Comprehensive Proteomics Analysis Identifies CD38-Mediated NAD+ Decline Orchestrating Renal Fibrosis in Pediatric Patients With Obstructive Nephropathy.

Obstructive nephropathy is one of the leading causes of kidney injury and renal fibrosis in pediatric patients. Although considerable advances have been made in understanding the pathophysiology of obstructive nephropathy, most of them were based on animal experiments and a comprehensive understanding of obstructive nephropathy in pediatric patients at the molecular level remains limited. Here, we performed a comparative proteomics analysis of obstructed kidneys from pediatric patients with ureteropelvic junction obstruction and healthy kidney tissues. Intriguingly, the proteomics revealed extensive metabolic reprogramming in kidneys from individuals with ureteropelvic junction obstruction. Moreover, we uncovered the dysregulation of NAD+ metabolism and NAD+-related metabolic pathways, including mitochondrial dysfunction, the Krebs cycle, and tryptophan metabolism, which led to decreased NAD+ levels in obstructed kidneys. Importantly, the major NADase CD38 was strongly induced in human and experimental obstructive nephropathy. Genetic deletion or pharmacological inhibition of CD38 as well as NAD+ supplementation significantly recovered NAD+ levels in obstructed kidneys and reduced obstruction-induced renal fibrosis, partially through the mechanisms of blunting the recruitment of immune cells and NF-κB signaling. Thus, our work not only provides an enriched resource for future investigations of obstructive nephropathy but also establishes CD38-mediated NAD+ decline as a potential therapeutic target for obstruction-induced renal fibrosis.

Triptolide promotes differentiation of human monocytes into immunosuppressive MDSCs.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) negatively modulate immune activity. Prior investigations have shown much promise in using MDSCs-assisted immunotherapy for organ transplantation patients. Additionally, owing to its immunosuppressive activity, MDSCs can also be used to manage immune-associated disorders. METHODS: Granulocyte-macrophage colony-stimulating factor (GM-CSF) was employed to stimulate myeloid progenitor cell differentiation. Triptolide (PG490) was introduced toward the later phases of in vitro MDSCs induction. Lastly, real-time PCR (RT-PCR) and flow cytometry were used to assess transcript expression and cell phenotype, and a mouse skin transplantation model was established to evaluate the MDSCs-mediated immune suppression in vivo. RESULTS: Co-stimulation with PG490 and GM-CSF potently induced myeloid-derived monocytes to form MDSCs, with remarkable immune-suppressive activity. The underlying mechanism involved downregulation of T cell proliferation, activation, enhancement of inflammatory cytokine release, as well as T cell conversion to Treg cells. PG490 strongly enhanced iNOS expression in MDSCs, and iNOS inhibition successfully reversed the immune-suppression. The PG490- and GM-CSF-induced MDSCs substantially extended survival duration of murine skin grafts, thereby validating their strong immune-suppressive activity in vivo. CONCLUSIONS: Herein, we presented a new approach involving MDSCs-based immunosuppression in vitro. PG490 and GM-CSF co-treatment strongly induced immuno-suppressive activity in MDSCs both in vitro and in vivo. Our findings highlight the promise of applying MDSCs-based therapy in clinical organ transplantation treatment.

[Preventive early intervention strategies for neurodevelopmental disorders of high-risk infants]. / é«˜å±å„¿ç¥žç»å‘è‚²éšœç¢é¢„é˜²æ€§æ—©æœŸå¹²é¢„ç ”ç©¶è¿›å±•.

Neurodevelopmental disorders in children have become a significant global public health concern, impacting child health worldwide. In China, the current intervention model for high-risk infants involves early diagnosis and early treatment. However, in recent years, overseas studies have explored novel preventive early intervention strategies for neurodevelopmental disorders in high-risk infants, achieving promising results. This article provides a comprehensive review of the optimal timing, methods, and intervention models of the preventive early intervention strategies for neurodevelopmental disorders in high-risk infants. The aim is to enhance the awareness and knowledge of healthcare professionals regarding preventive early intervention strategies for neurodevelopmental disorders in high-risk infants, facilitate clinical research and application of such interventions in China, and ultimately reduce the incidence of neurodevelopmental disorders in this high-risk population.

