Search

Abstract Rice kernel smut (RKS), caused by the fungus Tilletia horrida, has become a major disease in rice-growing areas worldwide, especially since the widespread cultivation of high-yielding hybrid rice varieties. The disease causes a significant yield loss during the production of rice male sterile lines by producing masses of dark powdery teliospores. This review mainly summarizes the pathogenic differentiation, disease cycle, and infection process of the T. horrida, as well as the decoding of the T. horrida genome, functional genomics, and effector identification. We highlight the identification and characterization of virulence-related pathways and effectors of T. horrida, which could foster a better understanding of the rice–T. horrida interaction and help to elucidate its pathogenicity molecular mechanisms. The multiple effective disease control methods for RKS are also discussed, included chemical fungicides, the mining of resistant rice germplasms/genes, and the monitoring and early warning signs of this disease in field settings.

Extreme events occur frequently and increase faults in power systems, providing negative effects on the safe and stable operation. In this regard, introducing efficient fault recovery methods to strengthen the resilience of active distribution networks (ADNs) against extreme events is very critical. This paper puts forward a novel fault recovery method for ADNs based on an improved binary particle swarm optimization (BPSO) algorithm, and the topology constraints are specially considered to accelerate the recovery operation. In addition, a resilience evaluation system is built for the ADNs for checking the performance of the proposed fault recovery method. The mathematical model, the fault recovery strategy, as well as the architecture of the resilience evaluation system, are stated in detail. Using MATLAB, an IEEE 33-node system with multiple distributed generators (DGs) is built, and different fault scenarios are imitated for verifying the effectiveness and suitability of the proposed method. From the comparative analysis of the fault recovery schemes with the traditional and improved BPSO algorithms, the proposed method enables to more effectively reduce the node voltage deviation, decrease the power loss and assist the important load recovery. In consequence, the resilience of the ADNs will be appreciatively boosted.

IntroductionAlthough several studies have explored the associations between single essential metals and serum uric acid (SUA), the study about the essential metal mixture and the interactions of metals for hyperuricemia remains unclear.MethodsWe performed a cross-sectional study to explore the association of the SUA levels with the blood essential metal mixture, including magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), zinc (Zn), manganese (Mn) in Chinese community-dwelling adults (n=1039). The multivariable linear regression, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were conducted to estimate the associations of blood essential metals with SUA levels and the BKMR model was also conducted to estimate the interactions of the essential metals on SUA.ResultsIn the multivariable linear regression, the association of blood Mg, Mn, and Cu with SUA was statistically significant, both in considering multiple metals and a single metal. In WQS regression [β=13.59 (95%CI: 5.57, 21.60)] and BKMR models, a positive association was found between the mixture of essential metals in blood and SUA. Specifically, blood Mg and Cu showed a positive association with SUA, while blood Mn showed a negative association. Additionally, no interactions between individual metals on SUA were observed.DiscussionIn conclusion, further attention should be paid to the relationship between the mixture of essential metals in blood and SUA. However, more studies are needed to confirm these findings.

Abstract Background The sustainable development of rice production is facing severe threats by a variety of pathogens, such as necrotrophic Rhizoctonia solani and hemibiotrophic Xanthomonas oryzae pv. oryzae (Xoo). Mining and applying resistance genes to increase the durable resistance of rice is an effective method that can be used to control these diseases. Results In this research, we isolated and characterized CYP716A16, which is a positive regulator of rice to R. solani AG1-IA and Xoo, and belongs to the cytochrome P450 (CYP450) protein 716A subfamily. Overexpression (OE) of CYP716A16 resulted in enhanced resistance to R. solani AG1-IA and Xoo, while RNA interference (RNAi) of CYP716A16 resulted in increased susceptibility compared with wild-type (WT) plants. Additionally, jasmonic acid (JA)-dependent defense responses and reactive oxygen species (ROS) were activated in the CYP716A16-OE lines after R. solani AG1-IA inoculation. The comparative transcriptomic and metabolomics analysis of CYP716A16-OE and the WT lines showed that OE of CYP716A16 activated the biosynthesis of flavonoids and increased the amounts of narcissoside, methylophiopogonanone A, oroxin A, and amentoflavone in plants. Conclusion Based on these results, we suggest that JA-dependent response, ROS level, multiple resistance-related proteins, and flavonoid contents play an important role in CYP716A16-regulated R. solani AG1-IA and Xoo resistance. Our results broaden our knowledge regarding the function of a P450 protein 716A subfamily in disease resistance and provide new insight into the molecular mechanism of rice immune response.

