Threat of soil formation rate to health of karst ecosystem.

Karst ecosystems are important to several billion people, so it is necessary to accurately diagnose and evaluate the health of these ecosystems for socioeconomic development; however, the existing evaluation methods have many limitations, so they cannot accurately evaluate the ecosystem health in karst areas. In particular, they ignore the influence and restriction of the soil formation rate on the ecosystem health. To this end, we established a new index to represent the actual health status of karst ecosystems. The soil formation rate was found to pose a threat to the health of 28 % of the world's karst ecosystems, covering an area of 594 km2. In addition, a dataset of global karst ecosystem health index values with a spatial resolution of about 8 km × 8 km from 2000 to 2014 was created, and the proportion of unhealthy areas was found to be as high as 75.91 %. This study highlights the contribution of the soil formation rate to karst ecosystem health and provides a new method and deeper scientific understanding for further accurate evaluation of karst ecosystem health, which can improve future ecosystem health research and social management.

Nitidine chloride induces cardiac hypertrophy in mice by targeting autophagy-related 4B cysteine peptidase.

Nitidine chloride (NC) is a standard active component from the traditional Chinese medicine Zanthoxylum nitidum (Roxb.) DC. (ZN). NC has shown a variety of pharmacological activities including anti-tumor activity. As a number of anti-tumor drugs cause cardiotoxicity, herein we investigated whether NC exerted a cardiotoxic effect and the underlying mechanism. Aqueous extract of ZN (ZNE) was intraperitoneally injected into rats, while NC was injected into beagles and mice once daily for 4 weeks. Cardiac function was assessed using echocardiography. We showed that both ZNE administered in rats and NC administered in mice induced dose-dependent cardiac hypertrophy and dysfunction, whereas administration of NC at the middle and high dose caused death in Beagles. Consistently, we observed a reduction of cardiac autophagy levels in NC-treated mice and neonatal mouse cardiomyocytes. Furthermore, we demonstrated that autophagy-related 4B cysteine peptidase (ATG4B) may be a potential target of NC, since overexpression of ATG4B reversed the cardiac hypertrophy and reduced autophagy levels observed in NC-treated mice. We conclude that NC induces cardiac hypertrophy via ATG4B-mediated downregulation of autophagy in mice. Thus, this study provides guidance for the safe clinical application of ZN and the use of NC as an anti-tumor drug.

Analysis for Key Points of Registration Applications and Difficulties of Process Control of 3D Printed Customized Dentures / 中国医疗器械杂志

With the highlighted advantages of 3D printing technology in the field of dental prosthodontics, there is increasing in the numbers of registration applications for additive manufacturing customized dentures. However, there is still a lack of unified analysis in the core elements of process control, the key points of registration and the safety production quality control. Based on the current research status of the industry, the study is intended to clarify confusion and difficulties, deeply analyse the mechanism of the product defects, sort the core elements of process control, then try to establish a systematic evaluation system from product performance research, key process verification, production quality control and the description of registration files, so that it can provide help for practitioners to clarify research direction, establishing quality management system, improving the efficiency of registration and ensuring product quality.

Quantitative evaluation of right atrial function in fetuses with moderate to severe tricuspid regurgitation by two-dimensional speckle tracking echocardiography / 中华超声影像学杂志

