Search

Background: The primary objective of this investigation was to assess the impact of pyrroline-5-carboxylate reductase 1 (PYCR1) on the progression of gastric cancer (GC), specifically focusing on tumor growth and metastatic potential. Methods: Surgical specimens from patients with different stages of GC were assayed for PYCR1 expression using immunohistochemistry. PYCR1 expression was manipulated by depletion or overexpression approaches in GC cells, and these cells were applied to explore the functional roles of PYCR1. Expression of apoptosis– and metastasis–related markers was quantified through quantitative real-time PCR and Western blot. Results: Higher PYCR1 expression was ascertained in surgical specimens from patients with GC as compared to noncancerous adjacent tissues. Additionally, PYCR1 overexpression in GC tissues was linked to adverse clinical outcomes. The depletion of PYCR1 in GC cells resulted in a pronounced reduction in proliferation, the induction of apoptosis, and the attenuation of invasion and metastasis. Conversely, its ectopic expression notably augmented proliferation, restricted apoptosis, and stimulated invasion and metastasis. In addition, the knockdown of PYCR1 resulted in a significant elevation in the activation of caspase 3, a key protein involved in apoptosis. This depletion also led to a decrease in the activation or expression of proteins associated with metastasis, such as phosphorylated (p)-phosphatidylinositol 3-kinase (PI3K), p-AKT serine/threonine kinase (AKT), and snail family transcriptional repressor 1 (Snail). Additionally, it resulted in an upregulation of E-cadherin expression. Conversely, the overexpression of PYCR1 notably increased the levels of p-PI3K, p-AKT, and Snail, while simultaneously reducing E-cadherin expression. Conclusion: PYCR1, by activating PI3K/AKT signaling, assumes a crucial role in governing malignant characteristics of GC cells, including proliferation, apoptosis, and metastasis. These findings underscore the promising potential of PYCR1 as a diagnostic biomarker and a target for tailored therapeutic interventions in patients with GC.

Water resources are scarce, and secondary soil salinization is severe in the Hetao Irrigation District. Farmland shelterbelt systems (FSS) play a critical role in regulating soil water and salt dynamics within the irrigation district. However, the understanding of soil water and salt migration within FSS during the freeze–thaw period remains unclear due to the complex and multifaceted interactions between water and salt. This study focused on a typical FSS and conducted comprehensive monitoring of soil moisture, salinity, temperature, and meteorological parameters during the freeze–thaw period. The results revealed consistent trends in air temperature and soil temperature overall. Soil freezing durations exceeded thawing durations, and both decreased with an increasing soil depth. At the three critical freeze–thaw nodes, the soil moisture content at a 0–20 cm depth was significantly lower than at a 40–100 cm depth (p < 0.05). The soil water content increased with time and depth at varying distances from the shelterbelt, with an average increase of 7.63% after freezing and thawing. The surface water content at the forest edge (0.3H, 4H) was lower than inside the farmland (1H, 2H, 3H). Soil salt accumulation occurred during both freezing stable periods and melting–thawing periods in the 0–100 cm soil layer near the forest edge (0.3H, 4H), with the highest soil salinity reaching 0.62 g·kg−1. After the freeze–thaw period, the soil salt content in each layer increased by 11.41–47.26% compared to before the freeze–thaw period. Salt accumulation in farmland soil near the shelterbelt was stronger than in the far shelterbelt. The multivariate statistical model demonstrated goodness of fit for soil water and salt as 0.94 and 0.72, respectively, while the BP neural network model showed goodness of fit for soil water and salt as 0.82 and 0.85, respectively. Our results provide an efficient theoretical basis for FSS construction and agricultural water management practices.

IntroductionsIdentifying biological markers of colorectal cancer (CRC) development and prognosis and exploring the intrinsic connection between these molecular markers and CRC progression is underway. However, a single molecular tumor marker is often difficult to assess and predict the progression and prognosis of CRC. Consequently, a combination of tumor-related markers is much needed. Ki67, Her-2, and mutant P53 (MutP53) proteins play pivotal roles in CRC occurrence, progression and prognosis.MethodsBased on the expressions by immunochemistry, we developed a risk model, nomogram and lymph node metastasis model by R software and Pythons to explore the value of these proteins in predicting CRC progression, prognosis, and examined the relationship of these proteins with the CRC clinicopathological features from 755 (training set) and 211 CRC (validation set) patients collected from the hospital.ResultsWe found that Ki67 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular invasion, organization differentiation, and adenoma carcinogenesis. Moreover, Her-2 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular and nerve invasion, pMMR/dMMR, signet ring cell carcinoma, and organization differentiation. MutP53 expression was significantly correlated with T-stage, N-stage, TNM-stage, vascular and nerve invasion, adenoma carcinogenesis, signet ring cell carcinoma, organization differentiation, and pMMR/dMMR. Increased expression of each of the protein indicated a poor prognosis. The established risk model based on the three key proteins showed high predictive value for determining the pathological characteristics and prognosis of CRC and was an independent influencer for prognosis. The nomogram prediction model, which was based on the risk model, after sufficient evaluation, showed more premium clinical value for predicting prognosis. Independent cohort of 211 CRC patients screened from the hospital verified the strong predictive efficacy of these models. The utilization of the XGBoost algorithm in a lymph node metastasis model, which incorporates three crucial proteins, demonstrated a robust predictive capacity for lymph node metastasis.DiscussionThe risk model, nomogram and lymph node metastasis model have all provided valuable insights into the involvement of these three key proteins in the progression and prognosis of CRC. Our study provides a theoretical basis for further screening of effective models that utilize biological markers of CRC.

