•We constructed a systematic classification model of farmland.•Farmland contiguity was analyzed from pixel scale.•We developed an evaluation model for comprehensive farmland productivity.•A model was ...proposed to delineate permanent basic farmland for plain areas in China.
The delineation of permanent basic farmland will safeguard the production baseline of China’s agricultural development by securing easily appropriated, high-quality farmland surrounding urban areas, thereby strictly controlling the use of farmland (especially high-quality farmland surrounding urban areas) facing accelerated urban expansion. This study researched the delineation of permanent basic farmland in a typical region undergoing rapid urbanization. By constructing a systematic classification model, farmland was classified into matrix, edge, and island farmlands in order to analyze farmland contiguity and fragmentation. Based on the indicator requirements of various plans related to farmland, an evaluation indicator system was constructed in order to develop an evaluation model for comprehensive farmland productivity. From the perspective of farmland spatial contiguity and highly efficient productivity, a delineation model for permanent basic farmland was proposed to delimit the permanent protection and utilization boundaries for high-quality farmland around urban areas. The results show the following: (1) matrix and edge farmlands can intuitively display farmland contiguity characteristics; (2) comprehensive farmland productivity was closely related to farmland spatial patterns, supporting infrastructure, and policy management and protection; and (3) there was a high degree of spatial overlap between contiguous and highly productive farmland. The model took both comprehensive farmland productivity and spatial clustering into consideration in order to delineate permanent basic farmland, which is a beneficial factor in protecting farmland quality and safeguarding sustainable farmland utilization. It can also be used as a control line to limit urban sprawl, guide urban cluster development, and improve economical and intensive urban land use.
Venous thromboembolism (VTE) is one of the most common and severe complications of multiple myeloma (MM). The aim of this study was to learn about the current awareness regarding MM-associated VTE ...among Chinese hematologists.
A nationwide, online, questionnaire-based survey was sent to the specialized hematologists in mainland China. The questionnaire investigated respondents' demographic and occupational characteristics, their ability to identify VTE risk factors, and their thromboprophylaxis decisions for different anti-MM regimens. Six clinical vignettes were used to evaluate hematologists' awareness of stratified thromboprophylaxis. The data were analyzed using SPSS software.
A total of 518 valid questionnaires were received. Of the 518 hematologists investigated, only 23.7% of them could identify VTE-related risk factors correctly. Most hematologists could select appropriate thromboprophylaxis for common anti-MM regimens such as VCd (bortezomib, cyclophosphamide, and dexamethasone) and VRd (bortezomib, lenalidomide, and dexamethasone), but not for uncommon ones such as VTD-PACE (bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide) and KRd (carfilzomib, lenalidomide, and dexamethasone). The results from the vignettes suggested that only 19.5% of the hematologists could be defined as the 'stratified thromboprophylaxis' group, and the awareness of stratified thromboprophylaxis depended significantly on physicians' age and working seniority.
The results of our study showed that a large proportion of Chinese hematologists failed to recognize the VTE risk factors, most of them cannot select appropriate thromboprophylaxis for different MM therapeutic regimens and lack awareness of stratified thromboprophylaxis for MM-associated VTE. A standard VTE prevention guideline is urgently needed for the Chinese myeloma group. Continuous education for new professionals should be encouraged. A VTE collaborative group is supposed to be established in each hospital to enhance the overall medical care for VTE patients.
To investigate the prognostic value of circulating plasma cells (CPC) and establish novel nomograms to predict individual progression-free survival (PFS) as well as overall survival (OS) of patients ...with newly diagnosed multiple myeloma (NDMM).
One hundred ninetyone NDMM patients in Wuhan Union Hospital from 2017.10 to 2020.8 were included in the study. The entire cohort was randomly divided into a training (
= 130) and a validation cohort (
= 61). Univariate and multivariate analyses were performed on the training cohort to establish nomograms for the prediction of survival outcomes, and the nomograms were validated by calibration curves.
When the cut-off value was 0.038%, CPC could well distinguish patients with higher tumor burden and lower response rates (
< 0.05), and could be used as an independent predictor of PFS and OS. Nomograms predicting PFS and OS were developed according to CPC, lactate dehydrogenase (LDH) and creatinine. The C-index and the area under receiver operating characteristic curves (AUC) of the nomograms showed excellent individually predictive effects in training cohort, validation cohort or entire cohort. Patients with total points of the nomograms ≤ 60.7 for PFS and 75.8 for OS could be defined as low-risk group and the remaining as high-risk group. The 2-year PFS and OS rates of patients in low-risk group was significantly higher than those in high-risk group (
< 0.001).
CPC is an independent prognostic factor for NDMM patients. The proposed nomograms could provide individualized PFS and OS prediction and risk stratification.