Objective:To explore the application value of two-dimensional speckle tracking echocardiography (2D-STE) in measuring the global longitudinal peak strain of the right atrium (PRAGLS) in normal fetuses and evaluating PRAGLS in assessing right atrial function in fetuses with moderate and severe tricuspid regurgitation (TR).Methods:A total of 25 fetuses diagnosed with moderate and severe TR, who underwent fetal echocardiography at Run Run Shaw Hospital, Zhejiang University College of Medicine between October 2020 and May 2022, were selected as the case group. Their gestational age ranged from 25.00(24.00, 30.00)weeks. Additionally, 100 normal singleton fetuses were chosen as the control group, with a gestational age of 25.83(23.00, 28.75)weeks. Standard basal or apical four-chamber clips were acquired and inputted into TOMTEC-ARENA offline cardiac analysis software for analysis. The fetal PRAGLS values of the two groups were obtained, as well as the routine obstetric ultrasound measurements and fetal echocardiographic parameters of both groups: fetal heart rate (FHR), biparietal diameter (BPD), femur length (FL), aortic annulus inner diameter (AO), pulmonary annulus inner diameter (PA), PA/AO ratio, right atrial end-systolic length (RAESL), right atrial end-systolic diameter (RAESD), right atrial end-systolic area (RAESA), right ventricular end-diastolic diameter (RVEDD), and tricuspid annular plane systolic excursion (TAPSE). The peak TR velocity and pressure gradient were simultaneously measured in the case group.The differences in fetal PRAGLS and other parameters between the two groups were compared and analyzed. The correlation between fetal PRAGLS and gestational age (GA) and routine measurements was assessed for both groups. Intra- and inter-observer repeatability tests were conducted using the intragroup correlation coefficient (ICC).Results:A significant difference in PRAGLS was observed between the two groups ( t=11.55, P<0.01). The TAPSE difference between the two groups was also statistically significant ( Z=3.45, P=0.01). Notable differences were found in AO, PA, PA/AO, RAESL, RAESD, and RAESA between the two groups (all P<0.05), but no significant differences were identified in age, GA, FHR, BPD, FL, and RVEDD between the two groups (all P>0.05). PRAGLS in the control group exhibited a moderate negative correlation with GA ( r=-0.47, P<0.01) and were correlated with BPD, FL, AO, PA, RAESL, RAESD, RAESA, and RVEDD ( r=-0.50, -0.46, -0.39, -0.43, -0.45, -0.36, -0.43, -0.32, all P<0.05). No significant correlation was observed with maternal age, FHR, PA/AO, and TAPSE (all P>0.05). No significant correlation between PRAGLS and GA or other conventional parameters was found in the case group (all P>0.05). The inter-measurer and intra-measurer ICC of PRAGLS in the control group were 0.87 and 0.79, respectively, while the inter-measurer and intra-measurer ICC of PRAGLS in the case group were 0.94 and 0.97, respectively, demonstrating good consistency. Conclusions:2D-STE exhibits strong feasibility and reproducibility in assessing fetal atrial function.Fetuses with moderate and severe TR display decreased PRAGLS, suggesting impaired right atrial reservoir function. Right atrial strain introduces a novel method for evaluating fetal cardiac function.

Preliminary study of cardiac morphology and function in fetuses with tetralogy of Fallot using fetal heart quantification / 中华超声影像学杂志

Objective:To evaluate the fetal heart shape and function in tetralogy of Fallot (TOF) by fetal heart quantitative analysis (fetal HQ).Methods:A total of 52 fetuses with TOF diagnosed by fetal echocardiography and 200 normal fetuses matched with their gestational weeks from March 2020 to March 2022 at Sir Run Run Shaw Hospital, Zhejiang University were retrospectively evaluated. The basic parameters of fetal cardiac blood vessels in the two groups were measured by fetal HQ technology and conventional M-mode ultrasound technology: aortic valve diameter(AV), pulmonary artery valve diameter(PV), main pulmonary artery diameter (MPA) and Z-score. The overall morphometric measurements including end-diastolic length diameter, transverse diameter, area, and global spherical index (GSI) of the fetal heart in the 4-chamber view(4CV), area and length of the right and left ventricles and their ratios. Measurements of left and right ventricular function included ejection fraction (EF), fraction area change rate (FAC), tricuspid annular plane systolic excursion (TAPSE), left and right ventricular global longitudinal strain (GLS), and left and right ventricular end-diastolic diameter (ED), spherical index (SI), and fractional shortening rate (FS) of 24-segments. The differences of above parameters between TOF group and control group were compared. In addition, the relationships between the absolute value of left and right ventricular GLS of TOF fetus and PV/AV, PV Z-score and MPA Z-score were analyzed. The optimal critical values of GSI, left ventricular EF and left ventricular FAC of TOF fetus were determined by ROC curve, and their corresponding sensitivity and specificity were obtained.Results:Compared with control group, there were significant differences in 4CV end-diastolic length, area, GSI, left ventricular area, left ventricular length, left ventricular EF, left ventricular FAC and left ventricular GLS in TOF group (all P<0.05). There were significant differences in ED between left ventricular 15-24 segments and right ventricular 1-21 segments (all P<0.05). There were significant differences in SI between left ventricular 1-16 segments, 21-24 segments and all segments of right ventricle (all P<0.05). The differences in FS were statistically significant (all P<0.05) when comparing all segments of the left ventricle and 1-2 segments of the right ventricular, and the remaining parameters were not statistically significant (all P>0.05). The left ventricular GLS absolute value of TOF fetuses was positively correlated with PV/AV, PV Z-score and MPA Z-score( rs=0.338, 0.441 and 0.458, all P<0.05), the right ventricular GLS absolute value of TOF fetuses was positively correlated with PV AV, PV Z-score and MPA Z-score( rs=0.418, 0.368 and 0.338, all P<0.05). The optimal critical values of GSI, left ventricular EF, and left ventricular FAC in the diagnosis of fetal TOF were 1.19, 59.05%, and 44.4%, respectively. At this time, the sensitivities of diagnosis of TOF were 0.78, 0.75, and 0.80, respectively. The specificities were 0.88, 0.88 and 0.83, respectively. The areas under ROC curve were 0.89, 0.88 and 0.89, respectively. Conclusions:Fetal HQ technology can provide a simple and reliable quantitative evaluation of fetal heart shape and function, and provide certain theoretical parameters for the study of fetal heart shape and function.

