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Abstract Insulin has been shown to modulate neuronal processes through insulin receptors. The ion channels located on neurons may be important targets for insulin/insulin receptor signaling. Both insulin receptors and acid-sensing ion channels (ASICs) are expressed in dorsal root ganglia (DRG) neurons. However, it is still unclear whether there is an interaction between them. Therefore, the purpose of this investigation was to determine the effects of insulin on the functional activity of ASICs. A 5 min application of insulin rapidly enhanced acid-evoked ASIC currents in rat DRG neurons in a concentration-dependent manner. Insulin shifted the concentration–response plot for ASIC currents upward, with an increase of 46.2 ± 7.6% in the maximal current response. The insulin-induced increase in ASIC currents was eliminated by the insulin receptor antagonist GSK1838705, the tyrosine kinase inhibitor lavendustin A, and the phosphatidylinositol-3 kinase antagonist wortmannin. Moreover, insulin increased the number of acid-triggered action potentials by activating insulin receptors. Finally, local administration of insulin exacerbated the spontaneous nociceptive behaviors induced by intraplantar acid injection and the mechanical hyperalgesia induced by intramuscular acid injections through peripheral insulin receptors. These results suggested that insulin/insulin receptor signaling enhanced the functional activity of ASICs via tyrosine kinase and phosphatidylinositol-3 kinase pathways. Our findings revealed that ASICs were targets in primary sensory neurons for insulin receptor signaling, which may underlie insulin modulation of pain.

IntroductionThe pattern of extraocular muscle involvement in ocular myasthenia gravis varies across different reports, diverging from our own observations. Thus, we employed two novel tools to discern this pattern.MethodsA retrospective analysis was conducted to collect and organize clinical data from 43 patients diagnosed with ocular myasthenia gravis. Each patient underwent both the computerized diplopia test and the Ocular Motor Nerve Palsy Scale assessment to evaluate the involvement of extraocular muscles.ResultsAmong the patients, there were 30 male and 13 female individuals, with a total of 113 affected extraocular muscles identified. Among all the affected extraocular muscles, the involvement of the levator palpebrae superioris muscle accounted for 35.40%, medial rectus muscle 7.7%, lateral rectus muscle 16.81%, superior rectus muscle 13.27%, inferior rectus muscle 12.39%, superior oblique muscle 1.77%, and inferior oblique muscle 2.65% of the total affected extraocular muscles. The positivity rates of the Neostigmine test were 89.19%, AChR antibody detection was 59.38%, and repetitive nerve stimulation was 34.38%. The AChR antibody positive rate among patients with only diplopia was 100%; among those with only ptosis, it was 80%; and among those with both diplopia and ptosis, it was 86.67%.ConclusionThe involvement of the extraocular muscles is not uniform. The levator palpebrae superioris exhibits the highest incidence rate, followed by the four rectus muscles and two oblique muscles. The inferior oblique involvement typically occurs when four or more EOMs are affected. Moreover, the levator palpebrae superioris and medial rectus show a higher tendency for bilateral involvement compared with other extraocular muscles.

Abstract Background Tobacco mosaic virus (TMV) is a harmful plant pathogen that causes a decline in the quality and yield of many economic crops. Natural products are important potential sources of biopesticides for the prevention and treatment of TMV. This study focuses on the discovery of anti-TMV active compounds from Aspergillus versicolor and investigates their activities against TMV. Results In this study, four isocoumarins 7-methoxy-3-(2-oxopropy)-5-hydroxymethyl-isocoumarin (1), 7-methyl-3-(2-oxopropy)-5-hydroxymethyl-isocoumarin (2), oryzaein A (4) and oryzaein B (5), two indole alkaloids aspergilline F (6) and aspergilline G (7), and one indole alkaloid and isocoumarin hybrid aspergillactone A (3) were isolated from Nicotiana tabacum-derived A. versicolor YNCA0363. Among them, compounds 1–3 are new isolates, compound 3 represents the first example of indole alkaloid and isocoumarin connected by C(12)-N(1′) bond. The inactivation efficacies for compounds 1, 2 and 3 were 58.9, 43.8 and 52.6% at the concentration of 50 μg/mL, respectively, which were significantly higher than that of positive control, ningnanmycin. The protective effects of these three compounds ranged from 48.6 to 62.3%, which were significantly higher than that of positive control. At the same time, the content of TMV-CP was also significantly lower than that of positive control, and compound 1 was the lowest. The curative efficacy for compound 1 was also much better than that of positive control. Transmission electron microscopy (TEM) showed that compound 1 could directly destroy viral particles into small fragments. The results of molecular docking showed that the binding ability of compounds 1, 3, 2 to TMV-CP protein decreased in turn, which was consistent with the results of activities assays. Conclusion Compounds 1–3 from A. versicolor showed potent antiviral activities against TMV including inactivation, protective and curative effects. Compound 1 can directly destroy the virus particles to achieve the effect of anti-TMV. In addition, compounds 1–3 can bind to TMV-CP protein in molecular docking experiments. The above experimental results show that TMV-CP was an important target for active indole alkaloid and isocoumarin derivatives to fracture TMV particle. The results provided evidence that indole alkaloid and isocoumarin derivatives from A. versicolor have the potential to control TMV. Graphical Abstract

