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Abstract Background In the treatment of ischemic cerebral stroke (ICS), most conventional treatments, including carotid endarterectomy and carotid artery stenting, may cause cerebral ischemia-reperfusion injury (CIRI). For treated ICS patients, changes in cerebral blood flow are directly related to brain function. At present, computed tomography perfusion, dynamic susceptibility contrast-enhanced perfusion weighted imaging and magnetic resonance arterial spin labeling perfusion imaging are used to monitor cerebral blood flow, but they still have some limitations. Our study aimed to monitor the changes in cerebral cortical blood flow by laser speckle contrast imaging (LSCI) in CIRI model mice and to propose a new method for predicting outcomes after CIRI. C57BL/6 N mice were used to establish a mouse CIRI model based on a modified thread-occlusion method and divided into a good outcome group and a poor outcome group according to survival within 7 days. The cerebral cortical blood flow of the area supplied by the left middle cerebral artery was monitored by LSCI at baseline (before modeling), 1 h after ischemia, immediately after reperfusion and 24 h after reperfusion. Then, the brains of the mice were removed immediately and stained with hematoxylin and eosin to observe the pathological changes in brain neurons. Results The cerebral cortical blood flow in the poor outcome group was obviously reduced compared with that less in the good outcome group at 24 h after reperfusion (180.8 ± 20.9 vs. 113.9 ± 6.4, p = 0.001), and at 24 h after reperfusion, the cerebral cortical blood flow was negatively correlated with the severity of brain tissue injury (p = − 0.710, p = 0.010). Conclusions LSCI can monitor the changes in cerebral cortical blood flow during CIRI in mice and could be used as a feasible method for predicting outcomes after CIRI in mice.

Synthetic mRNAs are rising rapidly as alternative therapeutic agents for delivery of proteins. However, the practical use of synthetic mRNAs has been restricted by their low cellular stability as well as poor protein production efficiency. The key roles of poly(A) tail on mRNA biology inspire us to explore the optimization of tail sequence to overcome the aforementioned limitations. Here, the systematic substitution of non-A nucleotides in the tails revealed that cytidine-containing tails can substantially enhance the protein production rate and duration of synthetic mRNAs both in vitro and in vivo. Such C-containing tails shield synthetic mRNAs from deadenylase CCR4-NOT transcription complex, as the catalytic CNOT proteins, especially CNOT6L and CNOT7, have lower efficiency in trimming of cytidine. Consistently, these enhancement effects of C-containing tails were observed on all synthetic mRNAs tested and were independent of transfection reagents and cell types. As the C-containing tails can be used along with other mRNA enhancement technologies to synergically boost protein production, we believe that these tails can be broadly used on synthetic mRNAs to directly promote their clinical applications.

Abstract Recent breakthroughs in the field of nanoparticle-based therapeutic delivery methods have changed the standpoint of cancer therapy by effectively delaying the process of disease development. Nanoparticles have a unique capacity of good penetrating ability than other therapeutic leads used in traditional therapeutics, and also, they have the highest impact on disease management. In the current study isolongifolene-loaded Chitosan nanoparticles have been formulated, synthesized and then characterized by the use of Fourier Transform Infrared Spectroscopy, X-ray Diffraction, Scanning Electron Microscopy and Transmission Electron Microscopy. Further, the characterized chitosan nano formulation was evaluated for hemocompatibility, plasma stability, and in-vitro release. Isolongifolene-loaded chitosan nanoparticles were found to be compatible with plasma and also, they exhibited a constant release pattern. Hence, chitosan-loaded nanoparticles could be employed as an excellent adjuvant in cancer therapeutic, to combat the multi-drug resistance in solid tumors.

The arc stability and droplet transfer phenomenon in welding process were analyzed with the help of a high-speed camera system, and the correlation mechanism was explored of arc voltage-arc physical phenomenon-weld morphology and microstructure-mechanical properties of joints in MIG welding of 4 mm-thick 304 stainless steel. The results show that when the voltage is 20.6 V, the welding arc heat distribution is uniform, and the droplet transfer form is a stable and continuous short-circuit transfer. The macroscopic shape of weld is good, and the microstructure is vermicular ferrite. The welded joint has high strength and plasticity. When the voltage drops to 16.6 V, the arc length becomes shorter, and the droplet has been short-circuited before it grows up. Heat conduction is slow, and undercut defects and grooves appear on the upper surface of weld. Part of lathy ferrite appears in the microstructure of weld. When the voltage increases to 24.6 V, the arc energy diverges severely, and the stability and continuity of droplet transfer decrease. Irregular fish scales appear on the surface of weld. Insufficient penetration appears on the back of weld. More lathy ferrite is formed in the lower layer of weld. When the voltage is lower and higher, the strength and plasticity of welded joint are reduced.

Abstract Background Induced hepatic stem cells (iHepSCs) with the capacities of self-renewal and bidifferentiation into hepatocytes and cholangiocytes were generated from mouse embryonic fibroblasts (MEFs) by lineage reprogramming in our previous research. However, the mechanism of iHepSC self-renewal has not been elucidated. Active demethylation regulated by Tet1 plays an important role in the self-renewal of stem cells, including pluripotent stem cells and adult stem cells. Here, we investigated the role and mechanism of Tet1-regulated demethylation in the self-renewal of iHepSCs. Methods The methylation levels and the expression of Tet1 in iHepSCs and MEFs were analyzed by immunofluorescent staining, quantitative reverse transcription PCR and western blotting. Then, the effects of Tet1 knockdown on the proliferation and self-renewal of iHepSCs were analyzed by CCK8, colony formation, and sphere formation assays. The mechanism by which Tet1 regulates the self-renewal of iHepSCs was investigated by chromatin immunoprecipitation, bisulfite sequence PCR, and methylation-sensitive restriction endonuclease-PCR. Results The high level of 5hmC and the low level of 5mC in iHepSCs were accompanied by high expression of Tet1. After Tet1 expression was knocked down by shRNA in iHepSCs, the proliferation and self-renewal capacities were inhibited, and the expression of Myc was also decreased. The higher expression level of Myc in iHepSCs maintained its self-renewal and was regulated by Tet1, which directly binds to CBS-1 and site A regions of the Myc promoter and demethylates the CpG cytosine. In addition, CTCF also binds to the CBS-1 and site A regions of the Myc promoter and regulates Myc expression along with TET1. Conclusion The self-renewal of iHepSCs was maintained by the higher expression of Myc, which was coregulated by TET1 and CTCF. This study may provide new insights into the self-renewal of stem cells, which can promote the research and application of ‘reprogrammed’ stem cells.

BackgroundNeuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative illness with characteristic brain magnetic resonance imaging (MRI) manifestations: diffuse symmetric white-matter hyperintensities in lateral cerebral ventricle areas in fluid-attenuated inversion recovery (FLAIR) and high-intensity signals along the corticomedullary junction of the frontal–parietal–temporal lobes in diffusion weighted imaging (DWI). Here, we report a case of adult-onset NIID who was misdiagnosed with Susac syndrome (SS) due to unusual corpus callosum imaging findings.Case presentationA 39-year-old man presented with chronic headache, blurred vision, tinnitus, and numbness in the hands as initial symptoms, accompanied by cognitive slowing and decreased memory. Brain MRI revealed round hypointense lesions on T1-weighted imaging (T1WI) and hyperintense lesions on T2WI/FLAIR/DWI in the genu and splenium of the corpus callosum. An initial diagnosis of SS was made based on the presence of the SS-typical symptoms and SS-characteristic radiology changes. Furthermore, the patient’s symptoms improved upon completion of a combined pharmacotherapy plan. However, no significant changes were evident 18 months after the brain MRI scan. Eventually, the patient was then diagnosed with NIID based on a skin biopsy and detection of expanded GGC (guanine, guanine, cytosine) repeats in the NOTCH2NLC gene.ConclusionThe present NIID case in which there was simultaneous onset of altered nervous and visual system functioning and atypical imaging findings, the atypical imaging findings may reflect an initial change of NIID leukoencephalopathy.