Construction of a Prognostic Model of Multiple Myeloma Based on Metabolism-Related Genes / 中国实验血液学杂志

OBJECTIVE@#To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes.@*METHODS@#The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score.@*RESULTS@#A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect.@*CONCLUSION@#Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.

Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients. @*Materials and Methods@#A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored. @*Results@#TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion. @*Conclusion@#This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.

Supervillin Isoform 4 (SV4) Regulates Mitosis by Enhancing Aurora A Activity / 中国生物化学与分子生物学报

Mitosis is important for cell proliferation in eukaryotes, and chromosome replication and accurate separation are essential for cell division. Supervillin is a membrane and microfilament actin binding protein. Previous studies have found that it regulates the dynamic changes of the cortical distribution of F-actin and myosin II in cytokinesis, thus ensuring the correct distribution of the contraction ring and participating in the final completion of cytoplasm divisions. But it is not clear whether it functions during metaphase. Supervillin has several splicing isomers, among which supervillin isoform 4 (SV4) is the largest splicing isomer. In this study, the expression of SV4 in cells was reduced by the RNA interference method, and the dynamic process of mitosis and the morphology of astral spindles were detected and observed by real-time microscopy and immunofluorescence staining, and the potential molecular mechanism of SV4 in mitosis was analyzed. The results showed abnormal cell divisions after SV4 reduction: delayed transition from metaphase to anaphase (P<0.001), abnormal assembly of microtubules, a twofold-increase of the number of cells with multipolar spindles, and decreased γ-tubulin signaling in the centrosome (P<0.001). Through GST pull-down and mass spectrometry experiments, we found that SV4 and Aurora A bind to each other, and SV4 regulates the localization and activation of Aurora A in the centrosome during mitosis. In summary, supervillin plays an important role in mitosis. The isomer SV4 regulates spindle integrity and γ-tubulin recruitment by interacting with Aurora A and recruiting it for proper localization and activation in the centrosome during the metaphase, thus promoting the correct assembly of bipolar spindles and ensuring the accurate separation of chromosomes and the smooth progress of mitosis.

Omics Analysis of Ferroptosis and Establishment of Prognostic Model for multiple myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients.@*METHODS@#Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM.@*RESULTS@#36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients.@*CONCLUSION@#Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.

Accelerating the Improvement of Human Well-Being in China through Economic Growth and Policy Adjustment.

