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Abstract Patients with traumatic brain injury (TBI) frequently exhibit concomitant immunosuppression. In this study, we evaluated the predictive values of soluble programmed death-1 (sPD-1) and soluble programmed death ligand-1 (sPD-L1) in patients with severe TBI. Peripheral blood sPD-1 and sPD-L1 levels were measured within 48 h of patient admission. A total of 20 healthy volunteers and 82 patients were enrolled in this study. The levels of sPD-1 and sPD-L1 were upregulated in patients with severe TBI (P

Abstract Background With the increasing application of neoadjuvant therapy in rectal adenocarcinoma, there remain many controversies in clinical practical applications. Preoperative radiotherapy (PR) can limit the surgical plane and potentially affect the quality of surgical treatment. This study aimed to investigate the potential impact of PR on the surgical quality of rectal adenocarcinoma. Methods This retrospective study analyzed the clinicopathological data from 6,585 AJCC stage I-III rectal adenocarcinoma in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Kaplan-Meier survival analysis and multivariate Cox proportional were used to assess the impact of PR on survival. Propensity score matching (PSM) was employed to balance the baseline covariates between the PR and non-PR groups and to compare postoperative pathological differences. Results After PSM, PR did not improve overall survival (OS) in stages I (p = 0.33), II (p = 0.37), and III (p = 0.14) patients. Multivariate Cox analysis indicated that PR was not an independent prognostic factor for patients. Restricted cubic spline (RCS) analysis demonstrated a nonlinear negative correlation between OS hazard ratios and both circumferential resection margin (CRM) and lymph node evaluation (LNE). Compared to the non-PR group, patients in the PR group had lower tumor deposits (TD) (p

Abstract Background Porcine epidemic diarrhea virus (PEDV) mainly causes acute and severe porcine epidemic diarrhea (PED), and is highly fatal in neonatal piglets. No reliable therapeutics against the infection exist, which poses a major global health issue for piglets. Luteolin is a flavonoid with anti-viral activity toward several viruses. Results We evaluated anti-viral effects of luteolin in PEDV-infected Vero and IPEC-J2 cells, and identified IC50 values of 23.87 µM and 68.5 µM, respectively. And found PEDV internalization, replication and release were significantly reduced upon luteolin treatment. As luteolin could bind to human ACE2 and SARS-CoV-2 main protease (Mpro) to contribute viral entry, we first identified that luteolin shares the same core binding site on pACE2 with PEDV-S by molecular docking and exhibited positive pACE2 binding with an affinity constant of 71.6 µM at dose-dependent increases by surface plasmon resonance (SPR) assay. However, pACE2 was incapable of binding to PEDV-S1. Therefore, luteolin inhibited PEDV internalization independent of PEDV-S binding to pACE2. Moreover, luteolin was firmly embedded in the groove of active pocket of Mpro in a three-dimensional docking model, and fluorescence resonance energy transfer (FRET) assays confirmed that luteolin inhibited PEDV Mpro activity. In addition, we also observed PEDV-induced pro-inflammatory cytokine inhibition and Nrf2-induced HO-1 expression. Finally, a drug resistant mutant was isolated after 10 cell culture passages concomitant with increasing luteolin concentrations, with reduced PEDV susceptibility to luteolin identified at passage 10. Conclusions Our results push forward that anti-PEDV mechanisms and resistant-PEDV properties for luteolin, which may be used to combat PED.

This paper considers the estimation of component reliability based on system lifetime data with known system signature using the minimum density divergence estimation method. Different estimation procedures based on the minimum density divergence estimation method are proposed. Standard error estimation and interval estimation procedures are also studied. Then, a Monte Carlo simulation study is used to evaluate the performance of those proposed procedures and compare those procedures with the maximum likelihood estimation method under different contaminated models. A numerical example is presented to illustrate the effectiveness of the proposed minimum density divergence estimation method. We have shown that the proposed estimation procedures are robust to contamination and model misspecification. Finally, concluding remarks with some possible future research directions are provided.

IntroductionCoronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), canine coronavirus (CCoV), and feline infectious peritonitis virus (FIPV), have the potential for interspecies transmission. These viruses can be present in complex environments where humans, dogs, and cats coexist, posing a significant threat to both human and animal safety.Methods and resultsIn this study, we developed a novel multiplex TaqMan-probe-based real-time PCR assay for the simultaneous detection and differentiation of SARS-CoV-2, CCoV, and FIPV. Specific primers and TaqMan fluorescent probes were designed based on the N region of SARS-CoV-2 and FIPV, as well as the S region of CCoV, which demonstrated a remarkable sensitivity and specificity toward the targeted viruses, as few as 21.83, 17.25 and 9.25 copies/μL for SARS-CoV-2, CCoV and FIPV, respectively. The standard curve constructed by the optimized method in our present study showed a high amplification efficiency within or near the optimal range of 91% to 116% and R(2) values were at least 0.95 for the abovementioned coronaviruses. A total of 91 samples, including six plasmid mixed mock samples, four virus fluid mixing simulated samples, and 81 clinical samples, were analyzed using this method. Results demonstrated strong agreement with conventional approaches.DiscussionBy enabling the simultaneous detection of three viruses, this method enhances testing efficiency while decreasing costs. Importantly, it provides a valuable tool for the prevalence and geographical distribution of suspected and co-infected animals, ultimately contributing to the advancement of both animal and public health.

In order to ensure the consistency and completeness of monitoring data in the safety monitoring system of coal mines, a design scheme for continuous transmission of disconnected data was proposed in response to faults in the monitoring substation equipment. The methods for fault recognition of data transmission, data preprocessing, data storage strategies, and data transmission protocols were studied. Based on the principle of invariable nonstorage, analog data with invalid values was cleaned up by bit storage compression of discrete transient data. Two-level storage of data was achieved by using FLASH and ferroelectric memory, and the data storage format and strategy were described. Network transmission protocols and bus transmission protocols were formulated separately to implement data continuation functions. The experimental results showed that after the main communication of the substation was interrupted, the monitoring data could be continuously stored for 7 days, and the correct rate of data continuation after the end of the failure reached 100%. This solution effectively solved the problem of missing data caused by equipment failure in the substation, ensured the integrity of monitoring data, and improved the reliability of the monitoring system.

