Postnatal renal tubule development: roles of tubular flow and flux.

PURPOSE OF REVIEW: Postnatal renal tubule development is critical to adult kidney function. Several postnatal changes regulate the differentiation and proliferation of renal tubular cells. Here, we review the literature and our efforts on thick ascending limb (TAL) development in Bartter syndrome (BS). RECENT FINDINGS: Glomerular filtrate quickly increases after birth, imposing fluid shear stress and circumferential stretch on immature renal tubules. Recent studies showed that kidney organoids under flow (superfusion) have better development of tubular structures and the expression of cilia and solute transporters. These effects are likely mediated by mechanosensors, such as cilia and the piezo1 channel. Improved renal oxygenation and sodium pump-dependent active transport can stimulate mitochondrial respiration and biogenesis. The functional coupling between transport and mitochondria ensures ATP supply for energy-demanding reactions in tubular cells, including cell cycle progression and proliferation. We recently discovered that postnatal renal medulla maturation and TAL elongation are impaired in Clc-k2-deficient BS mice. Primary cultured Clc-k2-deficient TAL cells have G1-S transition and proliferation delay. These developmental defects could be part of the early pathogenesis of BS and worsen the phenotype. SUMMARY: Understanding how tubular flow and transepithelial ion fluxes regulate renal tubule development may improve the treatment of congenital renal tubulopathies.

Diagnostic and prognostic value of parameters of erector spinae in patients with uremic sarcopenia.

AIM: This study aimed to investigate whether computed tomography (CT)-measured erector spinae parameters (ESPs) have diagnostic, severity assessment, and prognostic predictive value in uremic sarcopenia (US). MATERIALS AND METHODS: A total of 202 uremic patients were enrolled and divided into two groups: a control group and a sarcopenia group. Sarcopenia was classified into two types: severe and nonsevere. The area, volume, and density of the erector spinae (ES) were measured using chest CT images, and the relevant ESP, including the erector spinae index (ESI), total erector spinae volume (TESV), erector spinae density (ESD), and erector spinae gauge (ESG) were calculated. The occurrence of adverse events was followed-up for 36 months. The diagnostic value and severity of US were determined using the receiver operating characteristic (ROC) curve. Survival curves diagnosed using CT were plotted and compared with the curve drawn using the gold standard. Cox regression analysis was used to identify independent risk factors associated with survival in US. RESULTS: With an area under the curve (AUC) of 0.840 and 0.739, the combined ESP has diagnostic value and the ability to assess the severity of US. There was no significant difference in the survival curve between the combined ESP for the diagnosis of US and the gold standard (P > 0.05). ESI is a standalone predictor of survival in patients with US. CONCLUSION: ESP measured by CT has diagnostic values for US and its severity, as well as being a predictive value for the prognosis of US.

Relationship between parent-child attachment and depression among migrant children and left-behind children in China.

OBJECTIVES: The objective of this study was to examine the relationship between parent-child attachment and depression in migrant children (MC), left-behind children (LBC) and non-left-behind children (NLBC) in China. STUDY DESIGN: This was a cross-sectional study. METHODS: In total, 4294 children (4th to 9th grade) participated in this study, including 677 MC, 1411 LBC and 2206 NLBC from 17 different schools. RESULTS: The results showed that (1) the prevalence of depression among MC (21.0%) and LBC (14.0%) was significantly higher than that among NLBC (10.8%); (2) the quality of parent-child attachment among MC was statistically significantly lower than among LBC and NLBC (the proportion of children whose father-child and mother-child attachments were both insecure was 55.4% among MC, 29.9% among LBC and 33.7% among NLBC); and (3) depression was affected by the interaction between the group of children and parent-child attachment; compared with NLBC whose parent-child attachments were both secure, the odds ratio of depression among MC whose parent-child attachments were both insecure was 7.39, which was significantly higher than LBC (5.34) and NLBC (4.86) whose parent-child attachments were both insecure. CONCLUSIONS: The prevalence of depression among MC and LBC was significantly higher than that among NLBC in China. The quality of parent-child attachment among MC was statistically significantly lower than that of LBC and NLBC. Secure attachment could reduce the risk of depression and insecure parent-child attachment increased the risk of depression. Depression was affected by the interaction between the group of children and parent-child attachment; migration was a significant risk factor associated with child depression.