MALDI-TOF-MS for Rapid Screening and Typing of ß-Globin Variant and ß-Thalassemia through Direct Measurements of Intact Globin Chains.

BACKGROUND: Traditional phenotype-based screening for ß-globin variant and ß-thalassemia using hematological parameters is time-consuming with low-resolution detection. Development of a MALDI-TOF-MS assay using alternative markers is needed. METHODS: We constructed a MALDI-TOF-MS-based approach for identifying various ß-globin disorders and classifying thalassemia major (TM) and thalassemia intermedia (TI) patients using 901 training samples with known HBB/HBA genotypes. We then validated the accuracy of population screening and clinical classification in 2 separate cohorts consisting of 16 172 participants and 201 ß-thalassemia patients. Traditional methods were used as controls. Genetic tests were considered the gold standard for testing positive specimens. RESULTS: We established a prediction model for identifying different forms of ß-globin disorders in a single MALDI-TOF-MS test based on δ- to ß-globin, γ- to α-globin, γ- to ß-globin ratios, and/or the abnormal globin-chain patterns. Our validation study yielded comparable results of clinical specificity (99.89% vs 99.71%), and accuracy (99.78% vs 99.16%) between the new assay and traditional methods but higher clinical sensitivity for the new method (97.52% vs 88.01%). The new assay identified 22 additional abnormal hemoglobins in 69 individuals including 9 novel ones, and accurately screened for 9 carriers of deletional hereditary persistence of fetal hemoglobin or δß-thalassemia. TM and TI were well classified in 178 samples out of 201 ß-thalassemia patients. CONCLUSIONS: MALDI-TOF-MS is a highly accurate, predictive tool that could be suitable for large-scale screening and clinical classification of ß-globin disorders.

Spatiotemporal consistency effect of green finance on pollution emissions and its geographic attenuation process.

Improving the ecological quality is one of the essential goals of green finance, while interaction between green finance and environmental development has not reached an agreement yet. Using the panel data of 30 provinces from 2010 to 2020, based on the advantage of PTRM-SPDM (Spatial Panel Threshold Durbin Model), this study empirically analyses the relationship between green finance and pollutants emissions from the perspective of the spatiotemporal combination process. After confirming the characteristics of nonlinear constraints and spatial spillovers between green finance and pollutants emissions, the spatiotemporal consistency effects are explored, and the geographic attenuation process, including spatial spillover boundary and influencing dense areas, is also calculated. Results show that: (1) with the development of green finance in China, the environmental effects of green finance transfer gradually from local to adjacent areas, the unit elasticity of green finance decreases by 0.15, 0.19, and 0.22 on emissions of industrial sulfur dioxide, wastewater, and dust in local areas, respectively, while increases by 0.64, 0.02, and 0.82 in neighbouring regions correspondingly. (2) from the evolution trend of the peak value of Kernel density, it could be captured that the overall degree improves and the regional gap narrows for China's green finance in the past decade. (3) the effects of green finance on pollutants emissions merely exist in areas with a radius of about 1500-1750 km and reach the peak in the vicinity of around 1450-1750 km.

[Oxygen reserve index: a new parameter for oxygen therapy]. / 氧储备指数：氧疗监测的新方法.

Oxygen reserve index (ORI) is a novel dimensionless index used for noninvasive, real-time, and continuous monitoring of oxygenation, and ORI value ranges from 0 to 1, which reflects the range of 100-200 mmHg for arterial partial pressure of oxygen. ORI combined with pulse oximetry may help to accurately adjust the concentration of inspired oxygen and prevent hyperoxemia and hypoxemia. ORI is suitable for various clinical situations, and the medical staff should master this novel parameter and use it properly to assess the oxygenation of patients. In addition, several limitations of ORI should be noticed during clinical application.