Abstract Background The c-Jun N-terminal kinase (JNK) pathway is an evolutionarily conserved regulator of cell death, which is essential for coordinating tissue homeostasis. In this study, we have characterized the Drosophila Ste20-like kinase Slik as a novel modulator of JNK pathway-mediated apoptotic cell death. Results First, ectopic JNK signaling-triggered cell death is enhanced by slik depletion whereas suppressed by Slik overexpression. Second, loss of slik activates JNK signaling, which results in enhanced apoptosis and impaired tissue homeostasis. In addition, genetic epistasis analysis suggests that Slik acts upstream of or in parallel to Hep to regulate JNK-mediated apoptotic cell death. Moreover, Slik is necessary and sufficient for preventing physiologic JNK signaling-mediated cell death in development. Furthermore, introduction of STK10, the human ortholog of Slik, into Drosophila restores slik depletion-induced cell death and compromised tissue homeostasis. Lastly, knockdown of STK10 in human cancer cells also leads to JNK activation, which is cancelled by expression of Slik. Conclusions This study has uncovered an evolutionarily conserved role of Slik/STK10 in blocking JNK signaling, which is required for cell death inhibition and tissue homeostasis maintenance in development.

Enzootic bovine leukosis, a neoplastic disease caused by the bovine leukemia virus (BLV), was the primary cancer affecting cattle in China before 1985. Although its prevalence decreased significantly between 1986 and 2000, enzootic bovine leukosis has been re-emerging since 2000. This re-emergence has been largely overlooked, possibly due to the latent nature of BLV infection or the perceived lack of sufficient evidence. This study investigated the molecular epidemiology of BLV infections in dairy cattle in Henan province, Central China. Blood samples from 668 dairy cattle across nine farms were tested using nested polymerase chain reaction assays targeting the partial envelope (env) gene (gp51 fragment). Twenty-three samples tested positive (animal-level prevalence of 3.4%; 95% confidence interval: 2.2, 5.1). The full-length env gene sequences from these positive samples were obtained and phylogenetically analyzed, along with previously reported sequences from the GenBank database. The sequences from positive samples were clustered into four genotypes (1, 4, 6, and 7). The geographical annotation of the maximum clade credibility trees suggested that the two genotype 1 strains in Henan might have originated from Japan, while the genotype 7 strain is likely to have originated from Moldova. Subsequent Bayesian stochastic search variable selection analysis further indicated a strong geographical association between the Henan strains and Japan, as well as Moldova. The estimated substitution rate for the env gene ranged from 4.39 × 10−4 to 2.38 × 10−3 substitutions per site per year. Additionally, codons 291, 326, 385, and 480 were identified as positively selected sites, potentially associated with membrane fusion, epitope peptide vaccine design, and transmembrane signal transduction. These findings contribute to the broader understanding of BLV epidemiology in Chinese dairy cattle and highlight the need for measures to mitigate further BLV transmission within and between cattle herds in China.

Abstract A cross-sectional study was conducted to evaluate the risk factors associated with the Salmonella infection status of dairy herds in Henan and Hubei provinces, China. Herds were assigned a Salmonella status based on the isolation of Salmonella from fecal samples obtained from adult lactating dairy cows. Information on potential biosecurity risk factors was collected using a questionnaire template via a 15-min face-to-face interview with dairy cattle producers from May 2020 to March 2021. The questionnaire consisted of 23 questions across two broad categories of potential biosecurity risk factors: farm and biosecurity managemental factors. A total of 48 farms were surveyed. In all (100%, 48/48) of the surveyed farms, although sick animals were separated from healthy animals using fencing, there were no strict quarantine protocols for newly introduced animals. Mixed species rearing was practiced in 35.4% (17/48) of the farms. Feces were removed more than once a day in 45.8% (22/48) of the farms, whereas the remainder (54.2%, 26/48) only removed animal feces once a day. A total of 29.2% (14/48) of the farms were located

The co-occurrence of tuberculosis (TB) and diabetes mellitus (DM) presents a significant obstacle to TB eradication. Pulmonary cavitation can occur in severe cases of TB, particularly in patients with DM. From 1 May 2014 through 30 June 2019, we conducted a cross-sectional study of 1,658 smear- or culture-confirmed pulmonary TB (PTB) patients at the Second Department of Pulmonary Medicine and Tuberculosis, Shenzhen, China. A total of 861 participants who satisfied the criteria (chest CT scan for cavitation, interferon-gamma release assay (IGRA), diagnosis of diabetes mellitus), with the median age of 36.7 years, 63.6% of male, 79.7% IGRA positive, 13.8% with diabetes, and 40.8% with pulmonary cavitation, were included in the study. The association between diabetes and pulmonary cavitation was confirmed in these TB patients (adjusted OR, 2.54; 95% CI, 1.66–3.94; p < 0.001). No associations were observed between diabetes and IGRA, as well as between lung cavitary and IGRA. Based on the criteria of IGRA+/–, pulmonary cavitation+/–, and DM+/–, the further analysis with univariate and multivariate logistic regression were conducted in six subgroups. The significant association between diabetes and pulmonary cavitation was further confirmed in the IGRA+ subgroup (adjusted OR, 3.07; 95% CI, 1.86–5.16; p < 0.001) but not observed in IGRA- individuals. This observation suggests that different immunological mechanisms of pulmonary cavitary/DM may be employed in IGRA+ TB patients from IGRA- TB patients.

Growth is a crucial and intricate trait that significantly impacts clam breeding. BMP2, a member of the bone morphogenetic protein family, is widely recognized for its vital role in promoting growth and development. To study the possible functions of BMP2 in the razor clam Sinonovacula constricta, Sc-BMP2 was identified and characterized from S. constricta genome, and its correlations with growth traits were also analyzed. Compared with Sc-BMP3, Sc-BMP7 and Sc-BMP10, Sc-BMP2 had higher homology in the vertebrates and mollusks. The Sc-BMP2 highly conserved and exhibited an N-terminal signal peptide, Arg-X-X-Arg site and seven conserved cysteine. The results of tissue expression showed that Sc-BMP2 was expressed much higher in the mantle and foot (P

Mycobacterium bovis (M. bovis), the microorganism responsible for bovine tuberculosis (bTB), is transferred to people by the ingestion of unpasteurized milk and unprocessed fermented milk products obtained from animals with the infection. The identification of M. bovis in milk samples is of the utmost importance to successfully prevent zoonotic diseases and maintain food safety. This study presents a comprehensive description of a highly efficient molecular test utilizing recombinase-aided amplification (RPA)–clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (Cas) 13a–lateral flow detection (LFD) for M. bovis detection. In contrast to ELISA, RPA–CRISPR–Cas13a–LFD exhibited greater accuracy and sensitivity in the detection of M. bovis in milk, presenting a detection limit of 2 × 100 copies/μL within a 2 h time frame. The two tests exhibited a moderate level of agreement, as shown by a kappa value of 0.452 (95%CI: 0.287–0.617, p < 0.001). RPA–CRISPR–Cas13a–LFD holds significant potential as a robust platform for pathogen detection in complex samples, thereby enabling the more dependable regulation of food safety examination, epidemiology research, and medical diagnosis.

