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Abstract Background The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC. Methods Information for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (

Abstract Background Microdeletion of the human chromosomal region 16p11.2 (16p11.2 $${}^{+/-}$$ + / - ) is a prevalent genetic factor associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders. However its pathogenic mechanism remains unclear, and effective treatments for 16p11.2 $${}^{+/-}$$ + / - syndrome are lacking. Emerging evidence suggests that the gut microbiota and its metabolites are inextricably linked to host behavior through the gut-brain axis and are therefore implicated in ASD development. Despite this, the functional roles of microbial metabolites in the context of 16p11.2 $${}^{+/-}$$ + / - are yet to be elucidated. This study aims to investigate the therapeutic potential of indole-3-propionic acid (IPA), a gut microbiota metabolite, in addressing behavioral and neural deficits associated with 16p11.2 $${}^{+/-}$$ + / - , as well as the underlying molecular mechanisms. Results Mice with the 16p11.2 $${}^{+/-}$$ + / - showed dysbiosis of the gut microbiota and a significant decrease in IPA levels in feces and blood circulation. Further, these mice exhibited significant social and cognitive memory impairments, along with hyperactivation of hippocampal dentate gyrus neurons and reduced inhibitory synaptic transmission in this region. However, oral administration of IPA effectively mitigated the histological and electrophysiological alterations, thereby ameliorating the social and cognitive deficits of the mice. Remarkably, IPA treatment significantly increased the phosphorylation level of ERK1, a protein encoded by the Mapk3 gene in the 16p11.2 region, without affecting the transcription and translation of the Mapk3 gene. Conclusions Our study reveals that 16p11.2 $${}^{+/-}$$ + / - leads to a decline in gut metabolite IPA levels; however, IPA supplementation notably reverses the behavioral and neural phenotypes of 16p11.2 $${}^{+/-}$$ + / - mice. These findings provide new insights into the critical role of gut microbial metabolites in ASD pathogenesis and present a promising treatment strategy for social and cognitive memory deficit disorders, such as 16p11.2 microdeletion syndrome. Video Abstract

Abstract The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits, and this process requires the proper recruitment of adaptor molecules to selectively activate downstream pathways. Here, we identified that DOK6, a member of the Dok (downstream of tyrosine kinases) family, is required for the maintenance of peripheral axons, and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice, manifested as impaired sensory, abnormal posture, paw deformities, blocked nerve conduction, and dysmyelination. Furthermore, Dok6 is highly expressed in peripheral neurons but not in Schwann cells, and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding, axon destruction, and hindered retrograde axonal transport. Specifically, DOK6 acts as an adaptor protein for selectivity-mediated neurotrophic signal transduction and retrograde transport for TrkC and Ret but not for TrkA and TrkB. DOK6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation, including MAP1B, Tau and Dynein for axonal transport, and specifically activates the downstream ERK1/2 kinase pathway to maintain axonal survival and homeostasis. This finding provides new clues to potential insights into the pathogenesis and treatment of hereditary peripheral neuropathies and other degenerative diseases.

Abstract Previous work has shown that motor skill learning stimulates and requires generation of myelinating oligodendrocytes (OLs) from their precursor cells (OLPs) in the brains of adult mice. In the present study we ask whether OL production is also required for non-motor learning and cognition, using T-maze and radial-arm-maze tasks that tax spatial working memory. We find that maze training stimulates OLP proliferation and OL production in the medial prefrontal cortex (mPFC), anterior corpus callosum (genu), dorsal thalamus and hippocampal formation of adult male mice; myelin sheath formation is also stimulated in the genu. Genetic blockade of OL differentiation and neo-myelination in Myrf conditional-knockout mice strongly impairs training-induced improvements in maze performance. We find a strong positive correlation between the performance of individual wild type mice and the scale of OLP proliferation and OL generation during training, but not with the number or intensity of c-Fos+ neurons in their mPFC, underscoring the important role played by OL lineage cells in cognitive processing.

The gut-brain axis is evident in modulating neuropsychiatric diseases including autism spectrum disorder (ASD). Chromosomal 16p11.2 microduplication 16p11.2dp/+ is among the most prevalent genetic copy number variations (CNV) linked with ASD. However, the implications of gut microbiota status underlying the development of ASD-like impairments induced by 16p11.2dp/+ remains unclear. To address this, we initially investigated a mouse model of 16p11.2dp/+, which exhibits social novelty deficit and repetitive behavior characteristic of ASD. Subsequently, we conducted a comparative analysis of the gut microbial community and metabolomic profiles between 16p11.2dp/+ and their wild-type counterparts using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS). Our microbiota analysis revealed structural dysbiosis in 16p11.2dp/+ mice, characterized by reduced biodiversity and alterations in species abundance, as indicated by α/β-diversity analysis. Specifically, we observed reduced relative abundances of Faecalibaculum and Romboutsia, accompanied by an increase in Turicibacter and Prevotellaceae UCG_001 in 16p11.2dp/+ group. Metabolomic analysis identified 19 significantly altered metabolites and unveiled enriched amino acid metabolism pathways. Notably, a disruption in the predominantly histamine-centered neurotransmitter network was observed in 16p11.2dp/+ mice. Collectively, our findings delineate potential alterations and correlations among the gut microbiota and microbial neurotransmitters in 16p11.2dp/+ mice, providing new insights into the pathogenesis of and treatment for 16p11.2 CNV-associated ASD.