[The role and mechanism of autophagy in lipopolysaccharide-induced inflammatory response of A549 cells]. / 自噬在脂多糖诱导的A549ç»†èƒžç‚Žç—‡ååº”ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To study the role and mechanism of autophagy in lipopolysaccharide (LPS)-induced inflammatory response of human alveolar epithelial A549 cells. METHODS: A549 cells were stimulated with LPS to establish a cell model of inflammatory response, and were then grouped (n=3 each) by concentration (0, 1, 5, and 10 µg/mL) and time (0, 4, 8, 12, and 24 hours). The A549 cells were treated with autophagy inhibitor 3-methyladenine (3-MA) to be divided into four groups (n=3 each): control, LPS, 3-MA, and 3-MA+LPS. The A549 cells were treated with autophagy agonist rapamycin (RAPA) to be divided into four groups (n=3 each): control, LPS, RAPA, and RAPA+LPS. The A549 cells were transfected with the Toll-like receptor 4 (TLR4) overexpression plasmid to be divided into four groups (n=3 each): TLR4 overexpression control, TLR4 overexpression, TLR4 overexpression control+LPS, and TLR4 overexpression+LPS. The A549 cells were transfected with TLR4 siRNA to be divided into four groups (n=3 each): TLR4 silencing control,TLR4 silencing, TLR4 silencing control+LPS, and TLR4 silencing+LPS. CCK-8 assay was used to measure cell viability. Western blot was used to measure the protein expression levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4. RESULTS: After stimulation with 1 µg/mL LPS for 12 hours, the levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4 increased and reached the peak (P<0.05). Compared with the LPS group, the 3-MA+LPS group had reduced expression of autophagy-related proteins and increased expression of inflammation-related proteins and TLR4, while the RAPA+LPS group had increased expression of autophagy-related proteins and reduced inflammation-related proteins and TLR4 (P<0.05). The TLR4 overexpression+LPS group had reduced autophagy-related proteins and increased inflammation-related proteins compared with the TLR4 overexpression control+LPS group, and the TLR4 silencing+LPS group had increased autophagy-related proteins and reduced inflammation-related proteins compared with the TLR4 silencing control+LPS group (P<0.05). CONCLUSIONS: In the LPS-induced inflammatory response of human alveolar epithelial A549 cells, autophagic flux has a certain protective effect on A549 cells. TLR4-mediated autophagic flux negatively regulates the LPS-induced inflammatory response of A549 cells.

PMA induces the differentiation of monocytes into immunosuppressive MDSCs.

The induction of immune tolerance without the use of immunosuppressive drugs is a crucial problem in organ transplantation. The use of myeloid-derived suppressor cells (MDSCs) as a cell-based adjuvant immunosuppressive therapy is a bright clinical prospect in organ transplantation. MDSCs with stable immunosuppressive activities can be used to treat immune-related diseases. In this study, macrophage colony-stimulating factor (M-CSF) was used to promote myeloid progenitor cell differentiation, and phorbol 12-myristate 13-acetate (PMA) was added to induce MDSCs at the later stage of induction in vitro. Cell phenotypes were detected by flow cytometry and mRNA was detected by real-time-polymerase chain reaction (RT-PCR). A mouse skin transplantation model was used to investigate the cell inhibitory function. The combination of PMA and M-CSF induced the differentiation of myeloid-derived monocytes into MDSCs. MDSCs were found to induce immune tolerance by inhibiting the proliferation and activation of T cells, promoting cytokine secretion and inducing T cell transformation to regulatory T cells (Treg ). PMA significantly up-regulated the expression of Arg-1 and the Arg-1 protein expression in MDSCs and arginase 1 (Arg-1) inhibitor nor-NOHA reversed the MDSC immunosuppressive activity, indicating the involvement of the Arg-1 pathway in MDSC-mediated immunosuppression. M-CSF + PMA-induced MDSCs also significantly prolonged the survival time of skin grafts in mice, showing that MDSCs exert immunosuppressive effects in vivo. We describe a novel scheme to induce immunosuppressive MDSCs in vitro. MDSCs induced by M-CSF with PMA showed stable immunosuppression. MDSCs induced by this protocol may benefit patients with organ transplantation through immune regulation.

Bluetongue Viruses Act as Novel Oncolytic Viruses to Effectively Inhibit Human Renal Cancer Cell Growth In Vitro and In Vivo.

