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Abstract Bone defects pose a significant risk to human health. Medical polyetheretherketone (PEEK) is an excellent implant material for bone defect repair, but it faces the challenge of bone osteoconduction and osseointegration. Osteoconduction describes the process by which bone grows on the surface of the implant, while osseointegration is the stable anchoring of the implant achieved by direct contact between the bone and the implant. Bone defects repair depends on the implant’s three-dimensional spatial structure, including pore size, porosity, and interconnections to a great extent. However, it is challenging to fabricate the porous structures to meet specific requirements and to characterize them without causing damage. In this study, we designed and fabricated sandwich-like PEEK implants mimicking the three-layer structures of the skull, whose defects imposes a significant burden on young adulthood and paediatric populations, and performed in-line phase-contrast synchrotron X-ray microtomography to non-destructively investigate the internal porous microstructures. The sandwich-like three-layer microstructure, comprising a dense layer, a loose layer and a dense layer in succession, exhibits structural similarity to that in a natural skull. This work demonstrated the fabrication of the sandwich-like PEEK implant that could potentially enhance osteoconduction and osseointegration. Furthermore, the interior structures and residual porogen sodium chloride particles were observed within the PEEK implant, which cannot be realized by other microscopic methods without destroying the sample. It highlights the advantages and potential of using synchrotron X-ray microtomography to analyze the structure of biomedical materials. This study provides theoretical guidance for the further design and fabrication of PEEK bone repair materials and will advance the clinical application of innovative bioactive bone repair materials.

The Orthopoxvirus (OPXV) genus of the Poxviridae includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the P2L gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.

Summary: The hypothalamic supramammillary nucleus (SuM) projects heavily to the hippocampus to regulate hippocampal activity and plasticity. Although the projections from the SuM to the dentate gyrus (DG) and CA2 have been extensively studied, whether the SuM projects to CA1, the main hippocampal output region, is unclear. Here, we report a glutamatergic pathway from the SuM that selectively excites CA1 interneurons in the border between the stratum radiatum (SR) and the stratum lacunosum-moleculare (SLM). We find that the SuM projects selectively to a narrow band in the CA1 SR/SLM and monosynaptically excites SR/SLM interneurons, including vasoactive intestinal peptide-expressing (VIP+) and neuron-derived neurotrophic factor-expressing (NDNF+) cells, but completely avoids making monosynaptic contacts with CA1 pyramidal neurons (PNs) or parvalbumin-expressing (PV+) or somatostatin-expressing (SOM+) cells. Moreover, SuM activation drives spikes in most SR/SLM interneurons to suppress CA1 PN excitability. Taken together, our findings reveal that the SuM can directly regulate hippocampal output region CA1, bypassing CA2, CA3, and the DG.

IntroductionUnder the background of digitalization of traditional Chinese medicine (TCM), this study aimed to realize the digital identification and adulteration analysis of Codonopsis Radix (CR) and Stellariae Radix (SR) based on chemical analysis.MethodsThis study combined digitalization concepts and chemical analysis and conducted a chemical analysis of CR and SR from different batches based on UHPLC-QTOF-MSE. Furthermore, the shared ions were extracted from different batches of CR and SR as their “ion characterization” after digital quantization. Then, the data matrices of unique ions of CR relative to SR and SR relative to CR were screened out, and the top-N ions were outputted as the “digital identities” of CR and SR, sorted by ionic strength. Finally, the above “digital identities” of CR and SR were used as benchmarks for matching positive samples and market samples to provide feedback on the matching credibility (MC) for identification and adulteration analysis.ResultsThe results showed that based on the “digital identities” of CR and SR, the digital identification of CR, SR, and positive samples can be realized at the individual level of TCM efficiently and accurately, even if 3% of SR in the mixed samples can still be identified efficiently and accurately. Moreover, 1 of the 12 batches of market samples was identified as an adulterated sample.ConclusionIt proved that the identification and adulteration analysis of two herbs can be realized efficiently and quickly through the “digital identities” of chemical compositions. It has important reference significance for developing the digital identification of CR and SR at the individual level of Chinese medicine based on the “digital identity” of chemical compositions, which was beneficial to the construction of digital quality control of CR and SR.

Aim: The main objective of this study was to investigate the antitumor effect of a mouse anti-human glypican-1 (GPC1) monoclonal antibody (mAb) on non-small cell lung carcinoma (NSCLC) and associated molecular mechanisms. Methods: The anti-proliferative and anti-migratory activities of anti-GPC1 mAb were examined in A549 and H460 NSCLC cells and LL97A lung fibroblasts. The inhibitory effect of anti-GPC1 mAb on tumor growth was evaluated in an orthotopic lung tumor model. Results: The in vitro study showed that anti-GPC1 mAb profoundly inhibited the anchorage-independent growth of A549 and H460 NSCLC cells and exhibited relatively high cytotoxic activities towards LL97A lung fibroblasts, A549/LL97A and H460/LL97A coculture spheroids. Moreover, anti-GPC1 mAb significantly decreased the expression of phospho-Src (p-Src; Tyr416), p-Akt (Ser473) and β-catenin in the co-cultured LL97A lung fibroblasts, and the expression of phospho-mitogen-activated protein kinase kinase (p-MEK; Ser217/221) and phospho-90 kDa ribosomal s6 kinase (p-p90RSK; Ser380) in co-cultured A549 cells. When anti-GPC1 mAb was administered to tumor-bearing mice, the inhibitory effect of anti-GPC1 mAb on the orthotopic lung tumor growth was not statistically significant. Nonetheless, results of Western blot analysis showed significant decrease in the phosphorylation of fibroblast growth factor receptor 1 (FGFR1) at Tyr766, Src at Tyr416, extracellular signal-regulated kinase (ERK) at Thr202/Tyr204, 90 kDa ribosomal S6 kinase (RSK) at Ser380, glycogen synthase kinases 3α (GSK3α) at Ser21 and GSK3β at Ser9 in tumor tissues. These data implicate that anti-GPC1 mAb treatment impairs the interaction between tumor cells and tumor associated fibroblasts by attenuating the paracrine FGFR signal transduction. Conclusions: The relatively potent cytotoxicity of anti-GPC1 mAb in lung fibroblasts and its potential inhibitory effect on the paracrine FGFR signal transduction warrant further studies on the combined use of this mAb with targeted therapeutics to improve therapeutic outcomes in lung cancer.

Abstract Development of potent and broad‐spectrum drugs against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains one of the top priorities, especially in the cases of the emergence of mutant viruses and inability of current vaccines to prevent viral transmission. In this study, we have generated a novel membrane fusion‐inhibitory lipopeptide IPB29, which is currently under clinical trials; herein, we report its design strategy and preclinical data. First, we surprisingly found that IPB29 with a rigid linker between the peptide sequence and lipid molecule had greatly improved α‐helical structure and antiviral activity. Second, IPB29 potently inhibited a large panel of SARS‐CoV‐2 variants including the previously and currently circulating viruses, such as Omicron XBB.5.1 and EG.5.1. Third, IPB29 could also cross‐neutralize the bat‐ and pangolin‐isolated SARS‐CoV‐2‐related CoVs (RatG13, PCoV‐GD, and PCoV‐GX) and other human CoVs (SARS‐CoV, MERS‐CoV, HCoV‐NL63, and HCoV‐229E). Fourth, IPB29 administrated as an inhalation solution (IPB29‐IS) in Syrian hamsters exhibited high therapeutic and preventive efficacies against SARS‐CoV‐2 Delta or Omicron variant. Fifth, the pharmacokinetic profiles and safety pharmacology of IPB29‐IS were extensively characterized, providing data to support its evaluation in humans. In conclusion, our studies have demonstrated a novel design strategy for viral fusion inhibitors and offered an ideal drug candidate against SARS‐CoV‐2 and other coronaviruses.