Human well-being in many countries lags behind the gross domestic product (GDP) due to the rapid changes in the socio-economic environment that have occurred for decades. However, the mechanisms behind this complex phenomenon are still unclear. This study revealed the changes in human well-being in China from 1995 to 2017 by revising the genuine progress indicator (GPI) at the national level and further quantified the contribution of interfering factors that have driven the increase in the GPI. The results indicated that: (1) The per capita GPI of China showed an increasing trend with an annual growth rate of 12.43%. The changes in the GPI followed the same pattern as economic development, rather than presenting the phenomenon of economic growth combined with a decline in welfare that has been recorded in some countries and regions. (2) The increase in human well-being was mainly driven by economic growth, but it was most sensitive to social factors. (3) Increasing income inequality and the cost of lost leisure time contributed obvious negative impacts (24.69% and 23.35%, respectively) to the per capita GPI. However, the increase in personal consumption expenditures, the value of domestic labor, ecosystem service value, and net capital growth accelerated the rise in the GPI, with positive contribution rates of 30.69%, 23%, 20.54%, and 20.02%, respectively. (4) The continuous increase in economic investment and the strengthening of social management due to policy adjustments completely counteracted the negative impacts on human well-being, thus leading to a great increase in the per capita GPI. Such insights could provide theoretical support for decision making and policy implementation to improve global human well-being.

Brain age vector: A measure of brain aging with enhanced neurodegenerative disorder specificity.

Neuroimaging-driven brain age estimation has become popular in measuring brain aging and identifying neurodegenerations. However, the single estimated brain age (gap) compromises regional variations of brain aging, losing spatial specificity across diseases which is valuable for early screening. In this study, we combined brain age modeling with Shapley Additive Explanations to measure brain aging as a feature contribution vector underlying spatial pathological aging mechanism. Specifically, we regressed age with volumetric brain features using machine learning to construct the brain age model, and model-agnostic Shapley values were calculated to attribute regional brain aging for each subject's age estimation, forming the brain age vector. Spatial specificity of the brain age vector was evaluated among groups of normal aging, prodromal Parkinson disease (PD), stable mild cognitive impairment (sMCI), and progressive mild cognitive impairment (pMCI). Machine learning methods were adopted to examine the discriminability of the brain age vector in early disease screening, compared with the other two brain aging metrics (single brain age gap, regional brain age gaps) and brain volumes. Results showed that the proposed brain age vector accurately reflected disorder-specific abnormal aging patterns related to the medial temporal and the striatum for prodromal AD (sMCI vs. pMCI) and PD (healthy controls [HC] vs. prodromal PD), respectively, and demonstrated outstanding performance in early disease screening, with area under the curves of 83.39% and 72.28% in detecting pMCI and prodromal PD, respectively. In conclusion, the proposed brain age vector effectively improves spatial specificity of brain aging measurement and enables individual screening of neurodegenerative diseases.

A brainstem map for visceral sensations.

The nervous system uses various coding strategies to process sensory inputs. For example, the olfactory system uses large receptor repertoires and is wired to recognize diverse odours, whereas the visual system provides high acuity of object position, form and movement1-5. Compared to external sensory systems, principles that underlie sensory processing by the interoceptive nervous system remain poorly defined. Here we developed a two-photon calcium imaging preparation to understand internal organ representations in the nucleus of the solitary tract (NTS), a sensory gateway in the brainstem that receives vagal and other inputs from the body. Focusing on gut and upper airway stimuli, we observed that individual NTS neurons are tuned to detect signals from particular organs and are topographically organized on the basis of body position. Moreover, some mechanosensory and chemosensory inputs from the same organ converge centrally. Sensory inputs engage specific NTS domains with defined locations, each containing heterogeneous cell types. Spatial representations of different organs are further sharpened in the NTS beyond what is achieved by vagal axon sorting alone, as blockade of brainstem inhibition broadens neural tuning and disorganizes visceral representations. These findings reveal basic organizational features used by the brain to process interoceptive inputs.

High-resolution mapping of the global silicate weathering carbon sink and its long-term changes.