Introduction: Auricular acupressure (AA) has been widely utilized in the management of constipation, with several studies suggesting its efficacy in treating constipation patients. However, the safety and effectiveness of AA in constipation remain uncertain. Hence, the aim of this study was to assess the effectiveness and safety of AA for constipation.Methods and analysis: A total of eight electronic databases and three clinical trial registration platforms were searched from their inception to April 2023 for randomized controlled trials (RCTs) of AA for constipation. The included studies were appraised for quality using the Cochrane Collaboration’s Risk of Bias Assessment tool. The quality of evidence was assessed by two independent reviewers employing the Grading of Recommendations Assessment, Development, and Evaluation System (GRADE) evaluation tool. Meta-analysis of data and assessment of publication bias were performed using RevMan 5.4 and STATA 13.0 software, respectively.Results: This review included 34 randomized controlled trials conducted between 2007 and 2023, involving 2,465 participants. The findings of the study indicate that overall, AA is significantly associated with improved CSBMs (MD = 1.22, 95% CI [0.68, 1.77], p < 0.0001, I2 = 0%), BSF (MD = 0.72, 95%CI: [0.15,1.28], p = 0.01, I2 = 82%), CAS (MD = -3.28, 95%CI: [−5.95, −0.60], p = 0.02, I2 = 80%), responder rate (RR = 1.27, 95%CI: [1.16, 1.38], p < 0.00001, I2 = 79%), cure rate (RR = 1.84, 95% CI [1.56, 2.15], p < 0.00001, I2 = 0%), and PAC-QOL (MD = −2.73, 95% CI: [−3.41, −2.04], p < 0.00001, I2 = 98%) compared to the control group. However, no difference in PAC-SYM (MD = −0.15, 95%CI: [−0.38,0.07], p = 0.19, I2 = 67%) was found between the two groups. Additionally, there was no significant difference in adverse events (RR = 0.53, 95% CI: [0.24, 1.21], p = 0.13, I2 = 38%).Conclusion: Based on the available evidence, auricular acupressure appears to be a potentially safe and effective intervention for managing constipation in adults. Nonetheless, the overall quality of evidence for the identified outcomes was assessed as low to very low, highlighting the need for additional high-quality randomized controlled trials to further validate these findings.Systematic Review Registration:https://www.crd.york.ac.uk/prospero, identifier CRD42023425033.

Abstract Background Endomucin (EMCN) is a type I transmembrane glycoprotein and a mucin‐like component of the endothelial cell glycocalyx. The mechanism of EMCN action in colorectal cancer (CRC) remains unclear. Aims Our aim was to explore the role of EMCN in the progression of CRC. Materials & Methods We examined EMCN expression in CRC tissues and normal para‐carcinoma tissues. The function and mechanisms of EMCN were checked in CRC cell lines and in mouse xenograft. Additionally, we used co‐immunoprecipitation and mass spectrometry to identify the potential EMCN‐binding proteins. Functional annotation analysis showed where these genes were enriched. Results We found that EMCN was overexpressed in tumor tissues compared with that in normal para‐carcinoma tissues. We also found that overexpression of EMCN induced CRC proliferation and metastasis both in vitro and in vivo. EMCN knockdown prevents epithelial‐mesenchymal transition in vitro. We identified 178 potential EMCN‐binding partners. Furthermore, functional annotation analysis indicated that these genes were considerably enriched in carcinogenic‐related functions and pathways. Collectively, the identification of EMCN‐binding partners enhanced our understanding of the mechanism of EMCN‐mediated malignant phenotypes, and this research may provide valuable insights into the molecular mechanisms underlying CRC. Conclusion Tumor‐derived endomucin promotes colorectal cancer proliferation and metastasis. We identified 178 EMCN‐binding proteins and initially screened three potential EMCN‐interacting proteins: NALCN, and TPM2, ANKK1. Our study provides valuable insights into the molecular mechanisms underlying CRC development.

Abstract Background Since Nicotiana tabacum (tobacco) has important significance to humans for their medicinal uses, to find antivirus activities inhibitors from tobacco, increase its medicinal value, and comprehensive utilization of its by-products, our group had investigated the chemical constituents of the stems of Y-202, a cultivar of tobacco which high resistance to tobacco mosaic virus (TMV). Results Four new isoindolinone-type alkaloids, nicoisoindoles A–D (1–4), along with four known isoindole derivatives (5–8) were isolated. Compounds 1–4 represent a new subclass of isoindolinone alkaloids with rare cyclopenta[f]isoindole-1-one frameworks. Among them, nicoisoindole C (3) possesses an unusual N-2-(5-methoxy-6-methylpyridin-2-yl) ethyl moiety, while nicoisoindole D (4) has a novel a N-(3-methyl-6-oxo-1,6-dihydropyridin-2-yl)methyl substituent. Interestingly, compounds 1, 3, and 4 showed high anti-TMV activities with inhibition rates of 43.8%, 58.8%, and 67.8% at the concentration of 20 μM, and IC50 values of 23.6, 19.5 and 15.4 μM, respectively, even more potent than that of positive control. Conclusions The successful isolation and structure identification of new oxocyclopenta[f]isoindole-1-ones provide materials for the screening of antivirus activities inhibitors, and contribute to the development and utilization of the waste from tobacco cultivation. Graphical Abstract

ObjectiveTo investigate the correlation between the alteration of intestinal microbiota and disease in children with bronchiolitis.MethodsFifty seven children diagnosed with bronchiolitis from January 2020 to January 2022 in our pediatric department were included as the case group, and another 36 normal children were included as the control group. Stool and blood were collected from both groups for high-throughput sequencing, untargeted metabolite detection and ELISA. A mouse model of RSV infection was established to validate the results of clinical case detection.ResultsBody weight, passive smoking, and a host of other factors were possible as acute bronchiolitis influencing factors in the onset of acute bronchiolitis. The alpha diversity Shannon, Simpson and Pielou’s evenness indices were significantly lower in children with acute bronchiolitis than in healthy children with gated levels of Firmicutes, Bacteroidetes and genus levels of Clostridium and other short chain fatty acid-producing bacteria. The relative abundance of short-chain fatty acid (SCFAs)-producing bacteria decreased and the abundance of genus-level sphingolipid-producing bacteria Sphingomonas increased; the progression of acute bronchiolitis is likely to be associated with the abundance of Clostridium and Sphingomonas and higher fecal amino acid concentrations, including FF-MAS, L-aspartic acid, thioinosinic acid, picolinic acid; supplementation with Clostridium butyricum significantly alleviated RSV infection-induced lung inflammation.ConclusionThe progression of bronchiolitis may be associated with altered intestinal microbiota, decreased SCFAs and elevated sphingolipids metabolism in children. Some fecal bacteria and metabolites may predict the onset of bronchiolitis, and oral administration of Clostridium butyricum may alleviate RSV infection-induced pulmonary inflammation.