Perfluorooctanoic acid (PFOA), a typical perfluoroalkyl group compound, has received worldwide attention due to its significant environmental toxicity. Following regulatory bans on the production and emission of PFOA, concerns have been raised about the potential health risks and the safety of novel perfluoroalkyl analogues. HFPO-DA (trade name Gen-X) and HFPO-TA are two perfluoroalkyl analogues known to be bioaccumulative, whose level of toxicity and whether they are safe alternatives to PFOA remain unclear. In the following study, the physiological and metabolic effects of exposure to PFOA and its novel analogues were explored in zebrafish using 1/3 LC50 (PFOA 100 μM, Gen-X 200 μM, HFPO-TA 30 μM). At the same LC50 toxicological effect, exposure to PFOA and HFPO-TA resulted in abnormal phenotypes such as spinal curvature, pericardial edema and aberrant body length, while Gen-X was little changed. Metabolically, PFOA, HFPO-TA and Gen-X all significantly increased total cholesterol in exposed zebrafish with PFOA and HFPO-TA also increasing total triglyceride levels. Transcriptome analysis showed that the number of differentially expressed genes in PFOA, Gen-X, and HFPO-TA treated conditions compared to control groups were 527, 572, and 3, 933, respectively. KEGG and GO analysis of differentially expressed genes revealed pathways and functions related to lipid metabolism as well as significant activation of the peroxisome proliferators-activated receptor (PPARs) pathway. Furthermore, RT-qPCR analysis identified significant dysregulation in the downstream target genes of PPARα, which is responsible for lipid oxidative catabolism, and the SREBP pathway, which is responsible for lipid synthesis. In conclusion, both perfluoroalkyl analogues HFPO-TA and Gen-X exhibit significant physiological and metabolic toxicity to aquatic organisms and their environmental accumulation should be closely regulated.

CH4 is one of the most important greenhouse gases responsible for climate change. The effect of algal decomposition on CH4 emission fluxes in aquaculture environments is unknown. This study determined the relative abundance of methanogens in aquaculture in northern China. We determined various parameters in the water and sediment after the decomposition of Chaetomorpha valida. The results showed that the relative abundance of methanogens increased significantly during the decomposition of C. valida. The average CH4 emission flux was 50.64 mg m-2 h-1 when the density of C. valida was 25 mg cm-3, which was 11 times higher than that at a density of 0 mg cm-3. The concentrations of dissolved oxygen (DO), nitrite, nitrate and sulfate in the aquaculture pond significantly decreased during the decomposition of C. valida. The formation of a strong anaerobic reduction environment promoted the formation and release of CH4. Our results confirmed that the decomposition of C. valida enhanced the CH4 emission flux. The average CH4 emission fluxes ranged from 4.62 to 50.64 mg m-2 h-1. It is particularly important to remove decomposed algae in a timely manner and control greenhouse gas emissions from aquaculture ponds to mitigate climate change.

Background: This study explored the specific relationship between different lipid indicators and cognitive impairment and aimed to provide a reference for implementing targeted lipid regulation measures to prevent and alleviate cognitive impairment. Methods: We searched three databases (PubMed, Embase, and Web of Science) for literature related to hyperlipidaemia, lipid levels, and cognitive impairment, and used the Newcastle-Ottawa Scale to evaluate the quality of the identified literature. A meta-analysis was performed using RevMan 5.4, and the combined effect size ratio using a random-effects model (odds ratio [OR] and 95% confidence interval [CI]) was used to evaluate the association between dyslipidaemia and cognitive impairment. Results: Among initially identified 2247 papers, we ultimately included 18 studies involving a total of 758,074 patients. The results of the meta-analysis revealed that patients with hyperlipidaemia had a 1.23-fold higher risk of cognitive impairment than those with normal lipid levels (OR = 1.23, 95% CI: 1.04–1.47, p = 0.02). Further subgroup analysis showed that elevated total cholesterol (TC) levels increased the risk of cognitive impairment by 1.59-fold (OR = 1.59, 95% CI: 1.27–2.01, p < 0.0001) and were more significant in older or male patients. Moreover, elevated triglyceride levels were inversely correlated with cognitive disorders, whereas elevated low-density lipoprotein cholesterol levels were unrelated to cognitive impairment risk. Conclusions: Dyslipidaemia was strongly associated with cognitive impairment, and elevated TC levels were a risk factor for cognitive impairment. Furthermore, the damaging effects of elevated TC levels on cognition were more pronounced in older and male populations.

Background: Microcirculatory variations have been observed in the normal-appearing white matter (NAWM) of individuals affected by cerebral small vessel disease (CSVD). These variations collectively possess the potential to trigger neuroinflammation and edema, ultimately leading to an elevation in extracellular fluid (ECF). Nevertheless, the specific alterations in ECF within the NAWM of CSVD patients have remained inadequately understood. Methods: We reviewed the clinical and imaging characteristics of a cohort comprising 129 patients diagnosed with CSVD to investigate alterations in the ECF within NAWM. The severity of CSVD was assessed by total CSVD magnetic resonance (MR) score according to the four imaging markers, namely perivascular space, lacunar infarction, white matter hyperintensities and cerebral microbleed. ECF was evaluated by the parameter free water (FW), ranging from 0 to 1 generated from diffusion tensor imaging. Results: Significant differences in NAWM FW were observed in relation to the total CSVD MR score (p < 0.05). Patients with a total CSVD MR score of 0 exhibited significantly lower NAWM free water (FW) values compared to those with a score greater than 0 (p < 0.05). Similarly, patients with a total CSVD MR score of 1 also demonstrated notably lower NAWM FW values than those with a score greater than 1 (p < 0.05). After conducting multivariate regression analysis, age and total CSVD MR score was independently associated with FW in NAWM (p < 0.001). Further, the total CSVD MR score served as a partial mediator in the relationship between age and FW in the NAWM among patients with CSVD. Conclusions: ECF in NAWM is increased in CSVD patients, even during the early course of CSVD.

Male gametophyte development in plants relies on the functions of numerous genes, whose expression is regulated by transcription factors (TFs), non-coding RNAs, hormones, and diverse environmental stresses. Several excellent reviews are available that address the genes and enzymes associated with male gametophyte development, especially pollen wall formation. Growing evidence from genetic studies, transcriptome analysis, and gene-by-gene studies suggests that TFs coordinate with epigenetic machinery to regulate the expression of these genes and enzymes for the sequential male gametophyte development. However, very little summarization has been performed to comprehensively review their intricate regulatory roles and discuss their downstream targets and upstream regulators in this unique process. In the present review, we highlight the research progress on the regulatory roles of TF families in the male gametophyte development of flowering plants. The transcriptional regulation, epigenetic control, and other regulators of TFs involved in male gametophyte development are also addressed.

The cultivation of strawberries in controlled environments presents challenges related to environmental stressors, especially insufficient light. Melatonin, as a widely investigated plant growth regulator, was considered as a potential candidate to mitigate damage, and enhance photosynthesis stability. However, whether melatonin can improve photosynthesis under light deficiency in woodland strawberry (Fragaria vesca) remains elusive. In this study, we evaluated gas exchange parameters, Chlorophyll fluorescence parameters, photochemical efficiency, and the related genes’ expression levels to decipher the multifaceted impact of melatonin on photosynthesis. We found concentration-dependent effects of melatonin on photosynthetic parameters, with potential benefits at lower concentration and inhibitory effects at higher concentration. Notably, melatonin increased non-photochemical quenching (NPQ), a mechanism for dissipating excess light energy, while leaving photochemical quenching (qP) relatively stable. Further analysis showed that melatonin up-regulated key xanthophyll cycle-related genes (DHAR, VDE, and PsbS), indicating its involvement in energy dissipation processes. In conclusion, our study uncovered the dual and complex role of melatonin in the short-term response of photosynthesis in woodland strawberries under low-light conditions.