In this paper, we consider an integrated sensing, communication, and computation (ISCC) system to alleviate the spectrum congestion and computation burden problem. Specifically, while serving communication users, a base station (BS) actively engages in sensing targets and collaborates seamlessly with the edge server to concurrently process the acquired sensing data for efficient target recognition. A significant challenge in edge computing systems arises from the inherent uncertainty in computations, mainly stemming from the unpredictable complexity of tasks. With this consideration, we address the computation uncertainty by formulating a robust communication and computing resource allocation problem in ISCC systems. The primary goal of the system is to minimize total energy consumption while adhering to perception and delay constraints. This is achieved through the optimization of transmit beamforming, offloading ratio, and computing resource allocation, effectively managing the trade-offs between local execution and edge computing. To overcome this challenge, we employ a Markov decision process (MDP) in conjunction with the proximal policy optimization (PPO) algorithm, establishing an adaptive learning strategy. The proposed algorithm stands out for its rapid training speed, ensuring compliance with latency requirements for perception and computation in applications. Simulation results highlight its robustness and effectiveness within ISCC systems compared to baseline approaches.

Abstract The handy biometric data is a double-edged sword, paving the way of the prosperity of biometric authentication systems but bringing the personal privacy concern. To alleviate the concern, various biometric template protection schemes are proposed to protect the biometric template from information leakage. The preponderance of existing proposals is based on Hamming metric, which ignores the fact that predominantly deployed biometric recognition systems (e.g. face, voice, gait) generate real-valued templates, more applicable to Euclidean metric and Cosine metric. Moreover, since the emergence of similarity-based attacks, those schemes are not secure under a stolen-token setting. In this paper, we propose a succinct biometric template protection scheme to address such a challenge. The proposed scheme is designed for Euclidean metric and Cosine metric instead of Hamming distance. Mainly, the succinct biometric template protection scheme consists of distance-preserving, one-way, and obfuscation modules. To be specific, we adopt location sensitive hash function to realize the distance-preserving and one-way properties simultaneously and use the modulo operation to implement many-to-one mapping. We also thoroughly analyze the proposed scheme in three aspects: irreversibility, unlinkability and revocability. Moreover, comprehensive experiments are conducted on publicly known face databases. All the results show the effectiveness of the proposed scheme.

Abstract Electromagnetic cooperative strategy has been presented as a mainstream approach that can effectively optimize the matching thickness of dielectric loss dominant system. However, it is still challenging for dielectric–magnetic loss coexisting-type absorber to develop electromagnetic wave (EMW) performance with ultra-low matching thickness (≤ 1 mm). Breaking the limitation of traditional electromagnetic response at microscopic/mesoscopic scale, a ficus microcarpa-like magnetic aerogel with macroscopical electromagnetic cooperative effect was fabricated through highly oriented self-assembly engineering. The highly oriented Ni chains with unique macroscopic morphology (~ 1 cm in length) were achieved via a special magnetic field-induced growth. Strong magnetic coupling was observed in the Ni chains confirmed by the micromagnetic simulation. The deductive calculation validates that maintaining high value of electromagnetic parameters at high frequencies is the prerequisites of ultrathin absorber. The electromagnetic cooperative networks with uninterrupted and dual pathways spread through the entire aerogel skeleton, resulting in the impressive permittivity even at high frequencies. Consequently, the aerogel exhibits a remarkable EMW performance at an ultrathin thickness of 1 mm. Thus, based on the modulation of electromagnetic parameters, this work proposed a macroscopic ordered structure with the electromagnetic cooperative effect useful to develop a suitable strategy for achieving ultrathin EMW absorbers.

Strongylocentrotus nudus egg polysaccharide (SEP) extracted from sea urchins has potential anticancer activity. However, little is known about its pharmacokinetic properties. To investigate the pharmacokinetics of SEP, it was radiolabeled with tritium. Furthermore, a sensitive, selective, and rapid liquid scintillation counter (LSC) method for quantifying 3H-SEP in biological matrix was validated. The lower quantification limit of the method was 4 Bq. The relative standard deviations (RSDs) of the intra- and inter-day precision were

Abstract The rational construction of microstructure and composition with enhanced Maxwell-Wagner-Sillars effect (MWSE) is still a challenging direction for reinforcing electromagnetic wave (EMW) absorption performance, and the related EMW attenuation mechanism has rarely been elucidated. Herein, MWSE boosted β-chitin/carbon nano-onions/Ni–P composites is prepared according to the heterointerface engineering strategy via facile layer-by-layer electrostatic assembly and electroless plating techniques. The heterogeneous interface is reinforced from the aspect of porous skeleton, nanomaterials and multilayer construction. The composites exhibit competitive EMW response mechanism between the conductive loss and the polarization/magnetic loss, as describing like the story of “The Hare and the Tortoise”. As a result, the composites not only achieve a minimum reflection loss (RLmin) of − 50.83 dB and an effective bandwidth of 6.8 GHz, but also present remarkable EMW interference shielding effectiveness of 66.66 dB. In addition, diverse functions such as good thermal insulation, infrared shielding and photothermal performance were also achieved in the hybrid composites as a result of intrinsic morphology and chemicophysics properties. Therefore, we believe that the boosted MWSE open up a novel orientation toward developing multifunctional composites with high-efficient EMW response and thermal management.

The value of a novel soybean male-sterile mutation msLC01 in breeding practice was determined by its outcrossing properties. Then, the effects of different planting arrangements on the pod set characteristics of male-sterile plants were assessed by using orthogonal experiments at two sites. At the same time, the effects of msLC01 male sterility on other traits were assessed in two C2F2 populations. In addition, the nectar secretion and natural outcross of male-sterile plants from four msLC01 lines were compared with one ms1 line and one ms6 line. The results of the orthogonal experiment showed that the pod numbers and pod set rates of male-sterile plants were decisively different between the two experimental sites but not between the two levels of the other factors. Both increasing the ratio of paternal parent to maternal parent and planting the parental seeds in a mixed way, the proportion of seeds pollinated by the target parent pollen could be increased. Except for the pod number per plant trait, there was no significant difference between male-sterile plants and their fertile siblings. The amount of nectar significantly differed among the lines. Compared with ms1 and ms6 male-sterile plants, the four msLC01 lines possessed significantly more or similar numbers of pod sets. The results of this study lay a foundation for the future use of this mutant in soybean breeding.

