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Abstract As major terrestrial carbon sinks, forests play an important role in mitigating climate change. The relationship between the seasonal uptake of carbon and its allocation to woody biomass remains poorly understood, leaving a significant gap in our capacity to predict carbon sequestration by forests. Here, we compare the intra-annual dynamics of carbon fluxes and wood formation across the Northern hemisphere, from carbon assimilation and the formation of non-structural carbon compounds to their incorporation in woody tissues. We show temporally coupled seasonal peaks of carbon assimilation (GPP) and wood cell differentiation, while the two processes are substantially decoupled during off-peak periods. Peaks of cambial activity occur substantially earlier compared to GPP, suggesting the buffer role of non-structural carbohydrates between the processes of carbon assimilation and allocation to wood. Our findings suggest that high-resolution seasonal data of ecosystem carbon fluxes, wood formation and the associated physiological processes may reduce uncertainties in carbon source-sink relationships at different spatial scales, from stand to ecosystem levels.

Water quality predicted accuracy is beneficial to river ecological management and water pollution prevention. Owing to water quality data has the characteristics of nonlinearity and instability, it is difficult to predict the change of water quality. This paper proposes a hybrid water quality prediction model based on variational mode decomposition optimized by the sparrow search algorithm (SSA-VMD) and bidirectional gated recursive unit (BiGRU). First, the sparrow search algorithm selects fuzzy entropy (FE) as the fitness function to optimize the two parameters of VMD, which improves the adaptability of VMD. Second, SSA-VMD is used to decompose the original data into several components with different center frequencies. Finally, BiGRU is employed to predict each component separately, which significantly improves predicted accuracy. The proposed model is validated using data about dissolved oxygen (DO) and the potential of hydrogen (pH) from the Xiaojinshan Monitoring Station in Qiandao Lake, Hangzhou, China. The experimental results show that the proposed model has superior prediction accuracy and stability when compared with other models, such as EMD-based models and other CEEMDAN-based models. The prediction accuracy of DO can reach 97.8% and pH is 96.1%. Therefore, the proposed model can provide technical support for river water quality protection and pollution prevention. HIGHLIGHTS In order to overcome the problem of nonlinear instability of water quality data, an adaptive decomposition method of improved VMD by SSA is proposed. In the optimization process, fuzzy entropy (FE) is selected as the fitness function to evaluate the complexity between orders.; In order to fully explore the time characteristics of water quality, the BiGRU neural network is used as the prediction model.; The proposed model is applied to the prediction of DO and pH in real rivers.;

Abstract Actin nucleotide-dependent actin remodeling is essential to orchestrate signal transduction and cell adaptation. Rapid energy starvation requires accurate and timely reorganization of the actin network. Despite distinct treadmilling mechanisms of ADP- and ATP-actin filaments, their filament structures are nearly identical. How other actin-binding proteins regulate ADP-actin filament assembly is unclear. Here, we show that Spa2 which is the polarisome scaffold protein specifically remodels ADP-actin upon energy starvation in budding yeast. Spa2 triggers ADP-actin monomer nucleation rapidly through a dimeric core of Spa2 (aa 281-535). Concurrently, the intrinsically disordered region (IDR, aa 1-281) guides Spa2 undergoing phase separation and wetting on the surface of ADP-G-actin-derived F-actin and bundles the filaments. Both ADP-actin-specific nucleation and bundling activities of Spa2 are actin D-loop dependent. The IDR and nucleation core of Spa2 are evolutionarily conserved by coexistence in the fungus kingdom, suggesting a universal adaptation mechanism in the fungal kingdom in response to glucose starvation, regulating ADP-G-actin and ADP-F-actin with high nucleotide homogeneity.

Abstract Due to their responsiveness to modulation by external direct current fields, dielectric tunable materials are extensively utilized in integrated components, such as ferroelectric phase shifters. Barium strontium titanate ceramics have been considered the most potential tunable materials for a long time. However, the significant dielectric loss and high voltage drive have limited their further applications. Recently, Bi6Ti5WO22 ceramic has regained attention for its high dielectric tunability with low loss. In this study, we judiciously introduce Nb5+ with a larger ionic radius, replacing Ti4+ and W6+. This successful substitution enables the modulation of the phase transition temperature of Bi6Ti5WO22 ceramics to room temperature, resulting in superior tunable properties. Specifically, the 0.7Bi6Ti5WO22−0.3Bi6Ti4Nb2O22 ceramics exhibit giant tunability (~75.6%) with ultralow loss (

BackgroundIntegrated traditional Chinese medicine and biomedicine is an effective method to treat tuberculosis (TB). In our previous research, traditional Chinese medicine preparation NiuBeiXiaoHe (NBXH) achieved obvious anti-TB effects in animal experiments and clinical practice. However, the action mechanism of NBXH has not been elucidated.MethodPeripheral blood mononuclear cells (PBMCs) were collected to extract mRNA and differentially expressed (DE) genes were obtained using gene microarray technology. Finally, GEO databases and RT-qPCR were used to verify the results of expression profile.ResultAfter MTB infection, most upregulated DE genes in mice were immune-related genes, including cxcl9, camp, cfb, c4b, serpina3g, and ngp. Downregulated DE genes included lrrc74b, sult1d1, cxxc4, and grip2. After treatment with NBXH, especially high-dose NBXH, the abnormal gene expression was significantly corrected. Some DE genes have been confirmed in multiple GEO datasets or in pulmonary TB patients through RT-qPCR.ConclusionMTB infection led to extensive changes in host gene expression and mainly caused the host’s anti-TB immune responses. The treatment using high-dose NBXH partially repaired the abnormal gene expression, further enhanced the anti-TB immunity included autophagy and NK cell-mediated cytotoxicity, and had a certain inhibitory effect on overactivated immune responses.

Abstract Aiming at resolving the parameter uncertainty of the servo system under multi‐working conditions, a flatness‐based switched linear system model is proposed. Firstly, a fifth‐order linear switched discrete‐time system with uncertain parameters is established. The flatness properties of switched system is described and a de Bruijn's graph‐based framework is introduced for graphical description of the switched system. In addition, non‐linear bode diagrams are obtained via sweeping signals with multiple amplitudes. The discrete equations of the electromechanical servo system are established by the bode plots. The unknown parameters of the subsystems in switched model are identified by the simulated annealing algorithm, and compared with the least squares method to verify the accuracy of the identified parameters. Finally, the simulation model and experimental platform are constructed to verify the effectiveness of the proposed method. The switched model is compared with the classical transfer function model and single subsystems. The results indicate that the resolution of parameter uncertainty in servo systems is effective. The accuracy of the established switched model is about 99.5%. The accuracy of the switched linear system model of the electromechanical servo system is verified and the proposed modelling method is validated.

The adsorption of toxic and harmful gases through porous materials is an effective means of air pollution control. A multi-level porous carbon material with ultra-high-specific surface area was made based on rice husk biomass to improve the air pollution controlling efficiency and reduce its cost. The rice husk substrate was pretreated using T.viride spore suspension during the preparation of this material. This changes the proportion of various components in the matrix, thereby achieving an increase in the multi-level porous carbon material’s specific surface area. Its performance was analyzed through various means in the study. The results confirmed that when the activation treatment time was 60 minutes, the porous carbon material’s specific surface area was the highest, reaching 3714 m2/g. After 30 days of treatment with T.viride spore suspension, the cellulose content in rice husks decreased by about 40 g/kg. Compared to untreated porous carbon materials, after 20 days of treatment, the micropores and mesopores of these materials significantly increased. The research has successfully increased the multi-level porous carbon material’s specific surface area and achieved rapid absorption of atmospheric volatile organic compounds. The multi-level porous carbon material can enhance the air pollution controlling efficiency and reduce its cost.