Accurately predicting proton flux in the space radiation environment is crucial for satellite in-orbit management and space science research. This paper proposes a proton flux prediction method based on a hybrid neural network. This method is a predictive approach for measuring proton flux profiles via a satellite during its operation, including crossings through the SAA region. In the data preprocessing stage, a moving average wavelet transform was employed to retain the trend information of the original data and perform noise reduction. For the model design, the TPA-LSTM model was introduced, which combines the Temporal Pattern Attention mechanism with a Long Short-Term Memory network (LSTM). The model was trained and validated using 4,174,202 proton flux data points over a span of 12 months. The experimental results indicate that the prediction accuracy of the TPA-LSTM model is higher than that of the AP-8 model, with a logarithmic root mean square error (logRMSE) of 3.71 between predicted and actual values. In particular, an improved accuracy was observed when predicting values within the South Atlantic Anomaly (SAA) region, with a logRMSE of 3.09.

Objective: Colorectal cancer (CRC) patients respond differently to treatments and are sub-classified by different approaches. We evaluated a deep learning model, which adopted endoscopic knowledge learnt from AI-doscopist, to characterise CRC patients by histopathological features. Results: Data of 461 patients were collected from TCGA-COAD database. The proposed framework was able to 1) differentiate tumour from normal tissues with an Area Under Receiver Operating Characteristic curve (AUROC) of 0.97; 2) identify certain gene mutations (MYH9, TP53) with an AUROC > 0.75; 3) classify CMS2 and CMS4 better than the other subtypes; and 4) demonstrate the generalizability of predicting KRAS mutants in an external cohort. Conclusions: Artificial intelligent can be used for on-site patient classification. Although KRAS mutants were commonly associated with therapeutic resistance and poor prognosis, subjects with predicted KRAS mutants in this study have a higher survival rate in 30 months after diagnoses.

The upconversion detection is a promising method to detect infrared radiation. It is proved that the focused beam makes a contribution to improving the upconversion efficiency. A near-infrared detector at room-temperature based on sum frequency generation(SFG) with focused beams is demonstrated. To enhance the upconversion efficiency, the signal and pump beams are tightly focused by the same focal lens. To reduce that the dispersion of the focal lens has a negative effect on upconversion efficiency in a tightly focusing system, the relation between the upconversion efficiency and the focused beams in our system is investigated. In the setup, the signal and pump beams are combined by a polarization maintaining wavelength division multiplexer (PMWDM) that is connected on a collimator. The mixed beam is focused into a periodically poled lithium niobate (PPLN) bulk by a lens of 35 mm focal length. The signal pulse at 1550 nm is converted to 863 nm with a 172 mW continuous-wave pump beam at 1950 nm. The converted signal is measured by a photomultiplier tube(PMT) and results shows the maximum upconversion efficiency is $5.23 \times 10^{-4}$ while the pump power is 172 mW.

Although previous studies have examined the hepatotoxicity of single metal exposure, the associations between metal mixture and non-alcoholic fatty liver disease (NAFLD) or fibrosis remain unclear. This study investigated the associations of urinary metal mixture with the risks of NAFLD and liver fibrosis in US adults using data from the National Health and Nutrition Examination Survey (NHANES) from 2017.01 to 2020.03. Vibration-controlled transient elastography was used to detect the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), which are indicators of NAFLD and liver fibrosis respectively. Three novel mixture modeling approaches including the Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) were used to estimate the associations of the urinary fourteen-metal mixture with Ln CAP and Ln LSM. There were 2283 adults aged over 18 years (1209 women and 1074 men) were included. Among women, urinary metal mixture was positively associated with Ln CAP in the BKMR and qgcomp models (both P 0.05). The metal mixture was not associated with Ln LSM in the three models regardless of genders (all P > 0.05). In conclusion, we observed sex-specific associations between urinary metal mixture and the prevalence of NAFLD in US adults. These findings emphasize the role of environmental heavy metal exposure in the development of NAFLD, and confirm the need for more prospective cohort studies on sex-specific manner.