A significant correlation is observed between Fusobacterium nucleatum (F. nucleatum) and the evolution of inflammatory bowel disease (IBD). Particularly, FomA, a critical pathogenic element of F. nucleatum, inflicts substantial detriment to human intestinal health. Our research focused on the development of recombinant Lactobacillus plantarum that expresses FomA protein, demonstrating its potential in protecting mice from severe IBD induced by F. nucleatum. To commence, two recombinant strains, namely L. plantarum NC8-pSIP409-pgsA'-FomA and NC8-pSIP409-FnBPA-pgsA'-FomA, were successfully developed. Validation of the results was achieved through flow cytometry, ELISA, and MTT assays. It was observed that recombinant L. plantarum instigated mouse-specific humoral immunity and elicited mucosal and T cell-mediated immune responses. Significantly, it amplified the immune reaction of B cells and CD4+T cells, facilitated the secretion of cytokines such as IgA, IL4, and IL10, and induced lymphocyte proliferation in response to FomA protein stimulation. Finally, we discovered that administering recombinant L. plantarum could protect mice from severe IBD triggered by F. nucleatum, subsequently reducing pathological alterations and inflammatory responses. These empirical findings further the study of an innovative oral recombinant Lactobacillus vaccine.

Abstract Background Neutrophil extracellular traps (NETs) is the key means for neutrophils to resist bacterial invasion. Sepsis is a systemic inflammatory response syndrome caused by infection. Methods In our study, qRT-PCR was used to detect the gene expression in neutrophils, Western blot was used to detect the protein expression in mouse tissues and neutrophils, flow cytometry was used to detect the purity of neutrophils in the whole blood and immunofluorescence was used to detect the NETs formation. Results In this study, we analyzed the NETs formation in the blood of patients with sepsis. The results showed that a large number of NETs appeared. And the expression of GPR109A in neutrophils of patients with sepsis was significantly up regulated. Then we collected neutrophils from WT mice and GPR109A−/− mice and found that GPR109A knockout could significantly inhibit the early NETs formation of neutrophils. The results also showed that knockout of GPR109A or inhibition of the NETs formation could increase the inflammatory response of liver, spleen, lung and kidney in mice, thus affecting the disease process of sepsis. Then we observed the death of mice in 16 days. The results showed that inhibiting the NETs formation could significantly affect the early mortality of mice, while knocking out GPR109A could directly affect the mortality of the whole period. Conclusions This study confirmed the regulatory effect of GPR109A on early NETs formation for the first time, and provided a new target for the treatment of sepsis.

Background The coronavirus disease 2019 (COVID-19) pandemic has posed a great challenge to the healthcare system. This study evaluated the impact of the pandemic on the utilization of primary healthcare (PHC). Methods The outpatient data from 158 PHC institutions in Yinchuan from May 1, 2017 to April 30, 2020 were used. The difference in difference (DID) model was used to analyze the difference in the number of outpatient visits per day, total outpatient expenditure per day, and outpatient expenditure per visit between December 2019 and February 2020 compared with the same periods in two previous years. The autoregressive integrated moving average (ARIMA) modelling was used to investigate the association between the outpatient volume and the number of the last week’s new COVID-19 cases in Yinchuan, Ningxia, and China. Results From December 2019 to February 2020, the decline in the number of outpatient visits per day (DID: -367.21 times, P = .004) was larger than that in two previous years, and a similar trend can be seen in the outpatient expenditure per day. However, the rise in the outpatient expenditure per visit (DID: 19.06 thousand yuan, P = .003) was larger than that in two previous years. In 2020, the outpatient visits for most types of diseases decreased from week 3 and rebounded after week 5. The decline and rebound of outpatient visits in the population aged 45 years and older were steeper than in those younger. The outpatient volume was negatively associated with the number of the last week’s new COVID-19 cases. Conclusion This study indicated a significant impact of the pandemic on PHC service utilization. Since PHC service is the foundation of the healthcare system in most developing countries, measures should be taken to make PHC help cope with the crisis and relieve the burden of hospital care.

Abstract Background cblC deficiency is the most common type of methylmalonic aciduria in China. Late-onset patients present with various non-specific symptoms and are usually misdiagnosed. The purpose of this study is to investigate the clinical features of patients with late-onset cblC deficiency and explore diagnosis and management strategies around puberty. Results This study included 56 patients (35 males and 21 females) with late-onset cblC deficiency who were admitted to our clinic between 2002 and September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome, and associated genetic variants were examined. The onset age ranged from 10 to 20 years (median age, 12 years). Fifteen patients (26.8%) presented with symptoms after infection or sports training. Further, 46 patients (82.1%) had neuropsychiatric diseases; 11 patients (19.6%), cardiovascular diseases; and 6 patients (10.7%), pulmonary hypertension. Renal damage was observed in 6 cases (10.7%). Genetic analysis revealed 21 variants of the MMACHC gene in the 56 patients. The top five common variants detected in 112 alleles were c.482G > A (36.6%), c.609G > A (16.1%), c.658_660delAAG (9.8%), c.80A > G (8.0%), and c.567dupT (6.3%). Thirty-nine patients carried the c.482G > A variant. Among 13 patients who exhibited spastic paraplegia as the main manifestation, 11 patients carried c.482G > A variants. Six patients who presented with psychotic disorders and spastic paraplegia had compound heterozygotic c.482G > A and other variants. All the patients showed improvement after metabolic treatment with cobalamin, l-carnitine, and betaine, and 30 school-aged patients returned to school. Two female patients got married and had healthy babies. Conclusions Patients with late-onset cblC deficiency present with a wide variety of neuropsychiatric symptoms and other presentations, including multiple organ damage. As a result, cb1C deficiency can easily be misdiagnosed as other conditions. Metabolic and genetic studies are important for accurate diagnosis, and metabolic treatment with cobalamin, l-carnitine, and betaine appears to be beneficial.