This study investigated the growth, SPAD value, chlorophyll fluorescence and transcriptome response of endophyte uninoculated and inoculated rice seedlings under Pb stress after treatment of 1 d and 5 d. Inoculation of endophytes significantly improved the plant height, SPAD value, Fv/F0, Fv/Fm and PIABS by 1.29, 1.73, 0.16, 1.25 and 1.90 times on the 1 d, by 1.07, 2.45, 0.11, 1.59 and 7.90 times on the 5 d, respectively, however, decreased the root length by 1.11 and 1.65 times on the 1 d and 5 d, respectively under Pb stress. Analysis of rice seedlings leaves by RNA-seq, there were 574 down-regulated and 918 up-regulated genes after treatment of 1 d, 205 down-regulated and 127 up-regulated genes after treatment of 5 d, of which 20 genes (11 up-regulated and 9 down-regulated) exhibited the same changing pattern after treatment of 1 d and 5 d. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to annotate these DEGs, and it was found that many of DEGs involved in photosynthesis, oxidative detoxification, hormone synthesis and signal transduction, protein phosphorylation/kinase and transcription factors. These findings provide new insights into the molecular mechanism of interaction between endophyte and plants under heavy metal stress, and contribute to agricultural production in limited environments.

AbstractAbnormal nuclear morphology is suggested to be a hallmark of aging and one such abnormality is nuclear blebbing. However, little is known about whether and how nuclear blebbing participates in animal aging, and what regulates it. In this study, we show that the frequency of nuclear blebbing in the hypodermis increases during aging in wild-type C. elegansC. elegans

Abstract. Background:. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with loss of motor neurons. Our objective was to explore the epidemiology, clinical features, and survival factors of 1809 patients with ALS. Methods:. We analyzed 1809 ALS patients, who were recruited from the Peking University Third Hospital from January 2005 to December 2015. Demographic data and disease-related parameters were collected. Kaplan-Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors. Results:. The results showed that the average annual incidence in Beijing alone was 0.38 cases/100,000 person-years and the mean age of onset was 48.88 ± 11.35 (95% confidence interval [CI]: 48.17–49.85) years. The median survival time from onset to death/tracheostomy was 58.89 ± 33.03 (95% CI: 51.46–63.84) months. In the adjusted Cox proportional hazard model, age of onset, diagnosis delay, rate of disease progression (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised decline [points/month]), and body mass index all had an independent effect on survival in ALS. Conclusions:. Our study provides information on epidemiology, clinical features, and survival factors of patients with ALS in China. These results can be helpful in clinical practice, clinical trial design, and validation of new tools to predict disease progression.

How phosphorylation mediated by Insulin/IGF-1 Signaling kinases regulates lifespan remains unclear. Here the authors perform a large-scale quantitative phosphoproteomic analysis of wildtype and IIS mutant C. elegans strains to reveal detailed functional insights into longevity.

Hybrid rice significantly contributes to the food supply worldwide. Backbone parents play important roles in elite hybrid rice breeding systems. In this study, we performed pedigree-based analysis of the elite backbone parent rice variety, namely, Shuhui 527 (SH527, Oryza sativa), to exploit key genome regions during breeding. Twenty-four cultivars (including SH527, its six progenitors and 17 derived cultivars) were collected and analyzed with high-density single nucleotide polymorphism (SNP) array. Scanning all these cultivars with genome-wide SNP data indicated the unique contributions of progenitors to the SH527 genome and identified the key genomic regions of SH527 conserved within all its derivatives. These findings were further supported by known rice yield-related genes or unknown QTLs identified by genome-wide association study. This study reveals several key regions for SH527 and provides insights into hybrid rice breeding.

Lysophosphatidic acid (LPA), a lipid metabolite, plays a role in both neuropathic and inflammatory pain through LPA1 receptors. P2X3 receptor has also been shown to participate in these pathological processes. However, it is still unclear whether there is a link between LPA signaling and P2X3 receptors in pain. Herein, we show that a functional interaction between them in rat dorsal root ganglia (DRG) neurons. Pretreatment of LPA concentration-dependently enhanced α,β-methylene-ATP (α,β-meATP)-induced inward currents mediated by P2X3 receptors. LPA significantly increased the maximal current response of α,β-meATP, showing an upward shift of the concentration-response curve for α,β-meATP. The LPA enhancement was independent on the clamping-voltage. Enhancement of P2X3 receptor-mediated currents by LPA was prevented by the LPA1 receptor antagonist Ki16198, but not by the LPA2 receptor antagonist H2L5185303. The LPA-induced potentiation was also attenuated by intracellular dialysis of either G-protein inhibitor or protein kinase C (PKC) inhibitor, but not by Rho inhibitor. Moreover, LPA significantly changed the membrane potential depolarization and action potential burst induced by α,β-meATP in DRG neurons. Finally, LPA exacerbated α,β-meATP- induced nociceptive behaviors in rats. These results suggested that LPA potentiated the functional activity of P2X3 receptors in rat primary sensory neurons through activation of the LPA1 receptor and its downstream PKC rather than Rho signaling pathway, indicating a novel peripheral mechanism underlying the sensitization of pain.

Abstract Backgrounds Although kidney impairments have been reported following immune checkpoint inhibitors (ICIs) in clinical studies, there are few pharmacoepidemiology studies to compare the occurrences, clinical features, and prognosis of renal adverse effects. Methods Disproportionality and Bayesian analysis were used in data mining to screen the suspected renal adverse effects after the administration of different ICIs, based on FDA's Adverse Event Reporting System (FAERS) from January 2004 to September 2019. The time to onset, fatality and hospitalization rates of renal adverse effects were also investigated. Results We identified 1444 reports of renal adverse effects. Affected patients tended to be older than 65 years (52.7%). Renal effects were most commonly reported in nivolumab monotherapy (33.24%). Atezolizumab appeared the strongest association among six ICI monotherapies, based on the highest reporting odds ratio (ROR = 144.38, two‐sided 95% CI = 123.08 −169.37), proportional reporting ratio (PRR = 139.13, χ2 = 21 425.38), and empirical Bayes geometric mean (EBGM = 131.75, one‐sided 95% CI = 115.28). The combination treatments showed higher RORs, PRRs, and EBGMs, compared with either nivolumab or pembrolizumab monotherapy. The median onset time of renal adverse effects was 48 (interquartile range [IQR] 18.75‐121.25) days after the monotherapies of ICI regimens. Patients treated with the combination of nivolumab plus ipilimumab were younger than receivers in nivolumab monotherapy (63.81 ± 12.03 vs 66.39 ± 11.53, P = .004); The fatality rate of renal adverse effects appeared lower in the combination group, compared to nivolumab monotherapy (18.53% vs 27.50%, P = .004). The top hospitalization rates due to renal effects occurred in patients with combination therapies. Conclusion Based on the FAERS database, we profiled renal adverse effects after various ICIs with real‐world data in occurrences, clinical characteristics, and prognosis. Renal effects should be tightly monitored, especially within the first several months after ICIs administration. Particular concern should be paid for patients with a tendency for kidney impairments, such as old age.