Abstract Background Lung adenocarcinoma (LUAD) is one of the most invasive malignant tumor of the respiratory system. It is also the common pathological type leading to the death of LUAD. Maintaining the homeostasis of immune cells is an important way for anti‐tumor immunotherapy. However, the biological significance of maintaining immune homeostasis and immune therapeutic effect has not been well studied. Methods We constructed a diagnostic and prognostic model for LUAD based on B and T cells homeostasis‐related genes. Minimum absolute contraction and selection operator (LASSO) analysis and multivariate Cox regression are used to identify the prognostic gene signatures. Based on the overall survival time and survival status of LUAD patients, a 10‐gene prognostic model composed of ABL1, BAK1, IKBKB, PPP2R3C, CCNB2, CORO1A, FADD, P2RX7, TNFSF14, and ZC3H8 was subsequently identified as prognostic markers from The Cancer Genome Atlas (TCGA)‐LUAD to develop a prognostic signature. This study constructed a gene prognosis model based on gene expression profiles and corresponding survival information through survival analysis, as well as 1‐year, 3‐year, and 5‐year ROC curve analysis. Enrichment analysis attempted to reveal the potential mechanism of action and molecular pathway of prognostic genes. The CIBERSORT algorithm calculated the infiltration degree of 22 immune cells in each sample and compared the difference of immune cell infiltration between high‐risk group and low‐risk group. At the cellular level, PCR and CKK8 experiments were used to verify the differences in the expression of the constructed 10‐gene model and its effects on cell viability, respectively. The experimental results supported the significant biological significance and potential application value of the molecular model in the prognosis of lung cancer. Enrichment analyses showed that these genes were mainly related to lymphocyte homeostasis. Conclusion We identified a novel immune cell homeostasis prognostic signature. Targeting these immune cell homeostasis prognostic genes may be an alternative for LUAD treatment. The reliability of the prediction model was confirmed at bioinformatics level, cellular level, and gene level.

Abstract The tumor suppressor p53 (p53) is regulated by murine double minute 2 (Mdm2) and its homologous MdmX in maintaining the basal level of p53. Overexpressed Mdm2/MdmX inhibits cellular p53 activity, which is highly relevant to cancer occurrence. Coiled-coil domain-containing protein 106 (CCDC106) has been identified as a p53-interacting partner. However, the molecular mechanism of the p53/Mdm2/MdmX/CCDC106 interactions is still elusive. Here, we show that CCDC106 functions as a signaling regulator of the p53-Mdm2/MdmX axis. We identified that CCDC106 directly interacts with the p53 transactivation domain by competing with Mdm2 and MdmX. CCDC106 overexpression downregulates the cellular level of p53 and Mdm2/MdmX, and decreased p53 reversibly downregulates the cellular level of CCDC106. Our work provides a molecular mechanism by which CCDC106 regulates the cellular levels of p53 and Mdm2/MdmX.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes COVID-19, and so far, it has occurred five noteworthy variants of concern (VOC). SARS-CoV-2 invades cells by contacting its Spike (S) protein to its receptor on the host cell, angiotensin-converting enzyme 2 (ACE2). However, the high frequency of mutations in the S protein has limited the effectiveness of existing drugs against SARS-CoV-2 variants, particularly the Omicron variant. Therefore, it is critical to develop drugs that have highly effective antiviral activity against both SARS-CoV-2 and its variants in the future. This review provides an overview of the mechanism of SARS-CoV-2 infection and the current progress on anti-SARS-CoV-2 drugs.

Surface albedo plays a pivotal role in the Earth’s energy balance and climate. This study conducted an analysis of the spatial distribution patterns and temporal evolution of albedo, normalized difference vegetation index (NDVI), normalized difference snow index snow cover (NSC), and land surface temperature (LST) within the Qilian Mountains (QLMs) from 2001 to 2022. This study evaluated the spatiotemporal correlations of albedo with NSC, NDVI, and LST at various temporal scales. Additionally, the study quantified the driving forces and relative contributions of topographic and natural factors to the albedo variation of the QLMs using geographic detectors. The findings revealed the following insights: (1) Approximately 22.8% of the QLMs exhibited significant changes in albedo. The annual average albedo and NSC exhibited a minor decline with rates of −0.00037 and −0.05083 (Sen’s slope), respectively. Conversely, LST displayed a marginal increase at a rate of 0.00564, while NDVI experienced a notable increase at a rate of 0.00178. (2) The seasonal fluctuations of NSC, LST, and vegetation collectively influenced the overall albedo changes in the Qilian Mountains. Notably, the highly similar trends and significant correlations between albedo and NSC, whether in intra-annual monthly variations, multi-year monthly anomalies, or regional multi-year mean trends, indicate that the changes in snow albedo reflected by NSC played a major role. Additionally, the area proportion and corresponding average elevation of PSI (permanent snow and ice regions) slightly increased, potentially suggesting a slow upward shift of the high mountain snowline in the QLMs. (3) NDVI, land cover type (LCT), and the Digital Elevation Model (DEM, which means elevation) played key roles in shaping the spatial pattern of albedo. Additionally, the spatial distribution of albedo was most significantly influenced by the interaction between slope and NDVI.

Accurate prediction of estuarine salinity can effectively mitigate the adverse effects of saltwater intrusion and help ensure the safety of water resources in estuarine regions. Presently, diverse data-driven models, mainly neural network models, have been employed to predict tidal estuarine salinity and obtained considerable achievements. Due to the nonlinear and nonstationary features of estuarine salinity sequences, this paper proposed a multi-factor salinity prediction model using an enhanced Long Short-Term Memory (LSTM) network. To improve prediction accuracy, input variables of the model were determined through Grey Relational Analysis (GRA) combined with estuarine dynamic analysis, and hyperparameters for the LSTM model were optimized using a multi-strategy Improved Sparrow Search Algorithm (ISSA). The proposed ISSA-LSTM model was applied to predict salinity at the Cangqian and Qibao stations in the Qiantang Estuary of China, based on measured data from 2011–2012. The model performance is evaluated by mean absolute error (MAE), mean absolute percentage error (MAPE), root mean square error (RMSE), and Nash-Sutcliffe efficiency (NSE). The results show that compared to other models including Back Propagation neural network (BP), Gate Recurrent Unit (GRU), and LSTM model, the new model has smaller errors and higher prediction accuracy, with NSE improved by 8–32% and other metrics (MAP, MAPE, RMSE) improved by 15–67%. Meanwhile, compared with LSTM optimized with the original SSA (SSA-LSTM), MAE, MAPE, and RMSE values of the new model decreased by 13–16%, 15–16%, and 11–13%, and NSE value increased by 5–6%, indicating that the ISSA has a better hyperparameter optimization ability than the original SSA. Thus, the model provides a practical solution for the rapid and precise prediction of estuarine salinity.