This study systematically and comprehensively analyzed the characteristics of matrix metalloproteinases (MMPs) in gastric cancer (GC) and revealed the relationship between MMPs and prognoses, clinicopathological features, tumor microenvironment, gene mutations, and drug therapy response in patients with GC. Based on the mRNA expression profiles of 45 MMP-related genes in GC, we established a model that classified GC patients into three groups based on cluster analysis of the mRNA expression profiles. The 3 groups of GC patients showed significantly different prognoses as well as tumor microenvironmental characteristics. Next, we used Boruta’s algorithm and PCA method to establish an MMP scoring system and found that lower MMP scores were associated with better prognoses, lower clinical stages, better immune cell infiltration, lower degrees of immune dysfunction and rejection, and more genetic mutations. Whereas a high MMP score was the opposite. These observations were further validated with data from other datasets, showing the robustness of our MMP scoring system. Overall, MMP could be involved in the tumor microenvironment (TME), clinical features, and prognosis of GC. An in-depth study of MMP patterns can better understand the indispensable role of MMP in the development of GC and reasonably assess the survival prognosis, clinicopathological features, and drug efficacy of different patients, thus providing clinicians with a broader vision of GC progression and treatment.

The deterioration of farmland shelterbelts in the Ulan Buh desert oases could weaken their protective functions. Therefore, an accurate method is essential to assess tree decline degree in order to guide the rejuvenation and transformation of these shelterbelts. This study selected three typical farmland shelterbelts in the Ulan Buh desert oases as the objects. Terrestrial laser scanning (TLS) and airborne hyperspectral imagery (AHI) were used to acquire point cloud data and detailed spectral information of trees. Point cloud and spectral characteristics of trees with varying decline levels were analyzed. Six models were constructed to identify decline degree of shelterbelts, and model accuracy was evaluated. The coefficient of determination between the structural parameters of trees extracted by TLS and field measurements ranged from 0.76 to 0.94. Healthy trees outperformed declining trees in structural parameters, particularly in tridimensional green biomass and crown projection area. Spectral reflectance changes in the 740–950 nm band were evident among the three tree types with different decline levels, decreasing significantly with increased decline level. Among the TLS-derived feature parameters, the canopy relief ratio of tree points and point cloud density strongly correlated with the degree of tree decline. The plant senescence reflectance index and normalized difference vegetation index exhibited the closest correlation with tree decline in AHI data. The average accuracy of the models constructed based on the feature parameters of LiDAR, AHI, and the combination of both of them were 0.77, 0.61, and 0.81, respectively. The light gradient-boosting machine model utilizing TLS–AHI comprehensive feature parameters accurately determined tree decline. This study highlights the efficacy of employing feature parameters derived from TLS alone to accurately identify tree decline. Combining feature parameters from the TLS and AHI enhances the precision of tree decline identification. This approach offers guidance for decisions regarding the renewal and transformation of declining farmland shelterbelts.

BackgroundPatients with diabetic kidney disease (DKD) often have gastrointestinal dysfunction such as inflammatory bowel disease (IBD). This study aims to investigate the genetic mechanism leading to IBD in DKD patients through data mining and bioinformatics analysis.MethodsThe disease-related genes of DKD and IBD were searched from the five databases of OMIM, GeneCards, PharmGkb, TTD, and DrugBank, and the intersection part of the two diseases were taken to obtain the risk genes of DKD complicated with IBD. A protein–protein interaction (PPI) network analysis was performed on risk genes, and three topological parameters of degree, betweenness, and closeness of nodes in the network were used to identify key risk genes. Finally, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the risk genes to explore the related mechanism of DKD merging IBD.ResultsThis study identified 495 risk genes for DKD complicated with IBD. After constructing a protein–protein interaction network and screening for three times, six key risk genes were obtained, including matrix metalloproteinase 2 (MMP2), hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF2), interleukin (IL)-18, IL-13, and C–C motif chemokine ligand 5 (CCL5). Based on GO enrichment analysis, we found that DKD genes complicated with IBD were associated with 3,646 biological processes such as inflammatory response regulation, 121 cellular components such as cytoplasmic vesicles, and 276 molecular functions such as G-protein-coupled receptor binding. Based on KEGG enrichment analysis, we found that the risk genes of DKD combined with IBD were associated with 181 pathways, such as the PI3K-Akt signaling pathway, advanced glycation end product–receptor for AGE (AGE-RAGE) signaling pathway and hypoxia-inducible factor (HIF)-1 signaling pathway.ConclusionThere is a genetic mechanism for the complication of IBD in patients with CKD. Oxidative stress, chronic inflammatory response, and immune dysfunction were possible mechanisms for DKD complicated with IBD.