Using sewage sludge to produce biochar-based adsorbents to remove phosphate (P) from water can be a sustainable and cost-effective method of waste management. However, the adsorption efficiency of sewage sludge biochar is not high. In this study, lanthanum-modified sludge-based biochar (La-SBBC) was synthesized by combining lanthanum nitrate with dewatered sludge. La-SBBC exhibited the highest removal efficiency of 99.06% for an initial P concentration of 15 mg/L at pH 3.0 with a dosage of 1.3 g/L. The maximum adsorption capacity of La-SBBC for P was 152.77 mg/g at 35 °C. The adsorption process followed the pseudo-second-order kinetic model (R2 ≥ 0.973) and the Freundlich isothermal adsorption model (R2 ≥ 0.928). Multilayer chemisorption was identified as the controlling process. The primary mechanisms of P adsorption by La-SBBC involved electrostatic interactions, precipitation, and inner sphere complexation. Thermodynamic analysis revealed that the adsorption process of La-SBBC was a spontaneous endothermic reaction. The fixed-bed experiment demonstrated that La-SBBC had significant practical utility. La-SBBC maintained 76.6% of the original P removal efficiency after six cycles. Therefore, La-SBBC can be used as a promising adsorbent for P in practical applications.

Background: Based on susceptibility-weighted imaging (SWI) visibility, deep medullary vein (DMV) scores are related to white matter damage (WMD) in patients with cerebral small vessel disease (CSVD). However, whether mechanisms are associated with DMV changes is unclear. We examined extracellular fluid (ECF) roles in white matter associations between DMV scores and white matter integrity (WMI) in patients with CSVD. Methods: We examined magnetic resonance imaging (MRI) and clinical data from 140 patients with CSVD. DMV scores (0–18) were assigned on SWI according to DMV anatomic regions and signal continuity/visibility. WMI and ECF volumes were evaluated using free water (FW) and fractional anisotropy (FA) values by diffusion tensor imaging (DTI). Results: DMV scores were independently associated with FA after adjusting for vascular risk factors, age, white matter hyperintensity (WMH) volume, and CSVD burden [β (95% confidence interval (CI)): –0.219 (–0.375, –0.061), p = 0.006]. We also observed a significant indirect effect of DMV scores on FA in white matter (mediated by FW in white matter) after controlling for age, vascular risk factors, WMH volume, and CSVD burden. Conclusions: DMV scores were independently related to WMI and mediated by ECF in the white matter of patients with CSVD.

Objective: To solve the problem of sour taste in raw chestnut rose juice, and to develop its blended fruit-vegetable juice with good taste quality, sweet and sour taste and high stability. Methods: The raw chestnut rose juice was first deastringented with gelatin adsorption or β-cyclodextrin embedding, and then it was blended with freshly prepared pear juice and pumpkin pulp, finally the pasteurization parameters of blended fruit-vegetable juice were optimized. Results: By adding 0.5% gelatin, the tannin removal rate of raw chestnut rose juice could reach 63.00%. According to the sensory evaluation results and basic physical and chemical indexes, the optimal ratio of compound fruit and vegetable juice was determined as follows: The volume ratio of golden thorn pear juice:pear juice:pumpkin pulp was 34:40:26. As the blended fruit-vegetable juice was subjected to pasteurization at 85 °C for 3 min, total viable bacteria of it was1.38 lg CFU/mL, and the counts of yeasts and molds were under the detect limitation (

The thickness of Quaternary loose sediments in the city of Bayannur in the west of Inner Mongolia Autonomous Region is large, which provides basic conditions for the development of land subsidence. ALOS PALSAR (98 frames from 2007 to 2011) and RADARSAT-2 (10 frames from 2015 to 2016) are extracted to quantitatively analyze the land subsidence in the city of Bayannur, respectively, by using the PS-InSAR and SBAS-InSAR method for the first time, and field investigation is carried out to verify the reliability of InSAR monitoring results. The causes and development trend of land subsidence in this area are further analyzed, and important technical support for land subsidence disaster prevention and reduction are provided. The results indicate that (1) the land subsidence in the city of Bayannur exhibites a slow trend. The severity of subsidence is low and belongs to the stage of occurrence. (2) The subsidence rate was mainly concentrated in 0−10 mm/a from 2007 to 2011, and three concentrated land subsidence areas were observed: the Hanggin Rear Banner subsidence area (A), Linhe district subsidence area (B), and the water source area of development zone subsidence area (C). (3) From 2015 to 2016, the subsidence rate was mainly concentrated in 0−2.6 mm/a, and one concentrated land subsidence area was detected, that is, the Linhe district and north subsidence area (D)，where the land subsidence is based on the Linhe district subsidence area (B), and continues to expand to the surrounding areas and the north. (4) The main influencing factor of land subsidence in the city of Bayannur is the groundwater level drop caused by the development and utilization of groundwater. Besides, the consolidation and compaction of the sediments is also an essential factor for the land subsidence in this area, and the increase in surface load has a certain promoting effect on the land subsidence.

Introduction Intensive lifestyle intervention (ILI) has significantly reduced incidence of diabetes and improved many cardiovascular disease risk factors. We evaluated long-term effects of ILI on cardiometabolic risk factors, and microvascular and macrovascular complications among patients with diabetes in real-world clinical practice.Research design and methods We evaluated 129 patients with diabetes and obesity enrolled in a 12-week translational model of ILI. At 1 year, we divided participants into group A, who maintained

BackgroundRenal involvement is rarely reported in juvenile dermatomyositis and may be caused by the toxic effects of myoglobinuria or an autoimmune reaction. We report a case of dermatomyositis and nephrotic syndrome in a child to explore the association between juvenile dermatomyositis and renal involvement.Case presentationAn 8-year-old girl with skin rash, edema, proximal muscle weakness predominantly involving the lower extremities, low-grade fever, and foamy urine was admitted to our hospital. Her laboratory tests met the criteria of nephrotic syndrome. She had elevated creatine kinase and lactate dehydrogenase and was diagnosed with juvenile dermatomyositis after electromyography and muscle MRI. Anti-NXP2 antibodies were positive. Her proteinuria was relieved soon after treatment with prednisone and methotrexate, but her muscle strength progressively decreased. The disease was relieved after pulse methylprednisolone treatment and mycophenolate mofetil, but recurred after drug reduction with mild proteinuria. Adalimumab was used for treatment and helped reduce the doses of glucocorticoid and mycophenolate mofetil.ConclusionJuvenile dermatomyositis may be one of the rare causes of nephrotic syndrome. The mechanism involved in JDM combined with renal injury may be multifactorial. Autoantibodies may play important roles in both muscle and renal damage.

Renal cell carcinoma (RCC) is the most frequent renal malignancy in the world, and its incidence is increasing year by year. RCC is a well-known drug resistant tumor, and the treatment methods are limited. Most patients with RCC are discovered at the advanced stage, and thus have poor prognosis even after treatment. Therefore, it is very urgent to find new markers for the diagnosis and treatment of RCC. Accumulating evidence shows that lncRNAs participate in the occurrence and progression of RCC, which is achieved by the lncRNA-miRNA-mRNA axis. It is widely known that metabolic defect is an essential pathogenesis in RCC. As is the case with other tumors, RCC can satisfy the demands of cancerous cells for uncontrolled proliferation through aerobic glycolysis. However, whether lncRNAs can modulate RCC progression through metabolic pathway is still not clarified. Taken together, this review mainly summarized the metabolic regulatory mechanisms of lncRNAs in RCC progression, especially their roles in glucose metabolism, lipid metabolism, amino acid metabolism and mitochondrial dynamics, as well as the clinical applications of lncRNAs via targeting metabolism in RCC therapy. It will provide the new targets and approaches for early clinical diagnosis, treatment and prognosis of RCC.

