased expression of IL-1β could be restrained by treatment with TAK-242, a blocker of TLR4 signaling. The results prompted us that the activation of TLR4 may be involved in the inflammatory reactions and increased expression of IL-1β in patients with synovitis and participate in the mechanisms of the initiation and development of synovial injury by regulating the expression of inflammatory mediators like IL-1β in synovial membranes.

BackgroundHuman leukocyte antigen DP (HLA-DP) locus has been reported to be associated with hepatitis B virus (HBV) infection in populations of Japan and Thailand. We aimed to examine whether the association can be replicated in Han Chinese populations.Methodology/principal findingsTwo HLA-DP variants rs2395309 and rs9277535 (the most strongly associated SNPs from each HLA-DP locus) were genotyped in three independent Han cohorts consisting of 2 805 cases and 1 796 controls. By using logistic regression analysis, these two SNPs in the HLA-DPA1 and HLA-DPB1 genes were significantly associated with HBV infection in Han Chinese populations (P = 0.021∼3.36×10(-8) at rs2395309; P = 8.37×10(-3)∼2.68×10(-10) at rs9277535). In addition, the genotype distributions of both sites (rs2395309 and rs9277535) were clearly different between southern and northern Chinese population (P = 8.95×10(-5) at rs2395309; P = 1.64×10(-9) at rs9277535). By using asymptomatic HBV carrier as control group, our study showed that there were no associations of two HLA-DP variants with HBV progression (P = 0.305∼0.822 and 0.163∼0.881 in southern Chinese population, respectively; P = 0.097∼0.697 and 0.198∼0.615 in northern Chinese population, respectively).ConclusionsOur results confirmed that two SNPs (rs2395309 and rs9277535) in the HLA-DP loci were strongly associated with HBV infection in southern and northern Han Chinese populations, but not with HBV progression.