Abstract Background Cryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn. Methods This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed. Results Age at renal biopsy was 47 ± 12 years, with female/male ratio 3/4. Urine protein was 5.6 (3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations included purpura (n = 6), arthralgia (n = 1), peripheral neuropathy (n = 1), and cardiomyopathy (n = 1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) (n = 3), membranoproliferative Gn (n = 3), and mesangial proliferative Gn (n = 1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM (n = 5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. They were given corticosteroid alone (n = 2) or combined with cyclophosphamide (n = 4) or mycophenolate mofetil (n = 1). Two patients received plasmapheresis. The median follow-up time was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8–5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m2. The median cryocrit decreased to 1.0 (0, 5.75) %. Conclusions The etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early stage benefit patients’ renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.

Although tumor immune microenvironment plays an important role in antitumor therapy, few studies explored the gene signatures associated with the tumor immune microenvironment of bladder cancer after neoadjuvant chemotherapy. We examined and analyzed differentially expressed genes from 9 patients with stage I-III bladder cancer by RNA immune-oncology profiling platform. After neoadjuvant chemotherapy, the expressions of 43 genes in 19 pathways and 10 genes in 5 pathways were upregulated and downregulated, respectively. Neoadjuvant chemotherapy also promoted the expression of genes related to the activation of antitumor immune responses and decreased the expression of genes related to tumor proliferation pathways. In addition, neoadjuvant chemotherapy improved tumor response to immune checkpoint blockade. Furthermore, this study also identified several genes that can be used to predict the efficacy of neoadjuvant chemotherapy and their possible molecular mechanisms. In conclusion, neoadjuvant chemotherapy may promote the activation of antitumor effects, improve the suppressive tumor immune microenvironment, and increase the sensitivity of bladder cancer to immune checkpoint blockade.

Two unusual polyketide–sesquiterpene metabolites, craterodoratins T (1) and U (2), along with the known compound craterellin A (3), were isolated from the higher fungus Craterellus odoratus. The structures of isolated compounds were characterized based on nuclear magnetic resonance (NMR) and mass spectrum (MS) spectroscopic analysis, while the absolute configuration of the compounds was determined by theoretical NMR and electronic circular dichroism (ECD) calculations. Compound 1 possessed a rare structure with two aromatic groups. Compounds 1 and 3 showed immunosuppressive activity with IC50 values ranging from 5.516 to 19.953 μM.

Abstract Background Ankylosing spondylitis (AS) is a well-known male-predominant inflammatory disease. This study aimed to assess the gender disparity in chronic kidney disease (CKD) in AS patients in China. Methods AS patients were retrospectively studied at Peking Union Medical College hospital between January 2002 and June 2018. Results Among 616 patients with AS, 154 (25.0%) patients had CKD (age, 41.8 ± 14.2 years; male:female, 3.2:1). Overall, 80 (13.0%) patients had only microscopic hematuria, 62 (10.1%) had proteinuria with or without hematuria, and 33 (5.4%) exhibited a reduced estimated glomerular filtration rate (eGFR, ≤60 mL/min/1.73 m2). Male CKD patients had more frequent proteinuria (p

Aim: To compare the diagnostic values by using transthoracic echocardiography (ECHO) and multi-slice spiral CT coronary angiography (CTCA) for identifying coronary artery thrombosis in children with Kawasaki disease (KD).Methods: Total 97 KD children with coronary artery dilation complications in our hospital from June 2012 to December 2020 were included in the study. CTCA and ECHO were performed after over 1 month of illness.Results: Coronary artery thrombosis was found in 14 out of 97 patients. Among them, 10 were identified as positive by CTCA, 9 were identified as positive by ECHO, and 5 were identified as positive by both CTCA and ECHO.Conclusion: Both CTCA and ECHO can be used to diagnose coronary artery thrombosis. ECHO has advantage in identifying low-density thrombus, and CTCA is better for the clot in distal coronary artery. They can complement each other.

Nematode-trapping (NT) fungi play a significant role in the biological control of plant- parasitic nematodes. NT fungi, as a predator, can differentiate into specialized structures called “traps” to capture, kill, and consume nematodes at a nutrient-deprived condition. Therefore, trap formation is also an important indicator that NT fungi transition from a saprophytic to a predacious lifestyle. With the development of gene knockout and multiple omics such as genomics, transcriptomics, and metabolomics, increasing studies have tried to investigate the regulation mechanism of trap formation in NT fungi. This review summarizes the potential regulatory mechanism of trap formation in NT fungi based on the latest findings in this field. Signaling pathways have been confirmed to play an especially vital role in trap formation based on phenotypes of various mutants and multi-omics analysis, and the involvement of small molecule compounds, woronin body, peroxisome, autophagy, and pH-sensing receptors in the formation of traps are also discussed. In addition, we also highlight the research focus for elucidating the mechanism underlying trap formation of NT fungi in the future.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare cardiac disease in children, and can lead to sudden cardiac death (SCD). Propafenone is classIC antiarrhythmic medication, and its side effects include cardiovascular compromise in the form of hypotension, bradycardia, ventricular dysrhythmias, QRS widening, and heart block. Propafenone has been reported causing QRS widening, but rarely in children. In this article, we presented a boy diagnosed with ARVC who meets diagnosis criteria based on typical symptoms, electrocardiograph (ECG), echocardiography (Echo), cardiac magnetic resonance imaging (CMRI), sudden death of first family member, and genetic mutation in desmosomal DSG2 gene. Antiarrhythmic drugs have been used for treating patients with ARVC, by eliminating or decreasing the occurring frequency of arrhythmias. As his ECG showed frequent premature ventricular contractions (PVC), he was prescribed with oral propafenone. One day after the drug treatment, he presented dizziness accompanied with significant QRS widening in ECG. His dizziness was improved when Propafenone dose was reduced, and resolved after sotalol replacement, with ECG recovered to nearly normal state of QRS. Propafenone may lead to QRS widening and increase the risk of ventricular tachycardia, and it may not reduce ARVC associated mortality. This report may serve as a precaution for clinicians when providing cares for ARVC patients.