ObjectiveCblC deficiency, the most common cobalamin metabolic abnormality, is caused by pathogenic variants in the MMACHC gene. The renal complications of this disease have been described only in a small number of cases. This study aimed to better delineate renal phenotype and genetic characteristics in Chinese children with cblC defect.MethodsChildren with cblC deficiency who manifested as kidney damage were enrolled. Clinical, renal pathological, and genetic data were reviewed in detail.ResultsSeven cases were enrolled. Ages at disease onset ranged from 9 months to 5 years. All patients presented with hematuria and proteinuria, and 2/7 cases presented with nephrotic syndrome. Renal dysfunction was observed in 4/7 cases. Renal biopsy was performed in 5/7 cases, and all of them had renal thrombotic microangiopathy. Macrocytic anemia was detected in all seven patients. Six out of seven cases had hypertension, and 2/7 cases presented with pulmonary hypertension. Two of them had a mild intellectual disability, and one suffered from epilepsy. Increased urine methylmalonic acid and plasma homocysteine were detected in seven cases, while two patients had normal levels of urine methylmalonic acid at the initial evaluation. After diagnosis, all seven cases were treated with hydroxocobalamin IM. Six cases were followed-up for 3–8 years. After treatments, anemia was the first to be recovered, followed by proteinuria. Renal function recovered after 1 year in two cases, whereas patient 2 progressed to stage 2 chronic kidney disease 13 years after onset. While a case presented with end-stage kidney disease because of late diagnosis, one case died 3 months after disease onset due to giving up treatment. Three MMACHC pathogenic variants c.80A > G (8/14), c.609G > A (4/14), and c.658_660delAAG (2/14) were detected in all seven children.ConclusionMMACHC variant c.80A > G may be associated with prominent renal complications in Chinese cblC patients. Macrocytic anemia and hyperhomocysteinemia are useful clues for patients with hematuria and proteinuria caused by cblC defect. The most frequent renal pathological manifestation is thrombotic microangiopathy. Early diagnosis and treatment resulted in improving renal and hematological signs.

Complexity of forest structure is an important factor contributing to uncertainty in aboveground biomass estimates. In this study, we present a new method for reducing uncertainty in forest aboveground biomass (AGB) estimation based on plot-level terrestrial laser scanner (TLS) point clouds reconstruction. The method estimates the total AGB of plots with complex structures after automatically performing the steps of ground point filtering, single tree segmentation, and three-dimensional (3D) structure reconstruction. We used plot data from temperate and tropical forest ecosystems to verify the effectiveness of the method, reconstructing a 1300 m2 temperate plantation plot and a 5000 m2 mingled forest plot, respectively. The total biomass of 153 trees in the plantation plot was overestimated by 17.12 %, and the total biomass of 61 trees in the mingled forest plot was underestimated by 10.88 %. We found that the uncertainty of aboveground biomass estimation in tropical forests with more complex structures is not necessarily greater than in plantations. Therefore, in large-scale remote sensing observations of forest biomass, the number or area of plots can be increased to reduce the uncertainty of the results caused by the complex structure. The focus of this study is to explore TLS point clouds modeling methods to reduce the uncertainty in AGB estimation caused by the complexity of forest structures, and to provide reference cases for plot-level point clouds reconstruction methods. Forest ecologists can use this method to regularly observe forest growth and obtain indicators related to forest ecology without destroying trees.

Colorectal cancer (CRC) is a common type of malignant digestive tract tumor with a high incidence rate worldwide. Currently, the clinical treatment of CRC predominantly include surgical resection, postoperative chemotherapy, and radiotherapy. However, these treatments contain severe limitations such as drug side effects, the risk of recurrence and drug resistance. Some natural compounds found in plants, fungi, marine animals, and bacteria have been shown to inhibit the occurrence and development of CRC. Although the explicit molecular mechanisms underlying the therapeutic effects of these compounds on CRC are not clear, classical signaling transduction pathways such as NF-kB and Wnt/β-catenin are extensively regulated. In this review, we have summarized the specific mechanisms regulating the inhibition and development of CRC by various types of natural compounds through nine signaling pathways, and explored the potential therapeutic values of these natural compounds in the clinical treatment of CRC.

Understanding soil seed banks (SSBs) of Nitrariatangutorum nebkhas is critical for vegetation restoration and ecological management in desert–oasis ecotones. In this study, we conducted a survey in the field and a seed germination experiment in the laboratory to investigate the characteristics of SSB in different sizes and parts of nebkhas and to examine their relationship with aboveground vegetation. The results showed that there were 17 species of plants in six families in the SSB of Nitraria tangutorum nebkhas in a desert–oasis ecotone, dominated by Chenopodiaceae. The life forms were mainly annual herbs, accounting for 58.82%–71.43%. The number of species in the SSB were in the order of large nebkha > medium nebkha > small nebkha, and there was no significant difference in SSB density. However, SSB densities in different parts of each nebkha were in the order bottom > middle > top. The densities were significantly different and showed a decreasing trend as soil depth increased. Most of the plant seeds were distributed in the 0–5 cm soil layer. The similarity coefficient between the SSB of each nebkha and the aboveground vegetation was high. From the bottom to the top, the number of common species and similarity coefficient between the aboveground vegetation and the SSB decreased, and the number of species in the SSB was greater than that of the aboveground vegetation. Vegetation plays a decisive role in the initial development of a nebkha. When the nebkha develops to a certain extent, it reacts to the vegetation, thereby intensifying the differences in the composition of vegetation species in different parts of the nebkha and further affecting the SSB.