Climatic and non-climatic factors affect the chemical weathering of silicate rocks, which in turn affects the CO2 concentration in the atmosphere on a long-term scale. However, the coupling effects of these factors prevent us from clearly understanding of the global weathering carbon sink of silicate rocks. Here, using the improved first-order model with correlated factors and non-parametric methods, we produced spatiotemporal data sets (0.25° × 0.25°) of the global silicate weathering carbon-sink flux (SCSFα ) under different scenarios (SSPs) in present (1950-2014) and future (2015-2100) periods based on the Global River Chemistry Database and CMIP6 data sets. Then, we analyzed and identified the key regions in space where climatic and non-climatic factors affect the SCSFα . We found that the total SCSFα was 155.80 ± 90 Tg C yr-1 in present period, which was expected to increase by 18.90 ± 11 Tg C yr-1 (12.13%) by the end of this century. Although the SCSFα in more than half of the world was showing an upward trend, about 43% of the regions were still showing a clear downward trend, especially under the SSP2-4.5 scenario. Among the main factors related to this, the relative contribution rate of runoff to the global SCSFα was close to 1/3 (32.11%), and the main control regions of runoff and precipitation factors in space accounted for about 49% of the area. There was a significant negative partial correlation between leaf area index and silicate weathering carbon sink flux due to the difference between the vegetation types. We have emphasized quantitative analysis the sensitivity of SCSFα to critical factors on a spatial grid scale, which is valuable for understanding the role of silicate chemical weathering in the global carbon cycle.

Limitations of soil moisture and formation rate on vegetation growth in karst areas.

Vegetation changes in karst areas are controlled by the soil formation rate (SFR) and soil moisture (SM). However, little is known about their thresholds and global control patterns. To this end, based on high-precision climate and vegetation data for 2000-2014, using Pearson correlation analysis, the Hurst index, and change-point analysis, the thresholds of the SFR and SM in vegetation growth in karst areas were identified. Furthermore, a spatial map (0.125° × 0.125°) of the global karst ecosystem with a static/dynamic limitation zone was established. We found that the net primary productivity (NPP) in 70% of the global climate zones exhibited a dual restriction relationship with the SM and SFR. The limitations of the SFR and SM in vegetation growth were most obvious in subpolar and semi-arid climates. In addition, their ecological thresholds were 25.2 t km-2 yr-1 and 0.28 m3 m-3, respectively. The static limitation of the SFR on the NPP in karst areas accounted for 28.37%, and the influence of the SM enhanced this limit (21.79%). The limitation of the SFR on vegetation was mainly concentrated in Boreal forests (17%), and the limitation of the SM was mainly concentrated in tropical savannas (12%). The NPP and the Normalized Difference Vegetation Index (NDVI) were the most sensitive to changes in the SM and SFR. Moreover, the analysis based on 14 ecologically limitation karst areas further revealed that the reduction in these factors may cause the tropical rain forest to experience degradation. It can be seen that the SM enhanced the limiting effect of the SFR on vegetation in karst areas. In short, this interpretation of karst vegetation limitations provides a deeper understanding of and approach to ecosystem evolution and vegetation restoration in these regions.

Investigation of fetal cardiac size, morphology and function in fetuses with right ventricular outflow obstruction using fetal heart quantification / 中华超声影像学杂志

Objective:To investigate the application value of fetal heart quantification (fetal HQ) in the evaluation of fetal heart size, morphology and function in fetuses with right ventricular outflow obstruction (RVOTO).Methods:Fifty-five fetuses diagnosed as RVOTO by fetal echocardiography in Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University from April 2020 to February 2021 were selected. They were divided into simple pulmonary artery stenosis (PS) group and conus arteriosus malformation (CTD) group according to whether they were combined with other cardiovascular malformations. On the standard four chamber view, the end diastolic basal apical length (4CV length) and transverse width (4CV width) were obtained by fetal HQ analysis technique, and the cardiac global spherical index (4cv-gsi) was calculated. The left and right ventricles (LV and RV) were divided into 24 segments from the base to the apex. The endocardial curve was obtained by total HQ tracking. The 24 segment transverse width (ED), spherical index (SI), short axis shortening (FS) and its Z-score were calculated. The LV and RV of RVOTO fetuses were compared and analyzed from the aspects of heart size, morphology and function.Results:The 4CV length of RVOTO fetal heart was in the normal range, 4CV width increased in varying degrees, GSI decreased, and the whole heart showed spherical changes. In PS group, LV-ED was larger than that of RV and the difference was statistically significant in 5-24 segments( P<0.05). LV was more spherical than RV. There was no significant difference in ED between LV and RV in CTD group( P>0.05), and RV was more spherical than LV. Twenty-four segment FS decreased in different degrees in RVOTO fetal heart, and the decrease of RV was more obvious than that of LV. There was significant difference between the LV and RV in PS group from S5 to 19 ( P<0.05), and there was significant difference between the left and right ventricles in CTD group from S1 to 11 ( P<0.05). Conclusions:Fetal HQ can provide new insights of cardiac size, morphology and function in fetuses with RVOTO.