ObjectiveAlthough phthalates are common environmental pollutants, few studies have focused on the relationship of phthalates exposure with non-alcoholic fatty liver disease (NAFLD) or liver fibrosis, and especially, the alternative phthalates have been questioned in recent years about whether they are better choices. Thus, this study aimed to explore the associations of exposure to major phthalates or alternative phthalates with NAFLD and liver fibrosis.MethodsData of 1450 adults from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were collected. The urinary metabolite concentrations of di-2-ethylhexyl phthalate (DEHP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) were detected. Controlled attenuation parameter (CAP) and median liver stiffness measurement (LSM) were acquired for quantitative diagnosis of NAFLD and liver fibrosis by vibration-controlled transient elastography. Multivariate logistic regression analysis and linear regression analysis were performed to examine the associations between phthalates and NAFLD and liver fibrosis.ResultsAfter adjustment of the potential factors, the prevalence of NAFLD was significantly elevated among those in the fourth quartile of mono-(2-ethyl-5-carboxypentyl) phthalate (OR, 95%CI = 2.719, 1.296, 5.700, P = 0.016), mono (2-ethyl-5-hydroxyhexyl) phthalate (OR, 95%CI = 2.073, 1.111, 3.867, P = 0.037). No significant association was found between the alternative phthalates and NAFLD. The similar result was gained by linear regression analysis that MECPP was still significantly associated with Ln CAP (Q4 vs. Q1: β, 95%CI = 0.067, 0.017, 0.118, P = 0.027). After adjustment for the same covariates, no significant association between phthalates and liver fibrosis was found in logistics regression analysis.ConclusionsAll in all, higher prevalence of NAFLD is correlated with DEHP but not DINP or DIDP in American adults. There is no significant relationship between phthalates and liver fibrosis defined as LSM ≥ 8 Kpa. Nevertheless, further research is needed to provide evidence of causality.

BackgroundClinical research results on the relationship between folate and non-alcoholic fatty liver disease are contradictory. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed concept. Evidence about the relationship between serum folate and MAFLD, especially considering the status of serum vitamin C, is scarce. This study was aimed to investigate the association of serum folate levels with the prevalence of MAFLD, and further to analyze the potential impact of serum vitamin C status on their association.MethodsTotally 2,797 participants from National Health and Nutrition Examination Survey (NHANES) 2017–2018 were included. Vibration-controlled transient elastography was used to detect liver steatosis and fibrosis. Participants were divided in groups based on the tertiles of serum folate or vitamin C, and the serum folate or vitamin C level in T1 was low. Logistic regression analysis in the complex sample module was performed to illustrate the association of serum folate levels with the prevalence of MAFLD. Stratification analysis by serum vitamin C status was performed as well.ResultsCompared with the serum folate levels of T1 group, participants in the T3 group had 47.9% lower risk of MAFLD [OR = 0.521 (95% CI: 0.401–0.677)]. However, when participants were stratified by serum vitamin C levels, there was no association between the serum folate levels and MAFLD in the T1 or T2 group. Among participants in the T3 group of vitamin C status, participants in the T3 group of serum folate had a 63.6% lower risk of MAFLD compared with the T1 group [OR = 0.364 (95% CI: 0.147–0.903)].ConclusionsHigh serum folate level is associated with lower prevalence of MAFLD, especially in participants with sufficient vitamin C.