Soil salinization has become a major environmental factor severely threatening global food security. The application of porous minerals could significantly ameliorate soil fertility and promote plant productivity under salt stress conditions. However, the effects of porous minerals on improving the salt resistance of grain crops in coastal saline soils is not fully studied. In this work, the shoot growth and grain yield of wheat plants grown in coastal saline fields, respectively amended with the four naturally available porous minerals, diatomite, montmorillonite, bentonite and zeolite, were assessed. The application of porous minerals, especially zeolite, significantly improved the biomass and grain yield of wheat plants under saline conditions, as demonstrated by the augmented plant fresh mass (14.8~61.2%) and increased seed size (3.8~58.8%) and number (1.4~57.5%). Soil property analyses exhibited that porous-mineral amendment decreased soil sodium content and sodium absorption ratio, and increased soil nutrients in both the rhizosphere and nonrhizosphere of wheat plants. Further quantitative-PCR and 16S high-throughput sequencing analysis revealed that porous-mineral application also remarkably increased the abundance of bacterial 16S rRNA (0.8~102.4%) and fungal 18S rRNA (89.2~209.6%), and altered the composition of the soil microbial community in the rhizosphere of wheat. Our findings suggest that zeolite could be used as an ideal salt soil amendment, and the changes in soil properties and microorganisms caused by the application of porous minerals like zeolite improved the salt resistance of wheat plants in coastal saline land, leading to increased shoot growth and seed production.

Background and objective Dabrafenib+Trametinib/Dabrafenib targeted therapy has been approved for V-RAF murine sarcoma viral oncogene homolog B1 with amino acid substitution for valine at position 600 (BRAF V600E) in lung cancer patients, however, the targeted therapy strategy for lung cancer patients with BRAF non-V600E mutations has not been determined yet. This study intends to explore the efficacy of targeted therapy for BRAF non-V600E mutant lung cancer, and provide a reference for clinical treatment. Methods Computer search of PubMed, Cochrane Library, Embase, Web of Science, Clinicaltrials.gov, CBM, CNKI, Wanfang database. Collect the relevant literature relevant on the targeted therapy of BRAF non-V600E mutant lung cancer, and conduct a descriptive analysis of the included literature. Results There were 10 articles that met the inclusion criteria, including 3 cohort studies and 7 case reports. 18 patients with BRAF non-V600E mutant lung cancer were ineffective to vermurafenib; 1 patient obtained partial response (PR) after applying vermurafenib, 5 patients did not respond to BRAF inhibitors; 9 patients showed a potential clinical benefit rate of 34% after monotherapy with trametinib; 7 patients have different degrees of benefit from dabrafenib and trametinib on progression-free survival (PFS); 1 patient is effective to sorafenib. Conclusion At present, there is no standard treatment specification for BRAF non-V600E mutation targeted therapy. The challenge lies in the heterogeneous mutation of BRAF gene. Different mutation types respond differently to targeted therapy. In addtion, real-world research evidence is scarce, so it is necessary to carry out further large-sample high-quality research to provide reference for clinical practice.

Aiming at the problems of low accuracy of current detection methods and poor generalization of model, a honeypot contract detection method based on KOLSTM deep learning model was proposed.Firstly, by analyzing the characteristics of honeypot contract, the concept of key opcode was proposed, and a keyword extraction method which could be used to select the key opcode in smart contract was designed.Secondly, by adding the key opcode weight mechanism to the traditional LSTM model, a KOLSTM model which could simultaneously capture the sequence features and key opcode features hidden in the honeypot contract was constructed.Finally, the experimental results show that the model had a high recognition accuracy.Compared with the existing methods, the F-score is improved by 2.39% and 19.54% respectively in the two classification and multi-classification detection scenes.

The present study aimed to investigate the effects of octenyl succinic anhydride modified starch (OSAS) on soy protein (SP)-(-)-epigallocatechin-3-gallate (EGCG) binary covalently linked complexes. Mean diameters of OSAS-SP-EGCG complexes decreased from 379.6 ± 54.9 nm to 272.7 ± 47.7 nm as the OSAS-to-SP-EGCG ratio changed from 1:2 to 4:1, while ζ-potential decreased from -19.1 ± 0.8 mV to -13.7 ± 1.2 mV. Fourier transform infrared spectroscopy results revealed that the characteristic peaks at 1725 cm–1 and 1569 cm–1 for OSAS disappeared in the OSAS-SP-EGCG complexes, indicating an interaction between OSAS and SP-EGCG complexes. X-ray diffraction analysis showed that with the increase of OSAS content, the diffraction peak at approximately 8.0° decreased from 8.22° to 7.74°, implying that the structures of OSAS and SP-EGCG complexes were rearranged after forming into OSAS-SP-EGCG complexes. The contact angle of the OSAS-SP-EGCG complexes significantly increased from 59.1° to 72.1° with the addition of OSAS increased, revealing that the addition of OSAS improved hydrophobicity of the SP-EGCG complexes. Transmission electron microscopy images revealed that the individual OSAS-SP-EGCG complexes became smaller but stuck together to form large fragments, which was different from the morphology of OSAS and SP-EGCG complexes. Thus, the OSAS-SP-EGCG complexes developed in this study may be effective emulsifiers for improving the stability of emulsion systems in the food industry.

The frequent invasion of organisms poses a serious threat to biodiversity, ecosystem service functions, and economic development. Invasions from terrestrial systems have been well studied, but invasions from marine systems still lack a literature review, especially for invasive algae. With the frequent invasion of non-native algae, marine biodiversity and its sustainable use are threatened, and thus, the in-depth investigation of the biological mechanisms and ecological impacts of invasive alien marine algae has become particularly important. Here, we conducted a literature review of a series of studies that were undertaken by identified experts on algae invasions, including information on the classification of invasive algae in the ecosystem, mechanisms of invasion success (including the invader’s biological traits, interactions with native species, and adaptive evolution), and the impact on the native community and environment of the invaded area. In addition, we put forward suggestions for relevant research on invasive algae to overcome the current obstacles and provide references for future research on invasive marine algae. This review could be used to inform biological regulations and provides a scientific basis for the protection of marine biodiversity, sustainable environmental development, and the restoration of blue carbon ecosystems.

The aim of this study is to analyze the distribution characteristics of specific allergens based on the immunoglobulin E (IgE) test, performed using the sera of patients with allergic diseases in the Shanxi region of China. Sera from 3141 patients with allergic diseases were analyzed with immunoblotting for IgE antibodies specific to inhaled and ingested allergens. The distribution of allergens and association with factors such as disease profile, sex, age, and cosensitization of the patients who tested positive were analyzed. The most common positive rate of IgE specific to inhaled allergens was mugwort, followed by dust mite mix and common ragweed. The most common positive rate of IgE specific to ingested allergens was crab, followed by egg white and sea fish mix. When analyzed according to disease profile, mugwort was the most common allergen in asthma, rhinitis, and asthma combined with rhinitis. When analyzed by season, the allergens with the highest positive rates included tree mix (willow/poplar/elm), common ragweed, mugwort, and hop pollen from July through September. When analyzed by age, the allergens with the highest positive rates were tree mix, common ragweed, hop, house dust, cow’s milk, mutton/lamb, and peanut in participants aged 0–18 years and egg white in those aged ≥60 years. The radar charts showed cosensitization to multiple allergens. In the Shanxi region, the primary inhaled allergens were mugwort, dust mite mix (1: house dust mite/dust mite), and common ragweed. The primary ingested allergens were crab, egg white, and sea fish mix. There were differences in the positive rates of the allergens between genders, age groups, and seasons, and multiple allergens can cosensitize patients.