Desert ecosystems are vulnerable to climate change because of their fragile environment and poor self-regulation ability. Exploring the land–surface energy balance and the water/heat transfer processes of such regions for water resource management purposes is critical. The processes of surface water and heat transfer throughout the desert ecosystems and the effects of environmental factors on the energy distribution remain poorly studied. In this study, we used an eddy covariance system and surface meteorological data (2019–2021) to investigate the characteristics of the energy balance of Dengkou Desert ecosystem located in Inner Mongolia, northern China. Also, we evaluated the effects of different environmental factors on the energy distribution in this desert ecosystem. We found that the temporal patterns of both sensible heat flux (H) and latent heat flux (LE) with time are consistent with that of net radiation (Rn), and Rn is dominated by H. The sum of the daily average soil heat flux during the observation period was positive, indicating that soil was a heat sink and that the atmosphere transfers heat to the soil. During the observation period, the energy distribution of H/Rn fluctuated greatly, presenting a general U-shaped trend, while LE/Rn presented an inverted V-shaped trend. The main factor affecting H was Rn, followed by saturated vapor pressure, air temperature (Ta), and relative humidity. For LE, the main influencing factors were Ta, and Rn. The energy closure of the half-hour flux in the Inner Mongolian desert ecosystem during the observation period was 48%–68%, and the energy balance ratio was 0.54–0.74. The energy closure at the daily scale was higher than that at the half-hour scale, and the energy closure during daytime was higher than that at night.

Knowledge of the microclimate and wind regimes of different land landscapes can be used to support natural resource development and agricultural productivity in desert areas. The aim of this study is to provide a theoretical basis and technical support for the management of Ulan Buh Desert Oasis and the comprehensive prevention and control of sandstorms from the surrounding desert in northern China. We examined the microclimate and wind regime of three landscapes—desert, desert–oasis ecotone, and oasis—and discussed the factors underlying the observed variations. Similar patterns were found in annual temperature, annual relative humidity, and wind speed between the desert, desert–oasis, and the oasis. Compared with the desert and the desert–oasis ecotone, the average annual temperature and wind speed in the oasis were lower by 2.56%–5.38% and 32.99%–37.05%, respectively. Average annual relative humidity in the oasis was higher than in other areas by 1.31%–2.57%. The desert, desert–oasis ecotone, and the oasis were dominated by westerly winds. Wind direction was relatively stable in the oasis and variable in the desert and desert–oasis ecotone. There were intermediate wind energy fields in the desert and the desert–oasis ecotone and a low wind energy field in the oasis. In the desert–oasis ecotone, drift potential (DP), resultant drift potential (RDP), and resultant drift direction (RDD) were 231.87 VU, 97.21 VU, and 104.33°, respectively. In the desert, DP was 228.45 VU, RDP was 92.65 VU, and RDD was 76.05°. In the oasis, the DP was 61.85 VU, RDP was 38.04 VU, and RDD was 92.97°. In the desert and the desert–oasis ecotone, sediment transport potential was the highest in spring, second highest in autumn, third highest in winter, and lowest in summer. In the oasis, it was the highest in winter, second highest in autumn, third highest in spring, and lowest in summer. There are complex variations in the dominant sediment transport directions in the desert and desert–oasis ecotone in the study area. Variations in the dominant sediment transport direction in the oasis are less complicated and are associated with the seasons. The oasis is primarily threatened by sandstorms from the south-southeast in spring.

Photosystem II (PSII) of grapevine leaves is easily damaged under heat stress, but no such injury is observed when the leaves are heated in low light. To elucidate the mechanisms, we compared the photosynthetic characteristics of grapevine seedlings under heat treatments (42 °C) for 4 h in the dark or low light (200 μmol m−2 s−1). At 42 °C in the dark, the PSII maximum quantum yield (Fv/Fm) decreased significantly with the increase in time but did not change much in low light. The JIP (chlorophyll a fluorescence rise kinetics) test results showed that low light significantly alleviated the damage to the oxygen evolving complexes (OECs; the K-step was less visible) by heat stress. Further, in the presence of de novo D1 protein synthesis inhibitor chloramphenicol, Fv/Fm did not differ significantly between dark and light treatments under heat stress. The 50% re-reduction (RR50) of P700+ on cessation of far-red illumination was faster after light treatment than that in the dark. After exposure to 25 °C in a low light for 15 min, Y(NO) (the constitutive non-regulatory non-photochemical quenching) treated by heat stress and darkness was higher than that by heat stress and light. Overall, our results suggested that enhanced CEFs around PSI in low light could assist PSII against heat damage by maintaining the rate of PSII repair and inhibiting the non-radiative charge recombination in PSII reaction centers.

Introduction: Planted forests are of great significance in reducing wind erosion and controlling degraded land, and are the main measure to improve the ecological environment in arid and semi-arid areas. Afforestation is mainly based on tall trees, but forest belts consume a large amount of water, bringing significant pressure to the environmental carrying capacity. While shrubs generally consume less water than do trees, it remains understudied what role shrubs play in configuration of shelterbelts in arid areas. Methods: In this study, we conducted wind tunnel simulation experiments with the common used afforestation tree species Populus popularis and shrub species Salix psammophila. We set up single- or double-belt pure forest and mixed tree/ shrub configurations, to analyze their effects on the wind speed, flow field, and wind prevention efficiency of different forest belt types. Results: The results showed that: 1) the wind erosion resistance of the double-belt shelter forest was stronger than that of a single-belt forest. 2) Shelterbelts consisting of trees had a strong resistance to airflow disturbances, but their protective effect was reflected mainly in the canopy layer, with poor near-surface protection. 3) Shelterbelts consisting of shrubs had a good protective effect within effective height, and the wind speed in the double-shrub forest belt was 77% of that in the single-tree forest belt. 4) The wind prevention efficiency within the shrub forest belt was better than that of the tree forest belt, with wind prevention efficiency exceeding 40% in most double-shrub forests. Shrubs as a supplement to trees could increase the minimum wind prevention efficiency by up to 30%. Discussion: Therefore, the role of shrubs should be emphasized in afforestation in arid areas, especially in areas that need near-surface protection. [ABSTRACT FROM AUTHOR]