Depression is a common recurrent psychiatric disorder with a high lifetime prevalence and suicide rate. At present, although several traditional clinical drugs such as fluoxetine and ketamine, are widely used, medications with a high efficiency and reduced side effects are of urgent need. Our group has recently reported that a single administration of salmon calcitonin (sCT) could ameliorate a depressive-like phenotype via the amylin signaling pathway in a mouse model established by chronic restraint stress (CRS). However, the molecular mechanism underlying the antidepressant effect needs to be addressed. In this study, we investigated the antidepressant potential of sCT applied chronically and its underlying mechanism. In addition, using transcriptomics, we found the MAPK signaling pathway was upregulated in the hippocampus of CRS-treated mice. Further phosphorylation levels of ERK/p38/JNK kinases were also enhanced, and sCT treatment was able only to downregulate the phosphorylation level of p38/JNK, with phosphorylated ERK level unaffected. Finally, we found that the antidepressant effect of sCT was blocked by p38 agonists rather than JNK agonists. These results provide a mechanistic explanation of the antidepressant effect of sCT, suggesting its potential for treating the depressive disorder in the clinic.

Fibroblast growth factor receptor 4 (FGFR4) is a promising target for the treatment of hepatocellular carcinoma, but current FGFR4 covalent inhibitors target only one of the two cysteine residues (Cys477 or Cys552) that provide FGFR4-specificity. Here, a dual-warhead covalent FGFR4 inhibitor that can covalently target both cysteine residues of FGFR4 is reported, and strong selectivity for FGFR4 is observed.

Soil nutrient status is a crucial measure of soil fertility, which not only coordinates and provides the nutrients necessary for plant growth, but also stimulates the decomposition of soil humus and biogeochemical cycles. Therefore, understanding the distribution characteristics of soil nutrients in the Kyrgyzstan, while exploring the drivers of their variability, is important for understanding ecological processes and the distribution of soil resources. Simultaneously, the study of the spatial distribution of soil multifunctionality and its drivers across Kyrgyzstan can better elucidate the functions of the entire ecosystem, assist in optimizing the allocation of resources and serve as a reference material for the scientific and rational management of the country’s soil ecosystems. In this paper, We have used field sampling data from Kyrgyzstan, to examined the geographic variability and distribution of soil nutrients and soil multifunctionality within different soil depths, as well as the drivers in the country, using a combination of factor analysis and structural equation modeling (SEM). Findings indicated: (1)The topsoil of Kyrgyzstan (0–30 cm) stores 4.24 ± 0.59 Pg of SOC, 0.33 ± 0.06 Pg of total nitrogen (TN), 0.31 ± 0.03 Pg of total phosphorus (TP), and 5.12 ± 1.84 Pg of total potassium (TK). The nutrient reserves of various land-cover categories vary greatly across the nation, with grasslands accounting for the largest reserves (40%) but urban areas allocating the smallest proportion (0.3%). (2): the analysis revealed that using the linear or nonlinear fitting equations, the majority of soil nutrients exhibited a strong correlation with each other and also environmental parameters; (3): in Kyrgyzstan, soil multifunctionality varied substantially from –0.63 to 2.30 across regions. (4): according to the SEM results, NPP, wind speed (VS), MAP, longitude (Lon), SWC, and pH directly affected soil multifunctionality. In addition, several indirect effects of ST, MAT, Sard, and latitude (Lat) on soil multifunctionality were observed. Lon, map, SWC, and pH also had various direct and indirect impacts on soil multifunctionality. The findings of this study shed light on the functions of the entire soil ecosystem in the Kyrgyz Republic that help better predict the effects of environmental changes on ecosystem multifunctionality in drylands and provide a scientific basis for rational utilization of soil resources, efficient management of dryland soils, and prevention of land productivity decline in the country.

Plant 14-3-3 proteins mediate a wide range of functionally diverse proteins through protein–protein interactions that are typically phosphorylation-dependent. However, the interactions between 14-3-3 proteins and the major regulators of nature rubber (NR) biosynthesis in H. brasiliensis have not been fully elucidated. In this study, we obtained 81 essential client proteins that interacted with H. brasiliensis 14-3-3 proteins (HbGF14s) through yeast two-hybrid (Y2H) screening. These interaction partners were involved in plant signal transduction, metabolism, development, and NR biosynthesis including small rubber particle protein (SRPP), rubber elongation factor (REF), and MYC2, etc. Furthermore, the interaction of HbGF14c and HbSRPP of H. brasiliensis was confirmed in plants through bimolecular fluorescence complementation (BiFC) assays and in vitro with Pull-down assays. Specifically, the RVSSYLP motif was found to mediate the interaction between HbSRPP and HbGF14c. The findings of this study provide a theoretical basis for the elucidation of the molecular regulation mechanism of the 14-3-3 proteins involved in NR biosynthesis, which could be used to enhance the production of rubber trees through genetic improvement.

Depressive disorder is defined as a psychiatric disease characterized by the core symptoms of anhedonia and learned helplessness. Currently, the treatment of depression still calls for medications with high effectiveness, rapid action, and few side effects, although many drugs, including fluoxetine and ketamine, have been approved for clinical usage by the Food and Drug Administration (FDA). In this study, we focused on calcitonin as an amylin receptor polypeptide, of which the antidepressant effect has not been reported, even if calcitonin gene-related peptides have been previously demonstrated to improve depressive-like behaviors in rodents. Here, the antidepressant potential of salmon calcitonin (sCT) was first evaluated in a chronic restraint stress (CRS) mouse model of depression. We observed that the immobility duration in CRS mice was significantly increased during the tail suspension test and forced swimming test. Furthermore, a single administration of sCT was found to successfully rescue depressive-like behaviors in CRS mice. Lastly, AC187 as a potent amylin receptor antagonist was applied to investigate the roles of amylin receptors in depression. We found that AC187 significantly eliminated the antidepressant effects of sCT. Taken together, our data revealed that sCT could ameliorate a depressive-like phenotype probably via the amylin signaling pathway. sCT should be considered as a potential therapeutic candidate for depressive disorder in the future.