Purpose Altered DNA methylation, genetic alterations, and environmental factors are involved in tumorigenesis. As a tumor suppressor gene, abnormal EPHA5 methylation was found in gastric cancer (GC) tissues and was linked to the initiation, progression and prognosis of GC. In this study, the EPHA5 methylation level in peripheral blood leukocytes (PBLs) was detected to explore its relationship with GC risk and prognosis. Methods A total of 366 GC cases and 374 controls were selected as the subjects of this study to collect their environmental factors, and the EPHA5 methylation status was detected through the methylation-sensitive high-resolution melting method. Logistic regression analysis was utilized to evaluate the associations among EPHA5 methylation, environmental factors and GC risk. Meanwhile, the propensity score (PS) was used to adjust the imbalance of some independent variables. Results After PS adjustment, EPHA5 Pm (positive methylation) was more likely to increase the GC risk than EPHA5 Nm (negative methylation) (ORb = 1.827, 95% CI [1.202–2.777], P = 0.005). EPHA5 Pm had a more significant association with GC risk in the elderly (ORa = 2.785, 95% CI [1.563–4.961], P = 0.001) and H. pylori-negative groups (ORa = 2.758, 95% CI [1.369–5.555], P = 0.005). Moreover, the combined effects of EPHA5 Pm and H. pylori infection (ORca = 3.543, 95% CI [2.233–5.621], P < 0.001), consumption of alcohol (ORca = 2.893, 95% CI [1.844–4.539], P < 0.001), and salty food intake (ORca = 4.018, 95% CI [2.538–6.362], P < 0.001) on increasing the GC risk were observed. In addition, no convincing association was found between EPHA5 Pm and the GC prognosis. Conclusions EPHA5 methylation in PBLs and its combined effects with environmental risk factors are related to the GC risk.

Abstract High-performance electromagnetic wave absorption and electromagnetic interference (EMI) shielding materials with multifunctional characters have attracted extensive scientific and technological interest, but they remain a huge challenge. Here, we reported an electrostatic assembly approach for fabricating 2D/1D/0D construction of Ti3C2Tx/carbon nanotubes/Co nanoparticles (Ti3C2Tx/CNTs/Co) nanocomposites with an excellent electromagnetic wave absorption, EMI shielding efficiency, flexibility, hydrophobicity, and photothermal conversion performance. As expected, a strong reflection loss of -85.8 dB and an ultrathin thickness of 1.4 mm were achieved. Meanwhile, the high EMI shielding efficiency reached 110.1 dB. The excellent electromagnetic wave absorption and shielding performances were originated from the charge carriers, electric/magnetic dipole polarization, interfacial polarization, natural resonance, and multiple internal reflections. Moreover, a thin layer of polydimethylsiloxane rendered the hydrophilic hierarchical Ti3C2Tx/CNTs/Co hydrophobic, which can prevent the degradation/oxidation of the MXene in high humidity condition. Interestingly, the Ti3C2Tx/CNTs/Co film exhibited a remarkable photothermal conversion performance with high thermal cycle stability and tenability. Thus, the multifunctional Ti3C2Tx/CNTs/Co nanocomposites possessing a unique blend of outstanding electromagnetic wave absorption and EMI shielding, light-driven heating performance, and flexible water-resistant features were highly promising for the next-generation intelligent electromagnetic attenuation system. Highlights The 2D/1D/0D Ti3C2Tx/carbon nanotubes/Co nanocomposite is successfully synthesized via an electrostatic assembly. Nanocomposites exhibit an excellent electromagnetic wave absorption and a remarkable electromagnetic interference shielding efficiency. The flexible, waterproof, and photothermal conversion performances are achieved.

Ammonium transporter 1 (AMT1), a member of ammonia (NH3/NH4+) transport proteins, has been found to have ammonia transport activity in plants and microorganisms. However, the functional characteristics and molecular mechanisms of AMT1 in mollusks remain unclear. The razor clam (Sinonovacula constricta) is a suitable model species to explore the molecular mechanism of ammonia excretion because of the high concentration of ambient ammonia it is exposed to in the clam–fish–shrimp polyculture system. Here, the expression of AMT1 in S. constricta (Sc-AMT1) in response to high ammonia (12.85 mmol/L NH4Cl) stress was identified by real-time quantitative PCR (qRT-PCR), Western blotting, RNA interference, and immunofluorescence analysis. Additionally, the association between the SNP_g.15211125A > T linked with Sc-AMT1 and ammonia tolerance was validated by kompetitive allele-specific PCR (KASP). A significant upregulated expression of Sc-AMT1 was observed during ammonia exposure, and Sc-AMT1 was found to be localized in the flat cells of gill. Moreover, the interference with Sc-AMT1 significantly upregulated the hemolymph ammonia levels, accompanied by the increased mRNA expression of Rhesus glycoprotein (Rh). Taken together, our findings imply that AMT1 may be a primary contributor to ammonia excretion in S. constricta, which is the basis of their ability to inhabit benthic water with high ammonia levels.

Abstract Inspired by the nature, lotus leaf-derived gradient hierarchical porous C/MoS2 morphology genetic composites (GHPCM) were successfully fabricated through an in situ strategy. The biological microstructure of lotus leaf was well preserved after treatment. Different pores with gradient pore sizes ranging from 300 to 5 μm were hierarchically distributed in the composites. In addition, the surface states of lotus leaf resulted in the Janus-like morphologies of MoS2. The GHPCM exhibit excellent electromagnetic wave absorption performance, with the minimum reflection loss of − 50.1 dB at a thickness of 2.4 mm and the maximum effective bandwidth of 6.0 GHz at a thickness of 2.2 mm. The outstanding performance could be attributed to the synergy of conductive loss, polarization loss, and impedance matching. In particularly, we provided a brand-new dielectric sum-quotient model to analyze the electromagnetic performance of the non-magnetic material system. It suggests that the specific sum and quotient of permittivity are the key to keep reflection loss below − 10 dB within a certain frequency range. Furthermore, based on the concept of material genetic engineering, the dielectric constant could be taken into account to seek for suitable materials with designable electromagnetic absorption performance.

Background: Tumor microenvironment (TME) has been reported to have a strong association with tumor progression and therapeutic outcome, and epigenetic modifications such as DNA methylation can affect TMB and play an indispensable role in tumorigenesis. However, the potential mechanisms of TME and DNA methylation remain unclear in cervical cancer (CC).Methods: The immune and stromal scores of TME were generated by the ESTIMATE algorithm for CC patients in The Cancer Genome Atlas (TCGA) database. The TME and DNA methylation-related genes were identified by the integrative analysis of DNA promoter methylation and gene expression. The least absolute shrinkage and selection operator (LASSO) Cox regression was performed 1,000 times to further identify a nine-gene TME and DNA methylation-related prognostic signature. The signature was further validated in Gene Expression Omnibus (GEO) dataset. Then, the identified signature was integrated with the Federation International of Gynecology and Obstetrics (FIGO) stage to establish a composite prognostic nomogram.Results: CC patients with high immunity levels have better survival than those with low immunity levels. Both in the training and validation datasets, the risk score of the signature was an independent prognosis factor. The composite nomogram showed higher accuracy of prognosis and greater net benefits than the FIGO stage and the signature. The high-risk group had a significantly higher fraction of genome altered than the low-risk group. Eleven genes were significantly different in mutation frequencies between the high- and low-risk groups. Interestingly, patients with mutant TTN had better overall survival (OS) than those with wild type. Patients in the low-risk group had significantly higher tumor mutational burden (TMB) than those in the high-risk group. Taken together, the results of TMB, immunophenoscore (IPS), and tumor immune dysfunction and exclusion (TIDE) score suggested that patients in the low-risk group may have greater immunotherapy benefits. Finally, four drugs (panobinostat, lenvatinib, everolimus, and temsirolimus) were found to have potential therapeutic implications for patients with a high-risk score.Conclusions: Our findings highlight that the TME and DNA methylation-related prognostic signature can accurately predict the prognosis of CC and may be important for stratified management of patients and precision targeted therapy.