BACKGROUND The bluetongue virus (BTV) is the prototype virus in the genus Orbivirus within the family Reoviridae. Recent studies indicate that BTVs are capable of infecting and selectively lysing human hepatic carcinoma cells (Hep-3B) and prostate carcinoma cells (pc-3). This study was designed to evaluate the oncolytic potential of BTV in experimental models of human renal cancer in vitro and in vivo. MATERIAL AND METHODS Five human renal cancer cell lines, ACHN, CAKI-1, OS-RC-2, 786-O, and A498, were used in this study to analyze BTV replication. These cells were lysed by oncolysis compared to normal control. Xenograft models were used to assess the efficacy and toxicity of BTVs in vivo. Data were analyzed by one-way ANOVA or two-sided unpaired t tests. RESULTS The results showed HPTEC cells to be relatively resistant to cytotoxic effects of BTVs and exhibited normal growth rate even at high dose of BTVs. Nonetheless, the renal cancer cells showed a remarkably higher sensitivity to BTVs. Moreover, the ultramicroscopic subcellular changes were also detected in the renal cells. The viral particles were observed in all the RCC cell lines, but not in HPTEC cells. Intratumoral injections of BTVs significantly decreased the tumor volume as compared to animals that received no virus treatment. Infection with BTVs significantly increased the percentage of apoptotic renal cancer cells but not the HPTEC cells. Moreover, BTV triggered apoptosis in renal cancer cells via a mitochondria-mediated pathway. CONCLUSIONS This study for the first time demonstrated the oncolytic potential of BTV in experimental models of human renal cancer. BTV exhibits the potential to inhibit human renal cancer cell growth in vitro and in vivo.

Automatic Detection of Short-Term Atrial Fibrillation Segments Based on Frequency Slice Wavelet Transform and Machine Learning Techniques.

Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia and is often associated with other cardiovascular and cerebrovascular diseases, such as ischemic heart disease, chronic heart failure, and stroke. Automatic detection of AF by analyzing electrocardiogram (ECG) signals has an important application value. Using the contaminated and actual ECG signals, it is not enough to only analyze the atrial activity of disappeared P wave and appeared F wave in the TQ segment. Moreover, the best analysis method is to combine nonlinear features analyzing ventricular activity based on the detection of R peak. In this paper, to utilize the information of the P-QRS-T waveform generated by atrial and ventricular activity, frequency slice wavelet transform (FSWT) is adopted to conduct time-frequency analysis on short-term ECG segments from the MIT-BIH Atrial Fibrillation Database. The two-dimensional time-frequency matrices are obtained. Furthermore, an average sliding window is used to convert the two-dimensional time-frequency matrices to the one-dimensional feature vectors, which are classified using five machine learning (ML) techniques. The experimental results show that the classification performance of the Gaussian-kernel support vector machine (GKSVM) based on the Bayesian optimizer is better. The accuracy of the training set and validation set are 100% and 93.4%. The accuracy, sensitivity, and specificity of the test set without training are 98.15%, 96.43%, and 100%, respectively. Compared with previous research results, our proposed FSWT-GKSVM model shows stability and robustness, and it could achieve the purpose of automatic detection of AF.

LINC02532 Contributes to Radiosensitivity in Clear Cell Renal Cell Carcinoma through the miR-654-5p/YY1 Axis.

BACKGROUND: Studies have shown that long non-coding RNAs (lncRNAs) play essential roles in tumor progression and can affect the response to radiotherapy, including in clear cell renal cell carcinoma (ccRCC). LINC02532 has been found to be upregulated in ccRCC. However, not much is known about this lncRNA. Hence, this study aimed to investigate the role of LINC02532 in ccRCC, especially in terms of radioresistance. METHODS: Quantitative real-time PCR was used to detect the expression of LINC02532, miR-654-5p, and YY1 in ccRCC cells. Protein levels of YY1, cleaved PARP, and cleaved-Caspase-3 were detected by Western blotting. Cell survival fractions, viability, and apoptosis were determined by clonogenic survival assays, CCK-8 assays, and flow cytometry, respectively. The interplay among LINC02532, miR-654-5p, and YY1 was detected by chromatin immunoprecipitation and dual-luciferase reporter assays. In addition, in vivo xenograft models were established to investigate the effect of LINC02532 on ccRCC radioresistance in 10 nude mice. RESULTS: LINC02532 was highly expressed in ccRCC cells and was upregulated in the cells after irradiation. Moreover, LINC02532 knockdown enhanced cell radiosensitivity both in vitro and in vivo. Furthermore, YY1 activated LINC02532 in ccRCC cells, and LINC02532 acted as a competing endogenous RNA that sponged miR-654-5p to regulate YY1 expression. Rescue experiments indicated that miR-654-5p overexpression or YY1 inhibition recovered ccRCC cell functions that had been previously impaired by LINC02532 overexpression. CONCLUSIONS: Our results revealed a positive feedback loop of LINC02532/miR-654-5p/YY1 in regulating the radiosensitivity of ccRCC, suggesting that LINC02532 might be a potential target for ccRCC radiotherapy. This study could serve as a foundation for further research on the role of LINC02532 in ccRCC and other cancers.