ABSTRACTThe contamination of the plant phyllosphere with antibiotics and antibiotic resistance genes (ARGs), caused by application of antibiotics, is a significant environmental issue in agricultural management. Alternatively, biocontrol agents are environmentally friendly and have attracted a lot of interest. However, the influence of biocontrol agents on the phyllosphere resistome remains unknown. In this study, we applied biocontrol agents to control the wildfire disease in the Solanaceae crops and investigated their effects on the resistome and the pathogen in the phyllosphere by using metagenomics. A total of 250 ARGs were detected from 15 samples, which showed a variation in distribution across treatments of biocontrol agents (BA), BA with Mg2+ (T1), BA with Mn2+ (T2), and kasugamycin (T3) and nontreated (CK). The results showed that the abundance of ARGs under the treatment of BA-Mg2+ was lower than that in the CK group. The abundance of cphA3 (carbapenem resistance), PME-1 (carbapenem resistance), tcr3 (tetracycline antibiotic resistance), and AAC (3)-VIIIa (aminoglycoside antibiotic resistance) in BA-Mg2+ was significantly higher than that in BA-Mn2+ (P < 0.05). The abundance of cphA3, PME_1, and tcr3 was significantly negatively related to the abundance of the phyllosphere pathogen Pseudomonas syringae (P < 0.05). We also found that the upstream and downstream regions of cphA3 were relatively conserved, in which rpl, rpm, and rps gene families were identified in most sequences (92%). The Ka/Ks of cphA3 was 0 in all observed sequences, indicating that under the action of purifying selection, nonsynonymous substitutions are often gradually eliminated in the population. Overall, this study clarifies the effect of biocontrol agents with Mg2+ on the distribution of the phyllosphere resistome and provides evolutionary insights into the biocontrol process.IMPORTANCEOur study applied metagenomics analysis to examine the impact of biocontrol agents (BAs) on the phyllosphere resistome and the pathogen. Irregular use of antibiotics has led to the escalating dissemination of antibiotic resistance genes (ARGs) in the environment. The majority of BA research has focused on the effect of monospecies on the plant disease control process, the role of the compound BA with nutrition elements in the phyllosphere disease, and the resistome is still unknown. We believe BAs are eco-friendly alternatives for antibiotics to combat the transfer of ARGs. Our results revealed that BA-Mg2+ had a lower relative abundance of ARGs compared to the CK group, and the phyllosphere pathogen Pseudomonas syringae was negatively related to three specific ARGs, cphA3, PME-1, and tcr3. These three genes also present different Ka/Ks. We believe that the identification of the distribution and evolution modes of ARGs further elucidates the ecological role and facilitates the development of BAs, which will attract general interest in this field.

At the crucial period of addressing climate change, especially to the carbonization of land use change, it is vital that relevant actions are taken to enable two ambitious dual-carbon goals, namely, ensuring that carbon emissions peak before 2030 and achieving carbon neutrality before 2060. This research investigates the impacts of land use changes on carbon emissions using a novel approach that integrates Light Detection and Ranging (LiDAR) with Geographic Information System (GIS). This approach is innovative due to its high quality three-dimensional representation to quantified exact carbon stock and forest emissions occurring due to specific land-use change. Therefore, through actual LiDAR, this research helps demarcate the pattern emitting different land-use measures, including deforestation, urban programs, agricultural differences, and forest and land changes, over historical change records and verified carbonization formulas. Similar qualitative levels between LiDAR and GIS analysis help determine the varying degrees of carbonization occurring due to enhanced deforestation, urban additions, and agricultural contributions while reporting the possible procedural carbons acquired during reforestation and other measurements. The results helped clarify that the most distinct level of land utilization shows the least level of carbon sent into the air. Therefore, the implication is that strategic land use measures and better working conditions can curb carbon indications. These signals support land-use policy and preparedness goals in a low carbon level. This study creates valuable records for the land utilization and cartograph, created through the power of LiDAR and GIS analysis.

Brain metastasis (BMs) in small cell lung cancer (SCLC) has a very poor prognosis. This study combined WGCNA with the mfuzz algorithm to identify potential biomarkers in the peripheral blood of patients with BMs. By comparing the significantly differentially expressed genes present in BMs samples, we identified ADCY4 as a target for further study. Expression of ADCY4 was used to cluster mfuzz expression pattern, and 28 hub genes for functional enrichment. PPI network analysis were obtained by comparing with differentially expressed genes in BMs. GABRE, NFE4 and LMOD2 are highly expressed in patients with BMs and have a good diagnostic effect. Immunoinfiltration analysis showed that SCLC patients with BMs may be associated with memory B cells, Tregs, NK cell activation, macrophage M0 and dendritic cell activation. prophytic was used to investigate the ADCY4-mediated anti-tumor drug response. In conclusion, ADCY4 can be used as a promising candidate biomarker for predicting BMs, molecular and immune features in SCLC. PCR showed that ADCY4 expression was increased in NCI–H209 and NCI–H526 SCLC cell lines. In vitro experiments confirmed that the expression of ADCY4 was significantly decreased after anti-PD1 antibody treatment, while the expression of energy metabolism factors were significantly different. This study reveals a potential mechanism by which ADCY4 mediates poor prognosis through energy metabolism -related pathways in SCLC.

Background: Activation of the Hedgehog signaling pathway is linked to the initiation and development of human hepatocellular carcinoma (HCC). However, its impact on clinical outcomes and the HCC microenvironment remains unclear. Methods: We performed comprehensive analyses of Hedgehog pathway genes in a large cohort of HCC patients. Specifically, we utilized univariate Cox regression analysis to identify Hedgehog genes linked to overall survival, and the LASSO algorithm was used to construct a Hedgehog-related gene pattern. We subsequently examined the correlation between the Hedgehog pattern and the HCC microenvironment employing the CIBERSORT and ssGSEA algorithms. Furthermore, Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the anti-PD-L1 treatment dataset (IMvigor210) are used to evaluate the clinical response of the Hedgehog pattern in predicting immune checkpoint inhibitors. Results: We found that the Hedgehog activation score (HHAS), a prognostic score based on 11 Hedgehog genes, was significantly associated with HCC patient survival. Patients exhibiting high HHAS experienced markedly reduced survival rates compared to those with low HHAS, and HHAS emerged as an independent prognostic factor for HCC. Functional enrichment analysis unveiled the association of the HHAS phenotype with functions related to the immune system, and further investigation demonstrated that HCC patients exhibiting low HHAS displayed elevated levels of anti-tumor immune activation in CD8+ T cells, while high HHAS were linked to immune escape phenotypes and increased infiltration of immune suppressive cells. In addition, in the Immune Checkpoint Inhibitor (ICI) cohort of IMvigor210, patients with higher HHAS had worse ICI treatment outcomes and shortened survival time, indicating that the HHAS is a useful indicator for predicting patient response to immunotherapy. Conclusions: In summary, our study offers valuable insights for advancing research on Hedgehog and its impact on tumor immunity, which provides an opportunity to optimize prognosis and immune therapy for HCC.

Abstract Background Alanine dehydrogenase (AlaDH) belongs to oxidoreductases, and it exists in several different bacteria species and plays a key role in microbial carbon and nitrogen metabolism, spore formation and photosynthesis. In addition, AlaDH can also be applied in biosynthesis of L-alanine from cheap carbon source, such as glucose. Results To achieve a better performance of L-alanine accumulation, system evaluation and comparison of different AlaDH with potential application value are essential. In this study, enzymatic properties of AlaDH from Bacillus subtilis 168 (BsAlaDH), Bacillus cereus (BcAlaDH), Mycobacterium smegmatis MC2 155 (MsAlaDH) and Geobacillus stearothermophilus (GsAlaDH) were firstly carefully investigated. Four different AlaDHs have few similarities in optimum temperature and optimum pH, while they also exhibited significant differences in enzyme activity, substrate affinity and enzymatic reaction rate. The wild E. coli BL21 with these four AlaDHs could produce 7.19 g/L, 7.81 g/L, 6.39 g/L and 6.52 g/L of L-alanine from 20 g/L glucose, respectively. To further increase the L-alanine titer, competitive pathways for L-alanine synthesis were completely blocked in E. coli. The final strain M-6 could produce 80.46 g/L of L-alanine with a yield of 1.02 g/g glucose after 63 h fed-batch fermentation, representing the highest yield for microbial L-alanine production. Conclusions Enzyme assay, biochemical characterization and structure analysis of BsAlaDH, BcAlaDH, MsAlaDH and GsAlaDH were carried out. In addition, application potential of these four AlaDHs in L-alanine productions were explored. The strategies here can be applied for developing L-alanine producing strains with high titers.