Ginseng Radix et Rhizoma (GRR), Panacis Quinquefolii Radix (PQR), Notoginseng radix et rhizoma (NRR) and Platycodonis Radix (PR) are often confused in the material market because of similar appearances and characteristics. Moreover, chemical identification methods tend to characterize the whole herb with regard to a single or a few components, which is an inaccurate representation and does not demonstrate the effective utilization of unknown components, and the result is unconvincing. In order to strengthen quality control, improve identification efficiency, and realize digital identification at the individual level of traditional Chinese medicine (TCM), we have put forward the “matrix characteristics” of TCM, combined with a UHPLC-QTOF-MS analysis to explore and realize the digital identification of GRR, PQR, NRR, and PR. The mass spectrometry was quantized to extract common data from different batches of the same TCMs as their matrix characteristics, and the matching credibility (M) was given by matching the “matrix characteristics” with unknown Chinese medicines. The results show that within a reasonable parameter threshold range, the M of four TCMs was higher than 92.00% compared with their own “matrix characteristics”, which was significantly higher than the M ranked second. Furthermore, the digital identification of four TCMs can be successfully realized based on the UHPLC-QTOF-MS analysis and “matrix characteristics”. This has important reference significance for developing the digital identification of GRR at an individual level based on UPLC-QTOF-MS and “matrix characteristics”.

Background: Periplocae Cortex (PC), Acanthopanacis Cortex (AC), and Lycii Cortex (LC), as traditional Chinese medicines, are all dried root bark, presented in a roll, light and brittle, easy to break, have a fragrant scent, etc. Due to their similar appearances, it is tough to distinguish them, and they are often confused and adulterated in markets and clinical applications. To realize the identification and quality control of three herbs, in this paper, Ultra Performance Liquid Chromatography-Quadrupole Time of Flight Mass Spectrometry Expression (UHPLC-QTOF-MSE) combined with chemometric analysis was used to explore the different chemical compositions. Methods: LC, AC, and PC were analyzed by UHPLC-QTOF-MSE, and the quantized MS data combined with Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) were used to explore the different chemical compositions with Variable Importance Projection (VIP) > 1.0. Further, the different chemical compositions were identified according to the chemical standard substances, related literature, and databases. Results: AC, PC, and LC can be obviously distinguished in PCA and PLS-DA analysis with the VIP of 2661 ions > 1.0. We preliminarily identified 17 differential chemical constituents in AC, PC, and LC with significant differences (p < 0.01) and VIP > 1.0; for example, Lycium B and Periploside H2 are LC and PC’s proprietary ingredients, respectively, and 2-Hydroxy-4-methoxybenzaldehyde, Periplocoside C, and 3,5-Di-O-caffeoylquinic acid are the shared components of the three herbs. Conclusions: UHPLC-QTOF-MSE combined with chemometric analysis is conducive to exploring the differential chemical compositions of three herbs. Moreover, the proprietary ingredients, Lycium B (LC) and Periploside H2 (PC), are beneficial in strengthening the quality control of AC, PC, and LC. In addition, limits on the content of shared components can be set to enhance the quality control of LC, PC, and AC.

To mitigate the challenges posed by the confined spatial environment of greenhouses and various obstacles that frequently cause non-line-of-sight (NLOS) communication issues in ultra-wideband (UWB) localization systems, leading to localization difficulties and low accuracy, we propose a real-time greenhouse localization system that recognizes UWB ranging values prior to correction. First, the initial ranging value is obtained through double-sided two-way ranging (DS-TWR). Subsequently, a communication state identifier is designed based on the residual distribution of ranging values across two UWB communication modes. A correction model is then established by analyzing the causes of ranging value deviations. Finally, the NLOS localization deviation is corrected using an improved unscented Kalman filter (IUKF) algorithm. Experimental results in the greenhouse environment demonstrate that the proposed algorithm enhances positioning accuracy by 68% compared to the uncorrected localization method, offering a valuable reference for localization services in greenhouse settings.

Abstract Background Long non-coding RNAs (lncRNAs) play critical roles in various biological processes in plants. Extensive studies utilizing high-throughput RNA sequencing have revealed that many lncRNAs are involved in plant disease resistance. Oryza sativa RNase P protein 30 (OsRpp30) has been identified as a positive regulator of rice immunity against fungal and bacterial pathogens. Nevertheless, the specific functions of lncRNAs in relation to OsRpp30-mediated disease resistance in rice remain elusive. Results We conducted a comprehensive analysis of lncRNAs, miRNAs, and mRNAs expression patterns in wild type (WT), OsRpp30 overexpression (OsRpp30-OE), and OsRpp30 knockout (OsRpp30-KO) rice plants. In total, we identified 91 differentially expressed lncRNAs (DElncRNAs), 1671 differentially expressed mRNAs (DEmRNAs), and 41 differentially expressed miRNAs (DEmiRNAs) across the different rice lines. To gain further insights, we investigated the interaction between DElncRNAs and DEmRNAs, leading to the discovery of 10 trans- and 27 cis-targeting pairs specific to the OsRpp30-OE and OsRpp30-KO samples. In addition, we constructed a competing endogenous RNA (ceRNA) network comprising differentially expressed lncRNAs, miRNAs, and mRNAs to elucidate their intricate interplay in rice disease resistance. The ceRNA network analysis uncovered a set of gene targets regulated by lncRNAs and miRNAs, which were found to be involved in pathogen recognition, hormone pathways, transcription factor activation, and other biological processes related to plant immunity. Conclusions Our study provides a comprehensive expression profiling of lncRNAs, miRNAs, and mRNAs in a collection of defense mutants in rice. To decipher the putative functional significance of lncRNAs, we constructed trans- and cis-targeting networks involving differentially expressed lncRNAs and mRNAs, as well as a ceRNA network incorporating differentially expressed lncRNAs, miRNAs, and mRNAs. Together, the findings from this study provide compelling evidence supporting the pivotal roles of lncRNAs in OsRpp30-mediated disease resistance in rice.

This study systematically investigates the effect of Al2O3 insertions on the thermal stability of [Pt(1)/Al2O3(t)/Co(0.4)]3 films (unit: nm). The interdiffusion of Pt and Co was limited by inserting a thin Al2O3 at the Pt/Co interface for film after annealing. The increased perpendicular magnetic anisotropy (PMA) and decreased coercivity (Hc) were observed for the films with Al2O3 insertions after annealing at 400 °C. X-ray diffraction results show that CoPt3(111) is formed. Simultaneously, oxygen from the Al2O3 insertions combined with Co to form Co oxides that strengthened the PMA. The annealed film with the Al2O3 insertions has better CoPt3(111) crystallinity, lower Hc, and higher amount of Co oxides than those without Al2O3 insertions. To meet the application requirements for magnetic tunnel junction electrodes, it is critical to maintain strong PMA during the 400°C-annealing process, which can be achieved by inserting Al2O3 in the [Pt/Co]n multilayers.

Abstract Background The determination of nutrient content in the petiole is one of the important methods for achieving cotton fertilization management. The establishment of a monitoring system for the nutrient content of cotton petioles during important growth periods under drip irrigation is of great significance for achieving precise fertilization and environmental protection. Methods A total of 100 cotton fields with an annual yield of 4500–7500 kg/ha were selected among the main cotton-growing areas of Northern Xinjiang. The nitrate nitrogen (NO3 −–N), inorganic phosphorus (PO4 3−–P) and inorganic potassium (K+–K) content and yield of cotton petioles were recorded. Based on a yield of 6000 kg/ha as the dividing line, a two-level and yield-graded monitoring system for NO3 −–N, PO4 3−–P and K+–K in cotton petioles during important growth periods was established, and predictive yield models for NO3 −–N, PO4 3−–P and K+–K in petioles during important growth periods were established. Results The results showed found that the yields of the 100 cotton fields surveyed were normally distributed. Therefore, two yield grades were classified using 6000 kg/ha as a criterion. Under different yield-graded, the NO3 −–N, PO4 3−–P and K+–K content of petiole at important growth stages was significantly positively correlated with yield. Further, the variation range of NO3 −–N, PO4 3−–P and K+–K content in petioles could be used as a standard for yield-graded. In addition, a yield prediction model for the NO3 −–N, PO4 3−–P and K+–K content of petioles was developed. The SSO-BP validation model performed the best (R2 = 0.96, RMSE = 0.06 t/ha, MAE = 0.05 t/ha) in the full bud stage, which was 12.9% higher than the BP validation model. However, the RMSE and MAE were decreased by 86.7% and 88.1%, respectively. Conclusion The establishment of NPK nutrition monitor system of cotton petioles under drip irrigation based on yield-graded provides an important basis for nutrition monitor of cotton petiole under drip irrigation in Xinjiang. It also provides a new method for cotton yield prediction.