Study on establishing the reference range of atrial septal excursion index and foramen ovale membrane angle in normal fetuses aged 16-40 weeks / 中华超声影像学杂志

Objective:To establish the normal reference range of atrial septal excursion index (ASEI) and foramen ovale membrane angle in normal fetuses aged 16-40 weeks, and to analyze the correlation between ASEI and foramen ovale membrane angle in normal fetuses.Methods:A total of 378 normal singletons with gestational ages of 16-40 weeks undergoing by fetal echocardiography were selected in the Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine, from January to June 2021, and 349 fetuses successfully finished all measurements. After all fetuses completed the systematic fetal echocardiography, fetal foramen ovale diameter and foramen ovale membrane angle were measured on the four chamber view. The maximum distance of foramen ovale valve from the base of atrial septum to the free wall of left atrium and the transverse diameter of left atrium were measured, and ASEI was calculated. The differences of ASEI, foramen ovale membrane angle and foramen ovale diameter of the groups with different gestational weeks were compared. The correlations among ASEI, foramen ovale membrane angle and foramen ovale diameter were analyzed by Pearson correlation analysis.Results:All 349 fetuses were divided into 6 groups according to their gestational weeks, including 17 cases at 16-20 weeks, 46 cases at 21-24 weeks, 114 cases at 25-28 weeks, 105 cases at 29-32 weeks, 31 cases at 33-36 weeks and 36 cases at 37-40 weeks. The ± s of ASEI was 0.492 7±0.059 7, 95% CI was 0.486 4-0.499 0, 95% normal reference value range was 0.375 7-0.609 8. Significant differences were found in ASEI among different groups( P<0.05). The ± s of foramen ovale membrane angle was (44.03±5.48)°, 95% CI was 43.46-44.61°, 95% normal reference value range was 33.29-54.78°. Significant differences were found in the foramen ovale membrane angle among different groups( P<0.05). The ± s of foramen ovale diameter was (4.32±1.30)mm, 95% CI was 4.18-4.45 mm, the differences among different groups were significant( P<0.05) and foramen ovale diameter was found increased with the increase of gestational weeks. There was a significant positive correlation between ASEI and foramen ovale membrane angle ( r=0.558, P<0.05). There was no correlation between foramen ovale diameter and ASEI and foramen ovale membrane angle ( r=-0.166, -0.084; all P>0.05). Conclusions:The normal reference ranges of ASEI and foramen ovale valve angle of normal fetuses aged 16-40 weeks was successfully established. These parameters may be useful for evaluating diastolic cardiac function by assessing foramen ovale.

m7G-lncRNAs are potential biomarkers for prognosis and tumor microenvironment in patients with colon cancer / 南方医科大学学报

OBJECTIVE@#To assess the value of m7G-lncRNAs in predicting the prognosis and microenvironment of colorectal cancer (CRC).@*METHODS@#We screened m7G-lncRNAs from TCGA to construct an m7G-lncRNAs risk model using multivariate Cox analysis, which was validated using ROC and C-index curves. Calibration and nomogram were used to predict the prognosis of CRC patients. Point-bar charts and K-M survival curves were used to assess the correlation of risk scores with the patients' clinical staging and prognosis. CIBERSORT and ESTIMATE were used to explore the association between the tumor microenvironment and immune cell infiltration in patients in high and low risk groups and the correlation of risk scores with microsatellite instability, stem cell index and immune checkpoint expression. A protein-protein interaction network was constructed, and the key targets regulated by m7G-lncRNAs were identified and validated in paired samples of CRC and adjacent tissues by immunoblotting.@*RESULTS@#We identified a total of 1722 m7G-lncRNAs from TCGA database, from which 12 lncRNAs were screened to construct the risk model. The AUCs of the risk model for predicting survival outcomes at 1, 3 and 5 years were 0.727, 0.747 and 0.794, respectively. The AUC of the nomogram for predicting prognosis was 0.794, and the predicted results were consistent with actual survival outcomes of the patients. The patients in the high-risk group showed more advanced tumor stages and a greater likelihood of high microsatellite instability than those in the low-risk group (P < 0.05). The tumor stemness index was negatively correlated with the risk score (r=-0.19; P=7.3e-05). Patients in the high-risk group had higher stromal cell scores (P=0.0028) and higher total scores (P=0.007) with lowered expressions of activated mast cells (r=-0.11; P=0.045) and resting CD4+ T cells (r=-0.14; P=0.01) and increased expressions of most immune checkpoints (P < 0.05). ATXN2 (P= 0.006) and G3BP1 (P=0.007) were identified as the key targets regulated by m7G-lncRNAs, and their expressions were both higher in CRC than in adjacent tissues.@*CONCLUSION@#The risk model based on 12 m7G-lncRNAs has important prognostic value for CRC and can reflect the microenvironment and the efficacy of immunotherapy in the patients.