ABSTRACT The thick mucus layer covering of the intestinal epithelium has received increasing attention, owing to its protective role in intestinal infection. However, the exact mechanisms by which the mucus increases intestinal resistance against viral infection remain largely unclear. Here, we identify prominent antiviral activity of the small intestinal mucus and extracted total mucus proteins, as evidenced by their inhibitory effects against porcine epidemic diarrhea virus (PEDV) infection. Of all the extracted mucus proteins, mucin 2 and fraction III (~70 kDa) exhibited potent antiviral activity. We further evaluated the antiviral effects of three candidate factors in fraction III and found that calpain-1 contributed substantially to its antiviral activity. In vivo studies demonstrated that oral administration of calpain-1 provided effective protection against intestinal PEDV infection. As a calcium-activated cysteine protease, calpain-1 inhibited viral invasion by binding to and hydrolyzing the S1 domain of the viral spike protein. The region between amino acids 297 and 337 in the b domain of PEDV S1 protein was critical for calpain-1-mediated hydrolysis. Further investigation indicated that calpain-1 could be produced by goblet cells between intestinal epithelia. Taken together, the results of our study revealed calpain-1 to be a novel antiviral protein in porcine small intestinal mucus, suggesting that calpain-1 has potential for defending against intestinal infections. IMPORTANCE Although the antiviral activity of the intestinal mucus was recognized 20 years ago, the antiviral active ingredients in the mucus are poorly understood. Currently, most research on antiviral molecules in the intestinal mucus remains limited to members of the mucin family. This study identified the cysteine protease calpain-1 as a novel antiviral protein in porcine small intestinal mucus and revealed its underlying protective mechanism for the first time. This mechanism involves inhibiting porcine epidemic diarrhea virus (PEDV) invasion by binding and hydrolyzing the S1 domain of the viral spike protein. Furthermore, the results of our PEDV-challenge experiment in piglets indicated that calpain-1 provides effective protection against intestinal PEDV infection. Our findings provide new insights into the protective function of the small intestinal mucus. In addition to potential therapeutic implications for the swine industry, our analysis of antiviral proteins in the small intestinal mucus may have implications for the prevention and control of coronavirus infection in humans.

Follistatin-like protein 3 (FSTL3) is a type of FSTLs. By interacting with a disintegrin and metalloproteinase 12 (ADAM12), transforming growth factor-β ligands (activin, myostatin and growth differentiation factor (GDF) 11), FSTL3 can either activate or inhibit these molecules in human non-tumor pathophysiologies and cancers. The FSTL3 gene was initially discovered in patients with in B-cell chronic lymphocytic leukemia, and subsequent studies have shown that the FSTL3 protein is associated with reproductive development, insulin resistance, and hematopoiesis. FSTL3 reportedly contributes to the development and progression of many cancers by promoting tumor metastasis, facilitating angiogenesis, and inducing stem cell differentiation. This review summarizes the current pathophysiological roles of FSTL3, which may be a putative prognostic biomarker for various diseases and serve as a potential therapeutic target.

The CD13 inhibitor ubenimex is used as an adjuvant drug with chemotherapy for the treatment of cancer due to its function as an immunoenhancer, but it has limitations in its cytotoxic efficacy. The proteasome inhibitor ixazomib is a landmark drug in the treatment of multiple myeloma with a high anti-cancer activity. Herein, we conjugated the pharmacophore of ubenimex and the boric acid of ixazomib to obtain a dual CD13 and proteasome inhibitor 7 (BC-05). BC-05 exhibited potent inhibitory activity on both human CD13 (IC50 = 0.13 μM) and the 20S proteasome (IC50 = 1.39 μM). Although BC-05 displayed lower anti-proliferative activity than that of ixazomib in vitro, an advantage was established in the in vivo anti-cancer efficacy and prolongation of survival time, which may be due to its anti-metastatic and immune-stimulating activity. A pharmacokinetic study revealed that BC-05 is a potentially orally active agent with an F% value of 24.9%. Moreover, BC-05 showed more favorable safety profiles than those of ixazomib in preliminary toxicity studies. Overall, the results indicate that BC-05 is a promising drug candidate for the treatment of multiple myeloma.