[The 466th case:myasthenia,fever,blurred vision and pancytopenia].

A 45-year-old woman was admitted to the Department of Rheumatology and Immunology, Peking Union Medical College Hospital, due to weakness of the upper limbs, fever, and blurred vision. She was clinically diagnosed as systemic lupus erythematosus overlapped primary biliary cirrhosis, with renal, retinal, hematological and musculoskeletal involvement, combined with severe pulmonary infection and respiratory failure. Treated with glucocorticoids, ursodeoxycholic acid, antibiotics and respiratory support, the patient got better. A couple of days later, her fever recurred and platelets count dropped to 30×10(9)/L, hemoglobin to 78 g/L, fibrinogen to<1.5 g/L, ferritin to 1 640 ng/ml, natural killer (NK) cell count to 8/µl, the activity of NK cells 2% (reference value 9.5%-23.5%), considering the occurrence of hemophagocytic lymphohistiocytosis (HLH). Cytomegalovirus pp65 antigenemia test: 13 positive cells/2×10(5) WBC. Considered the possibility of HLH caused by cytomegalovirus infection and treated by 250 mg ganciclovir intravenous drip twice a day for a full course. The temperature of the patient was gradually reduced to 36.5 ℃, the count of platelets were increased to 229 ×10(9)/L, the hemoglobin was increased to 94 g/L, and the fibrinogen was increased to 3.26 g/L. When there were unexplained critical signs of the primary disease during systemic lupus erythematosus treatment, severe complications such as infection, HLH, thrombotic thrombocytopenic purpura should be taken into account.

A study on natural recovery of tassel fertilization and doubling method in maize haploids.

Doubling method is the technical barriers in maize haploid breeding. It was very important to establish the independent intellectual property rights for doubling method. In this experiment, the maize haploid inducer, TG15, was used for producing maternal haploids. Also, haploids were obtained from two kinds of maternal genotypes involved in the experiment, including high-oil type and common type. Significant differences were observed among offspring of various genotypes in the recovery of haploid fertilization. In 21 hybrid offspring haploids, the average powder rate was 8.28%, and the seed setting rate was 4.98%. The experimental results showed that when the hybrids were treated with 0.08% colchicine, the average powder rate and seed setting rate of offspring haploids were 35.53 and 20.30%, respectively, which were significantly higher than the hybrids with natural recovery ability. This study primarily established the doubling method of haploids called "bud seedling method" in China which was very practicably in maize doubled haploid breeding.

[Femtosecond lenticule extraction for correction of myopia: clinical results and recovery of subbasal nerves].

OBJECTIVE: To investigate the clinical efficacy, safety, predictability, corneal sensitivity, tear function and recovery of subbasal nerves after femtosecond lenticule extraction (FLEx) and laser in situ keratomileusis (LASIK). METHODS: In this prospective, nonrandomized, comparative clinical study, 49 patients (98 eyes) were divided into two groups. FLEx was performed to treat myopia by Visumax femtosecond laser system, and LASIK was performed by Allegretto Wave laser system. The patients were followed up for 6 months. Visual acuity, manifest refraction, intraocular pressure, slit-lamp examination, corneal topography by Pentacam, tear break-up time, Schirmer test, corneal sensitivity and confocal microscopy were assessed. RESULTS: Forty-four patients (88 eyes) completed the 6-month follow-up. Best corrected visual acuity (BCVA) was 0.89±0.14 in eyes with FLEx and 0.98±0.08 in eyes with LASIK at 1 day after surgery. After 10 days, BCVA was 0.98±0.09 and 1.02±0.09, respectively. At the final follow-up visit, the efficacy index was 1.09 in the FLEx group and 1.07 in the LASIK group, and the safety index was 1.12 and 1.07, respectively, in the two groups. Mean Schirmer score was (16.92±7.58) mm and (15.03±5.89) mm (t=1.316, P=0.192), mean tear break-up time was (8.94±2.57) s and (8.00±2.39) s (t=1.759, P=0.082), and corneal sensitivity was (56.46±4.49) mm and (51.38±8.16) mm (t=1.316, P=0.001) in the groups of FLEx and LASIK, respectively. At 10 days after surgery, the number of subbasal nerves was significantly decreased in the FLEx group, and in the LASIK group the subbasal nerve fibers were hardly observed. At 6 months, regenerated nerve fibers were evident in the subbasal area, which recovered faster in eyes with FLEx than in those with LASIK. CONCLUSIONS: Femtosecond lenticule extraction appears to be efficient, safe and predictable for myopia. FLEx surgery is superior over LASIK in less reduction of corneal sensation and lower risk of harm to the subbasal nerve fibers.