Tuberculosis is the second cause in infectious diseases leading to human death. Understanding the virulence mechanism is inevitable if the disease needs to be fully cured. Therefore, this study aimed to reveal this mechanism by comparing proteomic profiles of intracellular and extracellular virulent strain M.tb and bacille Calmette–Guérin (BCG) from infected THP-1cells. First, M.tb and BCG infected THP-1 at MOI 10:1. Twelve hours postinfection, intracellular bacteria of M.tb and BCG were collected, whereas the two bacilli cultured in 7H9 broth media were used as the control. Then four groups of bacilli were subjected to proteomic analysis, and differential proteomic profiles between M.tb and BCG were comparatively analyzed with bioinformatics tools. As a result, we identified a total of 1,557 proteins. Further, they were divided into four groups for comparison of M.tb versus BCG under 7H9 culture (shorten as out), M.tb in (intracellular) versus M.tb out, BCG in versus BCG out and M.tb in versus BCG in. Between M.tb in versus BCG in, a total of 211 differentially expressed proteins were found. Eight proteins like ESAT-6 distributed in six RDs and some known proteins related to virulence. Besides, five uncharacterized proteins were differentially expressed. Further analysis revealed enriched pathways were associated with glyoxylate and dicarboxylate metabolism pathways. In M.tb out versus BCG out, a total of 144 differential proteins were identified and mainly involved in metabolism pathways. Then, 121 differential proteins in the group of M.tb in versus M.tb out were enriched in ribosome and oxidative phosphorylation related to adaptation to the host environment. The group of BCG in versus BCG out shared the same trend of different pathways to the M.tb in versus M.tb out. Finally, 42 proteins were identified to be up-regulated only in intracellular M.tb including eight RD proteins, whereas 22 up-regulated uniquely in intracellular BCG. Besides, only two proteins (Pks13 and Rv1405c) were commonly up-regulated in intracellular M.tb and BCG. Further, some unknown proteins were uniquely up-regulated in the intracellular M.tb and BCG. These findings provide valuable data for further exploration of molecular mechanism for M.tb virulence and BCG immune response.

Long noncoding RNAs (lncRNAs) have diverse functions, including immune regulation. Increasing studies have reported immune-related lncRNAs in the prognosis of multiple cancers. In this study, we developed an individualized signature containing 13 immune-related lncRNA pairs (IRLPs) which could predict the overall survival, disease-free survival, progression-free survival, and disease-specific survival of gastric cancer (GC) patients in The Cancer Genome Atlas (TCGA) cohort, and internal and external validations, signature comparisons, and subgroup analyses further confirmed its superiority, stability, and generalizability. Notably, this signature also showed good applicability in discriminating the prognosis of pan-cancer patients. Then, we constructed and validated a nomogram for overall survival based on the signature and clinical factors, which allowed more accurate predictions of GC prognosis. In addition, we revealed that the low survival rate of patients with high-risk scores may be due to their aggressive clinical features, enriched cancer-related signaling pathways, the infiltration of specific immunosuppressive cells, and low tumor mutation burden. We further predicted obviously worse immunotherapeutic responses in the high-risk groups and identified some candidate compounds targeting GC risk group differentiation. This signature based on the IRLPs may be promising for predicting the survival outcomes and immunotherapeutic responses of GC patients in clinical practice.

To reveal functions of novel Mycobacterium tuberculosis (M. tb) proteins responsible for modulating host innate immunity is essential to elucidation of mycobacterial pathogenesis. In this study, we aimed to identify the role of a putative protein Rv0309 encoded within RD8 of M. tb genome in inhibiting the host inflammatory response and the underlying mechanism, using in-vitro and in-vivo experiments. A recombinant M. smegmatis strain Ms_rv0309 expressing Rv0309 and a mutant Bacillus Calmette-Guérin (BCG)ΔRS01790 strain with deletion of BCG_RS01790, 100% homologue of Rv0309 in BCG, were constructed. Rv0309 was found to localize in the cell wall and be able to decrease cell wall permeability. Purified recombinant rRv0309 protein inhibited lipopolysaccharide-induced IL-6 release in RAW264.7 cells. BCG_RS01790 in BCG or Rv0309 in Ms_rv0309 strain greatly inhibited production of IL-6, IL-1β, and TNF-α in RAW264.7 cells. Similarly, BCGΔRS01790 strongly induced expression of these cytokines compared with wild-type BCG and complement strain, cBCGΔRS01790::RS01790. Further BCG_RS01790 or Rv0309 suppressed cytokine production through NF-κB p65/IκBα and MAPK ERK/JNK signaling. Importantly, BCG_RS01790 in BCG and Rv0309 in Ms_rv0309 strain enhanced mycobacterial survival in macrophages. Mice infected with BCGΔRS01790 exhibited high levels of IFN-γ, TNF-α and IL-1β, and large numbers of neutrophils and lymphocytes in the early stage, and minimal lung bacterial load and inflammatory damage in late stage of the experiment. In conclusion, the cell wall protein Rv0309 or BCG_RS01790 enhanced mycobacterial intracellular survival after infection likely through inhibition of the pro-inflammatory response and decrease of bacterial cell wall permeability, thereby contributing to mycobacterial pathogenesis.

First identified as a new circovirus in Hunan Province in China in 2019, porcine circovirus (PCV4) is now widely detected in other Chinese provinces and South Korea. In recent years, the virus has threatened pig health and operations in the pig industry. Hence, early PCV4 detection and regular surveillance are required to control the spread of infection and prevent collateral damage to the industry. Due to PCV4 being difficult to isolate in vitro, molecular detection methods, such as conventional PCR and real-time PCR, and serological assays are currently the main methods used for the detection of PCV4 infection. However, they are time-consuming, labor-intensive, and complex and require professional personnel. To facilitate rapid pen-side PCV4 diagnoses, we used clustered regularly interspaced short palindromic repeats (CRISPR) and Cas13a technology to develop a quick testing kit. Five recombinase-aided amplification (RPA) primer sets were designed based on the conserved PCV4-Cap gene nucleotide region, which were used to determine several key lateral flow strip (LFD) characteristics (sensitivity, specificity, and accuracy). The results showed that the RPA-Cas13a-LFD reaction could detect PCV4 within 1.5 h in genomic DNA harboring a minimum of a single copy. Furthermore, the assay showed good specificity and absence of cross-reactivity with PCV2, PCV3, or other porcine viruses. When we tested 15 clinical samples, a high accuracy was also recorded. Therefore, we successfully developed a detection assay that was simple, fast, accurate, and suitable for on-site PCV4 testing.