[Clinical evaluation of Compound Chamomile and Lidocaine Hydrochloride Gel for postoperative hypospadias in children].

OBJECTIVE: To evaluate the clinical efficacy of Compound Chamomile and Lidocaine Hydrochloride Gel for postoperative hypospadias in children. METHODS: From January to December 2020, we treated 116 children with distal hypospadias in the Department of Urology, Department of Pediatrics and the Seventh Medical Center of the PLA General Hospital, 58 by primary Snodgrass urethroplasty only (the control group) and the other 58 with Compound Chamomile and Lidocaine Hydrochloride Gel smeared on the penis postoperatively in addition (the trial group). We compared the operation time and postoperative pain score, edema regression and incidence of infection between the two groups, followed by statistical analysis using T test and Chi-square test. RESULTS: All the operations were successfully completed by the same surgeon under general anesthesia. There were no statistically significant differences between the trial and control groups in age (ï¼»2.5 ± 0.8ï¼½ vs ï¼»2.4 ± 0.6ï¼½ yr, P > 0.05) or operation time (ï¼»95.6 ± 14.5ï¼½ vs ï¼»97.1 ± 15.2ï¼½ min, P > 0.05). No incision infection occurred in any of the cases. The pain scores at dressing removal were remarkably lower in the trial than in the control group at 2 hours (1.4 ± 1.0 vs 2.6 ± 1.3, P < 0.05), 24 hours (2.2 ± 1.3 vs 3.9 ± 1.6, P < 0.05), 48 hours (1.2 ± 0.7 vs 1.6 ± 0.9, P < 0.05) and 72 hours after surgery (2.5 ± 0.8 vs 3.7 ± 1.8, P < 0.05). Significantly more cases of edema regression were achieved in the trial than in the control group at 2 weeks postoperatively (35 vs 19, P < 0.05). CONCLUSIONS: Compound Chamomile and Lidocaine Hydrochloride Gel can effectively relieve pain, reduce edema and accelerate edema regression after surgery in children with hypospadias, and therefore deserves wide clinical application.、.

[Sudden unexpected postnatal collapse in a neonate].

A healthy full-term female neonate, aged 3 days and born by vaginal delivery (with a 1-minute Apgar score of 10 and a 5-minute Apgar score of 10), had unexpected cardiac and respiratory arrests in the early morning on day 3 after birth and recovered to spontaneous breathing and heartbeat after a 10-minute resuscitation. The child had poor response and convulsion after resuscitation. Blood gas analysis showed metabolic acidosis, and amplitude-integrated EEG showed a burst-suppression pattern. She was diagnosed with sudden unexpected postnatal collapse but improved after hypothermia and symptomatic/supportive treatment. This article reports the first case of sudden unexpected postnatal collapse in China and summarizes related risk factors, pathophysiological mechanisms, and preventive and treatment measures of this disorder.

[Continuous expression and functional prediction of circular RNA in mouse lung development].