Orobanche aegyptiaca Pers. is a holoparasitic plant that severely reduces tomato (Solanum lycopersicum L.) production in China. However, there is a lack of effective control methods and few known sources of genetic resistance. In this study, we focused on key genes in the JAZ family, comparing the JAZ family in Arabidopsis thaliana (L. Heynh.) to the tomato genome. After identifying the JAZ family members in S. lycopersicum, we performed chromosomal localization and linear analysis with phylogenetic relationship analysis of the JAZ family. We also analyzed the gene structure of the JAZ gene family members in tomato and the homology of the JAZ genes among the different species to study their relatedness. The key genes for O. aegyptiaca resistance were identified using VIGS (virus-induced gene silencing), and the parasitization rate of silenced tomato plants against O. aegyptiaca increased by 47.23–91.13%. The genes were localized in the nucleus by subcellular localization. Heterologous overexpression in A. thaliana showed that the key gene had a strong effect on the parasitization process of O. aegyptiaca, and the overexpression of the key gene reduced the parasitization rate of O. aegyptiaca 1.69-fold. Finally, it was found that the SLJAZ15 gene can positively regulate the hormone content in tomato plants and affect plant growth and development, further elucidating the function of this gene.

Abstract We evaluated the effect of acute hypobaric hypoxia (AHH) on the hippocampal region of the brain in early-stage spontaneously hypertensive male rats. The rats were classified into a control (ground level; ~ 400 m altitude) group and an AHH experimental group placed in an animal hypobaric chamber at a simulated altitude of 5500 m for 24 h. RNA-Seq analysis of the brains and hippocampi showed that differentially expressed genes (DEGs) were primarily associated with ossification, fibrillar collagen trimer, and platelet-derived growth factor binding. The DEGs were classified into functional categories including general function prediction, translation, ribosomal structure and biogenesis, replication, recombination, and repair. Pathway enrichment analysis revealed that the DEGs were primarily associated with relaxin signaling, PI3K-Akt signaling, and amoebiasis pathways. Protein–protein interaction network analysis indicated that 48 DEGs were involved in both inflammation and energy metabolism. Further, we performed validation experiments to show that nine DEGs were closely associated with inflammation and energy metabolism, of which two (Vegfa and Angpt2) and seven (Acta2, Nfkbia, Col1a1, Edn1, Itga1, Ngfr, and Sgk1) genes showed up and downregulated expression, respectively. Collectively, these results indicated that inflammation and energy metabolism-associated gene expression in the hippocampus was altered in early-stage hypertension upon AHH exposure.

Phelipanche aegyptiaca can infect many crops, causing large agricultural production losses. It is important to study the parasitism mechanism of P. aegyptiaca to control its harm. In this experiment, the P. aegyptiaca HY13M and TE9M from Tacheng Prefecture and Hami City in Xinjiang, respectively, were used to analyze the parasitical mechanism of P. aegyptiaca by means of transcriptome and proteome analyses. The parasitic capacity of TE9M was significantly stronger than that of HY13M in Citrullus lanatus. The results showed that the DEGs and DEPs were prominently enriched in the cell wall metabolism pathways, including “cell wall organization or biogenesis”, “cell wall organization”, and “cell wall”. Moreover, the functions of the pectinesterase enzyme gene (TR138070_c0_g), which is involved in the cell wall metabolism of P. aegyptiaca in its parasitism, were studied by means HIGS. The number and weight of P. aegyptiaca were significantly reduced when TR138070_c0_g1, which encodes a cell-wall-degrading protease, was silenced, indicating that it positively regulates P. aegyptiaca parasitism. Thus, these results suggest that the cell wall metabolism pathway is involved in P. aegyptiaca differentiation of the parasitic ability and that the TR138070_c0_g1 gene plays an important role in P. aegyptiaca’s parasitism.

Acute high-altitude hypoxia can lead to intestinal damage and changes in gut microbiota. Sustained and reliable oxygen enrichment can resist hypoxic damage at high altitude to a certain extent. However, it remains unclear whether oxygen enrichment can protect against gut damage and changes in intestinal flora caused by acute altitude hypoxia. For this study, eighteen male Sprague–Dawley rats were divided into three groups, control (NN), hypobaric hypoxic (HH), and oxygen-enriched (HO). The NN group was raised under normobaric normoxia, whereas the HH group was placed in a hypobaric hypoxic chamber simulating 7,000 m for 3 days. The HO group was exposed to oxygen-enriched air in the same hypobaric hypoxic chamber as the HH group for 12 h daily. Our findings indicate that an acute HH environment caused a fracture of the crypt structure, loss of epithelial cells, and reduction in goblet cells. Additionally, the structure and diversity of bacteria decreased in richness and evenness. The species composition at Phylum and Genus level was characterized by a higher ratio of Firmicutes and Bacteroides and an increased abundance of Lactobacillus with the abundance of Prevotellaceae_NK3B31_group decreased in the HH group. Interestingly, after oxygen enrichment intervention, the intestinal injury was significantly restrained. This was confirmed by an increase in the crypt depth, intact epithelial cell morphology, increased relative density of goblet cells, and higher evenness and richness of the gut microbiota, Bacteroidetes and Prevotellaceae as the main microbiota in the HO group. Finally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including Amino acid metabolism, energy metabolism, and metabolism. In conclusion, this study verifies, for the first time, the positive effects of oxygen enrichment on gut structure and microbiota in animals experiencing acute hypobaric hypoxia.

Abstract Background MicroRNAs are a type of non-coding single-stranded RNA, which is involved in the regulation of ovary insulin resistance (IR). This study aims to explore the underlying mechanisms of miR-133a-3p regulating ovary IR in obese polycystic ovary syndrome (PCOS). Methods Granulosa cells (GCs) were extracted from follicular fluids of PCOS patients (obese PCOS group and non-obese PCOS group) and healthy women (control group). The expression of miR-133a-3p in GCs was detected by qRT-PCR. The targets and pathways of miR-133a-3p were predicted by bioinformatics analyses. The protein levels of PI3K, p-AKT, GLUT4, p-GSK-3β, and p-FOXO1 were measured by Western blotting. Results MiR-133a-3p was highly expressed in GCs from PCOS patients, especially in obese PCOS patients. The protein levels of PI3K and p-AKT was downregulated in GCs from PCOS patients. There were 11 target genes of miR-133a-3p enriching in PI3K/AKT signaling pathway. miR-133a-3p mimic downregulated the expression of PI3K, p-AKT, and GLUT4, and upregulated the protein levels of p-GSK-3β and p-FOXO1. miR-133a-3p inhibitor presented the opposite effect of miR-133a-3p mimic. Conclusion MiR-133a-3p promotes ovary IR on GCs of obese PCOS patients via inhibiting PI3K/AKT signaling pathway. This study lays a foundation for further research on the mechanism of ovary IR in obese PCOS patients.

Abstract Proteinuria, an indication of kidney disease, is caused by the malfunction of podocytes, which play a key role in maintaining glomerular filtration. Angiopoietin-like 3 (ANGPTL3) has been documented to have a cell-autonomous involvement in podocytes, and deletion of Angptl3 in podocytes reduced proteinuria in adriamycin-induced nephropathy. Here, we developed a monoclonal antibody (mAb) against ANGPTL3 to investigate its effects on podocyte injury in an ADR nephropathy mouse model and puromycin (PAN) induced podocyte damage in vitro. The mAb against the human ANGPTL3-FLD sequence (5E5F6) inhibited the binding of ANGPTL3-FLD to integrin β3. Treatment with the 5E5F6 mAb in ADR nephropathy mice mitigated proteinuria and led to a significant decline in podocyte apoptosis, reactive oxygen species (ROS) generation and mitochondrial fragmentation. In PAN-induced podocyte damage in vitro, the 5E5F6 mAb blocked the ANPGPLT3-mediated activation of integrin αvβ3 and Rac1, which regulated the mitochondrial homeostasis. Altogether, anti-ANGPLT3-FLD mAb attenuates proteinuria and podocyte lesions in ADR mice models, as well as PAN-induced podocyte damage, in part through regulating mitochondrial functions. Our study provides a therapeutic approach for targeting ANGPTL3 in proteinuric kidney disease.