Myelin abnormalities have been observed in autism spectrum disorder (ASD). In this study, we seek to discover myelin-related changes in the striatum, a key brain region responsible for core ASD features, using the 16p11.2 deletion (16p11.2±) mouse model of ASD. We found downregulated expression of multiple myelin genes and decreased myelin thickness in the striatum of 16p11.2± mice versus wild type controls. Moreover, given that myelin is the main reservoir of brain lipids and that increasing evidence has linked dysregulation of lipid metabolism to ASD, we performed lipidomic analysis and discovered decreased levels of certain species of sphingomyelin, hexosyl ceramide and their common precursor, ceramide, in 16p11.2± striatum, all of which are major myelin components. We further identified lack of ceramide synthase 2 as the possible reason behind the decrease in these lipid species. Taken together, our data suggest a role for myelin and myelin lipids in ASD development.

Summary: The mediobasal hypothalamus (MBH; arcuate nucleus of the hypothalamus [ARH] and median eminence [ME]) is a key nutrient sensing site for the production of the complex homeostatic feedback responses required for the maintenance of energy balance. Here, we show that refeeding after an overnight fast rapidly triggers proliferation and differentiation of oligodendrocyte progenitors, leading to the production of new oligodendrocytes in the ME specifically. During this nutritional paradigm, ME perineuronal nets (PNNs), emerging regulators of ARH metabolic functions, are rapidly remodeled, and this process requires myelin regulatory factor (Myrf) in oligodendrocyte progenitors. In genetically obese ob/ob mice, nutritional regulations of ME oligodendrocyte differentiation and PNN remodeling are blunted, and enzymatic digestion of local PNN increases food intake and weight gain. We conclude that MBH PNNs are required for the maintenance of energy balance in lean mice and are remodeled in the adult ME by the nutritional control of oligodendrocyte differentiation.

The construction of protective forests in Nursultan is key to reducing near-surface wind speeds and snowstorm effects in urban areas. This study analyzed the effects of the number of plant rows and spacing of the shelterbelts on the flow field around protective forests to evaluate the wind protection benefits of the existing configuration of the shelterbelt in Nursultan and guide the construction of protective forests. We measured the airflow fields of four shelterbelts with different numbers of rows, seven double pure shelterbelts, and double mixed shelterbelts of arbors and shrubs with different spacings. The results showed that the airflow field around the shelterbelts can be divided into five characteristic regions based on shelter efficiency: a deceleration region before the shelterbelt, acceleration region above the canopy, strong deceleration region in the canopy layer, deceleration region behind the shelterbelt, and recovery region behind the shelterbelt. In terms of windproof ability, the wind protection benefits of a shelterbelt with six rows are the best in a single shelterbelt. Behind the shelterbelt, the wind protection benefits of double pure shelterbelts are greater than that of double mixed shelterbelts of arbor and shrub. On the contrary, the windbreak benefits of the latter are stronger than those of the former between the two shelterbelts.

Dragon’s blood is a traditional medicine in which flavonoids are the main bioactive compounds; however, the underlying formation mechanism of dragon’s blood remains largely poorly understood. Chalcone isomerase (CHI) is the key enzyme in the flavonoid biosynthesis pathway. However, CHI family genes are not well understood in Dracaena cambodiana Pierre ex Gagnep, an important source plant of dragon’s blood. In this study, 11 CHI family genes were identified from D. cambodiana, and they were classified into three types. Evolutionary and transcriptional profiling analysis revealed that DcCHI1 and DcCHI4 might be involved in flavonoid production. Both DcCHI1 and DcCHI4 displayed low expression levels in stem under normal growth conditions and were induced by methyl jasmonate (MeJA), 6-benzyl aminopurine (6-BA, synthetic cytokinin), ultraviolet-B (UV-B), and wounding. The recombinant proteins DcCHI1 and DcCHI4 were expressed in Escherichia coli and purified by His-Bind resin chromatography. Enzyme activity assay indicated that DcCHI1 catalyzed the formation of naringenin from naringenin chalcone, while DcCHI4 lacked this catalytic activity. Overexpression of DcCHI1 or DcCHI4 enhanced the flavonoid production in D. cambodiana and tobacco. These findings implied that DcCHI1 and DcCHI4 play important roles in flavonoid production. Thus, our study will not only contribute to better understand the function and expression regulation of CHI family genes involved in flavonoid production in D. cambodiana but also lay the foundation for developing the effective inducer of dragon’s blood.

Panax quinquefolium is a perennial herbaceous plant that contains many beneficial ginsenosides with diverse pharmacological effects. 24(R)-pseudoginsenoside F11 is specific to P. quinquefolium, a useful biomarker for distinguishing this species from other related plants. However, because of its nonconjugated property and the complexity of existing detection methods, this biomarker cannot be used as the identification standard. We herein present a stable 24(R)-pseudoginsenoside F11 fingerprint spectrum in the terahertz band, thereby proving that F11 can be detected and quantitatively analyzed via terahertz spectroscopy. We also analyzed the sample by high-performance liquid chromatography-triple quadrupole mass spectrometry. The difference between the normalized data for the two analytical methods was less than 5%. Furthermore, P. quinquefolium from different areas and other substances can be clearly distinguished based on these terahertz spectra with a standard principal component analysis. Our method is a fast, simple, and cost-effective approach for identifying and quantitatively analyzing P. quinquefolium.