OBJECTIVE: To study the continuous expression and potential function of circular RNA (circRNA), circ4:150439343|150477468 and circ15:73330849|73343359, in mouse lung development. METHODS: According to the stage of lung development, lung tissue samples were collected from mice on embryonic day 16.5 (E16.5), embryonic day 18.5 (E18.5), and postnatal day 2 (P2). Hematoxylin and eosin staining was performed to observe the morphology of lung tissue. Quantitative real-time PCR (qRT-PCR) was used to measure the mRNA expression of circ4:150439343|150477468 and circ15:73330849|73343359 during late lung development; miRanda and TargetScan were used to predict the target miRNAs of circRNAs, and then GO and KEGG analysis was performed for the target genes to predict the potential function of circRNAs. RESULTS: Type II alveolar epithelial cells were observed in the lung slices of E16.5 mice, with a gradual increase in number. On P2, the pulmonary alveoli expanded rapidly, the pulmonary interstitium became thinner, and the alveolar structure gradually became mature. The results of qRT-PCR showed that the relative expression of circ4:150439343|150477468 was continuously upregulated over time and the relative expression of circ15:73330849|73343359 was first downregulated and then upregulated (P<0.05). The KEGG and GO analysis showed that circRNAs were involved in the Notch, PI3K-Akt, and NF-κB signaling pathways. CONCLUSIONS: Circ4:150439343|150477468 and circ15:73330849|73343359 can participate in lung development through the Notch signaling pathway.

[A clinical epidemiological investigation of neonatal acute respiratory distress syndrome in southwest Hubei, China].

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS: Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.

miR-20a-5p regulates pulmonary surfactant gene expression in alveolar type II cells.

MicroRNA (miRNA) critically controls gene expression in many biological processes, including lung growth and pulmonary surfactant biosynthesis. The present study was conducted to investigate whether miR-20a-5p had such regulatory functions on alveolar type II (AT-II) cells. To accomplish this, miR-20a-5p-overexpressed and miR-20a-5p-inhibited adenoviral vectors were constructed and transfected into cultured AT-II cells that were isolated from rat foetal lungs of 19 days' gestation. Transfection efficiency was confirmed by observing the fluorescence of green fluorescent protein (GFP) carried by the viral vector, whereas miR-20a-5p levels were verified by real-time PCR. The CCK-8 assay was used to compare the proliferation ability of AT-II cells that had over- or underexpressed miR-20a-5p. The expression of surfactant-associated proteins (SPs) and phosphatase and tensin homolog (PTEN) was measured by real-time PCR and Western blotting. In AT-II cells, transfection resulted in over- or under-regulation of miR-20a-5p. While overexpression of miR-20a-5p promoted pulmonary surfactant gene expression, its underexpression inhibited it. Consistent with its role in negatively regulating the pulmonary surfactant gene, an opposite pattern was observed for miR-20a-5p regulation of PTEN. As a result, when miR-20a-5p was rendered overexpressed, PTEN was down-regulated. By contrast, when miR-20a-5p was underexpressed, PTEN was up-regulated. Neither overexpression nor underexpression of miR-20a-5p altered the cell proliferation. miR-20a-5p plays no role in proliferation of foetal AT-II cells but is a critical regulator of surfactant gene expression. The latter appears to be achieved through a regulatory process that implicates expression of PTEN.

Hypermethylated in cancer 1 (HIC1) suppresses bladder cancer progression by targeting yes-associated protein (YAP) pathway.

OBJECTIVES: Bladder cancer (BCa) is the most common malignant tumor in the urinary system. Growing evidence suggests that as a tumor suppressor gene, hypermethylated in cancer 1 (HIC1) is correlated with various malignancies in the modulation of tumor progression. This study aims to investigate the effect of HIC1 on regulating the proliferation, migration, and invasion of BCa. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB) were used to evaluate the expression of HIC1 messenger RNA and protein in human BCa tissues and cells. Proliferation, migration and invasion assays, and flow cytometry assay were performed to assess the biological functional role of HIC1 in BCa. Co-immunoprecipitation (Co-IP) examined the protein-protein interaction. The signaling pathways involved in the mode of action of HIC1 in BCa were also investigated. RESULTS: HIC1 was found downregulated in tested samples. Cloning formation assay and cell-proliferation activity analysis showed that overexpression of HIC1 significantly inhibited the proliferation of BCa cells, while knockdown led to the opposite, namely the promotion of the proliferation. Flow cytometry assay confirmed the arrest of the cell cycle at the G1 phase with overexpression of HIC1 observed. Moreover, HIC1 inhibited migration and invasion of BCa. Co-IP showed the binding between YAP (yes-associated protein) and TEAD (TEA domain/transcription enhancer factor family members) as well as the cancerostatic activity of HIC1, partially manifested via its negative regulation of YAP signaling pathway. CONCLUSIONS: Our data unprecedently showed that HIC1 was responsible for the inhibition of proliferation, migration, and invasion of BCa via the YAP signaling pathway. These findings suggested that therapeutic strategies regulating HIC1 expression might provide effective treatments for BCa.