Urbanisation in China has caused drastic changes in territorial utilisation patterns, and human-land conflict has become increasingly prominent. It is therefore urgent to investigate territorial ...utilisation quality. This study researched the evaluation of municipal territorial utilisation quality in Changzhou, a rapid urbanising city. By interpreting new-type urbanisation goals, five evaluation criteria (planning coordination, intensive efficiency, ecological civilisation, living suitability, and infrastructure sharing) were reorganised and an evaluation indicator system was constructed. A principal component analysis-analytic hierarchy process comprehensive weighting method was used for gridded multi-element overlay evaluation, and an evaluation model for territorial utilisation quality was established. Evaluation results showed that Changzhou’s planning coordination and living suitability levels were generally high, but numerous areas had a low level of infrastructure sharing. Changzhou’s overall territorial utilisation quality was relatively high, with Zhonglou exhibiting the highest quality level. High-and low-level areas exhibited good spatial matching with the actual development zones with different development levels. The direction for criterion optimisation can be figured out through the conceptual model for the territorial utilisation quality promotion. Moreover, the evaluation results can provide pertinent guidance in territorial spatial planning such as the delineation of urban development boundary and ecological red line.
Background:
DLBCL is the most commonly occurring type of non-Hodgkin's lymphoma, which may be found at various extranodal sites. But little is known about the particular trends of extranodal DLBCL.
...Methods:
A total of 15,882 extranodal DLBCL patients were included in incidence analysis from the Surveillance, Epidemiology, and End Results (SEER) database (1973–2015). The joinpoint regression software was used to calculate the annual percent change (APC) in rates. Nomograms were established by R software to predict overall survival (OS).
Results:
The extranodal DLBCL incidence continued to rise at a rate of 1.6% (95% CI, 0.4–2.8,
p
< 0.001) per year over the study period, until it declined around 2003. The incidence-based mortality trend of extranodal DLBCL had a similar pattern, with a decrease happening around 1993. Five-year survival rates improved dramatically from the 1970s to 2010s (44.15 vs. 63.7%), and the most obvious increase occurred in DLBCL patients with primary site in the head/neck. The C-index showed a value for OS of 0.708, which validated the nomograms performed well and were able to forecast the prognosis of patients with extranodal DLBCL. The calibration curves showed satisfactory consistency between true values and predicted values for 1-, 5-, and 10-year overall survival, respectively.
Conclusions:
The incidence and incidence-based mortality of extranodal DLBCL had been increasing for decades, followed by a promising downward trend in recent years. These findings may help scientists identify disease-related risk factors and better manage the disease. The prediction signature cloud identifies high-risk patients who should receive effective therapies to prevent the fatal nature of this disease, and low-risk patients to reduce over-treatment.
Background
The blood‐brain barrier (BBB) plays a principal role in the healthy and diseased central nervous systems, and BBB disruption after ischaemic stroke is responsible for increased mortality. ...Smyd2, a member of the SMYD‐methyltransferase family, plays a vital role in disease by methylation of diverse substrates; however, little is known about its role in the pathophysiology of the brain in response to ischaemia‐reperfusion injury.
Methods
Using oxygen glucose deprivation and reoxygenation (OGD/R)‐induced primary brain microvascular endothelial cells (BMECs) and Smyd2 knockdown mice subjected to middle cerebral artery occlusion, we evaluated the role of Smyd2 in BBB disruption. We performed loss‐of‐function and gain‐of‐function studies to investigate the biological function of Smyd2 in ischaemic stroke.
Results
We found that Smyd2 was a critical factor for regulating brain endothelial barrier integrity in ischaemia‐reperfusion injury. Smyd2 is upregulated in peri‐ischaemic brains, leading to BBB disruption via methylation‐mediated Sphk/S1PR. Knockdown of Smyd2 in mice reduces BBB permeability and improves functional recovery. Using OGD/R‐induced BMECs, we demonstrated that Sphk/S1PR methylation modification by Smyd2 affects ubiquitin‐dependent degradation and protein stability, which may disrupt endothelial integrity. Moreover, overexpression of Smyd2 can damage endothelial integrity through Sphk/S1PR signalling.
Conclusions
Overall, these results reveal a novel role for Smyd2 in BBB disruption in ischaemic stroke, suggesting that Smyd2 may represent a new therapeutic target for ischaemic stroke.
Smyd2 is upregulated in peri‐ischaemic brains after ischaemia‐reperfusion injury.
Increased Smyd2 levels disrupts BBB integrity via Sphk/S1PR pathway and results in neuronal dysfunction.
Knockdown of Smyd2 in mice reduces BBB permeability and improves functional recovery.
The development of transportation has triggered regional element flows by changing the location conditions of cities along the route. In recent years, with the full implementation of the National ...Medium and Long-term Railway Network Plan, China's high-speed railway network layout has continued to expand, and high-speed rail has become an important means of transportation for people. The development of high-speed railways will definitely have a wide-ranging and far-reaching impact on the concentration of elements along the route. This article takes the Beijing-Guangzhou high-speed rail as an example, adopts the matching idea as the high-speed rail experimental group to match the control group, and estimates the impact of high-speed rail on the accumulation of capital factors by constructing a double difference model. The results show that the completion of the Beijing-Guangzhou high-speed rail has made a significant contribution to capital agglomeration.