Tissue culture characteristics of maize (Zea mays L.) haploid coleoptile sections.

Doubled haploid (DH) technology, which is used for rapidly purifying genetic resources, is a key technology in modern maize breeding. The present study evaluated the tissue culture characteristics of maize haploid coleoptile sections, in order to provide a new way of haploid doubling. With 20 combinations of haploid coleoptile sections, obtained by hybridization within Reid, Tangsipingtou, and Term-tropical groups, as explants, we analyzed the induction and differentiation rate of callus, observed the number of root tip chromosomes in regenerated plants, and analyzed the pollen fertility. In addition, we used 47 SSR markers to analyze the genotypes of regenerated plants. The Reid and Tangsipingtou groups had significantly higher induction rates of haploid coleoptile callus compared to the Term-tropical group. Fifteen haploid plants were obtained which had 10 chromosomes in the root tips as assessed by I-KI staining. It was also noticed that the pollen of pollinated anthers were partially fertile. The haploid plants had genetic stability and showed no variation. The Reid and Tangsipingtou groups had good culture characteristics of haploid coleoptile sections, while the Term-tropical group had poor culture characteristics. Genotypes of haploid plants generated by tissue culture were evidenced to come from recombinant types of parents. Thus, this study established a tissue culture system of maize haploid coleoptile.

Interferon-α-2b as an adjuvant therapy prolongs survival of patients with previously resected oral muscosal melanoma.

Two major subtypes of melanoma include cutaneous melanoma and mucosal melanoma. The latter type is rare and usually occurs in the head and neck region. High-dose interferon-α-2b (IFN-α-2b) has proven effective in the treatment of cutaneous melanoma. Recently, a regimen of temozolomide plus cisplatin was reported more likely to improve relapse-free survival and overall survival than high-dose IFN-α-2b for mucosal melanoma. We conducted this study to analyze the therapeutic effect of high-dose IFN-α-2b for patients with oral mucosal melanoma who had received prior chemotherapy. One hundred and seventeen patients with stage III-IVa oral mucosal melanoma who had received chemotherapy were analyzed. The overall survival and relapse-free survival were compared between the patients with/without high-dose IFN-α-2b. The results indicate that the IFN-α-2b treatment group had a longer relapse-free survival rate (P = 0.0169) as compared to the control group. However, the overall survival was not significant between the two groups (P = 0.096), except in patients in stage IVa, whose overall survival increased by 20 months (P = 0.0146). The adverse reactions included a drug-induced influenza-like syndrome, gastrointestinal responses, myelosuppression, and hepatoxicity, which were predominantly of grade 1-2 and reversible. Thus, patients with resected oral mucosal melanoma, even those who have received chemotherapy, could benefit from the treatment of high-dose IFN-α-2b.

[Effect of prenatal stressful life event exposure on child emotional and behavioral problem at age 2-6 years].