Background: To evaluate the efficacy of stent-assisted coiling (SAC) for the treatment of carotid ophthalmic segment aneurysm segment aneurysms (OSAs) of the internal carotid artery (ICA) through detailed long-term follow-up of a large patient cohort. Methods: We retrospectively analyzed 88 consecutive patients with OSAs between January 2009 and January 2020 ​at our center. Angiographic results were evaluated using the modified Raymond grading system and clinical outcomes were evaluated using the mRS scale. The primary endpoints were major aneurysm recurrence and poor clinical outcomes for at least 18 months of follow-up. The patients were asked to attend clinical follow-up assessments and possibly undergo DSA or MR via telephone. Results: We enrolled 88 patients with 99 OSAs treated with coiling, of whom 76 were treated with SAC. The coiling procedures were successful in all 88 patients. Overall, complications occurred in 8 patients (9.1%). No procedure-related mortality was observed. 67 (76.1%) experienced immediate aneurysm occlusion at the end of the procedure. Long-term angiographic follow-up (18 months) was available in 45/88 aneurysms (51%) (average 18.7 ​± ​5.2 months). Four patients continued their follow-up for 5 years after initial aneurysm treatment. After a clinical follow-up time of 28.7 months (range, 12–51 months), 85 patients (95.5%) achieved favorable clinical outcomes (mRS scores of 0–2). Conclusions: This study indicates that SAC treatment is a safe and effective therapeutic alternative for ruptured and unruptured OSAs. The procedural risks are low with relatively long-term effectiveness.

Abstract In order to elucidate the effects of different nitrogen (N), phosphorus (P), and potassium (K) fertilization timing sequences management on nutrient absorption and utilization in drip irrigation cotton, field experiments were conducted from 2020 to 2021. There are six timing sequences management methods for NPK fertilization (S1–S6: 1/3Time N–1/3Time PK–1/3Time W, 1/3Time PK–1/3Time N–1/3Time W, 1/2Time NPK–1/2Time W, 1/4Time W–1/4Time N–1/4Time PK–1/4Time W, 1/3Time W–1/3Time NPK–1/3Time W), among which S6 is the current management method for field fertilization timing sequences, and S7 is the non N. The results showed that during the main growth stage, S5 accumulated more nitrate nitrogen (NO3 –-N) and ammonium nitrogen (NH4 +-N) content in soil between 20 and 40 cm, and accumulated more available phosphorus content in soil between 5–15 cm and 15–25 cm, S5 reducing N leaching and increasing P mobility. It is recommended to change the timing sequences management method of NPK fertilization for drip irrigation cotton to 1/4Time W–1/4Time PK–1/4Time N–1/4Time W, which is beneficial for plant nutrient absorption and utilization while reducing environmental pollution.

Bunyaviruses are a large group of important viral pathogens that cause significant diseases in humans and animals worldwide. Bunyaviruses are enveloped, single-stranded, negative-sense RNA viruses that infect a wide range of hosts. Upon entry into host cells, the components of viruses are recognized by host innate immune system, leading to the activation of downstream signaling cascades to induce interferons (IFNs) and other proinflammatory cytokines. IFNs bind to their receptors and upregulate the expression of hundreds of interferon-stimulated genes (ISGs). Many ISGs have antiviral activities and confer an antiviral state to host cells. For efficient replication and spread, viruses have evolved different strategies to antagonize IFN-mediated restriction. Here, we discuss recent advances in our understanding of the interactions between bunyaviruses and host innate immune response.

Tibet orbivirus (TIBOV) was first isolated from Anopheles maculatus mosquitoes in Xizang, China, in 2009. In recent years, more TIBOV strains have been isolated in several provinces across China, Japan, East Asia, and Nepal, South Asia. Furthermore, TIBOVs have also been isolated from Culex mosquitoes, and several midge species. Additionally, TIBOV neutralizing antibodies have been detected in serum specimens from several mammals, including cattle, sheep, and pigs. All of the evidence suggests that the geographical distribution of TIBOVs has significantly expanded in recent years, with an increased number of vector species involved in its transmission. Moreover, the virus demonstrated infectivity towards a variety of animals. Although TIBOV is considered an emerging orbivirus, detailed reports on its genome and molecular evolution are currently lacking. Thus, this study performed the whole-genome nucleotide sequencing of three TIBOV isolates from mosquitoes and midges collected in China in 2009, 2011, and 2019. Furthermore, the genome and molecular genetic evolution of TIBOVs isolated from different countries, periods, and hosts (mosquitoes, midges, and cattle) was systematically analyzed. The results revealed no molecular specificity among TIBOVs isolated from different countries, periods, and vectors. Meanwhile, the time-scaled phylogenetic analysis demonstrated that the most recent common ancestor (TMRCA) of TIBOV appeared approximately 797 years ago (95% HPD: 16-2347) and subsequently differentiated at least three times, resulting in three distinct genotypes. The evolutionary rate of TIBOVs was about 2.12 × 10-3 nucleotide substitutions per site per year (s/s/y) (95% HPD: 3.07 × 10-5, 9.63 × 10-3), which is similar to that of the bluetongue virus (BTV), also in the Orbivirus genus. Structural analyses of the viral proteins revealed that the three-dimensional structures of the outer capsid proteins of TIBOV and BTV were similar. These results suggest that TIBOV is a newly discovered and rapidly evolving virus transmitted by various blood-sucking insects. Given the potential public health burden of this virus and its high infectious rate in a wide range of animals, it is significant to strengthen research on the genetic variation of TIBOVs in blood-feeding insects and mammals in the natural environment and the infection status in animals.

The luminous characteristics of flip-chip type high-voltage (HV) blue mini-light-emitting diodes (LEDs), which consist of three serially connected sub-mesas, have been investigated for the first time. The cryogenic electroluminescence below 100 K partially originates from localized excitons. As the driving current reaches 1 μA, the contributions of Shockley–Read–Hall nonradiative recombination and radiative recombination exhibit a remarkably inverse temperature dependence, while the contributions of Auger recombination and carrier leakage are relatively negligible. The mesa corresponding to the anode of the HV blue mini-LED exhibits the lowest temperature among the three sub-mesas due to its smaller thermal resistance. To minimize the temperature-induced shift in chromaticity coordinates, it is necessary to adjust the driving current based on the operating temperature.

Background: As one of the four most valuable animal medicines, Fel Ursi, named Xiong Dan (XD) in China, has the effect of clearing heat, calming the liver, and brightening the eyes. However, due to the special source of XD and its high price, other animals’ bile is often sold as XD or mixed with XD on the market, seriously affecting its clinical efficacy and consumers’ rights and interests. In order to realize identification and adulteration analysis of XD, UHPLC-QTOF-MSE and multivariate statistical analysis were used to explore the differences in XD and six other animals’ bile. Methods: XD, pig gall (Zhu Dan, ZD), cow gall (Niu Dan, ND), rabbit gallbladder (Tu Dan, TD), duck gall (Yan Dan, YD), sheep gall (Yang Dan, YND), and chicken gall (Ji Dan, JD) were analyzed by UHPLC-QTOF-MSE, and the MS data, combined with multivariate analysis methods, were used to distinguish between them. Meanwhile, the potential chemical composition markers that contribute to their differences were further explored. Results: The results showed that XD and six other animals’ bile can be distinguished from each other obviously, with 27 ions with VIP > 1.0. We preliminarily identified 10 different bile acid-like components in XD and the other animals’ bile with significant differences (p < 0.01) and VIP > 1.0, such as tauroursodeoxycholic acid, Glycohyodeoxycholic acid, and Glycodeoxycholic acid. Conclusions: The developed method was efficient and rapid in accurately distinguishing between XD and six other animals’ bile. Based on the obtained chemical composition markers, it is beneficial to strengthen quality control for bile medicines.