This new decade has started with a global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), precipitating a worldwide health crisis and economic downturn. Scientists and clinicians have been racing against time to find therapies for COVID-19. Repurposing approved drugs, developing vaccines and employing passive immunization are three major therapeutic approaches to fighting COVID-19. Chicken immunoglobulin Y (IgY) has the potential to be used as neutralizing antibody against respiratory infections, and its advantages include high avidity, low risk of adverse immune responses, and easy local delivery by intranasal administration. In this study, we raised antibody against the spike (S) protein of SARS-CoV-2 in chickens and extracted IgY (called IgY-S) from egg yolk. IgY-S exhibited high immunoreactivity against SARS-CoV-2 S, and by epitope mapping, we found five linear epitopes of IgY-S in SARS-CoV-2 S, two of which are cross-reactive with SARS-CoV S. Notably, epitope SIIAYTMSL, one of the identified epitopes, partially overlaps the S1/S2 cleavage region in SARS-CoV-2 S and is located on the surface of S trimer in 3D structure, close to the S1/S2 cleavage site. Thus, antibody binding at this location could physically block the access of proteolytic enzymes to S1/S2 cleavage site and thereby impede S1/S2 proteolytic cleavage, which is crucial to subsequent virus-cell membrane fusion and viral cell entry. Therefore, the feasibility of using IgY-S or epitope SIIAYTMS-specific IgY as neutralizing antibody for preventing or treating SARS-CoV-2 infection is worth exploring.

Hepatocellular carcinoma (HCC) is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist. The specificity of 747 on CCR2 was demonstrated via calcium flux, the binding domain of CCR2 was identified in an extracellular loop by chimera binding assay, and in vivo antagonistic activity of 747 was confirmed through a thioglycollate-induced peritonitis model. In animals, 747 elevated the number of CD8+ T cells in tumors via blocking tumor-infiltrating macrophage-mediated immunosuppression and inhibited orthotopic and subcutaneous tumor growth in a CD8+ T cell-dependent manner. Further, 747 enhanced the therapeutic efficacy of low-dose sorafenib without obvious toxicity, through elevating the numbers of intra-tumoral CD8+ T cells and increasing death of tumor cells. Thus, we have discovered a natural CCR2 antagonist and have provided a new perspective on development of this antagonist for treatment of HCC. In mouse models of HCC, 747 enhanced the tumor immunosuppressive microenvironment and potentiated the therapeutic effect of sorafenib, indicating that the combination of an immunomodulator with a chemotherapeutic drug could be a new approach for treating HCC.

Abstract Myelin-gene Regulatory Factor (MyRF) is one of the master transcription factors controlling myelin formation and development in oligodendrocytes which is crucial for the powerful brain functions. The N-terminal of MyRF, which contains a proline-rich region and a DNA binding domain (DBD), is auto-cleaved from the ER membrane, and then enters the nucleus to participate in transcription regulation of the myelin genes. Here we report the crystal structure of MyRF DBD. It shows an Ig-fold like architecture which consists of two antiparallel β-sheets with 7 main strands, packing against each other, forming a β-sandwich. Compared to its homolog, Ndt80, MyRF has a smaller and less complex DBD lacking the helices and the big loops outside the core. Structural alignment reveals that MyRF DBD possess less interaction sites with DNA than Ndt80 and may bind only at the major groove of DNA. Moreover, the structure reveals a trimeric assembly, agreeing with the previous report that MyRF DBD functions as a trimer. The mutant that we designed based on the structure disturbed trimer formation, but didn’t affect the auto-cleavage reaction. It demonstrates that the activation of self-cleavage reaction of MyRF is independent of the presence of its N-terminal DBD homotrimer. The structure reported here will help to understand the molecular mechanism underlying the important roles of MyRF in myelin formation and development.

The hedgehog signal pathway is an essential agent in developmental patterning, wherein the local concentration of the Hedgehog morphogens directs cellular differentiation and expansion. Furthermore, the Hedgehog pathway has been implicated in tumor/stromal interaction and cancer stem cell. Nowadays searching novel inhibitors for Hedgehog Signal Pathway is drawing much more attention by biological, chemical and pharmological scientists. In our study, a solid computational model is proposed which incorporates various statistical analysis methods to perform a Quantitative Structure-Activity Relationship (QSAR) study on the inhibitors of Hedgehog signaling. The whole QSAR data contain 93 cyclopamine derivatives as well as their activities against four different cell lines (NCI-H446, BxPC-3, SW1990 and NCI-H157). Our extensive testing indicated that the binary classification model is a better choice for building the QSAR model of inhibitors of Hedgehog signaling compared with other statistical methods and the corresponding in silico analysis provides three possible ways to improve the activity of inhibitors by demethylation, methylation and hydroxylation at specific positions of the compound scaffold respectively. From these, demethylation is the best choice for inhibitor structure modifications. Our investigation also revealed that NCI-H466 served as the best cell line for testing the activities of inhibitors of Hedgehog signal pathway among others.

Large constellations, especially at low-Earth orbit, have become a popular solution for global telecommunication. With the proliferation of prospective constellations, more and more satellites will be launched and deployed in the future, which challenges the regulatory framework from several aspects. In the last decades, the International Telecommunication Union (ITU) has established a regulatory framework of space radiocommunication systems for the purpose of securing rights and protection from technical harmful interference of subsequent networks. The well-known steps in the Radio Regulations include the advance publication of information, coordination, notification, and recording of frequency assignments in the Master International Frequency Register. The network registration procedure ran well with the conventional geostationary-satellite orbit (GSO) and non-GSO satellites until the emergence of large constellations. The scope of this paper is to introduce the current approach for ITU to regulate the registration of large constellations and point out the underlying issues. Three issues come from unclear provisions. The first one is whether a non-GSO network can be kept active with fewer satellites on orbit after bringing into use and the milestone requirement. The second issue is whether a non-GSO satellite can be used for bringing into use of different networks. The third issue is whether there should be an error tolerance for the notified orbital parameters in practice. Possible solutions such as postmilestone procedure and tolerance of orbital parameters are discussed. The chance for both ITU and Committee on Peaceful Uses of Outer Space (COPUOS) to explore the potential was also analyzed to implement mutual reference for constellation registration. Furthermore, if the collaboration of the 2 regimes going deep, it could also explore to build up a one-to-one mapping database to figure out the relationship between Master International Frequency Register fillings with actual deployment of large constellations in space.