Detection of Congestive Heart Failure Based on LSTM-Based Deep Network via Short-Term RR Intervals.

Congestive heart failure (CHF) refers to the inadequate blood filling function of the ventricular pump and it may cause an insufficient heart discharge volume that fails to meet the needs of body metabolism. Heart rate variability (HRV) based on the RR interval is a proven effective predictor of CHF. Short-term HRV has been used widely in many healthcare applications to monitor patients' health, especially in combination with mobile phones and smart watches. Inspired by the inception module from GoogLeNet, we combined long short-term memory (LSTM) and an Inception module for CHF detection. Five open-source databases were used for training and testing, and three RR segment length types (N = 500, 1000 and 2000) were used for the comparison with other studies. With blindfold validation, the proposed method achieved 99.22%, 98.85% and 98.92% accuracy using the Beth Israel Deaconess Medical Center (BIDMC) CHF, normal sinus rhythm (NSR) and the Fantasia database (FD) databases and 82.51%, 86.68% and 87.55% accuracy using the NSR-RR and CHF-RR databases, with N = 500, 1000 and 2000 length RR interval segments, respectively. Our end-to-end system can help clinicians to detect CHF using short-term assessment of the heartbeat. It can be installed in healthcare applications to monitor the status of human heart.

A Novel, Portable and Fast Moisture Content Measuring Method for Grains Based on an Ultra-Wideband (UWB) Radar Module and the Mode Matching Method.

To perform fast and portable grain moisture measurements under field conditions, a novel moisture sensor was designed, which consisted of a coaxial waveguide, a circular waveguide, and an isolation layer. The electromagnetic characteristics of the sensor were simulated and measured. The analytical model, which represented the relationship between the reflection coefficient of the sensor and the complex permittivity of grain, was established by using the mode matching method. The reflection coefficient of the sensor was measured by using an ultra-wideband (UWB) radar module, and the moisture content of grains was calculated from the complex permittivity by using density-independent model. To verify the performance of the proposed method, wheat, rough rice, and barley were taken as examples. The measured results in the range from 1.0% to 26.0%, wet basis, agreed well with the reference values (R2 was more than 0.99), and the maximum absolute errors for wheat, rough rice, and barley were 1.1%, 1.0%, and 1.4%, respectively. In addition, the effect of isolation layer was discussed. Both the simulation results and the experimental results showed that the isolation layer improved the stability of sensor.

H2 Addition to Pincer Iridium Complexes Yielding trans-Dihydride Products: Unexpected Correlations of Bond Strength with Bond Length and Vibrational Frequencies.

R4PONOP-Ir-Me (R1) and R4POCOP-Ir-CO (R2), R = tBu or iPr, are known to undergo acid-catalyzed oxidative addition of H2 that yields octahedral products with two hydrides in a trans-configuration. We use density functional theory to study the free energies (Δ Gtrans) and equilibrium isotope effects (EIEtrans) for H2/D2 addition to R1, R2, and related complexes for R = tBu, iPr, and Me. For a given R, reaction of R1 is ∼5 kcal/mol more exergonic than R2. For a given subclass of complexes, Δ Gtrans is more exergonic for the smaller R. The computed values of Δ Gtrans vary between +5.1 and -17.4 kcal/mol. EIEtrans varies between 0.78 and 1.22. Counterintuitively, it is the less-exergonic reactions that afford products with shorter Ir-H bonds, greater symmetric and asymmetric trans-Ir-(H)2 stretching vibrational frequencies, and more inverse EIEtrans. This disparity is amplified in Me4PONOP-Os-CO, where Δ Gtrans is -35.2 kcal/mol, yet the Os-H bonds are long, and the Os-H vibrational frequencies are low as compared with the Ir-H bonds, and EIEtrans is high (1.20). Attempts are made to account for the inverted bond strength-bond length correlation based on the hydricity of the products and the total negative charge on the trans-Ir(H)2 unit as computed using the Quantum Theory of Atoms in Molecules.