Partial-admission impulse turbine is suitable for small-scale power cycles with a high expansion pressure ratio (EPR) and a low mass flow rate. However, the exit velocity of a single-stage turbine is very high, leading to a large exit loss. A new two-stage counter-rotating impulse turbine has been developed to recover the exit loss, which has a novel structure without stator between the two rotors. However, the internal flow characteristic of such a turbine is still unclear. In this study, the aerodynamic performance of the two-stage counter-rotating partial-admission impulse turbine is analyzed. The internal aerodynamic characteristics are estimated via CFD simulation. First, the geometric parameters are determined based on the mean-line model. Then, the characteristic line method is adopted to design the blade profile of the first supersonic stage based on the vortex flow theory. Subsequently, the performances are estimated under the design and off-design conditions via 3D CFD simulation. The results indicate that the modified convergent-divergent supersonic nozzle exhibits a better adaption with the impellers. The load is principally imposed on the upper zone of the blades. The power output of the turbine reaches 1501.3 W with an EPR of 52 and an efficiency of 45.99 % at the design point and the power of the first impeller accounts for 76.5 %. The mass flow rate increases almost linearly with the augmentation of the turbine inlet pressure. The power output proportion of the second impeller may arrive at 27.63 % under off-design conditions, showing the addition of the second stage can improve the turbine performance evidently.

This review provides an overview of the key role played by perivascular adipose tissue (PVAT) in the protection of cardiovascular health. PVAT is a specific type of adipose tissue that wraps around blood vessels and has recently emerged as a critical factor for maintenance of vascular health. Through a profound exploration of existing research, this review sheds light on the intricate structural composition and cellular origins of PVAT, with a particular emphasis on combining its regulatory functions for vascular tone, inflammation, oxidative stress, and endothelial function. The review then delves into the intricate mechanisms by which PVAT exerts its protective effects, including the secretion of diverse adipokines and manipulation of the renin-angiotensin complex. The review further examines the alterations in PVAT function and phenotype observed in several cardiovascular diseases, including atherosclerosis, hypertension, and heart failure. Recognizing the complex interactions of PVAT with the cardiovascular system is critical for pursuing breakthrough therapeutic strategies that can target cardiovascular disease. Therefore, this review aims to augment present understanding of the protective role of PVAT in cardiovascular health, with a special emphasis on elucidating potential mechanisms and paving the way for future research directions in this evolving field.

Objectives This work aimed to analyse the risk factors for poor outcomes and mortality among patients with anterior large vessel occlusion (LVO) ischaemic stroke, despite successful recanalisation.Setting and participants This study conducted a secondary analysis among patients who underwent successful recanalisation in the CAPTURE trial. The trial took place between March 2018 and September 2020 at 21 sites in China. The CAPTURE trial enrolled patients who had an acute ischaemic stroke aged 18–80 years with LVO in anterior circulation.Interventions Thrombectomy was immediately performed using Neurohawk or the Solitaire FR after randomisation in CAPTURE trial. Rescue treatment was available for patients with severe residual stenosis caused by atherosclerosis.Primary and secondary outcome measures The primary goal was to predict poor 90-day survival or mortality within 90 days post-thrombectomy. Univariate analysis, using the χ2 test or Fisher’s exact test, was conducted for each selected factor. Subsequently, a multivariable analysis was performed on significant factors (p≤0.10) identified through univariate analysis using the backward selection logistic regression approach.Results Among the 207 recruited patients, 79 (38.2%) exhibited poor clinical outcomes, and 26 (12.6%) died within 90 days post-thrombectomy. Multivariate analysis revealed that the following factors were significantly associated with poor 90-day survival: age ≥67 years, internal carotid artery (ICA) occlusion (compared with middle cerebral artery (MCA) occlusion), initial National Institutes of Health Stroke Scale (NIHSS) score ≥17 and final modified Thrombolysis in Cerebral Infarction (mTICI) score 2b (compared with mTICI 3). Additionally, the following factors were significantly associated with mortality 90 days post-thrombectomy: initial NIHSS score ≥17, ICA occlusion (compared with MCA occlusion) and recanalisation with more than one pass.Conclusions Age, NIHSS score, occlusion site, mTICI score and the number of passes can be independently used to predict poor 90-day survival or mortality within 90 days post-thrombectomy.Trial registration number NCT04995757.

AbstractAim: To investigate the treatment of intractable epistaxis after radiotherapy for nasopharyngeal carcinoma (NPC).Methods: This review focuses on the anatomy and pathophysiology, mechanism, and clinical treatments of epistaxis after NPC radiotherapy.Results: For treating NPC, radiation therapy is the primary therapeutic modality. However, radiotherapy can lead to varied degrees of harm to the neighboring tissues and is correlated with numerous complications. Among these complications, epistaxis is a common occurrence after NPC radiotherapy, owing to damage to the surrounding tissues caused by radiotherapy. Unfortunately, epistaxis, particularly carotid blowout, can have a dangerous course and a high mortality rate. Accurate understanding of epistaxis following radiotherapy, prompt bleeding cessation, and reduction of bleeding volume are key considerations. Nasal tamponade is a crucial rescue treatment, while tracheotomy is an active and effective method. Intravascular balloon embolization is a reliable and effective treatment method for ICA hemorrhage, and vascular embolization is the primary approach for treating external carotid artery maxillary bleeding. Implantation of a covered stent can achieve hemostasis without altering hemodynamics.Conclusion: A comprehensive approach utilizing these methods can improve the success rate of treating nosebleeds following NPC radiotherapy.HighlightsThe mortality rate for carotid blowout following radiotherapy for NPC is high.Radiation therapy and tumor condition are correlated with epistaxis in NPC.Treatment methods for NPC-related epistaxis include posterior nostril tamponade, endoscopic hemostasis, DSA, selective vascular embolization, and stent implantation.The use of a covered stent for NPC-related carotid blowout achieves hemostasis without altering blood perfusion.Effective and timely application of various hemostasis methods is key to improving the success rate of rescue, considering the characteristics of NPC-related epistaxis.

Abstract Long non-coding RNAs (lncRNAs) play an essential role in diverse biological processes and disease development. Accurate classification of lncRNAs and mRNAs is important for the identification of tissue- or disease-specific lncRNAs. Here, we present our tool LncDC (Long non-coding RNA detection) that is able to accurately predict lncRNAs with an XGBoost model using features extracted from RNA sequences, secondary structures, and translated proteins. Benchmarking experiments showed that LncDC consistently outperformed six state-of-the-art tools in distinguishing lncRNAs from mRNAs. Notably, the use of sequence and secondary structure (SASS) k-mer score features and flexible ORF features improved the classification capability of LncDC. We anticipate that LncDC will definitely promote the discovery of more and novel disease-specific lncRNAs. LncDC is implemented in Python and freely available at https://github.com/lim74/LncDC .