Taking China as an example, this paper analyzes the impact mechanism of agricultural green development and constructs a measurement system of agricultural green development level. The system includes seven subsystems (ensuring food security, optimizing agricultural structure, improving market mechanism, innovation-driven development, building ecological civilization, inheriting traditional culture, and benefiting the people) and 55 measurement indicators. Empirical research was carried out using entropy method and gray correlation to measure the level of green development of China's agriculture, analyze its spatial distribution law, and divide it into three levels according to the development level, then analyze the regional characteristics of each grade. The research shows that the overall level of agricultural green development in China is relatively low, and the constraints are obvious. It is easy to ignore the value of agricultural green development, and the phenomenon of non-green development still exists. Therefore, we must attach great importance to the green development of agriculture, change agricultural production from the pursuit of quantity to the pursuit of quality in the past, formulate an effective path to promote the comprehensive level of agricultural green development in the whole ecological chain, and build a collaborative research institution and information monitoring platform for agricultural green development.

Abstract Blood pressure(BP) varies drastically during the acute phase after stroke onset. BP level and BP variability may have a major impact on acute ischemic stroke (AIS) prognosis. However, the association between trajectories of blood pressure over time and clinical outcomes have not been established. This review sought out existing evidences for associations of systolic blood pressure (SBP) trajectories on outcomes after stroke to determine the connection between SBP trajectories and stroke prognosis. According to a pre‐designed search strategy, literature search was carried out in Embase, Pubmed and Web of Science. Two authors independently evaluated study eligibility and quality, and literature data were extracted. When the literature was eligible, we perform meta‐analysis to determine associations of SBP trajectories with clinical outcomes. Seven studies were finally screened out of 52 studies retrieved. Seven studies received a good risk of bias rating and reported BP measurement methods and intervals, BP trajectories modeling methods, outcome measures, but it was found that final systolic BP trajectories in various papers were significantly different. All studies reported statistically significant associations between systolic blood pressure trajectories and prognosis. Methodological heterogeneity is observed in studies. However, this systematic review suggests that the high SBP group after AIS is related to poor clinical outcomes, while the rapid decline or medium‐to‐low or low SBP group is associated with relatively better clinical outcomes at different period after stroke. More prospective studies are needed to report the full methodology according to standardized criteria and explore relationships between SBP trajectories and prognosis of stroke.

This paper proposes a series of optimized scalable contact-capacitive radio frequency micro- electro-mechanical systems (RF MEMS) switches for millimeter wave applications. Due to the contact-capacitive topology, the ON-state and OFF-state of the switch can be designed separately to obtain smaller $C_{ON}$ and larger $C_{OFF}$ , which results in high capacitance ratio ( $C_{r}$ ). The $C_{ON}$ is defined by capacitance of the contacts, and it is optimized for low insertion loss ( $IL_{ON}$ ). The $C_{OFF}$ is defined by the metal-insulator-metal (MIM) capacitor, and it is designed for working band and scalable performance. The measurements of the fabricated devices show acceptable agreements with design and simulation. The optimized switches perform well with $IL_{ON}$ better than 1.5dB and capacitive ratio about 124. The switches follow scaling rules from 20GHz to 110GHz. Linearity (IIP3) of the switches are tested to be higher than 60dBm, and calculated to be higher than 80dBm. Performances of the switch can be further improved and optimized in the future study.

Due to high salinity and low nutrient concentrations, the coastal zone is considered as one of the most vulnerable of the earth’s habitats. Thus, the effect of salt and nitrogen on growth and development of coastal halophytes has been extensively investigated in recent years, but insufficient attention has been paid to the crucial stages of plant establishment, such as seed germination and seedling growth. Thus, we carried out a field experiment to evaluate the effects of salt stress (6, 10 and 20 g/kg NaCl) and nitrogen supply (0, 6 and 12 gm−2year−1) on seed germination and seedling growth of three coastal halophytes (including two dominant herb species Glehnia littoralis and Calystegia soldanella, one constructive shrub species Vitex rotundifolia) from September 2020 to June 2021. The results of our experiment showed that seeds of G. littoralis exhibited an explosive germination strategy in the early spring of 2021 with 70% of the seeds germinating. Conversely, the seeds of V. rotundifolia exhibited slow germination in the late spring of 2021 with only 60% of the seeds germinating. C. soldanella seed germination exhibited two obvious peak periods, but only 6% of the seeds germinated, which means that most seeds may be stored in the soil by stratification or died. All three halophytes showed greater sensitivity to nitrogen than salt stress during the seed germination stage. Nitrogen supply significantly delayed seed germination and reduced the cumulative germination percentage, particularly for G. littoralis. Despite the large impact of nitrogen on seed germination, nitrogen had a larger impact on seedling growth suggesting that the seedling growth stage of halophytes is more vulnerable to changes in nitrogen supply. Moreover, nitrogen supply significantly reduced the individual biomass of G. littoralis, C. soldanella and V. rotundifolia, with greater decreases seen in the dominant species than in the constructive species. Conversely, nitrogen supply increased underground biomass allocation of G. littoralis and C. soldanella, suggesting that the constructive species were less sensitive to nitrogen and exhibited a stronger anti-interference ability than the dominant species. Therefore, increasing nitrogen supply may firstly affect the seed germination and seedling growth of the dominant species, but not the constructive species.