Due to their high bending stiffness, high torsional stiffness, and high local stability, rectangular section members of Al alloy space structures are frequently utilized as load-bearing elements. However, the joint construction is more complex because of the closed cross-section. To join rectangular section members without drilling holes in them, a variety of blind bolts that can be placed and fastened on one side have been devised. The blind bolts researched in this paper is known as BOM bolt. The shear resistance of BOM-bolted Al alloy connections is investigated using shear testing and finite element calculations of individual bolts and bolt groups. According to the test and numerical simulation results, the formulas for the compressive strength of the aluminum plate and the shear capacity reduction factor of BOM-bolted long connections are derived.

Abstract Background Rice (Oryza sativa) bacterial leaf blight (BLB), caused by the hemibiotrophic Xanthomonas oryzae pv. oryzae (Xoo), is one of the most devastating diseases affecting the production of rice worldwide. The development and use of resistant rice varieties or genes is currently the most effective strategy to control BLB. Results Here, we used 259 rice accessions, which are genotyped with 2 888 332 high-confidence single nucleotide polymorphisms (SNPs). Combining resistance variation data of 259 rice lines for two Xoo races observed in 2 years, we conducted a genome-wide association study (GWAS) to identify quantitative trait loci (QTL) conferring plant resistance against BLB. The expression levels of genes, which contains in GWAS results were also identified between the resistant and susceptible rice lines by transcriptome analysis at four time points after pathogen inoculation. From that 109 candidate resistance genes showing significant differential expression between resistant and susceptible rice lines were uncovered. Furthermore, the haplotype block structure analysis predicted 58 candidate genes for BLB resistance based on Chr. 7_707158 with a minimum P-value (–log 10 P = 9.72). Among them, two NLR protein-encoding genes, LOC_Os07g02560 and LOC_Os07g02570, exhibited significantly high expression in the resistant line, but had low expression in the susceptible line of rice. Conclusions Together, our results reveal novel BLB resistance gene resources, and provide important genetic basis for BLB resistance breeding of rice crops.

Background and objectiveSerum uric acid (UA) is related to many metabolic diseases. However, the association of UA with liver diseases was not very clear. The objective of this study is to clarify the relationship of UA with liver steatosis and fibrosis.MethodsThis is a cross-sectional study of 4364 people of National Health and Nutrition Examination Survey (NHANES) 2017-2018. Liver steatosis and fibrosis were assessed by controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) using Vibration-controlled transient elastography (VCTE). Linear and logistic regressions were performed.ResultsAfter adjusting for potential confounders, UA levels were associated with the prevalence of liver steatosis [OR=2.097 (95%CI: 1.245, 3.534)] and liver fibrosis [OR=2.983 (95%CI: 1.797, 4.952)]. Furthermore, the results were consistent in the subgroup analyses of males and females.ConclusionsUA levels were positively associated with the prevalence of liver steatosis and fibrosis.

Abstract We have designed a deep-learning model, an “Artificial Intelligent Endoscopist (a.k.a. AI-doscopist)”, to localise colonic neoplasia during colonoscopy. This study aims to evaluate the agreement between endoscopists and AI-doscopist for colorectal neoplasm localisation. AI-doscopist was pre-trained by 1.2 million non-medical images and fine-tuned by 291,090 colonoscopy and non-medical images. The colonoscopy images were obtained from six databases, where the colonoscopy images were classified into 13 categories and the polyps’ locations were marked image-by-image by the smallest bounding boxes. Seven categories of non-medical images, which were believed to share some common features with colorectal polyps, were downloaded from an online search engine. Written informed consent were obtained from 144 patients who underwent colonoscopy and their full colonoscopy videos were prospectively recorded for evaluation. A total of 128 suspicious lesions were resected or biopsied for histological confirmation. When evaluated image-by-image on the 144 full colonoscopies, the specificity of AI-doscopist was 93.3%. AI-doscopist were able to localise 124 out of 128 polyps (polyp-based sensitivity = 96.9%). Furthermore, after reviewing the suspected regions highlighted by AI-doscopist in a 102-patient cohort, an endoscopist has high confidence in recognizing four missed polyps in three patients who were not diagnosed with any lesion during their original colonoscopies. In summary, AI-doscopist can localise 96.9% of the polyps resected by the endoscopists. If AI-doscopist were to be used in real-time, it can potentially assist endoscopists in detecting one more patient with polyp in every 20–33 colonoscopies.