Aim: To explore the correlation between different phenotypes of arrhythmia and the prognosis in children with EFE/LVNC/DCM.Methods: A total of 167 children with cardiomyopathy diagnosed and treated in Shengjing Hospital between January 2010 and May 2019 were evaluated. After patient screening, 31 patients with endomyocardial fibroelastosis (EFE), left ventricular non-compaction, or dilated cardiomyopathy with significant arrhythmias were selected. In addition, 42 children with primary EFE were selected to evaluate the prognosis with or without arrhythmia. Follow-up was undertaken 0, 1, 3, 6, 9, and 12 months after treatment.Results: We revealed the outcomes for five types of cardiomyopathy: EFE patients with Wolff–Parkinson–White syndrome B and supraventricular tachycardia, intraventricular block and complete left bundle branch block recovered slower than EFE patients with atrial flutter and atrial fibrillation, even slower than EFE with ventricular tachycardia. The average recovering time for LVEF and LVED in EFE patients without arrythmia was 10 months after diagnosis, while 76.9% (3/13 cases) of those with significant arrythmia hadn't recovered until 24 months after diagnosis. Three of patients died at 6, 7, and 6 and half years after diagnosis.Conclusion: The long-term prognosis in children with cardiomyopathy is associated with the type of arrhythmia and time of intervention. The prognosis of EFE patients with arrhythmia is worse than EFE patients without arrhythmia. Patients with Wolff–Parkinson–White syndrome B, especially a significantly widen QRS complex, carry a poor prognosis if radiofrequency ablation is not undertaken. CLBBB patients have similar poor prognosis if proper pacemaker is not implanted timely.

To assess the effect of elevated CO2 on the development, fecundity, and population dynamic parameters of L. erysimi, the age-stage, two-sex life table was used to predict the individual fitness and population parameters of three successive generations of L. erysimi in this study. The results show that a significantly longer total pre-adult stage before oviposition (TPOP) was observed in the third generation compared with the first generation of L. erysimi under the 800 μL/L CO2 treatment. The fecundity is significantly lower in the 800 μL/L CO2 treatment than that in the 400 μL/L CO2 treatment in the third generation of L. erysimi, which indicates that elevated CO2 had a negative effect on the individual fitness parameters of L. erysimi. Additionally, the life expectancy (exj) is significantly lower under the 800 μL/L CO2 treatment than that under the 400 μL/L CO2 treatment in the three successive generations. A significantly higher intrinsic rate of increase (r) and finite rate of increase (λ) were found in the second generation compared with those in the first and third generations of L. erysimi under the 800 μL/L CO2 treatment. Moreover, significantly lower r and λ were observed under the 800 μL/L CO2 treatment compared with those under the 400 μL/L and 600 μL/L CO2 treatments in the first generation of L. erysimi, which indicates that elevated CO2 has a short-term effect on the population parameters (r and λ) of L. erysimi. Our experiment can provide the data for the comprehensive prevention and control of L. erysimi in the future with increasing CO2 levels.

Abstract Background Serum anti-phospholipase A2 receptor (PLA2R) antibody was correlated with disease activity of membranous nephropathy(MN). The predictive value of antibody titer changes on immunosuppressive response remains unknown. We investigated predictive value of dynamic change of anti-PLA2R antibody and 24-h urine protein (24hUP) for clinical response of MN. Methods This was a retrospective cohort study including 47 Chinese MN patients with positive anti-PLA2R antibody in a tertiary referral hospital between January 2012 and March 2014. Patients received cyclophosphamide (CTX, n = 23), or cyclosporine (CYA, n = 24) regimen, respectively. We monitored serum anti-PLA2R titer and 24hUP at one, three and six-month follow-up. Results At baseline, total patients were 42 ± 14 years old with 29/18 male/female ratio. The median 24hUP was 5.80(3.56,9.41) g/d. The median baseline anti-PLA2R antibody titer was 66.4(31.9, 188.0) RU/mL. Baseline 24hUP and eGFR between subgroups were not significantly different. The differences of relative reduction between antibody titer and 24hUP at one month were statistically significant (CTX group 94.2% vs. 46.8%, P

Abstract Background Lipodystrophy syndromes are rare disorders of variable body fat loss associated with potentially serious metabolic complications. Familial partial lipodystrophy (FPLD) is mostly inherited as an autosomal dominant disorder. Renal involvement has only been reported in a limited number of cases of FPLD. Herein, we present a rare case of proteinuria associated with type 4 FPLD, which is characterized by a heterozygous mutation in PLIN1 and has not been reported with renal involvement until now. Case presentation A 15-year-old girl presented with insulin resistance, hypertriglyceridaemia, hepatic steatosis and proteinuria. Her glucose and glycated haemoglobin levels were within normal laboratory reference ranges. A novel heterozygous frameshift mutation in PLIN1 was identified in the patient and her mother. The kidney biopsy showed glomerular enlargement and focal segmental glomerulosclerosis under light microscopy; the electron microscopy results fit with segmental thickening of the glomerular basement membrane. Treatment with an angiotensin-converting enzyme inhibitor (ACEI) decreased 24-h protein excretion. Conclusions We report the first case of proteinuria and renal biopsy in a patient with FPLD4. Gene analysis demonstrated a novel heterozygous frameshift mutation in PLIN1 in this patient and her mother. Treatment with ACEI proved to be beneficial.