Modality-Specific Modulation of Temperature Representations in the Spinal Cord after Injury.

Different types of tissue injury, such as inflammatory and neuropathic conditions, cause modality-specific alternations on temperature perception. There are profound changes in peripheral sensory neurons after injury, but how patterned neuronal activities in the CNS encode injury-induced sensitization to temperature stimuli is largely unknown. Using in vivo calcium imaging and mouse genetics, we show that formalin- and prostaglandin E2-induced inflammation dramatically increase spinal responses to heating and decrease responses to cooling in male and female mice. The reduction of cold response is largely eliminated on ablation of TRPV1-expressing primary sensory neurons, indicating a crossover inhibition of cold response from the hyperactive heat inputs in the spinal cord. Interestingly, chemotherapy medication oxaliplatin can rapidly increase spinal responses to cooling and suppress responses to heating. Together, our results suggest a push-pull mechanism in processing cold and heat inputs and reveal a synergic mechanism to shift thermosensation after injury.SIGNIFICANCE STATEMENT In this paper, we combine our novel in vivo spinal cord two-photon calcium imaging, mouse genetics, and persistent pain models to study how tissue injury alters the sensation of temperature. We discover modality-specific changes of spinal temperature responses in different models of injury. Chemotherapy medication oxaliplatin leads to cold hypersensitivity and heat hyposensitivity. By contrast, inflammation increases heat sensitivity and decreases cold sensitivity. This decrease in cold sensitivity results from the stronger crossover inhibition from the hyperactive heat inputs. Our work reveals the bidirectional change of thermosensitivity by injury and suggests that the crossover inhibitory circuit underlies the shifted thermosensation, providing a mechanism to the biased perception toward a unique thermal modality that was observed clinically in chronic pain patients.

The responses of weathering carbon sink to eco-hydrological processes in global rocks.

Eco-hydrological processes affect the chemical weathering carbon sink (CS) of rocks. However, due to data quality limitations, the magnitude of the CS of rocks and their responses to eco-hydrological processes are not accurately understood. Therefore, based on Global Erosion Model for CO2 fluxes (GEM-CO2 model), hydrological site data, and multi-source remote sensing data, we produced a 0.05° × 0.05° resolution dataset of CS for 11 types of rocks from 2001 to 2018. The results show that the total amount of CS of global rocks is 0.32 ± 0.02 Pg C, with an average flux of 2.7 t C km-2 yr-1, accounting for 53% and 3% of the "missing" carbon sink and fossil fuel emissions, respectively. This is 23% higher than previous research results, which may be due to the increased resolution. Although about 60% of the CS of global rocks are in a stable state, there are obvious differences among rocks. For example, the CS of carbonate rocks exhibited a significant increase (0.30 Tg C/yr), while the CS of siliceous clastic sedimentary rocks exhibited a significant decrease (-0.06 Tg C/yr). Although temperature is an important factor affecting the CS, the proportion of soil moisture in arid and temperate climate zones is higher (accounting for 24%), which is 3.6 times that of temperature. Simulations based on representative concentration pathways scenarios indicate that the global CS of rocks may increase by about 28% from 2050 to 2100. In short, we produced a set of high-resolution datasets for the CS of global rocks, which makes up for the lack of datasets in previous studies and improves our understanding of the magnitude and spatial pattern of the CS and its responses to eco-hydrological processes.