Seed germination is the most sensitive stage of plant life history. Studying its response to drought and salinity can analysis the response and adaptation characteristics of desert plants to the environment. In this experiment, the seeds of four common desert ephemeral plants in Xinjiang (Ixiolirion tataricum, Nepeta micrantha, Lepidium apetalum, and Plantago minuta) were used as materials. To study the germination characteristics of seeds under drought, we used salt stress, and coupled salt-drought stress under treatments and explored the germination recovery ability of rehydrated seeds after salt and drought stress treatments. The results showed that: (1) Under salt stress, the germination ability of four plant seeds was inhibited in different degrees. Overall, the degree of inhibition was proportional to the concentration of NaCl solution. (2) Drought stress slowed the seed germination process, and the greater the degree of stress, the more pronounced the slowdown; PEG treatment showed no significant effect on the germination of the four seeds at low concentrations and significant inhibition at medium and high concentrations. (3) The coupled salt-drought treatment significantly alleviated the stress effect of one factor and improved the germination characteristics of seeds. (4) Seeds that did not germinate under different concentrations of salt stress, drought stress, and coupled stresses rapidly recover germination when the stress was relieved or lifted. Ephemeral plants are sensitive to environmental changes, and this study aims to provide a reference basis for vegetation restoration and ecological rehabilitation in arid and semi-arid areas.

Abstract Background The niche of tissue development in vivo involves the growth matrix, biophysical cues and cell-cell interactions. Although natural extracellular matrixes may provide good supporting for seeding cells in vitro, it is evitable to destroy biophysical cues during decellularization. Reconstructing the bioactivities of extracellular matrix-based scaffolds is essential for their usage in tissue repair. Results In the study, a hybrid hydrogel was developed by incorporating single-wall carbon nanotubes (SWCNTs) into heart-derived extracellular matrixes. Interestingly, insoluble SWCNTs were well dispersed in hybrid hydrogel solution via the interaction with extracellular matrix proteins. Importantly, an augmented integrin-dependent niche was reconstructed in the hybrid hydrogel, which could work like biophysical cues to activate integrin-related pathway of seeding cells. As supporting scaffolds in vitro, the hybrid hydrogels were observed to significantly promote seeding cell adhesion, differentiation, as well as structural and functional development towards mature cardiac tissues. As injectable carrier scaffolds in vivo, the hybrid hydrogels were then used to delivery stem cells for myocardial repair in rats. Similarly, significantly enhanced cardiac differentiation and maturation(12.5 ± 2.3% VS 32.8 ± 5%) of stem cells were detected in vivo, resulting in improved myocardial regeneration and repair. Conclusions The study represented a simple and powerful approach for exploring bioactive scaffold to promote stem cell-based tissue repair. Graphic abstract

Plant C, N and P can reflect plant strategies of nutrient utilization and allocation. Precipitation is a key factor affecting plant nutrient uptake and utilization strategies especially in arid and semiarid regions, and it is predicted to increase in the cold deserts of Northwest China due to climate change. However, the balance of C, N and P stoichiometry in annual plants at different growth stages in response to increased precipitation is not known. Thus, we performed an experiment on the annual grass Eremopyrum distans in the Gurbantunggut Desert to determine the effect of increased precipitation on C, N and P utilization and allocation at different growth stages. In the control, organ C concentration was relatively stable during the life cycle, but leaf and root N and P concentration increased during the vegetative stage; culm N concentration decreased and P concentration increased and then decreased with plant growth. Increased precipitation significantly increased the leaf N and P concentration and decreased the C:N and C:P ratios at the vegetative growth stage, but leaf N:P was lower than 14 during the whole growth stage. Increased precipitation could improve the leaf N and P resorption efficiency to cope with the reproduction allocation, and the root nutrients are more sensitive to increased precipitation. These results indicate that increased precipitation could improve the nutrient absorption and utilization for vegetative and reproductive growth of E. distans, and the root system plays crucially important role to influence the stoichiometry under varied environment.

Promoting efficiency of liquid–liquid extraction at a high pH is a main challenge for the recovery of volatile fatty acids (VFAs) from organic wastes. In this study, the extraction efficiency of VFAs from artificial solution and acidification fermentation broth of kitchen wastes using ionic liquids (ILs) was assessed at high pH. The effect of ILs addition ratio in diluent, volumetric solvent to feed ratio (S/F) on extraction efficiency were investigated. The solvent consists of [P666,14][Cl] (IL101) and dodecane was found to be the promising solvent for VFA extraction at pH 6.0, especially for butyric acid. The IL-101 ratio in dodecane and S/F was significant factors for the liquid–liquid extraction of VFAs. In general, a higher IL-101 ratio and S/F can promote the extraction efficiency of single VFAs. As a result, the maximum extraction rate of acetic acid (38.4–49.9%) and butyric acid (66.0–92.1%) from different VFA concentration solutions was observed at 10% IL-101 in dodecane and S/F = 2/1. The solvent was also effective in different types of real fermentation broth of kitchen wastes. The maximum extraction rate and selectivity of butyric acid was 60.2%/70.5% in butyric acid type broth and 74.6%/62.7% in mixture acid type broth.

High-temperature processes, such as packaging and annealing, are challenges for Radio-Frequency Micro-Electro-Mechanical-Systems (RF MEMS) structures, which could lead to device failure. Coefficient of thermal expansion (CTE) mismatch and the material’s creep effect affect the fabrication and performance of the MEMS, especially experiencing the high temperature. In this paper, the Thermal–Mechanical-Stress-Creep (TMSC) effect during thermal processes from room temperature (RT) to 200 °C is modeled and measured, in which an Au-cantilever-based RF MEMS switch is selected as a typical device example. A novel Isolation-Test Method (ITM) is used to measure precise TMSC variation. This method can achieve resolutions of sub-nanometer (0.5 nm) and attofarad (1 aF). There are three stages in the thermal processes, including temperature ramping up, temperature dwelling, and temperature ramping down. In different stages, the thermal–mechanical stress in anchor and cantilever, the grain growth of gold, and the thermal creep compete with each other, which result in the falling down and curling up of the cantilever. These influencing factors are decoupled and discussed in different stages. The focused ion beam (FIB) is used to characterize the change of the gold grain. This study shows the possibility of predicting the deformation of MEMS structures during different high-temperature processes. This model can be extended for material selection and package temperature design of MEMS cantilever in the further studies.