Objective and accurate assessment of the degree of ocular motor nerve palsy is helpful not only in the evaluation of prognosis, but also for the screening of treatment methods. However, there is currently no comprehensive measure of its severity. In this study, we designed the Ocular Motor Nerve Palsy Scale and investigated its validity and reliability. Six experts were invited to grade and evaluate the scale. The study recruited 106 patients with a definite diagnosis of unilateral isolated ocular motor nerve palsy. Three physicians evaluated the patients using the scale. One of the three physicians evaluated the patients again after 24 hours. The content validity index (CVI) and factor analysis were used to analyze the scale's construct validity. The intraclass correlation coefficient and Cronbach's alpha were used to evaluate the inter-rater and test-retest reliability and the internal consistency. The CVI results (I-CVI = 1.0, S-CVI = 0.9, P = 0.016, K* = 1) indicated good content validity. Factor analysis extracted two common factors that accounted for 85.2% of the variance. Furthermore, the load value of each component was above 0.8, indicating good construct validity. The Ocular Motor Nerve Palsy Scale was found to be highly reliable, with an inter-rater reliability intraclass correlation coefficient of 0.965 (P < 0.01), a test-retest reliability intraclass correlation coefficient of 0.976 (P < 0.01), and Cronbach's alpha values of 0.63–0.70. In conclusion, the Ocular Motor Nerve Palsy Scale with good validity and reliability can be used to quantify the severity of ocular motor nerve palsy. This study was registered at Chinese Clinical Trial Registry (registration number: ChiCTR-OOC-17010702).

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized clinical entity that often involves multiple organs; it is characterized by high levels of serum immunoglobulin G4 (IgG4), dense infiltration of IgG4+ cells, and storiform fibrosis. Cellular immunity, particularly T cell-mediated immunity, has been implicated in the pathogenesis of IgG4-RD. The most frequent renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis, membranous glomerulonephropathy (MGN), and obstructive nephropathy secondary to urinary tract obstruction due to IgG4-related retroperitoneal fibrosis, prostatitis, or ureter inflammation. Kidney function impairment can be acute or chronic. In IgG4-MGN, proteinuria can be in the nephrotic range. The diagnosis of IgG4-related kidney disease should not be based solely on serum IgG4 levels or the number of tissue-infiltrating IgG4+ plasma cells. Diagnosis should be based on specific histopathological findings, confirmed by tissue immunostaining and an appropriate clinical context. Steroid treatment is the first-line therapy. For relapsing or refractory cases, immunosuppressants could be combined with steroids. In hydronephrosis patients, appropriate immunosuppressive therapy could preclude the implantation of a double J ureteral catheter. Keywords: IgG4, Kidney, Pathogenesis, Diagnosis, Treatment

Abstract Background Aging is characterized by a gradual breakdown of cellular structures. Nuclear abnormality is a hallmark of progeria in human. Analysis of age-dependent nuclear morphological changes in Caenorhabditis elegans is of great value to aging research, and this calls for an automatic image processing method that is suitable for both normal and abnormal structures. Results Our image processing method consists of nuclear segmentation, feature extraction and classification. First, taking up the challenges of defining individual nuclei with fuzzy boundaries or in a clump, we developed an accurate nuclear segmentation method using fused two-channel images with seed-based cluster splitting and k-means algorithm, and achieved a high precision against the manual segmentation results. Next, we extracted three groups of nuclear features, among which five features were selected by minimum Redundancy Maximum Relevance (mRMR) for classifiers. After comparing the classification performances of several popular techniques, we identified that Random Forest, which achieved a mean class accuracy (MCA) of 98.69%, was the best classifier for our data set. Lastly, we demonstrated the method with two quantitative analyses of C. elegans nuclei, which led to the discovery of two possible longevity indicators. Conclusions We produced an automatic image processing method for two-channel C. elegans nucleus-labeled fluorescence images. It frees biologists from segmenting and classifying the nuclei manually.

Background: Medullary cystic kidney disease (MCKD) is clinically indistinguishable from several other autosomal-dominant renal diseases; thus, molecular genetic testing is needed to establish a definitive diagnosis. A specific type of single cytosine insertion in the variable number tandem repeat (VNTR) of the mucin 1 (MUC1) gene is the only known cause of MCKD1; however, genetic analysis of this mutation is difficult and not yet offered routinely. To identify the causative mutation/s and establish a definitive diagnosis in a Chinese family with chronic kidney disease, clinical assessments and genetic analysis were performed, including using a modified genotyping method to identify the MUC1- VNTR single cytosine insertion. Methods: Clinical data from three patients in a Chinese family with chronic kidney disease were collected and evaluated. Linkage analysis was used to map the causative locus. Mutation analysis of uromodulin (UMOD) gene was performed using polymerase chain reaction (PCR) and direct sequencing. For MUC1 genotyping, the mutant repeat units were enriched by MwoI restriction, and then were amplified and introduced into pMD-18T vectors. The 192 clones per transformant were picked up and tested by colony PCR and second round of MwoI digestion. Finally, Sanger sequencing was used to confirm the MUC1 mutation. Results: Clinical findings and laboratory results were consistent with a tubulointerstitial lesion. Linkage analysis indicated that the family was compatible with the MCKD1 locus. No mutations were found in UMOD gene. Using the modified MUC1 genotyping method, we detected the MUC1-VNTR single cytosine insertion events in three patients of the family; and mutation-containing clones were 12/192, 14/192, and 5/96, respectively, in the three patients. Conclusions: Clinical and genetic findings could support the MCKD1 diagnosis. The modified strategy has been demonstrated to be a practical way to detect MUC1 mutation.