Background: Inherited kidney diseases (IKDs) are a group of kidney diseases characterized by abnormal kidney structure or function caused by genetic factors, but they are not easily diagnosed in childhood due to either nonspecific symptoms and signs or clinically silent symptoms in the early stages until the progressive stages, even end-stages. Early diagnosis of IKDs is very urgent for timely treatment and improving outcomes of patients. So far, the etiological diagnosis has been accelerated with the advance of clinical genetic technology, particularly the advent of next-generation sequencing (NGS) that is not only a powerful tool for prompt and accurate diagnosis of IKDs but also gives therapy guidance to decrease the risk of unnecessary and harmful interventions.Methods: The patients presenting with urinalysis abnormalities or structural abnormalities from 149 Chinese families were enrolled in this study. The clinical features of the patients were collected, and the potentially causative gene variants were detected using exome sequencing. The clinical diagnostic utility of the genetic testing was assessed after more detailed clinical data were analyzed.Result: In total, 55 patients identified having causative variants by exome sequencing were genetically diagnosed, encompassing 16 (29.1%) autosomal dominant IKDs, 16 (29.1%) autosomal recessive IKDs, and 23 (41.8%) X-linked IKDs, with 25 unreported and 45 reported variants. The diagnostic yield was 36.9%. The utility of the exome sequencing was accessed, 12 patients (21.8%) were confirmed to have suspected IKDs, 26 patients (47.3%) discerned the specific sub-types of clinical category, and 17 patients (30.9%) with unknown etiology or lack of typical manifestations were reclassified.Conclusion: Our study supported that genetic testing plays a crucial role in the early diagnosis for children with IKDs, which affected follow-up treatment and prognostic assessment in clinical practice. Moreover, the variant spectrum associated with IKDs was expanded.

Nafion by-product 2 (Nafion BP2), an emerging fluorinated sulfonic acid commonly used in polymer electrolyte membrane technologies, has been detected in various environmental and human matrices. To date, however, few studies have explored its toxicity. In this study, zebrafish embryos were exposed to Nafion BP2 at concentrations of 20, 40, 60, 80, 100, 120, 140, and 160 mg/L from fertilization to 120 post-fertilization (hpf), and multiple developmental parameters (survival rate, hatching rate, and malformation rate) were then determined. Results showed that Nafion BP2 exposure led to a significant decrease in survival and hatching rates and an increase in malformations. The half maximal effective concentration (EC50) of Nafion BP2 for malformation at 120 hpf was 55 mg/L, which is higher than the globally important contaminant perfluorooctane sulfonate (PFOS, 6 mg/L). Furthermore, exposure to Nafion BP2 resulted in additional types of malformations compared to PFOS exposure. Pathologically, Nafion BP2 caused abnormal early foregut development, with exfoliation of intestinal mucosa, damage to lamina propria, and aberrant proliferation of lamina propria cells. Nitric oxide content also decreased markedly. In addition, embryos showed an inflammatory response following Nafion BP2 exposure, with significantly increased levels of pro-inflammatory factors C4 and IL-6. Acidic mucin in the hindgut increased more than two-fold. 16 S rRNA sequencing revealed a marked increase in the pathogen Pseudomonas otitidis. Furthermore, pathways involved in intestinal protein digestion and absorption, inflammatory response, and immune response were significantly altered. Our findings suggest that the intestine is a crucial toxicity target of Nafion BP2 in zebrafish, thus highlighting the need to evaluate its health risks.

Abstract With the proliferation of smartphones and an increasing number of services provisioned by clouds, mobile edge computing (MEC) is emerging as a complementary technology of cloud computing. It could provide cloud resources and services by local mobile edge servers, which are normally nearby users. However, a significant challenge is aroused in MEC because of the mobility of users. User trajectory prediction technologies could be used to cope with this issue, which has already played important roles in service recommendation systems with MEC. Unfortunately, little attention and work have been given in service recommendation systems considering users mobility. Thus, in this paper, we propose a mobility-aware personalized service recommendation (MPSR) approach based on user trajectory and quality of service (QoS) predictions. In the proposed method, users trajectory is firstly discovered by a hybrid long-short memory network. Then, given users trajectories, service QoS is predicted, considering the similarity of different users and different edge servers. Finally, services are recommended by a center trajectory strategy through MPSR. Experimental results on a real dataset show that our proposed approach can outperform the traditional recommendation approaches in terms of accuracy in mobile edge computing.

The diversity and community structure of rhizospheric microbes are largely affected by soil physicochemical properties and plant species. In this work, high throughput sequencing and quantitative real-time PCR targeting nifH gene were used to assess the abundance and diversity of diazotrophic community in the coastal saline soils of Yellow River Delta (YRD). We demonstrated that the copy number of nifH gene encoding the Fe protein subunit of the nitrogenase in the nitrogen fixation process was significantly affected by soil physiochemical factors, and the abundance of diazotrophs in the rhizospheric soil samples collected from different locations was positively related with soil physicochemical properties. Soil salinity (P=0.003) and moisture (P=0.003) were significantly co-varied with the OTU-based community composition of diazotrophs. Taxonomic analysis showed that most diazotrophs belonged to the Alphaproteobacteria, Gammaproteobacteria and Deltaproteobacteria. Linear discriminant analysis (LDA) effect size (LEfSe) and canonical correspondence analysis (CCA) showed that diazotrophic community structure significantly varied with soil salinity, moisture, pH and total nitrogen, carbon, sulphur and nitrite (NO2–N) content. Our findings provide direct evidence toward the understanding of different effects of soil physicochemical properties and host plant traits such as halophytes types, life span and cotyledon type, on the community composition of diazotrophic populations in the rhizosphere of plants grown in coastal saline soils.

BackgroundThe prominent veins sign (PVS) on susceptibility-weighted imaging (SWI) has been suggested to be related to the prognosis of patients with acute ischemic stroke (AIS). This meta-analysis aims to clarify the association between PVS and the prognosis of patients with AIS.MethodsThis meta-analysis was registered in PROSPERO (no. CRD42022343795). We performed systematic research in PubMed, Web of Science, EMBASE, and Cochrane Library databases for studies investigating the prognostic value of PVS. Based on the enrolled studies, patients were divided into two groups as follows: those with PVS cohort and those without PVS cohort. Outcomes were unfavorable functional outcome, early neurological deterioration (END), and hemorrhagic transformation (HT). The random-effects models were used for the meta-analytical pooled. Heterogeneity was estimated using Cochran's Q-test and I2 value. Subgroup and sensitivity analyses were also performed to explore the potential sources of heterogeneity. Publication bias was assessed with funnel plots and using Begger's and Egger's tests.ResultsA total of 19 studies with 1,867 patients were included. PVS was correlated with an unfavorable functional outcome in patients with AIS (risk ratio [RR] 1.61, 95% CI 1.28–2.02), especially in those receiving recanalization therapy (RR 2.00, 95% CI 1.52–2.63), but not in those treated conservatively (RR 1.33, 95% CI 0.87–2.04). Moreover, PVS was related to END (RR 2.77, 95% CI 2.21–3.46), while without an increased risk of HT (RR 0.97, 95% CI 0.64–1.47).ConclusionPVS was associated with an unfavorable prognosis of patients with AIS and increased the risk of END, while not correlated with an increased risk of HT. PVS might be useful for predicting functional outcomes of patients with AIS as a novel imaging maker.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022343795.

Abstract Background This study aimed to investigate the effects of STOML2 and the relationship between STOML2 and PAI-1 in the development of multiple myeloma (MM). Methods Cell proliferation was tested using CCK-8 assay and cell colony formation assay. Glucose consumption, lactate production and ATP level were measured using commercial kits. The mRNA and protein expression were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Results Both mRNA and protein expression of STOML2 were upregulated in MM patients compared to healthy volunteers. CCK-8 and colony formation assays demonstrated that STOML2 silencing inhibited cell proliferation in MM cells. Knockdown of STOML2 reduced glucose consumption, lactate production and ATP/ADP ratios. STOML2 silencing by shSTOML2 led to reduced PAI-1 expression. Overexpression of PAI-1 reversed the inhibitory effects of shSTOML2 on MM cell growth. Conclusion Results from this study demonstrated that STOML2 silencing inhibits cell proliferation and glycolysis through downregulation of PAI-1 expression, suggesting a new therapeutic target for MM.