Ischemic stroke is known to cause the accumulation of misfolded proteins and loss of calcium homeostasis, leading to impairment of endoplasmic reticulum (ER) function and activating the unfolded ...protein response (UPR). PARP16 is an active (ADP‐ribosyl)transferase known tail‐anchored ER transmembrane protein with a cytosolic catalytic domain. Here, we find PARP16 is highly expressed in ischemic cerebral hemisphere and oxygen–glucose deprivation/reoxygenation (OGD/R)‐treated immortalized hippocampal neuronal cell HT22. Using an adeno‐associated virus‐mediated PARP16 knockdown approach in mice, we find PARP16 knockdown decreases infarct demarcations and has a better neurological outcome after ischemic stroke. Our data indicate PARP16 knockdown decreases ER stress and neuronal death caused by OGD/R, whereas PARP16 overexpression promotes ER stress‐mediated cell damage in primary cortical neurons. Furthermore, PARP16 functions mechanistically as ADP‐ribosyltransferase to modulate the level of ADP‐ribosylation of the corresponding PERK and IRE1α arm of the UPR, and such modifications mediate activation of PERK and IRE1α. Indeed, pharmacological stimulation of the UPR using Brefeldin A partly counteracts PARP16 knockdown‐mediated neuronal protection upon OGD/R treatment. In conclusion, PARP16 plays a crucial role in post‐ischemic UPR and PARP16 knockdown alleviates brain injury after ischemic stroke. This study demonstrates the potential of the PARP16‐PERK/IRE1α axis as a target for neuronal survival in ischemic stroke.
In response to ischemia injury, PARP16 is increased and modulates the level of ADP‐ribosylation of the corresponding PERK and IRE1α, leading to activating PERK and IRE1α during the UPR, which at least partly contributes to ER stress‐mediated neuronal damage.
The aberrant expression of methyltransferase Set7/9 plays a role in various diseases. However, the contribution of Set7/9 in ischemic stroke remains unclear. Here, we show ischemic injury results in ...a rapid elevation of Set7/9, which is accompanied by the downregulation of Sirt5, a deacetylase reported to protect against injury. Proteomic analysis identifies the decrease of chromobox homolog 1 (Cbx1) in knockdown Set7/9 neurons. Mechanistically, Set7/9 promotes the binding of Cbx1 to H3K9me2/3 and forms a transcription repressor complex at the Sirt5 promoter, ultimately repressing Sirt5 transcription. Thus, the deacetylation of Sirt5 substrate, glutaminase, which catalyzes the hydrolysis of glutamine to glutamate and ammonia, is decreased, promoting glutaminase expression and triggering excitotoxicity. Blocking Set7/9 eliminates H3K9me2/3 from the Sirt5 promoter and normalizes Sirt5 expression and Set7/9 knockout efficiently ameliorates brain ischemic injury by reducing the accumulation of ammonia and glutamate in a Sirt5-dependent manner. Collectively, the Set7/9-Sirt5 axis may be a promising epigenetic therapeutic target.
Abstract
MALAT1 is one of the most hopeful members implicated in angiogenesis in a variety of non-malignant diseases. In multiple myeloma (MM), MALAT1 is recognized as the most highly expressed long ...non-coding RNA. However, the functional roles of MALAT1 in angiogenesis and the responsible mechanisms have not yet been explored. Herein, we discovered a novel regulatory network dependent on MALAT1 in relation to MM tumorigenesis and angiogenesis. We observed that MALAT1 was upregulated in MM and significantly associated with poor overall survival. MALAT1 knockdown suppressed MM cell proliferation and promoted apoptosis, while restricting endothelial cells angiogenesis. Moreover, MALAT1 directly targeted microRNA-15a/16, and microRNA-15a/16 suppression partly reverted the effects of MALAT1 deletion on MM cells in vitro as well as tumor growth and angiogenesis in vivo. In addition, further study indicated that MALAT1 functioned as a competing endogenous RNA for microRNA-15a/16 to regulate vascular endothelial growth factor A (VEGFA) expression. Our results suggest that MALAT1 plays an important role in the regulatory axis of microRNA-15a/16–VEGFA to promote tumorigenicity and angiogenesis in MM. Consequently, MALAT1 could serve as a novel promising biomarker and a potential antiangiogenic target against MM.
MALATA1 was correlated with poor survival of MM and suppressed proliferation and angiogenesis of MM cells through MALAT1–miR-15a/16–VEGFA. Furthermore, MALAT1 plays significant roles in the regulatory axis of VEGFA in BM microenvironment, which could be served as a promising biomarker of MM.
Graphical Abstract
Graphical Abstract
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