Interannual seasonal variability in precipitation may strongly affect the life history and growth of desert annual plants. We compared the effects of dry and wet springs and dry and wet autumns on growth and F2 seed dormancy of plants from spring (SG)- and autumn (AG)-germinated seeds of the cold desert annual Erodium oxyrhinchum. Vegetative and reproductive growth and F2 seed dormancy and germination were monitored from September 2016 to November 2020 in the sandy Gurbantunggut Desert in NW China in Central Asia. Dry autumns decreased the density of AG plants, and dry springs decreased the density of SG plants and growth of SG and AG plants. In dry springs, SG plants were more sensitive to precipitation than AG plants, while in wet springs SG and AG plants had similar responses to precipitation. During growth in both dry and wet springs, most morphological characters of SG and AG plants initially increased rapidly in size/number and then plateaued or decreased, except for SG plants in dry springs. In dry springs, most morphological characters of AG plants were larger or more numerous than those of SG plants, and they were larger/more numerous for SG plants in wet than in dry springs. The percentage biomass allocated to reproduction in SG plants was slightly higher in a wet than in a dry spring. A much higher proportion of dormant seeds was produced by AG plants in a wet spring than in a dry spring. Projected changes in precipitation due to climate change in NW China are not likely to have much of an effect on the biology of this common desert annual plant.

Future climate is projected to increase in the intensity and frequency of extreme precipitation events, and the resulting ecological consequences are often more serious than those of normal precipitation events. In particular, in desert ecosystems, due to the low frequency and strong fluctuation of extreme precipitation, the destructive consequences for desert plants caused by extreme precipitation have not received enough attention for some time. Based on statistics of extreme precipitation events (1965–2018) in the Gurbantunggut Desert, we investigated the effects of extreme precipitation (+0%, CK; +50%, W1; +100%, W2; +200%, W3; maintenance of field capacity, W4) on the plant life-history of the spring-germinated (SG) and autumn-germinated (AG) ephemeral plant Erodium oxyrhynchum by monitoring seedling emergence, survival, phenology, organ size, biomass accumulation, and allocation. The results showed that extreme precipitation caused about 2.5% seedling emergence of E. oxyrhynchum in autumn 2018 and 3.0% seedling emergence in early spring 2019, which means that most seeds may be stored in the soil or have died. Meanwhile, extreme precipitation significantly improved the survival, organ size, and biomass accumulation of SG and AG plants, and W3 was close to the precipitation threshold of SG (326.70 mm) and AG (560.10 mm) plants corresponding to the maximum individual biomass; thus, AG plants with a longer life cycle need more water for growth. Conversely, W4 caused AG plants to enter the leaf stage in advance and led to death in winter, which indicates that extreme precipitation may not be good for AG plants. Root and reproduction biomass allocation of SG and AG plants showed a significantly opposite trend under extreme precipitation treatments, which might be related to their different life-history strategies. Therefore, when only taking into account the changing trend of extreme precipitation from the Coupled Model Intercomparison Project 6 (CMIP6) climate projections data, we speculate that extreme precipitation may promote the growth of SG and AG plants from the beginning to the middle of this century, but extreme precipitation in autumn exceeding a certain threshold may adversely affect the survival of AG plants at the end of the century.

With the booming development of satellite applications, the giant constellations of low Earth orbit (LEO) satellites have introduced challenges for the data relay service. The multi-beam satellite not only offers concurrent access to a large number of objects, but can also meet the high data requirements toward specific coverage of the LEO constellation. However, the multi-beam satellite often faces the mismatch problem of spot allocation and data requirements, which can cause an overload traffic jam or a waste of resources. An optimization algorithm on spot beam allocation is necessary to automatically place the spot centers with appropriate beam widths in line with the density of the traffic demands and to realize the uniformity of the beam occupation. Compared with the conventional K-means algorithm, two adjustable parameters α and β are introduced: one for tuning the ratio of two components making up the distance matrix, and the other for setting the obligatory minimum number of objects per beam. In this paper, the whole process of the proposed method is demonstrated, including the establishment of the low-orbit satellite constellation model, the extraction of the distribution features, and the implementation and evaluation of the modified K-means algorithm. The results prove the validity of the proposed algorithm. A larger value of β with a relative smaller value of α tends to obtain the uniformity of beam occupation; the minimum standard deviation of objects per beam is achieved when α is 0.2 and β is 0.8. This demonstrates that the uniformity of objects per beam can be realized by adjusting the parameters of the distance determination matrix and the obligatory minimal number of objects in each beam. The impact of parameter range on the results is also analyzed.

Precipitation change and nitrogen deposition are not only hot topics of current global change but also the main environmental factors affecting plant growth in desert ecosystems. Thus, we performed an experiment of increased precipitation, nitrogen, and precipitation plus nitrogen on the ephemeral annual species Nepeta micrantha and Eremopyrum distans in the Gurbantunggut Desert. We aimed to determine the life history responses of N. micrantha and E. distans to environment changes, and the germination percentage of the offspring (seeds) was also tested in the laboratory. The results showed that increased nitrogen and precipitation plus nitrogen increased the growth of both plant species, whereas increased precipitation inhibited the growth of N. micrantha but increased the growth of E. distans. This differential response of these two species to precipitation and nitrogen also affected the germination of their offspring. In response to increased nitrogen and precipitation plus nitrogen, the germination percentage of the offspring produced by two species decreased in conjunction with the plants exhibiting high reproduction, which may prevent overcrowding during the following year; however, the N. micrantha plants produced more nondormant offspring in conjunction with low reproduction under relatively greater amounts of precipitation, and N. micrantha offspring could occupy their habitat via rapid germination in suitable environments. Therefore, with increased precipitation and nitrogen deposition, these differences in offspring dormancy may affect their ecological niche in the community.

