How and what kind of cities benefit from the development of digital inclusive finance? Evidence from the upgrading of export in Chinese cities

Employing Chinese customs data and the Peking University Digital Financial Inclusion Index of China, this paper studies the impact of China’s digital finance development on the upgrading of export at the city level and further explores the heterogeneity across cities and the mechanisms through which digital finance influences export upgrading. Benchmark results suggest that digital inclusive finance can significantly promote the upgrading of export. The heterogeneity analysis shows that cities with a smaller size, lower wage, higher human capital level, and better location advantage experience greater facilitating effects of digital inclusive finance on promoting export upgrading. It suggests that, compared with ‘icing on the cake’, the digital inclusive finance plays a better role in ‘offering fuel in snowy weather’, whereas full exertion of the inclusiveness of digital finance requires higher human capital and location advantage. Further mechanism analysis shows that innovation effect and market effect are the main channels where digital inclusive finance promotes the upgrading of a city’s export

Cardiac-derived CTRP9 protects against myocardial ischemia/reperfusion injury via calreticulin-dependent inhibition of apoptosis.

Cardiokines play an essential role in maintaining normal cardiac functions and responding to acute myocardial injury. Studies have demonstrated the heart itself is a significant source of C1q/TNF-related protein 9 (CTRP9). However, the biological role of cardiac-derived CTRP9 remains unclear. We hypothesize cardiac-derived CTRP9 responds to acute myocardial ischemia/reperfusion (MI/R) injury as a cardiokine. We explored the role of cardiac-derived CTRP9 in MI/R injury via genetic manipulation and a CTRP9-knockout (CTRP9-KO) animal model. Inhibition of cardiac CTRP9 exacerbated, whereas its overexpression ameliorated, left ventricular dysfunction and myocardial apoptosis. Endothelial CTRP9 expression was unchanged while cardiomyocyte CTRP9 levels decreased after simulated ischemia/`reperfusion (SI/R) in vitro. Cardiomyocyte CTRP9 overexpression inhibited SI/R-induced apoptosis, an effect abrogated by CTRP9 antibody. Mechanistically, cardiac-derived CTRP9 activated anti-apoptotic signaling pathways and inhibited endoplasmic reticulum (ER) stress-related apoptosis in MI/R injury. Notably, CTRP9 interacted with the ER molecular chaperone calreticulin (CRT) located on the cell surface and in the cytoplasm of cardiomyocytes. The CTRP9-CRT interaction activated the protein kinase A-cAMP response element binding protein (PKA-CREB) signaling pathway, blocked by functional neutralization of the autocrine CTRP9. Inhibition of either CRT or PKA blunted cardiac-derived CTRP9\u27s anti-apoptotic actions against MI/R injury. We further confirmed these findings in CTRP9-KO rats. Together, these results demonstrate that autocrine CTRP9 of cardiomyocyte origin protects against MI/R injury via CRT association, activation of the PKA-CREB pathway, ultimately inhibiting cardiomyocyte apoptosis

Genomic analysis of the chromosome 15q11-q13 Prader-Willi syndrome region and characterization of transcripts for GOLGA8E and WHCD1L1 from the proximal breakpoint region

<p>Abstract</p> <p>Background</p> <p>Prader-Willi syndrome (PWS) is a neurobehavioral disorder characterized by neonatal hypotonia, childhood obesity, dysmorphic features, hypogonadism, mental retardation, and behavioral problems. Although PWS is most often caused by a paternal interstitial deletion of a 6-Mb region of chromosome 15q11-q13, the identity of the exact protein coding or noncoding RNAs whose deficiency produces the PWS phenotype is uncertain. There are also reports describing a PWS-like phenotype in a subset of patients with full mutations in the <it>FMR1 </it>(fragile X mental retardation 1) gene. Taking advantage of the human genome sequence, we have performed extensive sequence analysis and molecular studies for the PWS candidate region.</p> <p>Results</p> <p>We have characterized transcripts for the first time for two UCSC Genome Browser predicted protein-coding genes, <it>GOLGA8E </it>(golgin subfamily a, 8E) and <it>WHDC1L1 </it>(WAS protein homology region containing 1-like 1) and have further characterized two previously reported genes, <it>CYF1P1 </it>and <it>NIPA2</it>; all four genes are in the region close to the proximal/centromeric deletion breakpoint (BP1). <it>GOLGA8E</it> belongs to the golgin subfamily of coiled-coil proteins associated with the Golgi apparatus. Six out of 16 golgin subfamily proteins in the human genome have been mapped in the chromosome 15q11-q13 and 15q24-q26 regions. We have also identified more than 38 copies of <it>GOLGA8E</it>-like sequence in the 15q11-q14 and 15q23-q26 regions which supports the presence of a <it>GOLGA8E</it>-associated low copy repeat (LCR). Analysis of the 15q11-q13 region by PFGE also revealed a polymorphic region between BP1 and BP2. <it>WHDC1L1 </it>is a novel gene with similarity to mouse <it>Whdc1 </it>(WAS protein homology region 2 domain containing 1) and human JMY protein (junction-mediating and regulatory protein). Expression analysis of cultured human cells and brain tissues from PWS patients indicates that <it>CYFIP1 </it>and <it>NIPA2</it> are biallelically expressed. However, we were not able to determine the allele-specific expression pattern for <it>GOLGA8E </it>and <it>WHDC1L1 </it>because these two genes have highly related sequences that might also be expressed.</p> <p>Conclusion</p> <p>We have presented an updated version of a sequence-based physical map for a complex chromosomal region, and we raise the possibility of polymorphism in the genomic orientation of the BP1 to BP2 region. The identification of two new proteins <it>GOLGA8E</it> and <it>WHDC1L1</it> encoded by genes in the 15q11-q13 region may extend our understanding of the molecular basis of PWS. In terms of copy number variation and gene organization, this is one of the most polymorphic regions of the human genome, and perhaps the single most polymorphic region of this type.</p