The objective of this study was to estimate the fecal carriage of Salmonella spp. among culled adult dairy cows presented to an abattoir in Wuhan, China and to evaluate their antimicrobial resistance profiles. Rectal swabs from 138 culled cows were cultured. Laboratory analysis involved the identification of Salmonella, the susceptibility assessment and the presence of Extended Spectrum β-lactamases and mcr genes in the isolates. An overall prevalence of Salmonella of 29.0% was recorded with 63.4% (26/41) and 2.4% (1/41) of the isolates identified as S. Typhimurium and S. Dublin, respectively. The occurrence of Salmonella was higher (odd ratios: 3.3) in culled cows originating from the northeast zone of China than cows originating from the central and north zones. Twenty multi-drug resistant strains (resistant to three or more antimicrobial agents) were detected (48.8%) and overall, a high resistance to ampicillin (36/41) and tetracycline (15/41) was observed. Extended Spectrum β-lactamases phenotypes were found in 7/41 isolates, of which all contained the blaCTX-M resistance gene, and no mcr genes were found by polymerase chain reaction. The high prevalence of Salmonella fecal carriage and antimicrobial resistance may contribute to an increased risk of Salmonella transmission to food.

Mycobacterium tuberculosis is considered a successful pathogen with multiple strategies to undermine host immunity. The YrbE3A is encoded by Rv1964 within the RD15 region present in the genome of Mtb, but missing in M. bovis, M. bovis BCG (Pasteur) strain, and M. smegmatis (Ms). However, little is known about its function. In this study, the YrbE3A gene was cloned into pMV261 and expressed in Ms and BCG, while the strains with the vector served as the controls. The YrbE3A was expressed on the mycobacterial membrane, and the purified protein could stimulate RAW264.7 cells to produce IL-6. Furthermore, the effect of the recombinant strains on cytokine secretion by RAW264.7 was confirmed, which varied with the host strains. Ms_YrbE3A increased significantly higher levels of TNF-α and IL-6 than did Ms_vec, while BCG_YrbE3A enhanced higher TNF-α than BCG_vec. The pathways associated with NF-κB p65 and MAPK p38/JNK, other than Erk1/2, regulated this process. In addition, mice were infected with Ms_YrbE3A and Ms-vec and were kinetically examined. Compared to Ms-vec, Ms_YrbE3A induced more serious inflammatory damage, higher levels of TNF-α and IL-6, higher numbers of lymphocytes, neutrophils, and monocytes in a time-dependent way, but lower lung bacterial load in lung. These findings may contribute to a better understanding of Mtb pathogenesis.

Mycobacterium bovis (M. bovis) is a zoonotic pathogen that causes bovine and human tuberculosis. Dendritic cells play a critical role in initiating and regulating immune responses by promoting antigen-specific T-cell activation. Prostaglandin E2 (PGE2)-COX signaling is an important mediator of inflammation and immunity and might be involved in the pathogenesis of M. bovis infection. Therefore, this study aimed to reveal the character of PGE2 in the differentiation of naïve CD4+ T cells induced by infected dendritic cells (DCs). Murine bone marrow-derived DCs were pre-infected with M. bovis and its attenuated strain M. bovis bacillus Calmette-Guérin (BCG). Then, the infected DCs were co-cultured with naïve CD4+ T cells with or without the cyclooxygenase (COX) inhibitor indomethacin. Quantitative RT-PCR analysis and protein detection showed that PGE2/COX-2 signaling was activated, shown by the upregulation of PGE2 production as well as COX-2 and microsomal PGE2 synthase (mPGES1) transcription in DCs specifically induced by M. bovis and BCG infection. The further co-culture of infected DCs with naïve CD4+ T cells enhanced the generation of inflammatory cytokines IL-17 and IL-23, while indomethacin suppressed their production. Following this, the differentiation of regulatory T cells (Treg) and Th17 cell subsets was significantly induced by the infected DCs rather than uninfected DCs. Meanwhile, M. bovis infection stimulated significantly higher levels of IL-17 and IL-23 and the differentiation of Treg and Th17 cell subsets, while BCG infection led to higher levels of TNF-α and IL-12, but lower proportions of Treg and Th17 cells. In mice, M. bovis infection generated more bacterial load and severe abnormalities in spleens and lungs, as well as higher levels of COX-2, mPGE2 expression, Treg and Th17 cell subsets than BCG infection. In conclusion, PGE2/COX-2 signaling was activated in DCs by M. bovis infection and regulated differentiation of Treg and Th17 cell subsets through the crosstalk between DCs and naive T cells under the cytokine atmosphere of IL-17 and IL-23, which might contribute to M. bovis pathogenesis in mice.

This paper focuses on the dynamic responses of a metro train−bridge system under train-braking. Experiments were performed on the elevated Metro Line 21 of Guangzhou (China). A continuous, three-span, rigid-frame bridge (42 m + 65 m + 42 m) and a standard B-type metro train were selected. The acceleration signals were measured at the center-points of the main span and one side-span, and the acceleration signals of the car body and the bogie frame were measured simultaneously. The train−bridge system’s vibration characteristics and any correlations with time and frequency were investigated. The Choi−Williams distribution method and wavelet coherence were introduced to analyze the obtained acceleration signals of the metro train−bridge system. The results showed that the Choi−Williams distribution provided a more explicit understanding of the time−frequency domain. The correlations between different parts of the bridge and the train−bridge system under braking conditions were revealed. The present study provides a series of measured dynamic responses of the metro train−bridge system under train-braking, which could be used as a reference in further investigations.

The Mycobacterium tuberculosis complex causes tuberculosis (TB) in humans and other animal species, but Mycobacterium tuberculosis has a distinct host preference to humans. The present study aimed to determine whether a bovine M. tb strain 1458 has evolved some genetic properties in their genome that might be associated with their bovine adaptation. The genome of the M. tb strain 1458 was sequenced and subjected to an extensive comparative genomic analysis. A phylogenetic analysis showed that strain 1458 is most closely related to a Chinese M. tb strain, CCDC5079, of the same Beijing family. Compared with three human M. tb Beijing family strains, the strain 1458 has the fewest unique genes. However, there are most (21) IS6110 insertion sequences in the strain 1458 genome at either intragenic or intergenic sites, resulting in the interruption of 11 genes including three PPE family-encoding genes (PPE16, PPE38, and PPE59). Only the strain 1458 genome has the upstream insertion in esxS and phoP genes. PCR confirmed four upstream insertions and qPCR determined that transcription of esxS, phoP, dnaN, and ctpD genes differed significantly between M. tb strain 1458 and H37Rv or M. bovis. A Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the genes affected by non-synonymous SNPs are enriched in RNA polymerase. Moreover, 127 of the 133 unique SNPs in strain 1458 are either different to those in the M. bovis genome. In conclusion, some critical genes responsible for bacterial virulence and immunogenicity were interrupted in the genome of bovine M. tb strain 1458 by IS insertions and non-synonymous SNPs, which might contribute to its bovine adaptation, and the modification of its virulence and immunogenicity in cattle.