Abducens nerve palsy (ANP) is commonly seen in patients with diabetes mellitus. The validity of acupuncture as a traditional Chinese medicine method in peripheral nerve repair is well established. However, its efficacy in randomized controlled trials remains unclear. Herein, we designed a protocol for a prospective, single-center, randomized controlled trial to investigate the effect of intraorbital electroacupuncture on diabetic ANP. We plan to recruit 60 patients with diabetic ANP, and randomly divide them into treatment and control groups. Patients in both groups will continue their glucose-lowering therapy. A neural nutrition drug will be given to both groups for six weeks. The treatment group will also receive intraorbital electroacupuncture therapy. We will assess efficacy of treatment, eyeball movement, diplopia deviation and the levels of fasting blood-glucose and glycosylated hemoglobin before treatment at 2, 4, and 6 weeks after treatment. The efficacy and recurrence will be investigated during follow-up (1 month after intervention). This protocol was registered at Chinese Clinical Trial Registry on 16 January 2015 (ChiCTR-IPR-15005836). This study was approved by the Ethics Committee ofFirst Affiliated Hospital of Harbin Medical University of China (approval number: 201452). All protocols will be in accordance with Declaration of Helsinki, formulated by the World Medical Association. Written informed consent will be provided by participants. We envisage that the results of this clinical trial will provide evidence for promoting clinical use of this new therapy for management of ANP.

AIM: To estimate the adult reference values for measured deviations by a computerized diplopia test and testify the validity. METHODS: Totally 391 participants were recruited and taken the computerized diplopia test. The plots and amplitude of deviations were recorded. The differences in different gender, age and visual acuity groups were analyzed respectively. Of 30 subjects were enrolled to testify the interobserver reliability. Another 46 subjects (including 26 normal subjects and 20 patients) were taken the test and theirs deviations were recorded to testify the validity of the reference value. RESULTS: The max horizontal and vertical deviations were 2.55° and 0.76° with normal corrected visual acuity while 3.88° and 1.46° for subjects with poor corrected vision. The differences between age groups was insignificant (Z=3.615, 4.758; P=0.461, 0.313 for horizontal and vertical respectively). The max horizontal deviation of female was smaller than male (Z=-2.177; P=0.029)，but the difference in max vertical deviation was insignificant (Z=-1.296; P=0.195). The mean difference between observers were both -0.1°, with 95% confidence limits (CI) of -1.4° and 1.6° in max horizontal deviations while -2.1° and 1.8° in max vertical deviation. The mean deviation of 26 normal subjects was 1.02°±0.84° for horizontal and 0.47°±0.30° for vertical which both within the range of reference values. The mean deviation of 20 patients was 13.51°±11.69° for horizontal and 8.34°±8.58° for vertical which both beyond the reference range. CONCLUSION: The max amplitude of horizontal and vertical deviation is pointed as the numerical parameters of computerized diplopia test. The reference values are different between normal corrected visual acuity and poor corrected vision. These values may useful for evaluating patients with diplopia in veriety conditions during clinical practice.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic disease that can involve multiple organs and various clinical phenotypes. The purpose of this study was to analyze different types of organ involvement in IgG4-RD patients in China. Methods: We conducted a prospective cohort study on IgG4-RD patients to analyze the clinical manifestations and rare features of IgG4-RD. Patients were grouped into different types according to organ involvement regarding organ number and organ site. The constituent ratio in different types was also analyzed. Results: A total of 200 IgG4-RD patients, with a male:female ratio of 2.08:1, were grouped into different types. Cases having involvement of two or three organs were the most common whereas the fewest number of patients had multi-organ (≥4) involvement. Serum IgG4 and IgE levels, IgG4/IgG ratio, and percentage of eosinophils increased as the number of involved organs increased. In addition, constituent ratio analysis revealed that patients with salivary gland/lacrimal gland swelling, who also constituted the largest number of IgG4-RD patients, had higher serum IgG4 concentrations and IgG4/IgG values, had higher percentage of Eos, and were more likely to have had a history of allergies relative to patients with internal organ involvement. Conclusions: The characteristic feature of IgG4-RD is multiple organ involvement with various clinical manifestations and different types. Although serum IgG4 levels increased with the number of involved organs, serum IgG4 levels were higher for those patients with salivary gland/lacrimal gland swelling compared with those with internal organ involvement. Thus, valuable clues to the differential diagnosis of IgG4-RD could be obtained by examining the clinical patterns of organ involvement.

Background: The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. Methods: It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry. Results: The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18–0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44–96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54–12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (−6.72 [95% CI−9.46 to −3.98] ml·min−1·1.73 m−2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. Conclusions: Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients. Trial Registration: chictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.

We introduce a new interpretation and quantitative method for computerized diplopia test. By comparing this new method to the Hess screen test, we validate its applicability among 304 patients with ocular motor nerve palsy. This new method shows great assistant value as the Hess screen test in making accurate diagnosis and quantitative evaluation the severity of diplopia. Furthermore, it is more convenient and suitable for daily clinical use.

The herbal pair of Coptidis Rhizoma (CR) and Euodiae Fructus (EF) is a classical traditional Chinese medicine formula used for treating gastro-intestinal disorders. In this study, we established a systematic method for chemical profiling and quantification analysis of the major constituents in the CR-EF herbal pair. A method of ultra high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) for qualitative analysis was developed. Sixty-five compounds, including alkaloids, phenolics, and limonoids, were identified or tentatively assigned by comparison with reference standards or literature data. The UHPLC fingerprints of 19 batches of the CR-EF herbal pair samples were obtained and the reference fingerprint chromatograms were established. Furthermore, nine compounds among 24 common peaks of fingerprints were considered as marker components, which either had high contents or significant bioactivities, were applied to quality control of the CR-EF herbal pair by quantitative analysis. This UHPLC-DAD analysis method was validated by precision, linearity, repeatability, stability, recovery, and so on. The method was simple and sensitive, and thus reliable for quantitative and chemical fingerprint analysis for the quality evaluation and control of the CR-EF herbal pair and related traditional Chinese medicines.

The fragmentation of shock-melted metal material is an important scientific problem in shock physics and is suitable for experimentally investigating by the laser-driven x-ray backlighting technique. This letter reports on the exploration of laser shock-melted aluminum fragmentation by means of x-ray backlighting at the SGII high energy facility in China. High-quality and high-resolution radiographs with negligible motion blur were obtained and these images enabled analysis of the mass distribution of the fragmentation product.