Altered Ultrasonic Vocalization and Impaired Learning and Memory in Angelman Syndrome Mouse Model with a Large Maternal Deletion from Ube3a to Gabrb3

Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11–q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11–q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m−/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m−/p+), but not paternal (m+/p−), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone

MESIA: Understanding and Leveraging Supplementary Nature of Method-level Comments for Automatic Comment Generation

Code comments are important for developers in program comprehension. In scenarios of comprehending and reusing a method, developers expect code comments to provide supplementary information beyond the method signature. However, the extent of such supplementary information varies a lot in different code comments. In this paper, we raise the awareness of the supplementary nature of method-level comments and propose a new metric named MESIA (Mean Supplementary Information Amount) to assess the extent of supplementary information that a code comment can provide. With the MESIA metric, we conduct experiments on a popular code-comment dataset and three common types of neural approaches to generate method-level comments. Our experimental results demonstrate the value of our proposed work with a number of findings. (1) Small-MESIA comments occupy around 20% of the dataset and mostly fall into only the WHAT comment category. (2) Being able to provide various kinds of essential information, large-MESIA comments in the dataset are difficult for existing neural approaches to generate. (3) We can improve the capability of existing neural approaches to generate large-MESIA comments by reducing the proportion of small-MESIA comments in the training set. (4) The retrained model can generate large-MESIA comments that convey essential meaningful supplementary information for methods in the small-MESIA test set, but will get a lower BLEU score in evaluation. These findings indicate that with good training data, auto-generated comments can sometimes even surpass human-written reference comments, and having no appropriate ground truth for evaluation is an issue that needs to be addressed by future work on automatic comment generation.Comment: In 32nd IEEE/ACM International Conference on Program Comprehension (ICPC'24

Construction and application of a built-in dual luciferase reporter for microRNA functional analysis

Background: As key gene regulators, microRNAs post-transcriptionally modulate gene expression via binding to partially complementary sequence in the 3’ UTR of target mRNA. An accurate, rapid and quantitative tool for sensing and validation of miRNA targets is of crucial significance to decipher the functional implications of miRNAs in cellular pathways. Results: Taking advantage of an improved restriction-free cloning method, we engineered a novel built-in dual luciferase reporter plasmid where Firefly and Renilla luciferase genes were assembled in a single plasmid named “pFila”. This design eliminates the transfection of a separate control plasmid and thus minimizes the time and labor required for miRNA-target sensing assays. pFila consistently produces Firefly and Renilla luciferase activities when transfected into human-, monkey- and mouse-derived mammalian cell systems. Moreover, pFila is capable of recapitulating the interaction of miR-16 and its known target CCNE1 in Hela cells. Additionally, pFila is shown to be a sensitive miR-biosensor by evaluating the inhibition efficiency of endogenous miRNA. Conclusions: pFila would facilitate miRNA target identification and verification in a rapid and simplified manner. Also, pFila is a sensitive biosensor for active miRNA profiling in vivo

Machine learning-based analysis and prediction of meteorological factors and urban heatstroke diseases