Messenger RNA (mRNA)-based cancer vaccine has become a popular approach for developing personalized and effective antitumor immunotherapy. To achieve robust antitumor efficacy, mRNA-encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells for efficient antigen presentation; meanwhile, the vaccine would have adjuvant effect by stimulating innate immune response to boost the full activation of adaptive immunity. Recently, we reported a minimalist nanovaccine by formulating tumor antigen-encoding mRNA with a lipid-like material named C1, which could efficiently deliver mRNA into dendritic cells with simultaneous Toll-like receptor 4 (TLR4) stimulation, together induced T cell activation. Importantly, C1 mRNA nanovaccine exhibited significant antitumor efficacy on several tumor mouse models. Here, we discuss the nanovector-facilitated mRNA delivery and translation in dendritic cells, the self-adjuvant property of nanovectors, the challenges of personalized tumor antigen selection, and the potential strategies for developing efficacious mRNA cancer vaccines targeting the immunosuppressive tumor microenvironment.

Abstract Evidence from clinical cases indicates an association between the low success rate of in vitro fertilization (IVF) and ovarian injury due to previous methotrexate (MTX) administration. Therefore, it is necessary to develop and propose reasonable clinical drug guidelines to improve the quality of oocytes and the development of embryos before pregnancy. In this study, we established a mouse model with previous MTX exposure to validate the effects of MTX on reproductive function in female mice. We observed that MTX administration could result in a decrease in the success rate of fertilization and an aberrant embryonic development in both natural fertilization and IVF, even after completion of five to six ovulation cycles after MTX withdrawal. Further research revealed senescence and apoptosis of follicular granulosa cells (GCs), accompanied by arrested follicle development and aberrant estradiol and anti‐Mullerian hormone levels. Supportive evidence indicated that MTX administration induced senescence and apoptosis of human GCs in vitro, and the effects were consistent with the high levels of p21, p53, and oxidative stress. We further demonstrated that folic acid (FA) could improve oocyte function and embryonic development in vivo and in vitro by protecting GCs against apoptosis and senescence. Based on these findings, we propose the implementation of extended intervals between MTX exposure and conception or IVF and recommend FA as a special dietary supplement during this interval period; however, prospective inquiry in humans is necessary to further understand the relationship between MTX and FA recovery.

Desert shrubs play important roles in desertification control and vegetation restoration, which are particularly affected by droughts caused by climate change. However, the hydraulic strategies associated with hydraulic functional traits of desert shrubs remain unclear. Here, eight desert shrub species with different life forms and morphologies were selected for a common garden experiment at the southeast edge of the Tengger Desert in northern China to study the hydraulic strategies mediated by leaf hydraulic functional traits. Diurnal leaf water potential change, leaf hydraulic efficiency and safety, hydraulic safety margin, hydraulic capacitance, and water potential and relative water content at the turgor loss point were observed to significantly differ among species, suggesting that leaf hydraulic functional traits were strongly associated with species even when living in the same environment. Additionally, shrubs with greater leaf hydraulic efficiency had lower midday leaf water potential and leaf hydraulic safety, suggesting that leaf hydraulic efficiency had a strong trade-off with hydraulic safety and minimum leaf water potential, whereas there was also a coordination between leaf hydraulic safety and the leaf minimal water potential. Moreover, shrubs with higher leaf hydraulic capacitance had greater hydraulic safety margins, indicating coordination between leaf hydraulic capacitance and hydraulic safety margin. Overall, this study indicated that minimal daily leaf water potential, as an easily measured parameter, may be used preliminarily to predict leaf hydraulic conductivity and the resistance to embolism of desert shrubs, providing critical insights into hydraulic trade-off and coordination strategies for native shrubs as priority species in desert vegetation restoration and reconstruction.

ABSTRACT Fermented foods often have attractive flavor characteristics to meet various human demands. An ever-challenging target is the production of fermented foods with equal flavor profiles outside the product’s origin. However, the formation of geography-dependent flavor in high-complexity fermentations remains poorly understood. Here, taking Chinese liquor (baijiu) fermentation as an example, we collected 403 samples from 9 different locations in China across a latitude range of 27°N to 37°N. We revealed and validated the geography-dependent flavor formation patterns by using culture-independent (metabolomics, metagenomics, and metatranscriptomics) and culture-dependent tools. We found that the baijiu microbiomes along with their metabolites were flavor related and geography dependent. The geographical characteristics were determined mainly by 20 to 40 differentiated chemical markers in metabolites and the latitude-dependent fungal structure of the microbiome. About 48 to 156 core microbiota members out of 735 bacterial genera and 290 fungal genera contributed to the chemical markers. The contributions of both fungi and bacteria were greater than those from either bacteria or fungi alone. Representatively, we revealed that dynamic interdependent interactions between yeasts and Lactobacillus facilitated the metabolism of heterocyclic flavor chemicals such as 2-acetylpyrrole, 2,3,5-trimethylpyrazine, and 2-acetylfuran. Moreover, we found that the intraspecific genomic diversity and microbial structure were two biotic factors that contributed to dynamic microbiome assembly. Based on the assembly pattern, adjusting the composition and distribution of initial species was one option to regulate the formation of diverse flavor characteristics. Our study provided a rationale for developing a microbiome design to achieve a defined flavor goal. IMPORTANCE People consume many spontaneously fermented foods and beverages with different flavors on a daily basis. One crucial and hotly discussed question is how to reproduce fermented food flavor without geographical limitations to meet diverse human demands. The constantly enriched knowledge of the microbial contribution to fermented flavor offers valuable insights into flavor biotechnological development. However, we still have a poor understanding of what factors limit the reproduction of fermented flavor outside the product’s origin in high-complexity spontaneous fermentations. Here, taking baijiu fermentation as an example, we revealed that geography-dependent flavor was contributed mainly by fungus-bacterium cooperative metabolism. The distinct initial microbial composition, distribution, and intraspecific genomic diversity limited reproducible microbial interactions and metabolism in different geographical areas. The abundant microbial resources and predicted fungus-bacterium interactions found in baijiu fermentation enable us to design a synthetic microbial community to reproduce desired flavor profiles in the future.

Rhizoctonia solani Kühn naturally infects and causes Sheath blight disease in cereal crops such as wheat, rice and maize, leading to severe reduction in grain yield and quality. In this work, a new bacterial strain Bacillus halotolerans LDFZ001 showing efficient antagonistic activity against the pathogenic strain Rhizoctonia solani Kühn sh-1 was isolated. Antagonistic, phylogenetic and whole genome sequencing analyses demonstrate that Bacillus halotolerans LDFZ001 strongly suppressed the growth of Rhizoctonia solani Kühn sh-1, showed a close evolutionary relationship with B. halotolerans F41-3, and possessed a 3,965,118 bp circular chromosome. Bioinformatic analysis demonstrated that the genome of Bacillus halotolerans LDFZ001 contained ten secondary metabolite biosynthetic gene clusters (BGCs) encoding five non-ribosomal peptide synthases, two polyketide synthase, two terpene synthases and one bacteriocin synthase, and a new kijanimicin biosynthetic gene cluster which might be responsible for the biosynthesis of novel compounds. Gene-editing experiments revealed that functional expression of phosphopantetheinyl transferase (SFP) and major facilitator superfamily (MFS) transporter genes in Bacillus halotolerans LDFZ001 was essential for its antifungal activity against R. solani Kühn sh-1. Moreover, the existence of two identical chitosanases may also make contribution to the antipathogen activity of Bacillus halotolerans LDFZ001. Our findings will provide fundamental information for the identification and isolation of new sheath blight resistant genes and bacterial strains which have a great potential to be used for the production of bacterial control agents.ImportanceA new Bacillus halotolerans strain Bacillus halotolerans LDFZ001 resistant to sheath blight in wheat is isolated. Bacillus halotolerans LDFZ001 harbors a new kijanimicin biosynthetic gene cluster, and the functional expression of SFP and MFS contribute to its antipathogen ability.