Abstract Magnetic tunnel junction (MTJ) with magnesium oxide (MgO) tunnel barrier is the core element of spin transfer torque-based magnetic random access memory. For the application in the space environment, the total ionizing dose radiation effects on MTJs need to be evaluated. In this work, the MTJs were exposed to X-ray radiation with different doses of up to 10 Mrad(Si). Measurements of current induced magnetization switching (CIMS) behavior of these MTJs were performed before and after radiation. The results show negligible changes in the tunneling magnetoresistance and current switching properties after 8 Mrad(Si) X-ray radiation. However, with a total dose of 9 Mrad(Si), a significant reduction in junction resistance of a fairly large number of MTJs was observed, which showed characteristics of MTJ breakdown. Moreover, in this study, all experimental MTJs became functionally disabled due to MgO breakdown under 10 Mrad(Si) X-ray radiation. The CoFeB/MgO/CoFeB interface microstructure was observed using X-ray photoelectron spectroscopy and high-resolution transmission electron microscopy (HRTEM). Interfacial structural results indicate that the MgO degradation and breakdown behavior caused by X-ray ionizing radiation can give rise to radiation-induced oxygen vacancies across the tunnel barrier oxide layer.

IntroductionAdjuvants can effectively enhance the utilization rate of pesticides, but the application of adjuvants in plant growth regulators is rarely studied.MethodsThis work explored the effects of adjuvants dioctyl sulfosuccinate sodium salt (AOT) and methyl oleate (MO) on lime sulfur (LS), especially the drop behavior on flower and paraffin surface.ResultsThe results showed that the addition of AOT and AOT+MO can significantly reduce the static and dynamic surface tension of LS from 72mN/m to 28mN/m and 32mN/m respectively, and increase the spreading factor from 0.18 to 1.83 and 3.10 respectively, reduce the bounce factor from 2.72 to 0.37 and 0.27 respectively. The fluorescence tracer test showed that the addition of adjuvants could promote the spreading and permeation of droplets. The field test results revealed that the flower thinning rate of adjuvant and non-adjuvant were 80.55% and 54.4% respectively, and the flower thinning effect of adding adjuvant was the same as that of artificial which the flower thinning rate was 84.77%. The quality of apples treated with adjuvants was similar to that treated with artificial, and the weight of single fruit increased by 24.08% compared with CK (spray water).DiscussionThe application of tank-mixture adjuvant could reduce the dosage of LS for thinning agent application, improve apple’s quality, and decrease labor cost and improve the economic benefits of fruit planting and the environmental benefits of plant growth regulators.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths, posing a substantial threat to global public health. Viruses evolve different strategies to antagonize or evade host immune responses. While ectopic expression of SARS-CoV-2 accessory protein ORF6 blocks interferon (IFN) production and downstream IFN signaling, the role of ORF6 in IFN signaling during bona fide viral infection of respiratory cells is unclear. By comparing wild-type (WT) and ORF6-deleted (ΔORF6) SARS-CoV-2 infection and IFN signaling in respiratory cells, we found that ΔORF6 SARS-CoV-2 replicates more efficiently than WT virus and, thus, stimulates more robust immune signaling. Loss of ORF6 does not alter innate signaling in infected cells: both WT and ΔORF6 virus induce delayed IFN responses only in bystander cells. Moreover, expression of ORF6 in the context of SARS-CoV-2 infection has no effect on Sendai virus-stimulated IFN induction: robust translocation of IRF3 is observed in both SARS-CoV-2 infected and bystander cells. Furthermore, IFN pretreatment potently blocks WT and ΔORF6 virus replication similarly, and both viruses fail to suppress the induction of interferon-stimulated genes (ISGs) upon IFN-β treatment. However, upon treatment with IFN-β, only bystander cells induce STAT1 translocation during infection with WT virus, whereas ΔORF6 virus-infected cells now show translocation. This suggests that under conditions of high IFN activation, ORF6 can attenuate STAT1 activation. These data provide evidence that ORF6 is not sufficient to antagonize IFN production or IFN signaling in SARS-CoV-2-infected respiratory cells but may impact the efficacy of therapeutics that stimulate innate immune pathways. IMPORTANCE Previous studies identified several SARS-CoV-2 proteins, including ORF6, that antagonize host innate immune responses in the context of overexpression of viral proteins in non-respiratory cells. We set out to determine the role of ORF6 in IFN responses during SARS-CoV-2 infection of respiratory cells. Using a deletion strain, we observed no reduction of infection and no difference in evasion of IFN signaling, with responses limited to bystander cells. Moreover, stimulation of Sendai virus-induced IFN production or IFN-β-stimulated ISG expression was comparable between SARS-CoV-2 virus and SARS-CoV-2 lacking ORF6 virus, suggesting that ORF6 is not sufficient to counteract IFN induction or IFN signaling during viral infection.

To elucidate the variation characteristics of nitrogen (N), phosphorus (P), and potassium (K) content and accumulation in cotton at different yield levels, a two-year experiment was conducted using cotton variety Lumianyan 24 under four N treatments (506, 402.5, 299, and 195.5 kg ha−1, designated as N1, N2, N3, and N4, respectively). The four P and K fertilization ratios were (PK-M1, 25% P and K applied at squaring stage (SS) and 75% at the bloom-bolling stages (BS)), 50%:50% (PK-M2, 50% P and K applied at each stage), 75%:25% (PK-M3, 75% P and K applied at SS and 25% at the BS) and 100%:0% (PK-M4, total P and K applied at SS). The results showed that the N content (Nc), P content (Pc), and K content (Kc) of cotton plants at high yield levels were 23.3%, 44.2%, and 31.6% higher than those at low yield levels. In addition, the reproductive organs maintained higher Pc and Kc at high yield levels, and the Nc, Pc, and Kc exhibited positive linear correlations with yield, while Nc/Pc, Nc/Kc, and Kc/Pc had significant negative correlations with yield. In conclusion, seed cotton yield was mainly limited by Nc at low yield levels and affected by Pc and Kc at high yield levels. Then, when 0.85 < Nc/Kc < 1.0 at the full squaring stage (FS), 0.8 < Nc/Kc < 1.0 at the full flowering stage (FF), 4.3 < Nc/Pc < 6.7 at the early-full bolling stage (EFB) and 4.9 < Nc/Pc < 7.1 at the late-full bolling stage (LFB), there is a high yield potential of 7000–9000 kg ha−1. Furthermore, yields can be improved by reducing the application of N during the growing period and increasing the application of P fertilizer during the later growth period.

The accurate assessment of nitrogen (N) status is important for N management and yield improvement. The N status in plants is affected by plant densities and N application rates, while the methods for assessing the N status in drip-irrigated cotton under reduced nitrogen treatment and different plant densities are lacking. Therefore, this study was conducted with four different N treatments (195.5, 299, 402.5, and 506 kg N ha−1) and three sowing densities (6.9 × 104, 13.8 × 104, and 24 × 104 plants ha−1) by using a low-cost Unmanned Aerial Vehicle (UAV) system to acquire RGB imagery at a 10 m flight altitude at cotton main growth stages. We evaluated the performance of different ground resolutions (1.3, 2.6, 5.2, 10.4, 20.8, 41.6, 83.2, and 166.4 cm) for image textures, vegetation indices (VIs), and their combination for leaf N concentration (LNC) estimation using four regression methods (stepwise multiple linear regression, SMLR; support vector regression, SVR; extreme learning machine, ELM; random forest, RF). The results showed that combining VIs (ExGR, GRVI, GBRI, GRRI, MGRVI, RGBVI) and textures (VAR, HOM, CON, DIS) yielded higher estimation accuracy than using either alone. Specifically, the RF regression models had a higher accuracy and stability than SMLR and the other two machine learning algorithms. The best accuracy (R2 = 0.87, RMSE = 3.14 g kg−1, rRMSE = 7.00%) was obtained when RF was applied in combination with VIs and texture. Thus, the combination of VIs and textures from UAV images using RF could improve the estimation accuracy of drip-irrigated cotton LNC and may have a potential contribution in the rapid and non-destructive nutrition monitoring and diagnosis of other crops or other growth parameters.