Objective: To investigate the influence of prenatal stressful life event (SLE) exposure on child emotional and behavioral problem at age 2-6 years and identify the most risk exposure period. Methods: A total of 2 524 mother-child pairs were selected from Shanghai Maternal-Child Pairs Cohort based on pregnant women form 2016 to 2018 in Shanghai. Prenatal SLE exposure was assessed by Life Events Scale for Pregnant Women Questionnaire during the first and third trimester of pregnancy. Child emotional and behavioral problem was evaluated by Strengths and Difficulties Questionnaire at age 2-6 years. Multivariate binary logistic regression model and generalized estimating equation were conducted to quantify the association between prenatal SLE exposure and child emotional and behavioral problem at age 2-6 years, and identify the pregnancy period with strongest adverse effect. Results: The 2 524 mother-child pairs were divided into 4 groups: group with consistent low exposure to SLE (61.8%), group with high exposure to SLE in the first trimester (13.2%), group with high exposure to SLE in the third trimester (13.2%) and group with consistent high exposure to SLE (11.8%). The detection rates of emotional problem, hyperactivity, peer interaction problem and total difficulty score in children aged 3-6 years were highest in the group with consistent high exposure to SLE. Generalized estimating equation analysis showed that after controlling the confounding factors, compared with the consistent low exposure group, the children in the group with high exposure to SLE in the first trimester had significant increased risk for conduct problem at age 2-6 years (aOR=1.41, 95%CI:1.07-1.87). The children in the group with consistent high exposure to SLE were at increased risk for emotional problem, peer interaction problem, and high total difficulty score with the aOR of 1.41 (95%CI: 1.09-1.83), 1.46 (95%CI: 1.15-1.86) and 1.51(95%CI: 1.17-1.93). Conclusion: These findings indicated that prenatal exposure to SLE have adverse effect on child emotional and behavioral problem at age 2-6 years, especially the exposure in the first trimester.

Intraoperative Embolization during Inferior Vena Cava Tumor Thrombectomy for Renal Cell Carcinoma.

Intraoperative tumor thrombus embolization is a potentially lethal complication during inferior vena cava (IVC) thrombectomy for renal cell carcinoma (RCC). Intraoperative embolization is uncommonly encountered because IVC thrombectomy surgical technique is focused on avoiding this complication. Nonetheless, early recognition of embolization is essential so that emergent management can be instituted. When available, cardiopulmonary bypass (CPB) and embolectomy should be considered the gold standard for the management of intraoperative embolization. Several novel endovascular techniques are also available for selective use. We present the case of a 71-year-old female with a right renal mass and level II (retrohepatic) IVC tumor thrombus. During cytoreductive nephrectomy and IVC thrombectomy, tumor embolization was diagnosed during a period of hypotension based on transesophageal echocardiographic finding of new thrombus within the right atrium. This prompted sternotomy, CPB, and pulmonary artery embolectomy. The patient survived this embolization event and has a complete response to systemic therapy 9 months postoperatively. This case serves as the framework for a discussion on management considerations surrounding intraoperative embolization during IVC thrombectomy.

[Role of CaMK II in pancreatic injury in mice with severe acute pancreatitis].

OBJECTIVE: To investigate the expression of Ca2+/calmodulin-dependent protein kinase II (CaMK Ⅱ) in pancreatic tissues of mice with severe acute pancreatitis (SAP) and explore the protective effect of KN93, a CaMK Ⅱ inhibitor, against pancreatic injury in SAP and the possible mechanism. METHODS: Thirty-six healthy male C57 mice were randomly divided into sham operation group, SAP group, KN93 group and SAP + KN93 group (n=9). Serum and pancreatic tissue samples were collected 24 h after modeling. The pathological changes in the pancreatic tissues were observed using HE staining. Serum lipase and amylase activities and the levels of inflammatory factors were detected using ELISA. Western blotting was used to detect the expressions of CaMK Ⅱ, p-CaMK Ⅱ, p-NF-κB, MAPK and p-MAPK in mouse pancreas. RESULTS: Compared with those in sham operation group, the expressions of p-CaMK Ⅱ, p-NF-κB and p-MAPK were significantly increased in SAP group (P < 0.05). KN93 treatment obviously alleviated pathological injuries of the pancreas in SAP mice, and significantly lowered serum levels of lipase, amylase and inflammatory factors (TNF-α and IL-6) and phosphorylation levels of NF-κB, ERK and MAPK proteins (P < 0.05). CONCLUSION: The activity of CaMK Ⅱ is significantly increased in the pancreatic tissue of SAP mice. KN93 can alleviate pancreatic injury and inflammation in SAP mice possibly through the ERK/MAPK signaling pathway.