The basidiomycete fungus Tilletia horrida causes rice kernel smut (RKS), a crucial disease afflicting hybrid-rice-growing areas worldwide, which results in significant economic losses. However, few studies have investigated the pathogenic mechanisms and functions of effectors in T. horrida. In this study, we found that the candidate effector ThSCSP_12 caused cell necrosis in the leaves of Nicotiana benthamiana. The predicted signal peptide (SP) of this protein has a secreting function, which is required for ThSCSP_12 to induce cell death. The 1- 189 amino acid (aa) sequences of ThSCSP_12 are sufficient to confer it the ability to trigger cell death in N. benthamiana. The expression of ThSCSP_12 was induced and up-regulated during T. horrida infection. In addition, we also found that ThSCSP_12 localized in both the cytoplasm and nucleus of plant cells and that nuclear localization of this protein is required to induce cell death. Furthermore, the ability of ThSCSP_12 to trigger cell death in N. benthamiana depends on the (RAR1) protein required for Mla12 resistance but not on the suppressor of the G2 allele of Skp1 (SGT1), heat shock protein 90 (HSP90), or somatic embryogenesis receptor-like kinase (SERK3). Crucially, however, ThSCSP_12 induced a defense response in N. benthamiana leaves; yet, the expression of multiple defense-related genes was suppressed in response to heterologous expression in host plants. To sum up, these results strongly suggest that ThSCSP_12 operates as an effector in T. horrida–host interactions.

Tilletia horrida is a biotrophic basidiomycete fungus that causes rice kernel smut, one of the most significant diseases in hybrid rice-growing areas worldwide. Little is known about the pathogenic mechanisms and functions of effectors in T. horrida. Here, we performed functional studies of the effectors in T. horrida and found that, of six putative effectors tested, only ThSCSP_14 caused the cell death phenotype in epidermal cells of Nicotiana benthamiana leaves. ThSCSP_14 was upregulated early on during the infection process, and the encoded protein was secreted. The predicted signal peptide (SP) of ThSCSP_14 was required for its ability to induce the necrosis phenotype. Furthermore, the ability of ThSCSP_14 to trigger cell death in N. benthamiana depended on suppressing the G2 allele of Skp1 (SGT1), required for Mla12 resistance (RAR1), heat-shock protein 90 (HSP90), and somatic embryogenesis receptor-like kinase (SERK3). It is important to note that ThSCSP_14 induced a plant defense response in N. benthamiana leaves. Hence, these results demonstrate that ThSCSP_14 is a possible effector that plays an essential role in T. horrida–host interactions.

Increasing the energy density, power density as well as widening the operation voltage are essential to electrochemical capacitors to meet the practical energy demands. Herein, a novel flexible quasi-solid-state dual-ion asymmetric supercapacitor (ASC) with Ni(OH)2 and Nb2O5 nanosheets directly grown on stainless steel mesh is developed. In the dual-ion ASC, Nb2O5 negative and Ni(OH)2 positive electrodes react with Li+ and OH− respectively in alkaline gel electrolyte to store energy, which is quite different from conventional alkali metal ion SCs and alkaline SCs. The as-assembled flexible device has an extended working voltage of 1.7 V and delivers a capacity of 5.37 mAh cm−2, a maximum energy density and power density of 0.52 mWh cm−3 and 170 mW cm−3, respectively. The device maintains around 60% capacity retention after long cycling up to 1000 cycles. Moreover, our device can light up a LED light efficiently upon fast charging. The proposed quasi-solid-state dual-ion ASC has potential applications in future portable electronics and flexible energy storage devices. Keywords: Nickel hydroxide, Niobium pentoxide, Nanoarrays, Flexible supercapacitor, Dual ion capacitor