Salmonella enterica subsp. enterica serovar Typhimurium (S. typhimurium) is an important zoonotic pathogen with important public health significance. To understand S. typhimurium’s epidemiological characteristics in China, multi-locus sequence typing, biofilm-forming ability, antimicrobial susceptibility testing, and resistant genes of isolates from different regions and sources (human, food) were investigated. Among them, ST34 accounted for 82.4% (243/295), with ST19 ranking second (15.9%; 47/295). ST34 exhibited higher resistance levels than ST19 (p < 0.05). All colistin, carbapenem, and ciprofloxacin-resistant strains were ST34, as were most cephalosporin-resistant strains (88.9%; 32/36). Overall, 91.4% (222/243) ST34 isolates were shown to have multidrug resistance (MDR), while 53.2% (25/47) ST19 isolates were (p < 0.05). Notably, 97.8% (45/46) of the MDR-ACSSuT (resistance to Ampicillin, Chloramphenicol, Streptomycin, Sulfamethoxazole, and Tetracycline) isolates were ST34, among which 69.6% (32/46) of ST34 isolates were of human origin, while 30.4% (14/46) were derived from food (p < 0.05). Moreover, 88.48% (215/243) ST34 showed moderate to strong biofilm-forming ability compared with 10.9% (5/46) ST19 isolates (p < 0.01). This study revealed the emergence of high-level antibiotic resistance S. typhimurium ST34 with strong biofilm-forming ability, posing concerns for public health safety.

The photocatalytic performance of g-C3N4 materials prepared by different precursors for Rhodamine B (RhB) dye degradation was studied. Their crystal structure, morphologies, chemical compositions, functional groups, and optical and photoelectrochemical performances of prepared g-C3N4 were analysed and characterised using X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, UV-Vis diffuse reflectance spectra, photoluminescence, and electrochemical workstations. The degradation of RhB dye in the presence of visible light and sunlight was utilised to assess the photocatalytic efficiency of the g-C3N4 photocatalyst. The results of the photocatalytic comparison experiment showed that the g-C3N4 photocatalyst prepared with urea as a precursor (UCN) has the best photocatalytic performance, achieving 99.61% removal in 40 min. In addition, the photocatalyst UCN can completely degrade 10 mg/L RhB dye within 20 min under sunlight, demonstrating its potential for practical applications under natural sunlight conditions. After four cycles, the degradation rate remains above 99%, demonstrating excellent stability and reusability. Due to its lower average pore number, larger BET-specific surface area and volume of pores, UCN provides more activity spaces and facilitates the adsorption of pollutant molecules, thereby enhancing photocatalytic activity. It was established through the active substance trapping studies that the main reactive species involved in the photocatalytic degradation process of RhB dye is •O2−. This study showed that g-C3N4 synthesised with urea as the precursor has better photocatalytic performance in the degradation of RhB dye.

With the rapid development of 5G and 6G communications in recent years, there has been significant interest in space–air–ground integrated networks (SAGINs), which aim to achieve seamless all-area, all-time coverage. As a key component of SAGINs, flying ad hoc networks (FANETs) have been widely used in the agriculture and transportation sectors in recent years. Reliable communication in SAGINs requires efficient routing algorithms to support them. In this study, we analyze the unique communication architecture of FANETs in SAGINs. At the same time, existing routing protocols are presented and clustered. In addition, we review the latest research advances in routing algorithms over the last five years. Finally, we clarify the future research trends of FANET routing algorithms in SAGINs by discussing the algorithms and comparing the routing experiments with the characteristics of unmanned aerial vehicles.

In emergency situations, such as earthquakes, landslides and other natural disasters, the terrestrial communications infrastructure is severely disrupted and unable to provide services to terrestrial IoT devices. However, tasks in emergency scenarios often require high levels of computing power and energy supply that cannot be processed quickly enough by devices locally and require computational offloading. In addition, offloading tasks to server-equipped edge base stations may not always be feasible due to the lack of infrastructure or distance. Since Low Orbit Satellites (LEO) have abundant computing resources, and Unmanned Aerial Vehicles (UAVs) have flexible deployment, offloading tasks to LEO satellite edge servers via UAVs becomes straightforward, which provides computing services to ground-based devices. Therefore, this paper investigates the computational tasks and resource allocation in a UAV-assisted multi-layer LEO satellite network, taking into account satellite computing resources and device task volumes. In order to minimise the weighted sum of energy consumption and delay in the system, the problem is formulated as a constrained optimisation problem, which is then transformed into a Markov Decision Problem (MDP). We propose a UAV-assisted airspace integration network architecture, and a Deep Deterministic Policy Gradient and Long short-term memory (DDPG-LSTM)-based task offloading and resource allocation algorithm to solve the problem. Simulation results demonstrate that the solution outperforms the baseline approach and that our framework and algorithm have the potential to provide reliable communication services in emergency situations.

Abstract Background Fine tuned balance of reactive oxygen species (ROS) is essential for tumor cells and tumor cells use immune checkpoints to evade attack form immunity system. However, it’s unclear whether there is any crosstalk between these two pathways. CYB561D2, an antioxidant protein, is part of 5-gene prognosis signature in gliomas and its involvement in gliomas is unknown. Here, we aim to provide a detailed characterization of CYB561D2 in gliomas. Methods CYB561D2 expression was measured in clinical samples of gilomas and normal tissues. The effects of CYB561D2 on immunity related genes and tumor behaviors were investigated in glioma cell lines with various in vitro and in vivo assays. Results CYB561D2 expression was enhanced in gliomas compared to control tissues. CYB561D2 up-regulation was associated with high grading of gliomas and short survival in patients. CYB561D2 expression was induced by H2O2 in glioma cell lines. CYB561D2 and its functional product ascorbate activated STAT3 dose-dependently. CYB561D2 over-expression increased PD-L1, CCL2 and TDO2 expression, and induced immunosuppression in co-cultured T cells. In in vitro assays, CYB561D2 knock-down suppressed cell growth, colony formation, migration and promoted apoptosis. In contrast, CYB561D2 over-expression reduced survival rate in intracranial glioma model and this effect could be blocked by dominant negative-STAT3. The CYB561D2 up-regulation and the positive association of CYB561D2 with PD-L1, CCL2 and TDO2 expression were cross-validated in open-access datasets. Conclusions CYB561D2 up-regulation induces immunosuppression and aggression via activating STAT3 in gliomas and CYB561D2 mediates ROS-tumor immunity crosstalk.

BackgroundDementia is a chronic progressive neurodegenerative disease that can lead to disability and death in humans, but there is still no effective prevention and treatment. Due to the neuroprotective effects of vitamin E, a large number of researchers have explored whether vitamin E can reduce the risk of dementia. Some researchers believe that vitamin E can reduce the risk of dementia, while others hold the opposite conclusion. We therefore performed a meta-analysis to clarify the relationship between them.MethodsWe searched PubMed, Embase, and Web of Science databases for articles on the connection of dietary and supplementation vitamin E with dementia risk from inception through April 2022 using the main keywords “dementia,” “Alzheimer's disease,” “vitamin E,” and “tocopherol,” and used a random-utility model for pooled effect sizes. Odds ratios (OR) and 95% confidence intervals were derived using lower and higher doses as contrasts. Obtained data were shown and assessed using Stata12.0 free software.ResultsWe included 15 articles in sum. Among them, there were nine articles containing AD. By comparing the highest intake with the lowest intake, Combined ORs for high intake were as follows: dementia (OR = 0.79, 95% CI 0.70–0.88 I2 = 35.0%), Alzheimer's disease (OR = 0.78, 95% CI 0.64–0.94 I2 = 36.9%). Subgroup analyses were also performed by study type, diet and supplementation, and NOS score.ConclusionsHigh vitamin E intake from diet and supplements significantly reduces the risk of dementia and Alzheimer's disease.