Drying of colloidal suspensions and polymer solutions near the contact line: deposit thickness at low capillary number.

Drying experiments with a receding contact line have been performed with silica colloidal suspensions and polyacrylamide (PAAm) polymer solutions. The experimental setup allows to control the receding movement of the contact line and the evaporation flux separately. Deposit thickness as a function of these two control parameters has been investigated. The different systems exhibit a similar behavior: in the regime of very low capillary numbers the deposit thickness scaled by the solute volume concentration and the evaporation rate is proportional to the inverse of the contact line velocity. Both the scaling exponent and the constant (which has the dimension of a length) do not depend on the system under study. The observation of this evaporative regime confirms some recent results obtained by Le Berre et al. on a very different system (phospholipidic molecules) and fully supports their interpretation. Following their approach, a simple model based on mass balance accounts for these results. This implies that this regime is dominated by the evaporation and that the deformation of the meniscus induced by viscous forces does not play any significant role. When increasing the velocity, another regime is observed where the thickness does not depend significantly on the velocity.

[A cohort study on the association between dietary patterns which benefit for normal kidney function and the cognitive performance in the Chinese elderly].

Objective: To explore the association between dietary pattern which benefit for normal kidney function and the risk of cognitive decline or impairment in the elderly. Methods: In 2015, subjects aged 60 and over from four counties in the Nutrition and Chronic Disease Family Cohort project, were followed up in 2017. Cognitive function was repeatedly assessed, using the Mini Mental State Evaluation (MMSE) scale. Dietary pattern that benefit for normal kidney function was extracted, using the reduced rank regression method and followed by logistic regression models to explore the associations between scores that showing the kidney function on dietary patterns and the risk of cognitive deterioration and impairment in two years among those who were with normal cognition in 2015. Results: Dietary pattern that benefit for normal kidney function, was characterized by high consumption of cereal, vegetables, legume and fruits but with less meat and soy products. Comparing with the group with lowest score quartile on this dietary pattern, the risk of cognitive deterioration in the highest quartile group was significantly low (P<0.01) in two years, with an odds ratio as 0.57 (95%CI: 0.37-0.85). Linear trend was also obviously visible (P=0.007) in this group. The ones at the highest quartile group among the normal cognition ones in 2015, the risk of cognitive impairment also significantly reduced (P<0.05) in two years time, with an odds ratio as 0.52 (95%CI: 0.29-0.93). Also, linear trend could obviously be seen (P=0.01). Conclusion: Dietary pattern that benefit for normal kidney function was both inversely associated with cognitive deterioration and impairment, in two years.

Interactions between subdomains in the partially folded state of staphylococcal nuclease.

Staphylococcal nuclease can be roughly divided into a beta-subdomain in N-terminal and an alpha-subdomain in C-terminal. They fold sequentially under certain conditions, causing a partially folded intermediate state in which the native-like beta-barrel persists while alpha-helix regions largely disorder. To investigate the possible long-range interactions between the two subdomains in the intermediate, N-terminal fragments have been used as intermediate analogues, with polypeptide ending at positions 102, 110, 121 and 135 and with a tryptophan substitution at position 66 or 88 to facilitate the observation of the beta-barrel. Segment-resolved interactions between beta-barrel and residues 103-135 were identified by comparing their spectroscopic properties of fluorescence, circular dichroism and NMR and by their stability. Except for unstable V66W102, the guanidine and thermal denaturation of fragments are cooperative and well approximated by the two-state transition. Minimal stable structure units of both tryptophan-containing fragments comprise residues 1-110. With the main interaction in segment 103-135, residues 103-110 contribute approximate 2 kcal/mol to the stability. Elongation of C-terminal from 110 residue neither increases the stability nor alters the structure core of the G88W fragments. However, residues 111-121 influence the tertiary structure of the V66W fragments suggesting its minor interactions with beta-barrel.