Renal hypodysplasia and cystic kidney diseases, the common non-glomerular causes of pediatric chronic kidney disease (CKD), are usually diagnosed by their clinical and imaging characteristics. The high degree of phenotypic heterogeneity, in both conditions, makes the correct final diagnosis dependent on genetic testing. It is not clear, however, whether the frequencies of damaged alleles vary among different ethnicities in children with non-glomerular CKD, and this will influence the strategy used for genetic testing. In this study, 69 unrelated children (40 boys, 29 girls) of predominantly Han Chinese ethnicity with stage 2–5 non-glomerular CKD caused by suspected renal hypodysplasia or cystic kidney diseases were enrolled and assessed by molecular analysis using proband-only targeted exome sequencing and array-comparative genomic hybridization. Targeted exome sequencing discovered genetic etiologies in 33 patients (47.8%) covering 10 distinct genetic disorders. The clinical diagnoses in 13/48 patients (27.1%) with suspected renal hypodysplasia were confirmed, and two patients were reclassified carrying mutations in nephronophthisis (NPHP) genes. The clinical diagnoses in 16/20 patients (80%) with suspected cystic kidney diseases were confirmed, and one patient was reclassified as carrying a deletion in the hepatocyte nuclear factor-1-beta gene (HNF1B). The diagnosis of one patient with unknown non-glomerular disease was elucidated. No copy number variations were identified in the 20 patients with negative targeted exome sequencing results. NPHP genes were the most common disease-causing genes in the patients with disease onsets above 6 years of age (14/45, 31.1%). The children with stage 2 and 3 CKD at onset were found to carry causative mutations in paired box gene 2 (PAX2) and HNF1B gene (11/24, 45.8%), whereas those with stage 4 and 5 CKD mostly carried causative mutations in NPHP genes (19/45, 42.2%). The causative genes were not suspected by the kidney imaging patterns at disease onset. Thus, our data show that in Chinese children with non-glomerular renal dysfunction caused by renal hypodysplasia and cystic kidney diseases, the common causative genes vary with age and CKD stage at disease onset. These findings have the potential to improve management and genetic counseling of these diseases in clinical practice.

Abstract Background Both Pierson syndrome (PS) and isolated nephrotic syndrome can be caused by LAMB2 biallelic pathogenic variants. Only 15 causative splicing variants in the LAMB2 gene have been reported. However, the pathogenicity of most of these variants has not been verified, which may lead to incorrect interpretation of the functional consequence of these variants. Methods Using high‐throughput DNA sequencing and Sanger sequencing, we detected variants in a female with clinically suspected PS. A minigene splicing assay was performed to assess the effect of LAMB2 intron 20 c.2885‐9C>A on RNA splicing. We also performed the immunohistochemical analysis of laminin beta‐2 in kidney tissues. Results Two novel LAMB2 heteroallelic variants were found: a paternally inherited variant c.2885‐9C>A in intron 20 and a maternally inherited variant c. 3658C>T (p. (Gln1220Ter)). In vitro minigene assay showed that the variant c.2885‐9C>A caused erroneous integration of a 7 bp sequence into intron 20. Immunohistochemical analysis revealed the absence of glomerular expression of laminin beta‐2, the protein encoded by LAMB2. Conclusion We demonstrated the impact of a novel LAMB2 intronic variant on RNA splicing using the minigene assay firstly. Our results extend the mutational spectrum of LAMB2.

Northwest China is significantly affected by sandstorm disasters. To mitigate the negative impacts of sandstorm events, it is critical to understand the spatio-temporal variations in typical sand and dust storms and their influencing factors. In this work, using ground-based measurements of particulate matter and remote sensing data such as MODIS, OMI, and CALIPSO data, the sources of aerosol pollution and aerosol optical properties of a typical sandstorm event that occurred in Northwest China in 2018 was studied. In addition, the HYSPLIT model was used to explore the air mass trajectories in order to analyze the sand and dust migration process during the sandstorm event. Furthermore, the wind erosion sensitivity of Northwest China was analyzed via single factor analysis and multi-factor superposition of wind field intensity, soil drought index, vegetation coverage, and relief amplitude. Finally, the region of the study area having a high comprehensive wind erosion sensitivity was identified. The results showed that the PM10 concentrations exceeded 400 µg/m3 and the PM2.5/PM10 ratio did not exceeded 0.6 during the sandstorm event, indicating that natural particulate matter was dominant in the ambient air. At the epicenter of pollution, the aerosol optical depth (AOD) at 550 nm was 0.75–1. By combining AOD data with wind speed and direction data from field observation stations, it was found that the sandstorm event in 2018 mainly occurred between 1 April and 3 April, and affected all of Northwest China on 2 April and 3 April. The absorbed aerosol index (AAI) ranged between 2.5 and 4, indicating that the Taklimakan Desert was the main source of sandstorm events in Northwest China. The CALIPSO total attenuated backscatter coefficient at 532 nm indicated that the main component of tropospheric aerosol in this region was distributed in the range of 0–12.5 km. The simulated airflow track showed that it had the same dust source regions as AAI index studies. Moreover, investigation of wind erosion sensitivity in the study areas indicated that the Taklimakan Desert and other desert regions were the main ecologically sensitive areas. These conclusions can provide references and suggestions for the mitigation of damage caused by sandstorm events, in addition to the enhancement of ecological governance.