Abstract Background Neuroinflammation is an essential player in many neurological diseases including traumatic brain injury (TBI). Recent studies have identified that inflammasome complexes are responsible for inflammatory responses in many pathological conditions. Inflammasomes are intracellular multiprotein complexes which regulate the innate immune response, activation of caspase-1, production of pro-inflammatory cytokines IL-1β and IL-18, and induction of cell death (pyroptosis). Among inflammasome family members, the nucleotide-binding domain leucine-rich repeats family protein 3 (NLRP3) is the most extensively studied and its activation is induced following TBI. As a novel target, drug development targeting the formation and activation of NLRP3 inflammasome is a prospective therapy for TBI. We have recently developed a small molecule JC124 with specificity on NLRP3 inflammasome. In this study, we explored the therapeutic value of JC124 for TBI treatment. Methods Adult male Sprague-Dawley rats were subjected to a moderate cortical impact injury. Following TBI, animals received 4 doses of JC124 treatment with the first dose starting at 30 min, the second dose at 6 h after TBI, the third and fourth doses at 24 or 30 h following TBI, respectively. Animals were sacrificed at 2 days post-injury. Brain tissues were processed either for ELISA and western blotting analysis for inflammatory response, or for histological examination to assess degenerative neurons, acute inflammatory cell response and lesion volume. Results We found that post-injury treatment with JC124 significantly decreased the number of injury-induced degenerating neurons, inflammatory cell response in the injured brain, and cortical lesion volume. Injured animals treated with JC124 also had significantly reduced protein expression levels of NLRP3, ASC, IL-1 beta, TNFα, iNOS, and caspase-1. Conclusion Our data suggest that our novel NLRP3 inhibitor has a specific anti-inflammatory effect to protect the injured brain following TBI.

Drug resistance and relapse lead to high mortality in acute myeloid leukemia, and studies have shown that CXCR4 overexpression is highly correlated with poor prognosis and drug resistance in leukemia cells. Isolation and detection of AML cells with CXCR4 overexpression will be crucial to the treatment of AML. In this paper, magnetic nanoparticles were firstly prepared successfully by high-temperature thermal decomposition method, and then characterized by TEM, VSM and DLS. Subsequently CXCR4-targeted magnetic fluorescent nanoprobes conjugated with antibody 12G5 were constructed by stepwise coupling. In cell experiments, the obtained probes demonstrated excellent targeting efficacy to CXCR4 overexpressed AML cells HL-60. In addition, HL-60 cells labelled with the magnetic probes can be magnetic isolated successfully in one microfluidics chip, with efficiency of 82.92 ± 7.03%. Overall, this method utilizes the superiority of superparamagnetic nanomaterials and microfluidic technology to achieve the enrichment and capture of drug-resistant cells in a microfluidic chip, providing a new idea for the isolation and detective of drug-resistant acute myeloid leukemia cells.

Abstract MnO2 is one of the most studied cathodes for aqueous neutral zinc‐ion batteries. However, the diverse reported crystal structures of MnO2 compared to δ‐MnO2 inevitably suffer a structural phase transition from tunneled to layered Zn‐buserite during the initial cycles, which is not as kinetically direct as the conventional intercalation electrochemistry in layered materials and thus poses great challenges to the performance and multifunctionality of devices. Here, a binder‐free δ‐MnO2 cathode is designed and a favorable “layered to layered” Zn2+ storage mechanism is revealed systematically using such a “noninterferencing” electrode platform in combination with ab initio calculation. A flexible quasi‐solid‐state Zn–Mn battery with an electrodeposited flexible Zn anode is further assembled, exhibiting high energy density (35.11 mWh cm−3; 432.05 Wh kg−1), high power density (676.92 mW cm−3; 8.33 kW kg−1), extremely low self‐discharge rate, and ultralong stability up to 10 000 cycles. Even with a relatively high δ‐MnO2 mass loading of 5 mg cm−2, significant energy and power densities are still achieved. The device also works well over a broad temperature range (0–40 °C) and can efficiently power different types of small electronics. This work provides an opportunity to develop high‐performance multivalent‐ion batteries via the design of a kinetically favorable host structure.