Tissue engineering exploring the combination of scaffolds and seeding cells was proposed as a promising strategy for myocardial repair. However, the therapeutic outcomes varied greatly due to different selection of scaffolds and seeding cells. Herein, the potential of combining bioactive extracellular matrix (ECM) hydrogels and high cardiomyogenic seeding cells was explored for myocardial repair in vitro and in vivo. Temperature-sensitive ECM hydrogels were prepared from decellularized rat hearts, and cardiomyogenic seeding cells were isolated from brown adipose (brown adipose-derived stem cells (BADSCs)). The in vitro studies demonstrated that ECM hydrogel significantly supported the proliferation and cardiomyogenic differentiation of BADSCs. Importantly, the function and maturation of BADSC-derived cardiomyocytes were also promoted as evidenced by Ca2+ transient’s measurement and protein marker expression. After myocardial transplantation, the combination of BADSCs and ECM hydrogels significantly preserved cardiac function and chamber geometry compared with BADSCs or ECM hydrogels alone. Meanwhile, the ECM hydrogel also enhanced BADSC engraftment and myocardial regeneration in vivo. These results indicated that heart-derived ECM hydrogels exerted significant influence on the fate of cardiomyogenic cells toward benefiting myocardial repair, which may explain the enhanced stem cell therapy by the scaffold. Collectively, it indicated that the combination of ECM hydrogel and the cardiomyogenic cells may represent a promising strategy for cardiac tissue engineering.

In this study, new microencapsulated phase change material, with organic composite phase change as the core material and polymethylmethacrylate as the shell, was prepared by in situ interfacial polymerization reaction. The surface morphology of the formed microcapsule was observed by scanning electron microscopy, and its phase change temperature and phase change heat were measured by differential scanning calorimetry. The results of this study indicate that the mean diameter is in the range 2–3 µm, with a uniform size distribution, and the phase change temperature and enthalpy of microencapsulated phase change material are of 26.2°C and 139.68 J/g, respectively. The prepared microcapsule was mixed with ordinary paint in a 1:1 ratio for performing the comparative tests in two rooms with the same dimension and settings. The results indicated that with the introduction of a 2- to 3-mm-thick coating containing microencapsulated phase change material the temperature amplitude decreased by 5°C–6°C. The power monitoring results for the period of the highest temperature in 1 day indicated that the start-up time of air conditioner significantly decreased, thus saving about 26% electric consumption.

Objective: To compare the effects of biventricular electrical pacing and conventional single-ventricular pacing for cardiac contractility modulation (CCM) on cardiac contractile function and to delineate the underlying molecular mechanisms. Methods: Forty rabbits were divided into four groups before surgery: healthy control, HF sham, HF left ventricular pacing CCM (LVP-CCM), and HF biventricular pacing CCM (BVP-CCM) groups with n=10 for each group. A rabbit model of chronic heart failure was established by ligating ascending aortic root of rabbits. Then electrical stimulations during the absolute refractory period were delivered to the anterior wall of left ventricle in the LVP-CCM group and on the anterior wall of both left and right ventricles in the BVP-CCM group lasting six hours per day for seven days. Changes in ventricular structure, cardiac function and electrocardiogram were monitored before and after CCM stimulation. Results: Compared with the sham-operated group, heart weight, heart weight index, LV end-systolic diameter (LVESD), LV end-diastolic diameter (LVEDD) in the LVP-CCM and BVP-CCM groups were significantly decreased (ppp2+-ATPase (SERCA2a) protein levels were upregulated by 1.7 and 2.4 fold, along with simultaneous upregulation of a cardiac-enriched microRNA miR-133 levels by 2.6 and 3.3 fold, in LVP-CCM and BVP-CCM, respectively, compared to sham. Conclusions: Biventricular pacing CCM is superior to conventional monoventricular pacing CCM, producing greater improvement cardiac contractile function. Greater upregulation of SERCA2 and miR-133 may account, at least partially, for the improvement by BVP-CCM.

In this study, the soil moisture content was measured, and the quantitative characteristics of this sedge species were compared. The phenotypic plasticity of each parameter and the linear regression relationships were analyzed. The results showed that the soil moisture content was significantly affected by location, soil depth, and sampling date. The aboveground biomass, underground biomass, biomass density, and population density at the peak were significantly higher than elsewhere on the dune. However, the morphological plasticity index of the quantitative characteristics was higher at the base and middle of the dune. When the soil moisture content decreased, the underground biomass and ramet biomass density increased. The aboveground and underground biomasses were strongly negatively correlated, but the ramet height and aboveground biomass were strongly positively correlated. These results indicated that the soil water content significantly affected the clonal growth of C. physodes. The responsiveness of C. physodes may be adaptive when the soil resource supply is low. The strong morphological plasticity of the species appears to be ecologically important for the maintenance and dominance of this species in the dune habitat.

Seed dispersal and germination were examined for 70 species from the cold Gurbantunggut Desert in northwest China. Mean and range (3 orders of magnitude) of seed mass were smaller and narrower than those in other floras (5–8 orders of magnitude), which implies that selection favors relatively smaller seeds in this desert. We identified five dispersal syndromes (anemochory, zoochory, autochory, barochory, and ombrohydrochory), and anemochorous species were most abundant. Seed mass (F=3.50, P=0.01), seed size (F=8.31, P