The hydrophobic pocket in the HIV-1 gp41 N-terminal heptad repeat (NHR) domain plays an important role in viral fusion and entry into the host cell, and serves as an attractive target for development of HIV-1 fusion/entry inhibitors. The peptide anti-HIV drug targeting gp41 NHR, T-20 (generic name: enfuvirtide; brand name: Fuzeon), was approved by the U.S. FDA in 2003 as the first HIV fusion/entry inhibitor for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, because T20 lacks the pocket-binding domain (PBD), it exhibits low anti-HIV-1 activity and short half-life. Therefore, several next-generation HIV fusion inhibitory peptides with PBD have been developed. They possess longer half-life and more potent antiviral activity against a broad spectrum of HIV-1 strains, including the T-20-resistant variants. Nonetheless, the clinical application of these peptides is still limited by the lack of oral availability and the high cost of production. Thus, development of small molecule compounds targeting the gp41 pocket with oral availability has been promoted. This review describes the main approaches for identification of HIV fusion/entry inhibitors targeting the gp41 pocket and summarizes the latest progress in developing these inhibitors as a new class of anti-HIV drugs.

Natural angiotensin converting enzyme (ACE)-inhibitory peptides, which are derived from marine products, are useful as antihypertensive drugs. Nevertheless, the activities of these natural peptides are relatively low, which limits their applications. The aim of this study was to prepare efficient ACE-inhibitory peptides from sea cucumber-modified hydrolysates by adding exogenous proline according to a facile plastein reaction. When 40% proline (w/w, proline/free amino groups) was added, the modified hydrolysates exhibited higher ACE-inhibitory activity than the original hydrolysates. Among the modified hydrolysates, two novel efficient ACE-inhibitory peptides, which are namely PNVA and PNLG, were purified and identified by a sequential approach combining a sephadex G-15 gel column, reverse-phase high-performance liquid chromatography (RP-HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS), before we conducted confirmatory studies with synthetic peptides. The ACE-inhibitory activity assay showed that PNVA and PNLG exhibited lower IC50 values of 8.18 ± 0.24 and 13.16 ± 0.39 μM than their corresponding truncated analogs (NVA and NLG), respectively. Molecular docking showed that PNVA and PNLG formed a larger number of hydrogen bonds with ACE than NVA and NLG, while the proline at the N-terminal of peptides can affect the orientation of the binding site of ACE. The method developed in this study may potentially be applied to prepare efficient ACE-inhibitory peptides, which may play a key role in hypertension management.

Strongylocentrotus nudus egg polysaccharide (SEP) extracted from sea urchins has potential anticancer activity. However, little is known about its pharmacokinetic properties. To investigate the pharmacokinetics of SEP, it was radiolabeled with tritium. Furthermore, a sensitive, selective, and rapid liquid scintillation counter (LSC) method for quantifying 3H-SEP in biological matrix was validated. The lower quantification limit of the method was 4 Bq. The relative standard deviations (RSDs) of the intra- and inter-day precision were <3.0% and <3.9%, respectively. 3H-SEP was successfully applied to investigate the pharmacokinetics of SEP after intravenous administration of 20, 40, and 80 mg/kg (40 µCi/kg) in rats and 5, 10, and 20 mg/kg (6 µCi/kg) in beagles. The AUC(0-t) of SEP at three different doses was 487.81 ± 39.99 mg/L*h, 1,003.10 ± 95.94 mg/L*h, and 2,188.84 ± 137.73 mg/L*h in rats and 144.12 ± 3.78 mg/L*h, 322.62 ± 28.03 mg/L*h, and 754.17 ± 37.79 mg/L*h in beagles. The terminal elimination half-life (t1/2) of SEP was longer in beagles (204.29 ± 139.34 h) than in rats (35.48 ± 6.04 h). The concentration of SEP in plasma declined rapidly in both rats and beagles. All the study results provide detailed pharmacokinetic profiles of SEP in two kinds of animals, which will be helpful for further development. [ABSTRACT FROM AUTHOR]

Autophagy is a highly conserved programmed degradation process that regulates a variety of physiological and pathological activities in health, aging, and disease. To identify additional factors that modulate autophagy, we utilized serum-free starvation or Torin1 to induce autophagy in HeLa cells for unbiased mRNA-sequencing analysis and identified SNAI2, a crucial player in epithelial-to-mesenchymal transition and cancer progression, as a regulator of autophagy. Mechanistically, SNAI2 promotes autophagy by physically interacting with FOXO3 and enhancing FOXO3 binding affinity to its response elements in autophagy-related genes. Intriguingly, binding to the DNA targets appears necessary and sufficient for FOXO3 to antagonize its CRM1-dependent nuclear export, illustrating a critical role of DNA in regulating protein nuclear localization. Moreover, stress-elevated SNAI2 expression is mediated by FOXO3, which activates SNAI2 transcription by directly binding to its promoter. Herein, FOXO3 and SNAI2 form a coherent feedforward regulatory loop to reinforce autophagy genes induction in response to energy stress. Strikingly, a dFoxO-Snail feed-forward circuit also regulates autophagy in Drosophila, suggesting this mechanism is evolutionarily conserved from fly to human. [ABSTRACT FROM AUTHOR]

Deep learning technology can improve sensing efficiency and has the ability to discover potential patterns in data; the efficiency of user behavior recognition in the field of smart homes has been further improved, making the recognition process more intelligent and humanized. This paper analyzes the optical sensors commonly used in smart homes and their working principles through case studies and explores the technical framework of user behavior recognition based on optical sensors. At the same time, CiteSpace (Basic version 6.2.R6) software is used to visualize and analyze the related literature, elaborate the main research hotspots and evolutionary changes of optical sensor-based smart home user behavior recognition, and summarize the future research trends. Finally, fully utilizing the advantages of cloud computing technology, such as scalability and on-demand services, combining typical life situations and the requirements of smart home users, a smart home data collection and processing technology framework based on elderly fall monitoring scenarios is designed. Based on the comprehensive research results, the application and positive impact of optical sensors in smart home user behavior recognition were analyzed, and inspiration was provided for future smart home user experience research.

The phase III clinical trial results for eribulin mesylate (E7389), a synthetic analogue of the marine natural product halichondrin B which could be used for cancer treatment is described. The obtained results revealed that suppression of dynamic instability is attributed to the binding of eribulin with high affinity to microtubule plus ends.