IntroductionHeatstroke is a serious clinical condition caused by exposure to high temperature and high humidity environment, which leads to a rapid increase of the core temperature of the body to more than 40°C, accompanied by skin burning, consciousness disorders and other organ system damage. This study aims to analyze the effect of meteorological factors on the incidence of heatstroke using machine learning, and to construct a heatstroke forecasting model to provide reference for heatstroke prevention.MethodsThe data of heatstroke incidence and meteorological factors in a city in South China from May to September 2014–2019 were analyzed in this study. The lagged effect of meteorological factors on heatstroke incidence was analyzed based on the distributed lag non-linear model, and the prediction model was constructed by using regression decision tree, random forest, gradient boosting trees, linear SVRs, LSTMs, and ARIMA algorithm.ResultsThe cumulative lagged effect found that heat index, dew-point temperature, daily maximum temperature and relative humidity had the greatest influence on heatstroke. When the heat index, dew-point temperature, and daily maximum temperature exceeded certain thresholds, the risk of heatstroke was significantly increased on the same day and within the following 5 days. The lagged effect of relative humidity on the occurrence of heatstroke was different with the change of relative humidity, and both excessively high and low environmental humidity levels exhibited a longer lagged effect on the occurrence of heatstroke. With regard to the prediction model, random forest model had the best performance of 5.28 on RMSE and dropped to 3.77 after being adjusted.DiscussionThe incidence of heatstroke in this city is significantly correlated with heat index, heatwave, dew-point temperature, air temperature and zhongfu, among which the heat index and dew-point temperature have a significant lagged effect on heatstroke incidence. Relevant departments need to closely monitor the data of the correlated factors, and adopt heat prevention measures before the temperature peaks, calling on citizens to reduce outdoor activities

The complete mitochondrial genome of a new species of the genus <i>Schizothorax</i> from Sichuan, China (Cypriniformes: Cyprinidae)

Schizothorax gulinensis sp. nov. is a new species of the genus Schizothorax from Sichuan, China (Cypriniformes: Cyprinidae). In this study, we have first reported the complete mitochondrial genome of S. gulinensis with Illumina sequencing. There were 16,587 nucleotide pairs in the mitochondrial genome (mitogenome) of S. gulinensis, including 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs), and 22 transfer RNAs (tRNAs), as well as one non-coding control region (CR). The proportion of nucleotides in mitochondrial genome was 29.67% (A), 25.45% (T), 17.84% (G), 27.05% (C), and A + T content was 55.12%. All PCGs have the same start codon of the standard ATG, excepting for that of NADH dehydrogenase subunit 1 (nad1) which was the ATC, NADH dehydrogenase subunit 5 (nad5) which was the ATT and cytochrome c oxidase 1 (cox1) which was the ATC. Phylogenetic analysis results supported that S. gulinensis was closely related to Schizothorax grahami. The complete mitochondrial sequence of S. gulinensis will contribute to mitochondrial genome database and provide useful resources for population genetics and evolution analyses.</p

Short-Duration Swimming Exercise after Myocardial Infarction Attenuates Cardiac Dysfunction and Regulates Mitochondrial Quality Control in Aged Mice

Background. Exercise benefits to cardiac rehabilitation (CR) following stable myocardial infarction (MI). The suitable exercise duration for aged patients with coronary heart disease (CHD) remains controversial, and the underlying molecular mechanism is still unclear. Methods and Results. 18-Month-old mice after stable MI were randomly submitted to different durations of exercise, including 15 and 60 min swimming training (ST) once per day, five times a week for 8 weeks. Compared to sedentary mice, 15 min ST, rather than 60 min ST, significantly augmented left ventricular function, increased survival rate, and suppressed myocardial fibrosis and apoptosis. 15 min ST improved mitochondrial morphology via regulating mitochondrial fission-fusion signaling. 15 min ST regulated mitophagy signaling via inhibiting LC3-II and P62 levels and increasing PINK/Parkin expression. 15 min ST also inhibited ROS production and enhanced antioxidant SOD2 activity. Notably, 15 min ST significantly increased sirtuin (SIRT) 3 level (2.7-fold) in vivo while the inhibition of SIRT3 exacerbated senescent H9c2 cellular LDH release and ROS production under hypoxia. In addition, SIRT3 silencing impairs mitochondrial dynamics and mitophagy in senescent cardiomyocytes against simulated ischemia (SI) injury. Conclusion. Collectively, our study demonstrated for the first time that sustained short-duration exercise, rather than long-duration exercise, attenuates cardiac dysfunction after MI in aged mice. It is likely that the positive regulation induced by a short-duration ST regimen on the elevated SIRT3 protein level improved mitochondrial quality control and decreased apoptosis and fibrosis contributed to the observed more resistant phenotype