Summary: Coronins play critical roles in actin network formation. The diverse functions of coronins are regulated by the structured N-terminal β propeller and the C-terminal coiled coil (CC). However, less is known about a middle “unique region” (UR), which is an intrinsically disordered region (IDR). The UR/IDR is an evolutionarily conserved signature in the coronin family. By integrating biochemical and cell biology experiments, coarse-grained simulations, and protein engineering, we find that the IDR optimizes the biochemical activities of coronins in vivo and in vitro. The budding yeast coronin IDR plays essential roles in regulating Crn1 activity by fine-tuning CC oligomerization and maintaining Crn1 as a tetramer. The IDR-guided optimization of Crn1 oligomerization is critical for F-actin cross-linking and regulation of Arp2/3-mediated actin polymerization. The final oligomerization status and homogeneity of Crn1 are contributed by three examined factors: helix packing, the energy landscape of the CC, and the length and molecular grammar of the IDR.

Abstract Our previous research developed a novel tuberculosis (TB) DNA vaccine ag85a/b that showed a significant therapeutic effect on the mouse tuberculosis model by intramuscular injection (IM) and electroporation (EP). However, the action mechanisms between these two vaccine immunization methods remain unclear. In a previous study, 96 Mycobacterium tuberculosis (MTB) H37Rv‐infected BALB/c mice were treated with phosphate‐buffered saline, 10, 50, 100, and 200 μg ag85a/b DNA vaccine delivered by IM and EP three times at 2‐week intervals, respectively. In this study, peripheral blood mononuclear cells (PBMCs) from three mice in each group were isolated to extract total RNA. The gene expression profiles were analyzed using gene microarray technology to obtain differentially expressed (DE) genes. Finally, DE genes were validated by real‐time reverse transcription‐quantitive polymerase chain reaction and the GEO database. After MTB infection, most of the upregulated DE genes were related to the digestion and absorption of nutrients or neuroendocrine (such as Iapp, Scg2, Chga, Amy2a5), and most of the downregulated DE genes were related to cellular structural and functional proteins, especially the structure and function proteins of the alveolar epithelial cell (such as Sftpc, Sftpd, Pdpn). Most of the abnormally upregulated or downregulated DE genes in the TB model group were recovered in the 100 and 200 μg ag85a/b DNA IM groups and four DNA EP groups. The pancreatic secretion pathway downregulated and the Rap1 signal pathway upregulated had particularly significant changes during the immunotherapy of the ag85a/b DNA vaccine on the mouse TB model. The action targets and mechanisms of IM and EP are highly consistent. Tuberculosis infection causes rapid catabolism and slow anabolism in mice. For the first time, we found that the effective dose of the ag85a/b DNA vaccine immunized whether by IM or EP could significantly up‐regulate immune‐related pathways and recover the metabolic disorder and the injury caused by MTB.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease mainly on account of hypercholesterolemia and may progress to cirrhosis and hepatocellular carcinoma. The discovery of effective therapy for NAFLD is an essential unmet need. Angiopoietin-like protein 3 (ANGPTL3), a critical lipid metabolism regulator, resulted in increased blood lipids and was elevated in NAFLD. Here, we developed a nanobody-heavy chain antibody (VHH-Fc) to inhibit ANGPTL3 for NAFLD treatment. Results In this study, we retrieved an anti-ANGPTL3 VHH and Fc fusion protein, C44-Fc, which exhibited high affinities to ANGPTL3 proteins and rescued ANGPLT3-mediated inhibition of lipoprotein lipase (LPL) activity. The C44-Fc bound a distinctive epitope within ANGPTL3 when compared with the approved evinacumab, and showed higher expression yield. Meanwhile, C44-Fc had significant reduction of the triglyceride (~ 44.2%), total cholesterol (~ 36.6%) and LDL-cholesterol (~ 54.4%) in hypercholesterolemic mice and ameliorated hepatic lipid accumulation and liver injury in NAFLD mice model. Conclusions We discovered a VHH-Fc fusion protein with high affinity to ANGPTL3, strong stability and also alleviated the progression of NAFLD, which might offer a promising therapy for NAFLD. Graphical Abstract

Melon (Cucumis melo L.) is an economically important crop in Xinjiang, China, but its production is constrained by the parasitic plant Phelipanche aegyptiaca that attaches to the roots of many crops and causes severe stunting and loss of yield. Rhizotron, pot, and field experiments were employed to evaluate the resistance of 27 melon cultivars to P. aegyptiaca. Then, the resistant and susceptible cultivars were inoculated with P. aegyptiaca from six populations to assess their resistance stability and broad spectrum. Further microscopic and histological analyses were used to clarify the resistance phenotypes and histological structure. The results showed that Huangpi 9818 and KR1326 were more resistant to P. aegyptiaca compared to other cultivars in the rhizotron, pot, and field experiments. In addition, compared to the susceptible cultivar K1076, Huangpi 9818 and KR1326 showed broad-spectrum resistance to six P. aegyptiaca populations. These two resistant cultivars had lower P. aegyptiaca biomass and fewer and smaller P. aegyptiaca attachments on their roots compared to susceptible cultivar K1076. KR1326 (resistant) and K1076 (susceptible) were selected to further study resistance phenotypes and mechanisms. Germination-inducing activity of root exudates and microscopic analysis showed that the resistance in KR1326 was not related to low induction of P. aegyptiaca germination. The tubercles of parasite on KR1326 were observed slightly brown at 14 days after inoculation (DAI), the necrosis and arrest of parasite development occurred at 23 DAI. Histological analysis of necrosis tubercles showed that the endophyte of parasite had reached host central cylinder, connected with host xylem, and accumulation of secretions and callose were detected in neighbouring cells. We concluded that KR1326 is an important melon cultivar for P. aegyptiaca resistance that could be used to expand the genetic basis of cultivated muskmelon for resistance to the parasite.

Tobacco target spot disease is caused by a ubiquitous soil-borne phytopathogen Rhizoctonia solani; the pathogenic mechanisms underlying the effects of R. solani remain unclear. Deeper understanding of the functional responses to R. solani during host plant infection would help identify the molecular mechanisms essential for successful host invasion. In this study, we performed global transcriptional analysis of R. solani during various stages (12, 24, 48, 72, 96, and 120 h) of tobacco infection via an RNA sequencing method, while utilizing the pathosystem model R. solani AG3–tobacco (Nicotiana tabacum L.). After R. solani inoculation, the number of differentially expressed genes of R. solani differed at the various time points. Moreover, several gene ontology and Kyoto encyclopedia of genes and genomes pathways were unique in different infection stages, especially with respect to the genes involved in plant cell wall degradation and catalysis of biotransformation reactions, such as the pectin metabolic process and pectin catabolic process. The overexpressing-PD8 N. benthamiana plants enhanced the susceptibility to R. solani. In addition, we found that large amounts of reactive oxygen species (ROS) were generated in tobacco after infected by R. solani. R. solani encoding FAD/NAD binding oxidoreductase and peroxidase gene family to eliminating ROS and counteract oxidative stress. Moreover, Perox3 was validated that can enhance the ability of scavenging ROS by co-injecting. Overall, our findings show that pectin-degrading enzymes and cytochrome P450 genes are critical for plant infection. These results provide comprehensive insights into R. solani AG3 transcriptome responses during tobacco invasion.