BackgroundDespite years of public cardiopulmonary resuscitation (CPR) training efforts, the training rate and survival following out-of-hospital cardiac arrest (OHCA) have increased modestly in China. Access is imperative to increase the public CPR training rate, which is determined by both demand- (e.g., the lay public) and supply-side (e.g., CPR trainers) factors. We aimed to explore the demand and supply determinants of access to CPR training for the lay public in China.MethodsQualitative semi-structured interviews were conducted with 77 laypeople (demand side) and eight key stakeholders from CPR training institutions (supply side) in Shanghai, China. The interview guide was informed by Levesque et al. healthcare access framework. Data were transcribed, quantified, described, and analyzed through thematic content analysis.ResultsOn the demand side, the laypeople's ability to perceive their need and willingness for CPR training was strong. However, they failed to access CPR training mainly due to the lack of information on where to get trained. Overestimation of skills, optimism bias, and misconceptions impeded laypeople from attending training. On the supply side, trainers were able to meet the needs of the trainees with existing resources, but they relied on participants who actively sought out and registered for training and lacked an understanding of the needs of the public for marketing and encouraging participation in the training.ConclusionInsufficient information and lack of initiative on the demand side, lack of motivation, and understanding of public needs on the supply side all contributed to the persistently low CPR training rate in China. Suppliers should integrate resources, take the initiative to increase the CPR training rate, innovate training modes, expand correct publicity, and establish whole-process management of training programs.

Background and purposeSpinal dural arteriovenous fistulas located in the lumbosacral region are rare and present with nonspecific clinical signs. The purpose of this study was to find out the specific radiologic features of these fistulas.MethodsWe retrospectively reviewed the clinical and radiological data of 38 patients diagnosed with lumbosacral spinal dural arteriovenous fistulas in our institution from September 2016 to September 2021. All patients underwent time-resolved contrast-enhanced three-dimensional MRA and DSA examinations, and were treated with either endovascular or neurosurgical strategies.ResultsMost of the patients (89.5%) had motor or sensory disorders in both lower limbs as the first symptoms. On MRA, the dilated filum terminale vein or radicular vein was seen in 23/30 (76.7%) patients with lumbar spinal dural arteriovenous fistulas and 8/8 (100%) patients with sacral spinal dural arteriovenous fistulas. T2W intramedullary abnormally high signal intensity areas were found in all lumbosacral spinal dural arteriovenous fistula patients, with involvement of the conus present in 35/38 (92.1%) patients. The “missing piece sign” in the intramedullary enhancement area was seen in 29/38 (76.3%) patients.ConclusionDilatation of the filum terminale vein or radicular vein is powerful evidence for diagnosis of lumbosacral spinal dural arteriovenous fistulas, especially for sacral spinal dural arteriovenous fistulas. T2W intramedullary hyperintensity in the thoracic spinal cord and conus, and the missing-piece sign could be indicative of lumbosacral spinal dural arteriovenous fistula.

ObjectiveThe Neurohawk retriever is a new fully radiopaque retriever. A randomized controlled non-inferiority trial was conducted to compare the Neurohawk and the Solitaire FR in terms of safety and efficacy. In order to evaluate the efficacy and safety of endovascular treatment in acute ischemic stroke (AIS) caused by intracranial atherosclerotic disease (ICAD) larger vessel occlusion (LVO), a sub-analysis was performed.MethodsAcute ischemic stroke patients aged 18–80 years with LVO in the anterior circulation were randomly assigned to undergo thrombectomy with either the Neurohawk or the Solitaire FR. The primary efficacy endpoint was successful reperfusion (mTICI 2b-3) rate by the allocated retriever. A relevant non-inferiority margin was 12.5%. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and all-cause mortality within 90 days. Secondary endpoints included first-pass effect (FPE), modified FPE, and favorable outcomes at 90 days. In subgroup analysis, the patients were divided into the ICAD group and non-ICAD group according to etiology, and baseline characteristics, angiographic, and clinical outcomes were compared.ResultsA total of 232 patients were involved in this analysis (115 patients in the Neurohawk group and 117 in the Solitaire group). The rates of successful reperfusion with the allocated retriever were 88.70% in the Neurohawk group and 90.60% in the Solitaire group (95%CI of the difference, −9.74% to 5.94%; p = 0.867). There were similar results in FPE and mFPE in both groups. The rate of sICH seemed higher in the Solitaire group (13.16% vs. 7.02%, p = 0.124). All-cause mortality and favorable outcome rates were comparable as well. In subgroup analysis, 58 patients were assigned to the ICAD group and the remaining 174 to the non-ICAD group. The final successful reperfusion and favorable outcome rates showed no statistically significant differences in two groups. Mortality within 90 days was relatively lower in the ICAD group (6.90% vs. 17.24%; p = 0.054).ConclusionThe Neurohawk retriever is non-inferior to the Solitaire FR in the mechanical thrombectomy of large vessel occlusion-acute ischemic stroke (LVO-AIS). The sub-analysis suggested that endovascular treatment including thrombectomy with the retriever and essential rescue angioplasty is effective and safe in AIS patients with intracranial atherosclerotic disease-larger vessel occlusion (ICAD-LVO).Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04995757, number: NCT04995757.

Energy-efficient compact alternatives to fully digital computing strategies could be achieved by implementations of artificial neural networks (ANNs) that borrow analog techniques. In-memory computing based on crossbar device architectures with memristive materials systems that execute, in an analog way, multiply-and-accumulate operations prevalent in ANN is a notable example. Ferroelectric (FE) materials are promising candidates for achieving ANN thanks to their excellent down-scalability, improved electrical control, and high energy efficiency. However, it remains challenging to develop a crossbar device architecture using FE materials. The difficulty stems from decreasing the leakage current of FE hardware and, simultaneously, reducing the film thickness for achieving compact systems. Here, we have performed density-functional-theory calculations to investigate the electronic, energy-based, and structural signatures of wurtzite FE material Al0.75Sc0.25N with a nitrogen vacancy (VN) in different charge states. We find that VN can introduce two defect states, viz., the singlet state above the valence band maximum (VBM) and a triplet state below the conduction band minimum in wurtzite AlScN models. The calculations reveal that the group of transition levels E3+/2+/E2+/1+ with small formation energies occur at ∼0.78/1.03 eV above the VBM in the wurtzite AlScN with a relaxed configuration, which may shift by a large degree to lower energy levels if atoms surrounding the defect are not fully relaxed. Theoretical studies elucidate the vacancy-enhanced increase in the leakage current utilizing large AlScN supercells. These findings render atomistic insights that can provide a path forward for the design of next-generation portable low-power electronic systems.

Approximately 50–60% of patients with a clinical transient ischemic attack (TIA) do not have diffusion-weighted imaging (DWI) evidence of cerebral ischemia. The purpose of this study was to assess the added diagnostic value of diffusion kurtosis imaging (DKI) in the evaluation of patients with TIA who have normal DWI findings. From September 2014 to May 2017, a total of 179 consecutive patients with suspected TIA were eligible for enrollment in our study. The inclusion criteria were a confirmed diagnosis of TIA confirmed by a stroke neurologist, MRI (including DWI and DKI) within 24 h after symptom onset, no stroke history, and no DWI lesion. A follow-up DWI was performed to establish stroke recurrence within a period of 90 days. A total of 98 patients who had no lesions on the baseline DWI were included for data analysis. Of these 98 patients, 31 (31.6%) had positive findings on the initial DKI. In 29 of the 31 (93.5%) patients, the location of the abnormality observed on DKI was consistent with the clinical symptoms. During the 90-day follow-up period, 14 (14.3%) patients developed recurrent stroke. The prevalence of recurrent stroke was higher in the DKI-positive group than in the DKI-negative group (29.0% vs. 7.5%, p = 0.01). A comparison between the patients with and without recurrent stroke showed that an abnormality on the baseline DKI was associated with stroke recurrence. Furthermore, 8 of the 9 stroke patients in the DKI-positive group developed a new ischemic lesion in the artery territory corresponding to the initial DKI abnormality. The new findings suggest the predictive value of DKI on the recurrence of stroke in the patients with TIA who have negative findings on conventional DWI.