Camptothecin (CPT) is a cytotoxic quinoline alkaloid isolated from the bark and branches of the Chinese tree Camptotheca acuminata. CPT inhibits topoisomerase I. It possesses various antitumor activities and is mainly used in the treatment of colon, ovarian, liver, and bone cancers as well as leukemia. CPT inhibits the expressions of inflammatory genes and can prevent death from chronic inflammation. Therefore, we investigated the effect of CPT treatment in ulcerative colitis (UC) using DSS-induced UC mouse model; after that, we explored its potential mechanisms. Here, we found that CPT exerted protection on DSS-induced UC in rats. In addition, the administration prominently reduced the disease activity index as well as colon length of the model rats and remarkably reduced the inflammatory cytokines. Further, CPT significantly reduced several vital proinflammatory proteins in LPS-induced RAW264.7 cells. In summary, our findings demonstrate that CPT is hopefully to act as a therapeutic agent for UC.

Abstract Background To characterize the phenotypic spectrum and assess the antialbuminuric response to angiotensin converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB) therapy in a cohort of children with Dent disease. Methods The patients’ clinical findings, renal biopsy results, genetic and follow‐up data were analyzed retrospectively. Mutations in CLCN5 or OCRL were detected by next‐generation sequencing or Sanger sequencing. Results Of 31 Dent disease boys, 24 carried CLCN5 and 7 carried OCRL mutations. Low molecular weight proteinuria and albuminuria were detected in all cases. Nephrotic‐range proteinuria and severe albuminuria were identified in 52% and 62% of cases, respectively; by 7 years of age, 6 patients had hematuria and nephrotic‐range proteinuria, and 7 patients had hematuria and moderate to severe albuminuria. In addition to disease‐related renal features, patients with Dent‐1 disease also presented with congenital cataract (1/9) and developmental delay (2/7). Seventeen of 31 patients underwent renal biopsy. Glomerular changes included mild glomerular lesions, mesangial proliferative glomerulonephritis and focal segmental glomerular sclerosis. Thirteen of the 31 patients had follow‐up records and received ACE inhibitor and/or ARB treatment for more than 3 months. After a median 1.7 (range 0.3–8.5) years of treatment, a reduction in the urinary microalbumin‐to‐creatinine ratio was observed in 54% of children. Conclusions Hematuria with nephrotic‐range proteinuria or moderate to severe albuminuria was common in Dent disease patients. Extrarenal manifestations were observed in Dent‐1 patients, which extends the phenotypic spectrum. In addition, ACE inhibitors and ARBs are well tolerated, and they are partially effective in controlling albuminuria.

Background: A false interpretation of homozygosity for pathogenic variants causing autosomal recessive disorders can lead to improper genetic counseling. The aim of this study was to demonstrate the underlying etiologies of presumed homozygous disease-causing variants harbored in six unrelated children with five different genetic renal diseases when the same variant was identified in a heterozygous state in only one of the two parents from each family using direct sequencing.Methods: Peripheral blood genomic DNA samples were extracted. Six short tandem repeats were used to verify the biological relationships between the probands and their parents. Quantitative PCR was performed to detect mutant exons with deletions. Single nucleotide polymorphism analysis and genotyping with polymorphic microsatellite markers were performed to identify uniparental disomy (UPD).Results: Each proband and his/her parents had biological relationships. Patients 2, 4, and 6 were characterized by large deletions encompassing a missense/small deletion in DGKE, NPHP1, and NPHS1, respectively. Patients 1 and 5 were caused by segmental UPD in NPHS2 and SMARCAL1, respectively. In patient 6, maternal UPD, mosaicism in paternal sperm or de novo variant in NPHP1 could not be ruled out.Conclusions: When a variant analysis report shows that a patient of non-consanguineous parents has a pathogenic presumed homozygous variant, we should remember the need to assess real homozygosity for the variant, and a segregation analysis of the variants within the parental DNAs and comprehensive molecular tests to evaluate the potential molecular etiologies, such as a point variant and an overlapping exon deletion, UPD, germline mosaicism and de novo variant, are crucial.

Alport syndrome is a hereditary progressive chronic kidney disease caused by mutations in type IV collagen genes COL4A3/4/5. X-linked Alport syndrome (XLAS) is caused by mutations in the COL4A5 gene and is the most common form of Alport syndrome. A strong correlation between the type of COL4A5 mutation and the age developing end-stage renal disease in male patients has been found. Mutation to the α (IV) chain causes retention of the protein to the endoplasmic reticulum lumen, which causes endoplasmic reticulum stress (ERS) and subsequent exertion of deleterious intracellular effects through the activation of ERS. The exact time point that mutant type IV collagen α chain exerts its deleterious effects remains elusive. In this study, we explored the relationship between the COL4A5 genotype and cell type in ERS activation. We obtained skin fibroblasts from Alport syndrome patients with different COL4A5 mutation categories [i.e., a missense mutation (c.4298G > T, p.Gly1433Val) in exon 47, a splicing mutation (c.1949–1G > A) in intron 25 and an insertion (c.573_c.574insG, p. Pro193Alafs*23) in exon 10], and then reprogrammed these fibroblasts into induced pluripotent stem cells (iPSCs). Interestingly, no significant dysregulation of ERS pathway markers was observed for the three COL4A5 mutant iPSCs; however, significant activation of ERS in COL4A5 mutant fibroblasts was observed. In addition, we found that the activation levels of some ERS markers in fibroblasts varied among the three COL4A5 mutation types. Mutant COL4A5 proteins were demonstrated to have different effects on cells at different stages of ontogenesis, providing a theoretical basis for choosing the timing of intervention. The observed differences in activation of ERS by the COL4A5 mutant fibroblasts may contribute to the intracellular molecular mechanisms that describe the correlation between genotype and clinical features in XLAS.