Silicosis is a diffuse fibrotic lung disease in which excessive inflammatory responses are triggered by silica exposure. Pyroptosis, a pro-inflammatory mode of programmed cell death, is mediated by gasdermin and may play a pivotal role in the development of silicosis. The caspase-1 inhibitor, VX-765, was used in vivo and in vitro to investigate the effects of silica-induced early inflammatory injury and later lung fibrosis. Our findings show that VX-765 reduces inflammatory lung injury by inhibiting silica-induced pyroptosis of alveolar macrophages in a silicosis mouse model. VX-765 limits the infiltration of inflammatory M1 alveolar macrophages, decreasing expression of inflammatory cytokines, including IL-1β, TNF-α, IL-6, CCL2, and CCL3, and down-regulating endogenous DAMPs and inflammatory immune-related cell pattern recognition receptors TLR4 and NLRP3. Furthermore, VX-765 alleviates fibrosis by down-regulating α-smooth muscle actin (α-SMA), collagen, and fibronectin. In this study, we illustrate that Alveolar macrophages pyroptosis occur in the early stages of silicosis, and VX-765 can alleviate the development of silicosis by inhibiting the pyroptosis signaling pathway. These results may provide new insight into the prevention and treatment of early-stage silicosis.

IntroductionThe pathogenic mechanisms of diabetic nephropathy (DN) include podocyte injury, inflammatory responses and metabolic disorders. Although the antagonism of Angiopoietin-like protein 3 (ANGPTL3) can alleviate proteinuria symptoms by inhibiting the activation of integrin αvβ3 on the surface of podocytes, it can not impede other pathological processes, such as inflammatory responses and metabolic dysfunction of glucolipid. Interleukin-22 (IL-22) is considered to be a pivotal molecule involved in suppressing inflammatory responses, initiating regenerative repair, and regulating glucolipid metabolism.MethodsGenes encoding the mIL22IgG2aFc and two chains of anti-ANGPTL3 antibody and bifunctional protein were synthesized. Then, the DN mice were treated with intraperitoneal injection of normal saline, anti-ANGPTL3 (20 mg/kg), mIL22Fc (12 mg/kg) or anti-ANGPTL3 /IL22 (25.3 mg/kg) and irrigation of positive drug losartan (20mg/kg/d) twice a week for 8 weeks.ResultsIn this research, a novel bifunctional fusion protein (anti-ANGPTL3/IL22) formed by the fusion of IL-22 with the C-terminus of anti-ANGPTL3 antibody exhibited favorable stability and maintained the biological activity of anti-ANGPTL3 and IL-22, respectively. The fusion protein showed a more pronounced attenuation of proteinuria and improved dysfunction of glucolipid metabolism compared with mIL22Fc or anti-ANGPTL3. Our results also indicated that anti-ANGPTL3/IL22 intervention significantly alleviated renal fibrosis via inhibiting the expression of the inflammatory response-related protein nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) p65 and NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Moreover, transcriptome analysis revealed the downregulation of signaling pathways associated with injury and dysfunction of the renal parenchymal cell indicating the possible protective mechanisms of anti-ANGPTL3/IL22 in DN.ConclusionCollectively, anti-ANGPTL3/IL22 bifunctional fusion protein can be a promising novel therapeutic strategy for DN by reducing podocyte injury, ameliorating inflammatory response, and enhancing renal tissue recovery.

Resistance to targeted drugs is now a challenging clinical problem in the treatment of non-small cell lung cancer (NSCLC). So far, there are no approved targeted therapeutic drugs for patients with disease progression after the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor osimertinib resistance (OR). Super-enhancers (SEs) are large clusters of transcriptional enhancers that drive gene expression. In this study, we aimed to explore the potential pathogenic SEs and their driven genes in OR NSCLC. OR cell line was established by exposure of H1975 cells to incremental dosing of osimertinib. RNA-sequencing and H3K27ac ChIP-sequencing were used to identify the differential expressed genes (DEGs) and SEs in parental and resistant cells. Gene ontology analysis for the OR-specific SEs-associated genes showed that histone citrullination, protein citrullination, and peptidyl-arginine modification are the top three biological processes, and the DEGs involved in these biological processes, including peptidyl arginine deiminase 1 (PADI1), PADI2, and PADI3. Realtime-PCR and western blot detections confirmed these genes were highly expressed in OR cells. SE inhibitor decreases their expression, ensuring that SEs regulate their transcriptional expressions. The PADI inhibitor inhibited OR cells’ proliferation, invasion, and colony formation. This study demonstrates that SE-driven PADI family genes are potential biomarkers and targets for OR NSCLC.

Abstract Background Ambrosia artemisiifolia and Ambrosia trifida are globally distributed harmful and invasive weeds. High density clusters play an important role in their invasion. For these two species, the early settled populations are distributed at low densities, but they can rapidly achieve high population densities in a short period of time. However, their response to intraspecific competition to improve the fitness for rapid growth and maintenance of high population densities remains unclear. Therefore, to determine how these species form and maintain high population densities, individual biomass allocations patterns between different population densities (low and high), and plasticity during seedling, vegetative, breeding and mature stages were compared. In 2019, we harvested seeds at different population densities and compared them, and in 2020, we compared the number of regenerated plants across the two population densities. Results Most biomass was invested in the stems of both species. Ambrosia trifida had the highest stem biomass distribution, of up to 78%, and the phenotypic plasticity of the stem was the highest. Path analysis demonstrated that at low-density, total biomass was the biggest contributor to seed production, but stem and leaf biomass was the biggest contributors to high-density populations. The number of seeds produced per plant was high in low-density populations, while the seed number per unit area was huge in high-density populations. In the second year, the number of low-density populations increased significantly. A. artemisiifolia and A. trifida accounted for 75.6% and 68.4% of the mature populations, respectively. Conclusions High input to the stem is an important means to regulate the growth of the two species to cope with different densities. These two species can ensure reproductive success and produce appropriate seed numbers. Therefore, they can maintain a stable population over time and quickly form cluster advantages. In the management, early detection of both species and prevention of successful reproduction by chemical and mechanical means are necessary to stop cluster formation and spread.

Abstract Background The coronavirus disease 2019 (COVID-19) has become a pandemic. Few studies have been conducted to investigate the spatio-temporal distribution of COVID-19 on nationwide city-level in China. Objective To analyze and visualize the spatiotemporal distribution characteristics and clustering pattern of COVID-19 cases from 362 cities of 31 provinces, municipalities and autonomous regions in mainland China. Methods A spatiotemporal statistical analysis of COVID-19 cases was carried out by collecting the confirmed COVID-19 cases in mainland China from January 10, 2020 to October 5, 2020. Methods including statistical charts, hotspot analysis, spatial autocorrelation, and Poisson space–time scan statistic were conducted. Results The high incidence stage of China’s COVID-19 epidemic was from January 17 to February 9, 2020 with daily increase rate greater than 7.5%. The hot spot analysis suggested that the cities including Wuhan, Huangshi, Ezhou, Xiaogan, Jingzhou, Huanggang, Xianning, and Xiantao, were the hot spots with statistical significance. Spatial autocorrelation analysis indicated a moderately correlated pattern of spatial clustering of COVID-19 cases across China in the early phase, with Moran’s I statistic reaching maximum value on January 31, at 0.235 (Z = 12.344, P = 0.001), but the spatial correlation gradually decreased later and showed a discrete trend to a random distribution. Considering both space and time, 19 statistically significant clusters were identified. 63.16% of the clusters occurred from January to February. Larger clusters were located in central and southern China. The most likely cluster (RR = 845.01, P