The dynamic fragmentation of shock-melted metal is a topic of increasing interest in shock physics. However, high-quality experimental studies of the phenomenon are limited, and data that are essential for developing predictive models of the phenomenon, such as the mass and particle sizes distributions, are quite sparse. In-line holography is an effective non-contact technique for measuring particle size distribution, but critical technical requirements, in particular, particle density limits, complicate its application to the subject phenomenon. These challenges have been reasonably overcome in the present study, allowing for successful in situ measurements of the size distribution of the fragmentation product from laser-shock-melted aluminum. In this letter, we report on our experiments and present the measured data.

The ultrasound-assisted extraction (UAE) was initially applied to extract gallic acid from Suaeda glauca Bge. using 70% ethanol as extraction solvent. Temperature, liquid-solid ratio, and extraction time were optimized by response surface methodology (RSM), obtaining maximum levels of gallic acid (6.30 mg·g−1) at 51°C, 19.52 mL·g−1, and 42.68 min, respectively. The obtained model was statistically significant (p

Retinoids has been used widely in the topical and systemic treatments of various dermatoses: psoriasis, disorders of keratinization (DOK), keratotic genodermatosis, and severe acne. Moreover, it is also used in the treatment and/or chemoprevention of skin cancer and other neoplasms. Retinoids display key regulatory functions and most dermatologists are familiar with the FDA-approved indication of this medication. Retinoic acid is a potent signaling molecule that is essential for many biological processes, and its levels are tightly regulated by mechanisms that are only partially understood. This article will review these recent findings and attempt to synthesize their meaning to provide a view into the off-label uses of retinoids in dermatology with an emphasis on oral isotretinoin and acitrein.

Thirteen new triazoles containing 1,3-dioxolane rings were synthesized and their identities confirmed by means of IR, NMR, MS, elemental analysis and X-ray crystallography. The results of preliminary biological tests show that all of these compounds possess some fungicidal and plant growth regulant activities.

A new formal solution for the multiple scattering of plane harmonic waves by a group of arbitrary configuration tubular piles in an elastic total space is derived. Each order of scattering satisfies prescribed boundary conditions at the interface of tubular piles, which is delivered as the sum of incident and scattering waves. The first order performs the scattering wave by each scattered pile and the subsequent orders resulted from the excitation of each pile of first order of scattering from the remaining tubular piles. Advanced scattering orders can be regarded as the same manners. Several series of scattering coefficients are figured out with the aids of addition theorem so that the exact steady-state solution for the scattered displacement and stress is obtained. Particularly, when internal diameter of tubular piles tends to be infinitely small, it degenerates to a solid pile problem. By imposing the normalized displacement amplitudes and transmissibility indices, the influences of specific parameters such as scattering orders, internal and external diameter ratio of piles, pile material rigidity, position and distances between tubular pile and pile rows, and pile numbers are discussed. Certain recommended conclusions have been drawn as the guidelines of practical engineering design for discontinuous barrier of tubular piles.

OBJECTIVE: To establish equations for the estimation of glomerular filtration rates (eGFRs) based on serum creatinine (SCr) and/or serum cystatin C (SCysC) in Chinese patients with chronic kidney disease (CKD), and to compare the new equations with both the reference GFR (rGFR) and the literature equations to evaluate their applicability. METHODS: The 788 Chinese CKD patients were randomly divided into two groups, the training group and the testing group, to establish new eGFR-formulas based on serum CysC and to validate the established formulas, respectively. (99m)Tc-DTPA clearance (as the rGFR), serum Cr, and serum CysC were determined for all patients, and GFR was calculated using the Cockcroft-Gault equation (eGFR1), the MDRD formula (eGFR2), the CKD-EPI formulas (eGFR3, eGFR4), and the Chinese eGFR Investigation Collaboration formulas (eGFR5, eGFR6). The accuracy of each eGFR was compared with the rGFR. RESULTS: The training and testing groups' mean GFRs were 50.84±31.36 mL/min/1.73 m(2) and 54.16±29.45 mL/min/1.73 m(2), respectively. The two newly developed eGFR formulas were fitted using iterative computation: [Formula: see text] and [Formula: see text]. Significant correlation was observed between each eGFR and the rGFR. However, proportional errors and constant errors were observed between rGFR and eGFR1, eGFR2, eGFR4, eGFR5 or eGFR6, and constant errors were observed between eGFR3 and rGFR, as revealed by the Passing & Bablok plot analysis. The Bland-Altman analysis illustrated that the 95% limits of agreement of all equations exceeded the previously accepted limits of

BACKGROUND: Typhoid and paratyphoid fever are endemic in Hongta District and their prevalence, at 113 per 100,000 individuals, remains the highest in China. However, the exact sources of the disease and its main epidemiological characteristics have not yet been clearly identified. METHODS AND FINDINGS: Numbers of typhoid and paratyphoid cases per day during the period 2006 to 2010 were obtained from the Chinese Center of Disease Control (CDC). A number of suspected disease determinants (or their proxies), were considered for use in spatiotemporal analysis: these included locations of discharge canals and food markets, as well as socio-economic and environmental factors. Results showed that disease prevalence was spatially clustered with clusters decreasing with increasing distance from markets and discharge canals. More than half of the spatial variance could be explained by a combination of economic conditions and availability of health facilities. Temporal prevalence fluctuations were positively associated with the monthly precipitation series. Polluted hospital and residential wastewater was being discharged into rainwater canals. Salmonella bacteria were found in canal water, on farmland and on vegetables sold in markets. CONCLUSION: DISEASE TRANSMISSION IN HONGTA DISTRICT IS DRIVEN PRINCIPALLY BY TWO SPATIOTEMPORALLY COUPLED CYCLES: one involving seasonal variations and the other the distribution of polluted farmland (where vegetables are grown and sold in markets). Disease transmission was exacerbated by the fact that rainwater canals were being used for disposal of polluted waste from hospitals and residential areas. Social factors and their interactions also played a significant role in disease transmission.

In the title hydrated molecular salt, 2C3H7N6+·HPO42−·3H2O, three of the O atoms of the hydrogen phosphate anion are disordered over two positions, with relative occupancies of 0.763 (1) and 0.237 (1). In the crystal, the components are linked by N—H...N, N—H...O and O—H...O hydrogen bonds