KEA4, KEA5, and KEA6 are members of the Arabidopsis (Arabidopsis thaliana) K+ efflux antiporter (KEA) family that share high sequence similarity but whose function remains unknown. Here, we show their gene expression pattern, subcellular localization, and physiological function in Arabidopsis. KEA4, KEA5, and KEA6 had similar tissue expression patterns, and the three KEA proteins localized to the Golgi, the trans-Golgi network, and the prevacuolar compartment/multivesicular bodies, suggesting overlapping roles of these proteins in the endomembrane system. Phenotypic analyses of single, double, and triple mutants confirmed functional redundancy. The triple mutant kea4 kea5 kea6 had small rosettes, short seedlings, and was sensitive to low K+ availability and to the sodicity imposed by high salinity. Also, the kea4 kea5 kea6 mutant plants had a reduced luminal pH in the Golgi, trans-Golgi network, prevacuolar compartment, and vacuole, in accordance with the K/H exchange activity of KEA proteins. Genetic analysis indicated that KEA4, KEA5, and KEA6 as well as endosomal Na+/H+exchanger5 (NHX5) and NHX6 acted coordinately to facilitate endosomal pH homeostasis and salt tolerance. Neither cancelling nor overexpressing the vacuolar antiporters NHX1 and NHX2 in the kea4 kea5 kea6 mutant background altered the salt-sensitive phenotype. The NHX1 and NHX2 proteins in the kea4 kea5 kea6 mutant background could not suppress the acidity of the endomembrane system but brought the vacuolar pH close to wild-type values. Together, these data signify that KEA4, KEA5, and KEA6 are endosomal K+ transporters functioning in maintaining pH and ion homeostasis in the endomembrane network. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide. It is a complicated and often fatal cancer, and is related to a high disease-related mortality. Around 90% of mortalities are caused by the metastasis of CRC. Current treatment statistics shows a less than 5% 5-year survival for patients with metastatic disease. The development and metastasis of CRC involve multiple factors and mechanisms. The Hedgehog (Hh) signaling plays an important role in embryogenesis and somatic development. Abnormal activation of the Hh pathway has been proven to be related to several types of human cancers. The role of Hh signaling in CRC, however, remains controversial. In this review, we will go through previous literature on the Hh signaling and its functions in the formation, proliferation, and metastasis of CRC. We will also discuss the potential of targeting Hh signaling pathway in the treatment, prognosis, and prevention of CRC. [ABSTRACT FROM AUTHOR]

The aim of the present study was to establish an improved method for in vitro guinea pig airway smooth muscle (ASM) cell culture and to evaluate the effect of 2-(4-amino-3-chloro-5-trifluomethyl-phenyl)-2-tert-butylamino-ethanol hydrochloride (SPFF), a novel β2-adrenoceptor agonist, on the release of intracellular calcium in cells. A procedure for the efficient isolation, culture, passage and characterization of the cells was described. Primary ASM cells of guinea pigs were cultured by modified tissue cultivation. The cells were identified by their morphological characteristics and immunocytochemistry. The relative inhibition of the release of intracellular calcium by drugs in the cells was measured by fluorometric quantification with fluorochrome Fura-2/AM. The results were as follows: a) The ASM cells of the guinea pigs were successfully cultured and subcultured by using our improved method and typical peak-valley characteristics were observed under the phase contrast microscope; b) data from immunocytochemical staining with specific α-smooth muscle actin (α-SMA) demonstrated that the cells were ASM cells; c) the growth characteristics and cell viability demonstrated that the cells were in good condition and were able to be applied in the follow-up studies; d) the inhibitory effect of SPFF on the release of intracellular calcium was concentration-dependent when compared with the control and e) the potential mechanisms of SPFF on the inhibition of intracellular calcium may be independent of the ryanodine receptor, but may be closely associated with the inositol 1,4,5-trisphosphate receptor. [ABSTRACT FROM AUTHOR]

The hydrophobic pocket in the HIV-1 gp41 N-terminal heptad repeat (NHR) domain plays an important role in viral fusion and entry into the host cell, and serves as an attractive target for development of HIV-1 fusion/entry inhibitors. The peptide anti-HIV drug targeting gp41 NHR, T-20 (generic name: enfuvirtide; brand name: Fuzeon), was approved by the U.S. FDA in 2003 as the first HIV fusion/entry inhibitor for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, because T20 lacks the pocket-binding domain (PBD), it exhibits low anti-HIV-1 activity and short half-life. Therefore, several next-generation HIV fusion inhibitory peptides with PBD have been developed. They possess longer half-life and more potent antiviral activity against a broad spectrum of HIV-1 strains, including the T-20-resistant variants. Nonetheless, the clinical application of these peptides is still limited by the lack of oral availability and the high cost of production. Thus, development of small molecule compounds targeting the gp41 pocket with oral availability has been promoted. This review describes the main approaches for identification of HIV fusion/entry inhibitors targeting the gp41 pocket and summarizes the latest progress in developing these inhibitors as a new class of anti-HIV drugs. [ABSTRACT FROM AUTHOR]

During the aqueous enzymatic extraction of vegetable oils, a stable emulsion is often formed, which greatly limits the extraction of oil. The structure and properties of the interfacial membrane formed by interfacial proteins, phospholipids and carbohydrates affect the stability of the emulsion. Interfacial proteins are one of the most important components of the interfacial membrane, and their quantity, structure and properties have a significant impact on the properties and stability of the emulsion, and demulsification of the emulsion is the key to increasing the oil content. This article briefly introduces the major components, properties and influential factors of the emulsion, reviews the effects of interfacial protein concentration, structure and properties on the stability of the emulsion, and summarizes the demulsification mechanism of the emulsion from the perspective of changes in interfacial proteins, in order to provide a theoretical reference for future research on the demulsification of the emulsion during the aqueous enzymatic extraction of plant oils.

A correction to the article "Process Development of Halaven®: Synthesis of the C1-C13 Fragment from D-(&#8211)-Gulono-1,4-lactone," by Charles E. Chase and colleagues that was published in the 2013 issue is presented.

A key barrier against developing preventive and therapeutic human immunodeficiency virus (HIV) vaccines is the inability of viral envelope glycoproteins to elicit broad and potent neutralizing antibodies. However, in the presence of fusion inhibitor enfuvirtide, we show that the nonneutralizing antibodies induced by the HIV type 1 (HIV-1) gp41 N-terminal heptad repeat (NHR) domain (N63) exhibit potent and broad neutralizing activity against laboratory-adapted HIV-1 strains, including the drug-resistant variants, and primary HIV-1 isolates with different subtypes, suggesting the potential of developing gp41-targeted HIV therapeutic vaccines. [ABSTRACT FROM AUTHOR]