From January 1995 to June 2018, 14 patients with congenital nephrotic syndrome (CNS) were diagnosed in the Department of Pediatrics, Peking University First Hospital. The clinical data were retrospectively studied. Eight patients underwent genetic testing; 7 of them had NPHS1 mutations (primary CNS), and 1 did not have a mutation. Of the 7 patients with NPHS1 mutations, 6 died, and 1 had proteinuria. Of the 14 patients, 8 had cytomegalovirus (CMV) infection, and anti-CMV therapy was administered to 7 of them. The other patient was hospitalized in critically ill condition and died before anti-CMV therapy administration. Of the 7 patients who were administered anti-CMV therapy, proteinuria disappeared in 2 patients; 2 patients died; 2 patients were lost to follow up; and 1 patient still had 3+ proteinuria. Three patients had both NPHS1 mutations and CMV infection. After anti-CMV therapy, proteinuria was resolved in 1 patient but relapsed to 3+ proteinuria due to a new infection. The other 2 patients died. Of 14 patients, only 1 patient underwent renal biopsy, with results showing mesangial proliferative glomerulonephritis pathology, negative CMV inclusion body, and CMV-DNA. In this study, genetic defect could play a primary role in CNS, and CMV could play a secondary role. Primary CNS with NPHS1 mutations has a poor prognosis. Primary CNS might be accompanied by CMV infection that responds poorly to antiviral treatment. Secondary CNS caused by CMV infection may be cured with antiviral therapy. However, genetic analysis is necessary to exclude genetic defects.

Abstract Background The aim of this study was to analyze the diverse phenotypes of children with PAX2‐related disorder so as to improve our understanding of this disease. Methods The clinical data of ten children with PAX2 mutations, detected by targeted region capture sequencing or whole‐exome sequencing, were retrospectively analyzed. Family members of index cases were verified by Sanger sequencing and family segregation analysis was performed. Results The age of first symptom of 10 unrelated children (six girls and four boys) was 6.4 (ranged from postnatal day to 14.8) years old. Proteinuria, abnormal renal function, and structure were found in all patients. Renal hypoplasia and renal cysts were found in 10 of 10 and five of 10 cases, respectively. Three patients progressed to chronic kidney disease stage 5 and the onset age of end‐stage renal disease was 9.8–16.4 years old. PAX2‐related ocular abnormalities were found in five of seven cases and three patients were observed to have more than one ocular findings involved. In addition to diverse renal and ocular findings, new phenotypes including congenital ventricular septal defect, skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and relatively rare extrarenal manifestations such as growth retardation, gout, and microcephaly were also found. Three novel mutations were reported for the first time. De novo mutations occurred in all patients who were carried out segregation analysis. Patients with the same mutation had different manifestations. PAX2‐related disorder showed remarkable clinical variability and phenotypic heterogeneity. Conclusion We firstly reported skeletal deformity (fourth metatarsal microsomia), ovarian teratoma, and congenital ventricular septal defect as new phenotypes of PAX2‐related disorder which enlarged the phenotypic spectrum. Gout was firstly reported as the onset symptom of PAX2‐related disorder. The diagnosis of PAX2‐related disorder should be considered without family history due to a much higher percentage of De novo mutations.

The energy balance (EB), turbulent vapour transport (TVT), Penman-Monteith (PM) and Bowen ratio energy balance (BREB) equation were used to estimate dewfall based on meteorological data. Initially there were big disagreements between the estimates from these four equations. However, after multiplying the heat and vapour conductance terms by 0.33 the agreement was much better. This implies that the disagreements derived from improper conductance values. Initially we did not consider the effect of atmospheric stability on the conductances. With stability correction the conductances were on average 0.5 times the values without stability correction. To arrive at the aforementioned 0.33, the conductances with stability correction still need to be lower by a factor of 0.66. The value of the von Karman constant and the relationships for the zero plane displacement and the roughness length we used in our conductance computations are widely used, but not the only possible ones. With different values and relationships also suggested in the literature one can reach this factor. However, it is also possible that our wind speed data contributed to the fact that the conductances we computed were too high. Their computation for a given canopy—atmosphere system requires wind speeds from a wind profile in equilibrium with the vegetation. This in turn requires an adequate fetch around the investigated surface. The highly varied vegetation in and around the site where the study was conducted makes adequate fetch rather doubtful. To obtain valid conductance values the atmospheric stability conditions must be considered, the appropriate values for the von Karman constant, the zero plane displacement and roughness length must be used, and there must be adequate fetch. The BREB equation does not contain a conductance term and therefore does not suffer from the problems just stated. The other three equations do. However, the BREB, like the EB and TVT equations, need the surface temperature which is not routinely measured. This then leaves the PM equation from which this temperature has been eliminated as the only option. Hence, in a future study dewfall estimates from the PM equation should be compared with direct measurements with a high precision weighing lysimeter.