Abstract Macrophage cell membrane-camouflaged nanocarriers can effectively reduce immune cell clearance and actively target tumors. In this study, a macrophage cell membrane-camouflaged mesoporous silica nanorod (MSNR)-based antitumor drug carrier equipped with a cationic polymer layer was developed. As drug carriers, these MSNRs were loaded with the thermosensitive phase change material L-menthol (LM), the chemotherapy drug doxorubicin (DOX) and the fluorescent molecule indocyanine green (ICG). The rod-like shape of the MSNRs was shown to enhance the penetration of the drug carriers to tumors. In the weakly acidic tumor microenvironment, the cationic polymer exhibited a proton sponge effect to trigger macrophage cell membrane coating detachment, promoting tumor cell uptake. Following nanocarrier uptake, ICG is heated by near-infrared (NIR) irradiation to make LM undergo a phase transition to release DOX and generate a synergistic effect of thermochemotherapy which kills tumor cells and inhibits tumor growth together with reactive oxygen species (ROS) produced by ICG. Overall, this nanohybrid drug delivery system demonstrates an intelligent cascade response, leads to tissue-cell specific targeting and improves drug release accuracy, thus proving to be an effective cancer therapy. Graphical Abstract

Abstract In the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection.

Abstract Background Estimation of nitrate nitrogen (NO3 −–N) content in petioles is one of the key approaches for monitoring nitrogen (N) nutrition in crops. Rapid, non-destructive, and accurate evaluation of NO3 −–N contents in cotton petioles under drip irrigation is of great significance. Methods In this study, we discussed the use of hyperspectral data to estimate NO3 −–N contents in cotton petioles under drip irrigation at different N treatments and growth stages. The correlations among trilateral parameters and six vegetation indices and petiole NO3 −–N contents were first investigated, after which a traditional regression model for petioles NO3 −–N content was established. A wavelet neural network (WNN) model for estimating petiole NO3 −–N content was also established. In addition, the performance of WNN was compared to those of random forest (RF), radial basis function neural network (RBF) and back propagation neural network (BP). Results Between the blue edge amplitude (Db) and blue edge area (SDb) of the blue edge parameters was the optimal index for the estimation model of petiole NO3 −–N content. We found that the prediction results of the blue edge parameters and WNN were 7.3% higher than the coefficient of determination (R2) of the first derivative vegetation index and WNN. Root mean square error (RMSE) and mean absolute error (MAE) were 25.2% and 30.9% lower than first derivative vegetation, respectively, and the performance was better than that of RF, RBF and BP. Conclusions An inexpensive approach consisting of the WNN algorithm and blue edge parameters can be used to enhance the accuracy of NO3 −–N content estimation in cotton petioles under drip irrigation.

The treatment of complex cerebrovascular diseases (CCVDs) at the skull base, such as complex intracranial aneurysms, carotid-cavernous sinus fistulas, and intracranial artery traumatic injuries, is a difficult clinical problem despite advances in endovascular and surgical therapies. Covered stents or stent graft insertion is a new concept for endovascular treatment that focuses on arterial wall defect reconstruction, differing from endovascular lesion embolization or flow diverter therapies. In recent years, covered stents specifically designed for cerebrovascular treatment have been applied in the clinical setting, allowing thousands of patients with CCVDs to undergo intraluminal reconstruction treatment and achieving positive results, even in the era of flow diverters. Since there is no unified reference standard for the application of covered stents for treating CCVDs, it is necessary to further standardize and guide the clinical application of this technique. Thus, we organized authoritative experts in the field of neurointervention in China to write an expert consensus, which aims to summarize the results of covered stent insertion in the treatment of CCVDs and propose suitable standards for its application in the clinical setting. Based on the contents of this consensus, clinicians can use individualized intraluminal reconstruction treatment techniques for patients with CCVDs.

Gold nanoparticles (Au NPs) with enzyme-like activities are useful glucose oxidase mimics, but the insights into the mechanism of this reaction are limited. Here, the authors show that the process of glucose oxidation by Au NPs is analogous to the one catalysed by glucose oxidase, involving dehydrogenation and oxygen reduction to H2O2; and that other noble metal NPs also catalyse glucose dehydrogenation, but oxygen is preferably reduced to water.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12885-019-5593-5.

Soil fumigation with chloropicrin (CP) is an effective means of overcoming continuous cropping obstacles (CCO) in Panax notoginseng and improving its yield and quality. CP fumigation can change the microbial community of soil. Therefore, a key step after CP fumigation is the rapid restoration of soil microorganisms and the promotion of beneficial microorganism proliferation as the dominant flora. In this study, continuously cropped soil of P. notoginseng was fumigated with CP, and general organic fertilizer (GOF) or microbial organic fertilizer (MOF) was used to restore soil microorganisms after fumigation. Soil physical and chemical properties, soil microorganisms, and quality of P. notoginseng were investigated. The application of MOF and GOF after CP fumigation promoted increases in soil nitrogen (9.88% and 8.21%, respectively), phosphorus (21.39% and 11.57%, respectively), potassium (7.99% and 2.75%, respectively), and the quality of P. notoginseng; it also promoted the accumulation of saponins in the main roots (23.62% and 9.12%, respectively). Application of MOF and GOF can restore the diversity of microorganisms in the soil. MOF increased the relative abundance of the beneficial soil microorganisms Glomeromycota, Mortierellomycota, Humicola and Bacillus, thereby lowering the relative abundance of the harmful Ascomycota and Fusarium relative to GOF. In summary, CP fumigation reduces the diversity of microorganisms in the soil. The addition of organic fertilizer can promote microbial diversity and increase the relative abundance of beneficial species. Moreover, the promotion effect of MOF is better than that of GOF, thereby improving soil fertility and ultimately promoting the quality and yield of P. notoginseng.

Sorafenib has attracted much attention as the first drug approved by the FDA for the treatment of advanced hepatocellular carcinoma (HCC). Because of the drug tolerance, the overall outcomes were far from satisfactory. Current studies suggest that changes in glucose metabolism induced by sorafenib are the pivotal resistant mechanism of HCC cells, but the specific regulatory mechanism remains unclear, which makes it difficult to increase drug sensitivity by targeting glycolysis. As a metabolic-recycling pathway, autophagy regulates multiple important pathways involved in cell survival and death. In this study, we found the expression of key autophagy proteins were closely related to the prognosis and progression of HCC patients. Based on in vitro experiments, our studies showed sorafenib induced autophagy in HCC cells. Inhibition of autophagy by chloroquine could significantly increase the sensitivity of HCC cells to sorafenib and reverse the enhancement of glycolysis. Furthermore, sorafenib-induced autophagy promoted the deacetylase activity of HDAC6 by degrading p62, which promoted the activity of PKM2 by regulating the acetylation of its critical substrate HSP90. In this study, we investigated the role of autophagy-induced HDAC6 in regulating the key glycolytic enzyme PKM2, which may be helpful to clarify the relationship between autophagy and glycolysis in a sorafenib-resistant mechanism. Targeting p62/HDAC6/HSP90 could herald a potential improvement in HCC therapy.

The role of miRNAs as crucial components in carcinogenesis has been well documented. However, whether and how miR-214 influences oral cancer cells’ drug resistance remains to be elucidated, and its downstream targets are still under investigation. Hence, this research is aimed at determining miR-214 and ULK1 expression in oral cancer before and after chemotherapy and their correlations with cancer cell growth. Human oral normal epithelial cells and human tongue squamous cell carcinoma CAL-27 cells were cultured to detect miR-214 and ULK1 levels. It was found that before chemotherapy, miR-214 was higher, while ULK1 was underexpressed in CAL-27 cells, versus normal epithelial cells. After chemotherapy, miR-214 decreased obviously in CAL-27 cells, while ULK1 level increased significantly. In addition, autophagy-related genes (Beclin 1, mTOR, and P53) in CAL-27 cells were found to be significantly inhibited before chemotherapy and were obviously increased after chemotherapy. Moreover, to further determine the impacts of miR-214 and ULK1 on oral cancer cell growth after chemotherapy, the two were overexpressed or silenced in CAL-27 cells after transfection. We found that ULK1 could effectively decrease the activity and invasion of CAL-27 cells and increase their apoptosis level, while miR-214 could antagonize its antitumor effect. Therefore, miR-214 can be used as an early prognostic biomarker for oral cancer, and ULK1 is a new candidate therapeutic target.