This study seeks to evaluate the effects of a reversal of sedentary lifestyles on the improvement of metabolic profiles in patients with NAFLD. The PubMed, Cochrane Library, Web of Science, and CNKI databases were searched up to May 15, 2021. Ten randomized controlled trials on changes in the sedentary lifestyle of patients with NAFLD were included in the analysis. Data from self-controlled case arms of randomized controlled trials investigating sedentary lifestyle alterations were extracted, and the effect size was reported as the MD and 95% CI. A total of 455 participants in 10 studies met the selection criteria. The results showed that changing a sedentary lifestyle can significantly improve ALT [MD = 4.35 (U/L), 95% CI: 0.53, 8.17], CHOL [MD = 0.31 (mmol/L), 95% CI: 0.19, 0.43], TG [MD = 0.22 (mmol/L), 95% CI: 0.10~0.34], LDL-C [MD = 0.30 (mmol/L), 95% CI: 0.02, 0.57], fasting blood glucose [MD = 0.17 (mmol/L), 95% CI: 0.03, 0.31], insulin [MD = 3.23 (pmol/L), 95% CI: 1.37~5.08], and HOMA-IR levels (MD = 0.39, 95% CI: 0.15, 0.63). Changing sedentary lifestyle can also significantly improve body mass index (BMI) [MD = 1.12 (kg/m 2 ), 95% CI: 0.66, 0.58], body fat (%) [MD = 0.34 (%), 95% CI: 0.13, 0.55] and VO 2peak levels [MD = −4.00 (mL/kg/min), 95% CI: −5.93, −2.06]. No differences in AST or GGT were noted before or after lifestyle changes. Altering a sedentary lifestyle to a lifestyle with regular exercise can slightly improve the levels of liver enzymes, blood lipids, blood glucose, insulin resistance, and body mass index in NAFLD patients.

Abstract Background The normalization of liver biochemical parameters usually reflects the histological response to treatment for nonalcoholic fatty liver disease (NAFLD). Researchers have not clearly determined whether different liver enzymes exhibit various metabolic changes during the follow-up period in patients with NAFLD. Methods We performed a retrospective analysis of patients with NAFLD who were receiving therapy from January 2011 to December 2019. Metabolism indexes, including glucose levels, lipid profiles, uric acid levels and liver biochemical parameters, were measured. Magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) and liver ultrasound were used to evaluate steatosis. All patients received recommendations for lifestyle modifications and guideline-recommended pharmacological treatments with indications for drug therapy for metabolic abnormalities. Results Overall, 1048 patients with NAFLD were included and received lifestyle modification recommendations and pharmaceutical interventions, including 637 (60.7%) patients with abnormal GGT levels and 767 (73.2%) patients with abnormal ALT levels. Patients with concurrent ALT and GGT abnormalities presented higher levels of metabolism indexes and higher liver fat content than those in patients with single or no abnormalities. After 12 months of follow-up, the cumulative normalization rate of GGT was considerably lower than that of ALT (38% vs. 62%, P

Background Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear. Methods Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Results There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals. Conclusion A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.

BackgroundFew studies focused on the general situation of telemedicine in China.ObjectivesThe purpose of this review is to investigate telemedicine in China, from the aspects of necessity, history, scale, and operation procedure, to improve the further development and implementation of telemedicine service.MethodsA literature search for peer-reviewed studies was conducted using the primary electronic databases. Additional documents from the official websites of Chinese government departments involved telemedicine was also collected. We extracted telemedicine related information focused on China from the final retrieved materials, and the general situation of telemedicine was drawn.ResultsIn China, telemedicine offers a feasible solution to the unequal allocation of healthcare resources, which makes telemedicine increasingly become an important alternative to close the gap between rural and urban in the capability and quality of medical services. China initiated telemedicine in the late 1980s. In 2018, China's telemedicine network has covered more than 3,000 hospitals across the country. As of 2019, almost all of the 31 provinces and municipalities in mainland have established regional telemedicine centers, and the market size of telemedicine reached about USD 2.68 billion. Based on the telemedicine network, remote rural patients can apply for healthcare services of top-tier urban hospitals through local county-level medical institutions.ConclusionsThrough improving the capacity, quality, and efficiency of healthcare in underserved areas, and reducing the unequal distribution of medical resources, telemedicine can help solve the problems of the difficulty and high cost to access to medical services in China.

Stipa purpurea (S. purpurea), a dominant herbage resource in alpine steppe, has an important impact on animal husbandry and the maintenance of natural environmental stability in the Tibetan Plateau (TP). As a hot spot of global warming, the TP has been greatly affected by climate change. Based on the MaxEnt model, we simulated the potential habitat changes of S. purpurea on the TP in the 21st century using 197 distribution records combined with current (2000–2018) and future (2021–2100) climate data. We also analyzed the critical factors influencing habitat distribution and driving habitat change. The results showed that the MaxEnt model performed well, with the area under the curve (AUC) value of training data and test data being 0.845 and 0.722, respectively. Annual precipitation, elevation, and annual average temperature were identified as the most critical environmental factors shaping the potential distribution of S. purpurea, and temperature was identified as the most critical factor driving S. purpurea habitat change. Under the current climate, the potential habitat area of S. purpurea was 55.15 × 104 km2, mainly distributed in the Eastern Qinghai-Qilian montane steppe, Southern Tibet montane shrub-steppe, and Ngari montane desert. By the end of the 21st century, the potential habitat area of S. purpurea showed an overall increasing trend, under two shared socio-economic pathways (SSP245 and SSP585) was 87.37 × 104 km2 and 57.80 × 104 km2, respectively. A comparison of warming scenarios indicated that warming had a positive effect on the distribution of S. purpurea within a certain temperature range, but continued warming would limit distribution ranges. In response to climate warming in the 21st century, potential habitats of S. purpurea will shift northwestward and to higher altitudes. These results will provide a reference for implementing long-term conservation and management strategies on the TP and similar regions.

CO2 injection technology into coal seams to enhance CH4 recovery (CO2-ECBM), therefore presenting the dual benefit of greenhouse gas emission reduction and clean fossil energy development. In order to gaze into the features of CO2 injection’s influence on reservoir pressure and permeability, the Thermal-Hydraulic-Mechanical coupling mechanism of CO2 injection into the coal seam is considered for investigation. The competitive adsorption, diffusion, and seepage flowing of CO2 and CH4 as well as the dynamic evolution of fracture porosity of coal seams are considered. Fluid physical parameters are obtained by the fitting equation using MATLAB to call EOS software Refprop. Based on the Canadian CO2-ECBM project CSEMP, the numerical simulation targeting shallow low-rank coal is carried out, and the finite element method is used in the software COMSOL Multiphysics. Firstly, the direct recovery (CBM) and CO2-ECBM are compared, and it is confirmed that the injection of CO2 has a significant improvement effect on methane production. Secondly, the influence of injection pressure and temperature is discussed. Increasing the injection pressure can increase the pressure difference in the reservoir in a short time, so as to improve the CH4 production and CO2 storage. However, the increase in gas injection pressure will also lead to the rapid attenuation of near-well reservoir permeability, resulting in the weakening of injection capacity. Also, when the injection temperature increases, the CO2 concentration is relatively reduced, and the replacement effect on CH4 is weakened, resulting in a slight decrease in CBM production and CO2 storage.

On the basis of the photoelectric properties and hydrophilicity and multimode interference of Graphene Oxide (GO), this study proposes an all-fiber humidity sensor. Two core-offset regions are constructed with a fiber fusion splicer, and a GO film is coated on a single-mode fiber (SMF) between the core-offset regions to form a humidity-sensitive Mach–Zehnder interference structure. As the external humidity environment changes, the refractive index of the GO changes, and the light in the SMF is modulated by humidity. External humidity is measured by detecting the changes in the wavelength of the transmission spectrum of the sensing structure. A saturated salt solution is used to build a stable humidity environment. The sensitivity of the sensor is 0.05 nm/% relative humidity (RH) at 35.3%–95.8% RH, and the linear relationship between the characteristic wavelength and RH is 88%. In addition, the linear relationship between the light intensity and the RH of the sensor at a single wavelength at 1571 nm is analyzed, and the linearity is 97.45%. According to this finding, photoelectric conversion is used to convert the light intensity signal into a voltage signal. The data are processed by a computer to achieve the real-time and visual monitoring of the humidity environment. The fiber optic humidity sensor proposed in this work has a simple structure, simple production, low cost, and high sensitivity. This work provides a new method for humidity sensing.