Comparative studies of the conformation of the N-terminal fragments of staphylococcal nuclease R in solution.

In order to elucidate the folding of nascent peptide, five peptide fragments of staphylococcal nuclease R starting from N-terminal end and of different chain lengths are made by deletion of 47, 39, 28, 14 and 8 amino-acid residues from its C-terminal end, respectively. Changes in conformation of the N-terminal fragments have been compared by using Fourier-transform infrared spectra, far-ultraviolet circular dichroism spectra and analysis of surface hydrophobicity. The experiments indicate that all the five fragments have certain amounts of residual structure; in general, with increasing the peptide chain, the contents of secondary structure and the enzyme's activity of the peptide increase, and the exposed hydrophobic side chains brought about by the deletion of C-terminal residues are gradually buried in the interior of the nuclease. However, the ordered secondary structures do not always increase with increasing the peptide chain. Further growth of the length of the peptide chain could have an important effect on the conformation of the peptide fragment already synthesized, suggesting some structural adjustments should be necessary in order for the newly synthesized polypeptide to attain its final native conformation. These results support Tsou's nascent peptide folding hypothesis (Tsou, C.-L. (1988) Biochemistry 27, 1809-1812).

Conformational adjustments of SNase R and its N-terminal fragments probed by monoclonal antibodies.

Two monoclonal antibodies specific for staphylococcal nuclease R (SNase R) (McAb2C9 and McAb1B8) were prepared and used to probe protein folding during peptide elongation, by measuring antibody binding to seven N-terminal fragments (SNR141, SNR135, SNR121, SNR110, SNR102, SNR79 and SNR52) of SNase R. Comparative studies of the conformations of the N-terminal fragments have shown that all seven fragments of SNase R have a certain amount of residual structure, indicating that folding may occur during elongation of the nascent peptide chain. We show that the binding abilities of the intact enzyme and its seven fragments to the monoclonal antibodies are not simply proportional to the length of the peptide chain, suggesting that there may be continuous conformational adjustment in the nascent peptide chain as new C-terminal amino acids are added. A folding intermediate close in structure to the native state but with structural features in common with SNR121 is highly populated in 0.6 M GuHCl, and is also formed transiently during folding.

Free luciferase may acquire a more favorable conformation than ribosome-associated luciferase for its activity expression.

A variant of firefly luciferase in which the C-terminal end was extended with 44 amino acid residues served as a model protein in this study. After transcription and translation in vitro, the enzyme activity was measured when still attached to the ribosome and when released from the ribosome by incubation with RNase A or puromycin. It was found that the C-terminally extended luciferase already had activity when linked to the ribosome, but its activity was greatly increased when released from the ribosome. These results indicate that the luciferase is folded during synthesis on the ribosome; however, some conformational adjustments occur after its release from the ribosome which are required for the full expression of its enzymatic activity.

Conformational and functional significance of residue proline 17 in chicken muscle adenylate kinase.

The effect of mutation proline 17 on the multiple conformations and catalytic function in chicken muscle adenylate kinase (AK) has been studied. The substitution of proline 17 with glycine or valine altered the distribution of multiple conformations. Compared with the wild-type enzyme, the P17G and P17V mutants contained decreased fraction of minor conformer from 18% to 9% and 11%, respectively. Due to the mutation, the enzyme showed lower secondary structural content, poorer affinity to substrates or substrate analogues, and reduced catalytic efficiency. The results revealed the significance of proline 17 in the conformation and function of AK.