The dynamic exit sign has been verified as an effective means to guide the pedestrian during evacuation. The most critical mechanism with dynamic exit sign guidance is to balance the pedestrian flow on each exit route by optimizing the direction of signs. This paper formulates a bi-level programming model for the direction optimization problem of dynamic signs in buildings. In the bi-level program, the upper-level model is a system optimal model, aiming to minimize the total travel time by optimizing the dynamic sign direction. The lower-level model is a pedestrian assignment model satisfying the dynamic user optimal principle that describes the evacuee exit/route choice behaviour to achieve a balanced pedestrian distribution on the route. A method based on the fundamental diagram, the cell transmission model, and the point-queuing theory is developed to estimate evacuation travel time considering congestion and queuing. A heuristic algorithm is extended to solve the bi-level program. Finally, the proposed methodology is validated with numerical examples. Results reveal that the proposed model can produce the optimal dynamic sign direction, significantly improving the evacuation efficiency.

Melatonin, insulin, and Δ9-tetrahydrocannabinol (THC) have been shown to reverse cognitive deficits and attenuate neuropathologies in transgenic mouse models of Alzheimer’s disease (AD) when used individually. Here, we evaluated the therapeutic properties of long-term intranasal treatment with a novel nanoformulation containing melatonin, insulin, and THC in aged APPswe/PS1ΔE9 (APP/PS1) mice, a transgenic model of AD. Transgenic mice at the age of 12 months were intranasally administered with a new nanoformulation containing melatonin, insulin, and THC at doses of 0.04, 0.008, and 0.02 mg/kg, respectively, once daily for 3 months. The spatial memory of the mice was assessed using the radial arm water maze (RAWM) test before and after drug treatment. Brain tissues were collected at the end of the treatment period for the assessment of Aβ load, tauopathy state, and markers of mitochondrial function. The RAWM test revealed that the treatment with the melatonin–insulin–THC (MIT) nasal spray improved the spatial learning memory of APP/PS1 mice significantly. Results of protein analyses of brain homogenates indicated that MIT treatment significantly decreased the tau phosphorylation implicated in tau toxicity (p < 0.05) and the expression of CKMT1 associated with mitochondrial dysfunction. Moreover, MIT significantly decreased the expression of two mitochondrial fusion-related proteins, Mfn2 and Opa1 (p < 0.01 for both), while increasing the expression of a mitophagy regulator, Parkin, suggesting a compensatory enhancement of mitophagy due to MIT-promoted mitochondrial fusion. In conclusion, this study was the first to demonstrate the ability of an MIT nanoformulation to improve spatial memory in AD mice through its multi-targeting effects on Aβ production, tau phosphorylation, and mitochondrial dynamics. Thus, MIT may be a safe and effective therapeutic for AD.

Natural organic matter (NOM) has always been considered the main precursor of disinfection by-products (DBPs) during the chlorine disinfection of drinking water. This research focuses on investigating the correlation between the functional group (carboxyl and carbonyl groups) content of NOM and the formation of trichloromethane (TCM) and chloral hydrate (CH). The quantitative determination of carboxyl groups, carbonyl groups, TCM, and CH were conducted during the drinking water treatment processes with different coagulant dosages and with/without pre-oxidation by KMnO4 or NaClO. The most appropriate coagulant for the removal of conventional components was polyaluminum chloride (PAC), and the dosage was 110 mg/L. Up to 43.7% and 14.5% of the carboxyl and carbonyl groups, respectively, were removed through the coagulation and sedimentation processes, which can be enhanced by increasing PAC dosage. The filtration process further increased the removal rates of these two functional groups to 59.8% and 33.5%, respectively. The formation potential of the TCM and CH decreased as the PAC dosage increased. Pre-oxidation by KMnO4 (0.8–1.0 mg/L) effectively controlled the formation of DBPs while increasing the carboxyl and carbonyl group content. Pre-oxidation by NaClO decreased the formation of TCM rather than CH, and a suitable amount (0.5–1.0 mg/L) decreased the carboxyl and carbonyl groups. It was found that there was a good linear correlation between carboxyl groups and TCM and CH. The linear fit R2 values of the carboxyl groups to TCM and CH were 0.6644 and 0.7957, respectively. The linear fit R2 values of the carbonyl groups to TCM and CH were 0.5373 and 0.7595, respectively.

This study was targeted to investigate the effect of the combination of aqueous ozone (AO) and sodium citrate (SC) pretreatment on quality of vacuum packaged beef stored at chilling temperature. The steers were randomly divided into five treatment groups, containing the group C (steers without any treatment), DW (steers pretreated with distilled water), AO, SC and AO+SC. During processing, the parameters included total Viable Count (TVC), total Volatile Basic Nitrogen (TVB-N), pH, meat color, metmyoglobin (Met-Mb), thiobarbituric acid reactive substances (TBArs), Warner–Bratzler shear force (WBSF), and purge loss were measured and compared. Firstly, the TVC in beef steaks of group AO+SC was significantly lower than group AO and SC during the whole storage (P

Using data of regional radar mosaic products, MICAPS, 6-hourly reanalysis data of CFSR with horizontal resolution of 0.5°×0.5°, and data of national meteorological observatories and regional automatic stations in Guangdong Province, the train effect features of an extremely severe rainfall event in Guangdong with a record-breaking rainfall of 1 056.7 mm within 24 hours in Gaotan of Huidong from 30 to 31 August 2018 is analyzed. The result is shown as follows. The train effect took place in the environment of a favorable atmospheric circulation induced by slowly moving monsoon depression. The most remarkable characteristic was that the high value of vapor flux divergence and potential pseudo-equivalent temperature mainly appeared in the boundary layer below 925 hPa. The wind direction in the boundary layer near Shanwei gradually shifts from southwest to south. The air current produced an upward movement of convergence around the central region of Shanwei. The storm cells of the severe rainfall moved along with southwest monsoon and the Lianhua Moutain from southwest to northeast. Surface mesoscale convergence line, the pulses of southwest-south airflows and the special terrain distribution triggered the generation and development of the train effect. The conditions presented above have resulted in the extremely severe precipitation breaking historical records in Gaotan.

Abstract Background Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy with a high incidence worldwide. Accumulating evidence indicates that circular RNAs (circRNAs) play a vital role in modulating tumor development. However, the mechanism of circRNA action in human OSCC remains largely unknown. Methods By using high-throughput transcriptome sequencing technology, we conducted a comprehensive study of circRNAs in human OSCC. The effect of circRNA hsa_circ_0005379 on OSCC tissues and cell lines was monitored by qRT-PCR, Transwell assay, flow cytometry, and western blot analysis. Xenograft mouse models were used to assess tumor growth and animal survival. Results We found that circRNA hsa_circ_0005379 expression is significantly lower in OSCC tissue compared to paired non-cancerous matched tissue and is associated with tumor size and differentiation. Overexpression of hsa_circ_0005379 effectively inhibits migration, invasion, and proliferation of OSCC cells in vitro and suppresses OSCC growth in nude mice in vivo. Mechanistic studies revealed that hsa_circ_0005379 may be involved in the regulation of the epidermal growth factor receptor (EGFR) pathway. Furthermore, we found that high expression of hsa_circ_0005379 could significantly enhance the sensitivity of OSCC to the cetuximab drug. Conclusions Our findings provide evidence that hsa_circ_0005379 regulates OSCC malignancy and may be a new therapeutic target for OSCC treatment.