Abstract Doxorubicin (DOX) induced myocardial toxicity may limit its therapeutic use in clinic. Psoralen (PSO), a major active tricyclic furocoumarin extracted from Psoralea corylifolia, is widely used as an antineoplastic agent in treatment of leukemia and other cancers. This study is aim to find the protective effect of psoralen polymer lipid nanoparticles (PSO-PLN) on doxorubicin-induced myocardial toxicity in mice. The model of myocardial toxicity induced by DOX was established. The experiment was divided into 6 groups: normal saline group, DOX + Sulfotanshinone Sodium, DOX + PSO-PLN (3 mg/kg), DOX + PSO-PLN (6 mg/kg), DOX + PSO-PLN (9 mg/ kg), DOX group. DOX alone treated mice lead to a significant decrease in the body weight, heart weight, and increase in the serum levels of lactate dehydrogenase (LDH), creatine kinase (CK) and malondialdehyde (MDA) markers of cardiotoxicity. However, DOX reduced glutathione (GSH) content and activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX), were recovered by PSO-PLN. And PSO-PLN also decreased markers of cardiotoxicity in the serum. Western blotting data showed that the protective effects of PSO-PLN might be mediated via regulation of protein kinase A (PKA) and p38. Our study suggest that PSO-PLN possesses antioxidant activities, inactivating PKA and p38 effect, which in turn protect the heart from the DOX-induced cardiotoxicity.

Lipids and their metabolic enzymes are a critical point of regulation for the membrane curvature required to induce membrane fusion during synaptic vesicle recycling. One such enzyme is diacylglycerol kinase θ (DGKθ), which produces phosphatidic acid (PtdOH) that generates negative membrane curvature. Synapses lacking DGKθ have significantly slower rates of endocytosis, implicating DGKθ as an endocytic regulator. Importantly, DGKθ kinase activity is required for this function. However, protein regulators of DGKθ’s kinase activity in neurons have never been identified. In this study, we employed APEX2 proximity labeling and mass spectrometry to identify endogenous interactors of DGKθ in neurons and assayed their ability to modulate its kinase activity. Seven endogenous DGKθ interactors were identified and notably, synaptotagmin-1 (Syt1) increased DGKθ kinase activity 10-fold. This study is the first to validate endogenous DGKθ interactors at the mammalian synapse and suggests a coordinated role between DGKθ-produced PtdOH and Syt1 in synaptic vesicle recycling.

Chronic kidney injury has gradually become a worldwide public health problem currently affecting approximately 10% of the population and can eventually progress to chronic end-stage renal disease characteristic by the result of epithelial atrophy. Interleukin-22 (IL-22) is a cytokine produced by activated immune cells, while acting mainly on epithelial cells ranging from innate immune response to tissue regeneration to maintain barrier integrity and promote wound healing. Accumulating data suggests that IL-22 has emerged as a fundamental mediator of epithelial homeostasis in the kidney through promoting tissue repair and regeneration, inhibiting oxidative stress, and producing antimicrobial peptides. Binding of IL-22 to its transmembrane receptor complex triggers janus kinase/tyrosine kinase 2 phosphorylation, which further activates a number of downstream cascades, including signal transducer and activator of transcription 3, MAP kinase, and protein kinase B, and initiates a wide array of downstream effects. However, the activation of the IL-22 signaling pathways promotes the activation of complement systems and enhances the infiltration of chemokines, which does harm to the kidney and may finally result in chronic renal failure of different autoimmune kidney diseases, including lupus nephritis, and IgA nephropathy. This review describes current knowledge of the basic features of IL-22, including structure, cellular origin and associated signaling pathways. Also, we summarize the latest progress in understanding the physiological and pathological effects of IL-22 in the kidney, suggesting the potential strategies for the specific application of this cytokine in the treatment of kidney disease.

Abstract During pregnancy in humans, the physiology of the mother and foetus are finely regulated by many factors. Inappropriate regulation can result in pregnancy disorders, such as complications and foetal abnormalities. The early prediction or accurate diagnosis of related diseases is a concern of researchers. Liquid biopsy can be analysed for circulating cells, cell-free nucleic acids, and exosomes. Because exosomes can be detected in the peripheral blood of women in early pregnancy, these vesicles and their contents have become the focus of early prediction or diagnostic biomarker research on pregnancy complications and foetal developmental disorders. In this review, we focus on recent studies addressing the roles of peripheral blood exosomes and circulating miRNAs in pregnancy complications and in pregnancies with abnormal foetal developmental disorders, with particular attention paid to the potential application value of exosomes and circulating miRNAs as disease-specific biomarkers.

Background: The outbreak of novel coronavirus disease 2019 (COVID-19) has led to tremendous individuals visit medical institutions for healthcare services. Public gatherings and close contact in clinics and emergency departments may increase the exposure and cross-infection of COVID-19.Objectives: The purpose of this study was to develop and deploy an intelligent response system for COVID-19 voice consultation, to provide suggestions of response measures based on actual information of users, and screen COVID-19 suspected cases.Methods: Based on the requirements analysis of business, user, and function, the physical architecture, system architecture, and core algorithms are designed and implemented. The system operation process is designed according to guidance documents of the National Health Commission and the actual experience of prevention, diagnosis and treatment of COVID-19. Both qualitative (system construction) and quantitative (system application) data from the real-world healthcare service of the system were retrospectively collected and analyzed.Results: The system realizes the functions, such as remote deployment and operations, fast operation procedure adjustment, and multi-dimensional statistical report capability. The performance of the machine-learning model used to develop the system is better than others, with the lowest Character Error Rate (CER) 8.13%. As of September 24, 2020, the system has received 12,264 times incoming calls and provided a total of 11,788 COVID-19-related consultation services for the public. Approximately 85.2% of the users are from Henan Province and followed by Beijing (2.5%). Of all the incoming calls, China Mobile contributes the largest proportion (66%), while China Unicom and China Telecom are accounted for 23% and 11%. For the time that users access the system, there is a peak period in the morning (08:00–10:00) and afternoon (14:00–16:00), respectively.Conclusions: The intelligent response system has achieved appreciable practical implementation effects. Our findings reveal that the provision of inquiry services through an intelligent voice consultation system may play a role in optimizing the allocation of healthcare resources, improving the efficiency of medical services, saving medical expenses, and protecting vulnerable groups.

BackgroundProgressive overloads of intrahepatic triglycerides are related to metabolic dysregulation of multiple lipid and lipoprotein profiles, but whether similar dose effects are found in each subtype of metabolic associated fatty liver disease (MAFLD) remains unclear. We aimed to characterize the lipid profiles associated with liver fat content (LFC) in MAFLD patients who were overweight, lean/normal weight, or had diabetes.MethodsWe conducted a cross-sectional study enrolling 1,182 consecutive participants (144 non-MAFLD and 1,038 MAFLD) who underwent MRI proton density fat fraction measurement (MRI-PDFF) from 2011 to 2020. Lipid and apolipoprotein profiles, free fatty acid (FFA), liver and metabolism parameters, and anthropometric measurements were also assessed.ResultsMAFLD patients with type 2 diabetes or overweight/obesity had a higher proportion of abnormal lipid and lipoprotein profiles than those who were lean/normal weight. The degree of LFC had a positive correlation with total cholesterol, triglyceride, ApoB, and ApoE in patients with overweight/obesity and type 2 diabetes. In those with overweight/obesity, there were dose–response relationships between moderate-to-severe steatosis and total cholesterol, triglyceride, HDL-c, LDL-c, ApoB, ApoE, and Lp(a). A similar trend was observed for triglyceride in those with type 2 diabetes and for HDL-c in patients who were lean/normal weight (all p for trend