ABSTRACT Traditional fermentation processes are driven by complex fungal microbiomes. However, the exact means by which fungal diversity affects fermentation remains unclear. In this study, we systematically investigated the diversity of a fungal community and its functions during the multibatch Baijiu fermentation process. Metabolomics analysis showed that the metabolic profiles of the Baijiu were enhanced with an increase in the fermentation time, as determined from the characteristic volatile flavors. High-throughput sequencing technology revealed that the major fungal species involved in sauce-flavor Baijiu fermentation are Pichia sp. (41.75%, average relative abundance), Saccharomyces sp. (13.07%), thermophilic species (9.16%), Monascus sp. (6.80%), Aspergillus sp. (4.69%), Schizosaccharomyces sp. (3.76%), Thermomyces sp. (3.74%), and Zygosaccharomyces sp. (1.41%). In addition, the fungal diversity increased as the number of fermentation batches increased. Moreover, the increased fungal diversity contributed to the modularity of the fungal communities, wherein Pichia sp., Torulaspora sp., and Saccharomyces sp. maintained the stability of the fungal community. In addition, metatranscriptomics sequencing technologies were used to reconstruct the key metabolic pathways during fermentation, and it was found that the increased microbial diversity significantly promoted glucose-mediated carbon metabolism. Finally, functional gene analysis showed that functional microorganisms, such as Zygosaccharomyces and Pichia, can enhance fermentation as a result of the high expression of pyruvate decarboxylase and propanol-preferring alcohol dehydrogenase during the metabolism of pyruvate. These results indicate that fungal biodiversity can be exploited to enhance fermentation-based processes via network interactions and metabolism during multiple-batch fermentation. IMPORTANCE Biodiversity and network interactions act simultaneously on the microbial community structure in the Baijiu fermentation process, thereby rendering the microbiome dynamics challenging to manage and predict. Understanding the complex fermentation community and its relationship to community functions is therefore important in the context of developing improved fermentation biotechnology systems. Our work demonstrates that multiple-batch fermentation steps increase microbial diversity and promote community stability. Crucially, the enhanced modularity in the microbial network increases the metabolism of flavor compounds and ethanol. This study highlights the power of biodiversity and network interactions in regulating the function of the microbiome in food fermentation ecosystems.

In the presence of dry ice, a series of graphitic materials with carboxylated edges (ECGs) were synthesized by ball milling graphite for varied times (24, 36, and 46 h). The influence of carboxylation on the physiochemical characteristics and electrochemical performance as effective electrodes for supercapacitors were assessed and compared with pure graphite. Several characterization techniques were employed to investigate into the morphology, texture, microstructure, and modification of the materials. Due to its interconnected micro-mesoporous carbon network, which is vital for fast charge-discharge at high current densities, storing static charges, facilitating electrolyte transport and diffusion, and having excellent rate performance, the ECG-46 electrode among the investigated samples achieved the highest specific capacitance of 223 F g−1 at 0.25 A g−1 current density and an outstanding cycle stability, with capacitance retention of 90.8% for up to 10,000 cycles. Furthermore, the symmetric supercapacitor device based on the ECG-46 showed a high energy density of 19.20 W h kg−1 at 450.00 W kg−1 power density. With these unique features, ball milling of graphitic material in dry ice represents a promising approach to realize porous graphitic material with oxygen functionalities as active electrodes.

Introduction Immune-inflammatory response plays a key role in the pathogenesis of atherosclerosis. IgG N-glycosylation is reported to be associated with the 10-year atherosclerotic cardiovascular disease risk score and subclinical atherosclerosis. However, the relationship of IgG glycosylation with actual clinical cardiovascular disease (CVD) events and plaque phenotypes has rarely been investigated. Therefore, this study aims to understand whether IgG glycosylation traits are correlated with actual clinical CVD events and plaque phenotypes.Methods and analysis Designed to verify the efficacy of IgG glycosylation as a risk for CVD events and screen potential biomarkers of CVD to prevent atherosclerosis occurrence, this longitudinal prospective cohort study will be conducted at the First Affiliated Hospital of Shantou University Medical College, China. In total, 2720 participants routinely examined by carotid ultrasound will be divided into different groups according to plaque phenotype characteristics. Ultra-performance liquid chromatography will be performed to separate and detect IgG N-glycans in serum collected at baseline and at the end of the first, second and third years. The primary outcome is the actual clinical CVD composite events, including non-fatal myocardial infarction, death due to coronary heart disease, and fatal or non-fatal stroke.Ethics and dissemination The Clinical Ethics Committee of the First Affiliated Hospital of Shantou University Medical College approved this study (number: B-2021-127). Findings of this study will be submitted for publication in peer-reviewed journals.Trial registration number ChiCTR2100048740.

Nitrofuran antibiotics have been widely used in the prevention and treatment of animal diseases due to the bactericidal effect. However, the residual and accumulation of their metabolites in vivo can pose serious health hazards to both humans and animals. Although their usage in feeding and process of food-derived animals have been banned in many countries, their metabolic residues are still frequently detected in materials and products of animal-derived food. Many sensitive and effective detection methods have been developed to deal with the problem. In this work, we summarized various immunological methods for the detection of four nitrofuran metabolites based on different types of detection principles and signal molecules. Furthermore, the development trend of detection technology in animal-derived food is prospected.

Biochar-amended landfill cover soil (BLCS) can promote CH4 and O2 diffusion, but it increases rainwater entry in the rainy season, which is not conducive to CH4 emission reduction. Hydrophobic biochar–amended landfill cover soil (HLCS) was prepared to investigate the changes in CH4 emission reduction and biological characteristics, and BLCS was prepared as control. Results showed that rainwater retention time in HLCS was reduced by half. HLCS had a higher CH4 reduction potential, achieving 100% CH4 removal at 25% CH4 content of landfill gas, and its main contributors to CH4 reduction were found to be at depths of 10–30 cm (upper layer) and 50–60 cm (lower layer). The relative abundances of methane-oxidizing bacteria (MOB) in the upper and lower layers of HLCS were 55.93% and 46.93%, respectively, higher than those of BLCS (50.80% and 31.40%, respectively). Hydrophobic biochar amended to the landfill cover soil can realize waterproofing, ventilation, MOB growth promotion, and efficient CH4 reduction.

Focal segmental glomerulosclerosis (FSGS) is a common clinical condition with manifestations of nephrotic syndrome and fibrosis of the glomeruli and interstitium. Yi-Shen-Hua-Shi (YSHS) granule has been shown to have a good effect in alleviating nephrotic syndrome (NS) in clinical and in animal models of FSGS, but whether it can alleviate renal fibrosis in FSGS and its mechanism and targets are not clear. In this study, we explored the anti-fibrotic effect and the targets of the YSHS granule in an adriamycin (ADR)-induced FSGS model and found that the YSHS granule significantly improved the renal function of ADR-induced FSGS model mice and also significantly reduced the deposition of collagen fibers and the expression of mesenchymal cell markers FN, vimentin, and α-SMA in the glomeruli of ADR-induced FSGS mice, suggesting that the YSHS granule inhibited the fibrosis of sclerotic glomeruli. Subsequently, a network pharmacology-based approach was used to identify the potential targets of the YSHS granule for the alleviation of glomerulosclerosis in FSGS, and the results showed that the YSHS granule down-regulated the expressions of BMP2, GSTA1, GATS3, BST1, and S100A9 and up-regulated the expressions of TTR and GATM in ADR-induced FSGS model mice. We also proved that the YSHS granule inhibited the fibrosis in the glomeruli of ADR-induced FSGS model mice through the suppression of the BMP2/Smad signaling pathway.